THE GLOBAL EPIDEMIOLOGY OF INFECTIOUS DISEASES...The global epidemiology of infectious diseases [electronic resource] / edited by Christopher J. L. Murray, Alan D. Lopez, Colin D

GLOBAL BURDEN OF DISEASE AND INJURY SERIES VOLUME IV

THE GLOBAL EPIDEMIOLOGY OF INFECTIOUS DISEASES

World Health OrganizationGeneva

Edited By:Christopher J. L. MurrayAlan D. LopezColin D. Mathers

Edited by

World Health Or gan i za tionGeneva

GLOBAL BURDEN OF DISEASE AND INJURY SERIES

V O L U M E I V

The Global

Epidemiology

of Infectious Diseases

Christopher J. L. Murray

Alan D. Lopez

Colin D. Mathers

WHO Library Cataloguing-in-Publication Data

The global epidemiology of infectious diseases [electronic resource] / edited by Christopher J. L. Murray, Alan D. Lopez, Colin D. Mathers.

1 PDF. -- (Global burden of disease and injury series ; volume 4)

1.Communicable diseases - epidemiology I. Murray, Christopher J. L. II. Lopez, Alan D. III. Mathers, Colin D.

ISBN 92 4 159230 3 (NLM classifi cation: WC 100)

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Table of Contents

List of Tables ........................................................................ v

List of Figures ..................................................................... xi

Global Burden of Disease and Injury Series ForewordRalph H. Henderson ..........................................................xiv

Global Burden of Disease and Injury Series ForewordDean T. Jamison.................................................................xvi

Preface ..............................................................................xxiv

Acknowledgments ..............................................................xxv

Chapter 1: Diarrhoeal DiseasesCaryn Bern .......................................................................... 1

Chapter 2: PertussisArtur M Galazka, Susan E Robertson.................................. 29

Chapter 3: DiptheriaArtur M Galazka, Susan E Robertson.................................. 55

Chapter 4: MeaslesCJ Clements, GD Hussey ................................................... 75

Chapter 5: PoliomyelitisKenji Shibuya, Christopher JL Murray............................... 111

Chapter 6: TetanusA Galazka, M Birmingham, M Kurian, FL Gasse ............... 151

Chapter 7: LeprosyD Daumerie..................................................................... 201

Chapter 8: Dengue and dengue haemorrhagic feverJames W LeDuc, Karin Esteves, Norman G. Gratz ............. 219

iv Global Epidemiology of Infectious Diseases

Chapter 9: Intestinal nematode infectionsDAP Bundy, MS Chan, GF Medley, D Jamison, L Savioli .... 243

Chapter 10: Trachoma-Related Visual LossB Thylefors, K Ranson, A-D Négrel, R Pararajasegaram...... 301

Chapter 11: Chagas DiseaseA Moncayo ...................................................................... 325

Chapter 12: SchistosomiasisKE Mott .......................................................................... 349

vTable of Contents

List of Tables

Chapter 1

1.1 International Classification of Diseases (ICD) codes corresponding to watery diarrhoea and dysentery ............ 3

1.2 Previous estimates of diarrhoeal disease burden for children younger than 5 years in developing countries ................... 4

1.3 Diarrhoeal morbidity and mortality in 276 surveys in children younger than 5 years, using WHO methodology, 1981–1986 .................................................................... 5

1.4 Review of empirical databases on morbidity from diarrhoea: longitudinal studies measuring incidence ........ 7

1.5 Review of empirical databases on mortality from diarrhoea: studies measuring annual deaths per 1000 children ........ 10

1.6 Review of databases on mortality from diarrhoea: estimated from vital registration data in Latin America and the Caribbean .............................................................. 13

1.7 Review of empirical databases on morbidity from diarrhoea: morbidity in various age groups.................... 14

1.8 Review of empirical databases on mortality from diarrhoea: various age groups ....................................................... 15

1.9 Studies of persistent diarrhoea and distribution of mortality by type of diarrhoea ..................................................... 16

1.10 Regional summary estimates for morbidity from diarrhoeal disease ........................................................................ 18

1.11 Regional summary estimates for mortality from diarrhoeal disease ........................................................................ 18

1.12 Estimates for distribution of episodes by type of diarrhoea according to age .......................................................... 19

1.13 Assignment of disability weights according to type of diarrhoea; classification used for calculation of disability-adjusted life years ........................................................ 19

Chapter 2

2.1 Pertussis attack rates, by age, during pertussis outbreaks in Côte d’Ivoire, Guatemala, and Indonesia ................... 33

2.2 Pertussis case fatality rates, by age, United States of America 1927–1989, England and Wales 1980–1991, and Kenya 1974–1976 ........................................................ 36

2.3 Complication rates attributable to pneumonia, seizures, and encephalopathy among pertussis patients in seven studies ......................................................................... 38

2.4 Ninth Revision of the International Classification of Diseases (ICD-9) codes for pertussis ............................. 41

2.5 Number of pertussis cases reported to WHO, by demographic region, 1980, 1985 and 1990 .................... 43

vi Global Epidemiology of Infectious Diseases

2.6 World Health Organization EPI Information System method for estimating number of cases and deaths attributable to pertussis ................................................ 45

2.7 Assumptions concerning completeness of reporting and case fatality rates used in estimating the number of pertussis cases and deaths by demographic region, 1990 .............. 46

2.8 Estimated global number of pertussis cases and deaths in 1990, based on two methods of estimation .................... 47

2.9 Estimated number of pertussis cases, by age, in developing countries, developed countries, and worldwide, 1990 ..... 47

2.10 Estimated number of pertussis deaths, by age, developing countries, developed countries, and worldwide, 1990 ..... 47

2.11 Regional and global levels of coverage with three doses of diphtheria-pertussis-tetanus (DPT) vaccine among children by age 12 months for 1985, 1990 and 1995................... 48

Chapter 3

3.1 Ninth revision of the International Classification of Diseases (ICD-9) codes for diphtheria ........................... 58

3.2 Number of diphtheria cases reported to the World Health Organization from developing and developed countries, and percentage of total cases occurring in developing countries, 1974–1994, based on reports received as of March 1996 ................................................................. 60

3.3 Cyclic occurrence of diphtheria in the world, 16th–20th centuries ...................................................................... 62

3.4 Mortality attributable to diphtheria, by age groups, Hampton Falls, New Hampshire, 1735 .......................... 63

3.5 Diphtheria case fatality rates in urban and rural areas, Ukraine, 1992 and 1993 ............................................... 64

3.6 Estimated number cases of diphtheria, and proportion, by age group, in developing countries, developed countries, and worldwide, 1990.................................................... 66

3.7 Estimated number of diphtheria cases and deaths, by age group, worldwide, 1990 ............................................... 66

3.8 Estimated number of diphtheria cases and deaths, by World development report region, 1990................................... 67

Chapter 4

4.1 Complications of measles.............................................. 784.2 Studies from five countries on the frequency of

complications in measles (as a percentage) ..................... 784.3 Distribution of measles deaths by cause ......................... 804.4 Measles case fatality rates in prospective community

studies, Africa .............................................................. 81

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4.5 Measles case fatality rates in prospective community studies, Americas ........................................................ 83

4.6 Measles case fatality rates in prospective community studies, Asia................................................................ 84

4.7 The estimated burden of measles by World Bank Region 884.8 Annual estimated burden of measles by World Bank

Region, 1990, unadjusted for background mortality....... 904.9 Incidence rates of pneumonia, croup and diarrhoea and

respective case fatality rates in hospitalized patients with measles ....................................................................... 94

4.10 Frequency of bacterial isolates and complications following lung and tracheal aspirates in measles-associated pneumonia ................................................................... 95

4.11 Association between nutritional status and complications974.12 Frequency of central nervous system complications in

measles ........................................................................ 99

Chapter 5

5.1 Percentage distribution of notified cases of poliomyelitis by age-group and median age of notified cases: England and Wales, 1912–19 and 1944–50 ..................................... 113

5.2 Annual incidence of poliomyelitis per 100 000 total population during the period 1976–1980..................... 114

5.3 Poliomyelitis cases in Greater Bombay: clinical outcome1185.4 Change in OPV coverage (percentage) by region .......... 1235.5a Epidemiological estimates for poliomyelitis, 1990,

males ......................................................................... 1275.5b Epidemiological estimates for poliomyelitis, 1990,

females ...................................................................... 130

Chapter 6

6.1 Case fatality ratios in tetanus patients by age, India 1954–1968 and 1975, Nigeria 1974–1984 ............................ 155

6.2 Case fatality ratios associated with tetanus, 1920–1995 1576.3 Age distribution of tetanus cases (percentage of cases

< 20 and > 50 years of age), 1954–1992 ...................... 1636.4 Gender ratios of tetanus cases and deaths, 1944–1990 . 1656.5 Notification efficiencies of tetanus cases, 1969–1992 ... 1676.6 Estimated neonatal mortality rates and neonatal tetanus

mortality rates, and proportion of all neonatal deaths due to tetanus, 1953–1995 ................................................ 172

6.7 Estimated number of non-neonatal tetanus cases and deaths by age in developing and developed countries, 1990..... 182

6.8 Percentage of children immunized in the first year of life with 3 doses of DTP vaccine and percentage of pregnant

viii Global Epidemiology of Infectious Diseases

women immunized with at least 2 doses of tetanus toxoid, by WHO Region, 1993 ............................................... 186

Chapter 7

7.1 Detection and prevalence of leprosy in five African countries, 1986–1989 ................................................. 208

7.2 Detection rates per 1000 by age and sex in five African countries (people 0–14 years of age not included in the sample) ..................................................................... 209

7.3 Detection by age group and type of leprosy in four districts, India, 1993 .................................................. 209

7.4 Incidence rates by age, sex and type of leprosy, Polambakkam, India, 1967–1971 ............................... 210

7.5 Detection rates of leprosy, Brazil: actual rates, 1950 to 1983; predicted rate, 2000.......................................... 210

7.6 Age-specific and type-specific prevalence of leprosy in four Governorates, Egypt, 1986 ......................................... 211

7.7 Prevalence of disability among leprosy patients before the implementation of multidrug therapy: results of various studies ....................................................................... 212

7.8 Impact of multidrug therapy on disability related to leprosy—prevalence of disability: results of various studies ....................................................................... 214

Chapter 8

8.1 Estimates of the burden of dengue haemorrhagic fever, Other Asia and Islands ............................................... 225

8.2 Estimates of the burden of dengue haemorrhagic fever, India.......................................................................... 227

8.3 Estimates of the burden of dengue haemorrhagic fever, China ........................................................................ 228

8.4 Estimates of the burden of dengue haemorrhagic fever, Sub-Saharan Africa ........................................................... 229

8.5 Reported cases of dengue fever, dengue haemorrhagic fever, and deaths attributable to dengue haemorrhagic fever in Latin America and the Caribbean, 1988 to 1992 .......... 230

8.6 Estimates of the burden of dengue haemorrhagic fever, Latin America and the Caribbean ................................ 231

8.7 Dengue haemorrhagic fever reported, selected countries, Other Asia and Islands, 1982–1992............................. 233

8.8 Crude estimate for the global burden of disease attributable to dengue haemorrhagic fever, 1994 ............................ 234

Chapter 9

9.1 Worm burden thresholds for morbidity used in the model ........................................................................ 251

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9.2 Age weights for prevalences used in the model ............. 2529.3 Prevalence classes and reference (set) prevalences used in

the model................................................................... 2569.4a Transition matrix for Ascaris lumbricoides .................. 2579.4b Transition matrix for Trichuris trichiura...................... 2579.4c Transition matrix for hookworms ............................... 2579.5a Estimates of numbers infected and at risk of disability for

Ascaris lumbricoides, by World Bank region ............... 2599.5b Estimates of numbers infected and at risk of disability for

Ascaris lumbricoides, by age group ............................. 2599.6a Estimates of numbers infected and at risk of disability for

Trichuris trichiura, by World Bank region ................... 2609.6b Estimates of numbers infected and at risk of disability for

Trichuris trichiura, by age group ................................. 2609.7a Estimates of numbers infected and at risk of disabililty for

hookworm, by World Bank region............................... 2619.7b Estimates of numbers infected and at risk of disability for

hookworm, by age...................................................... 2619.8 Summary of global burden of helminth infections, by World

Bank region and country or area ................................. 2639.9 Data for DALY calculation, ascariasis, both sexes,

1990.......................................................................... 2689.10 Data for DALY calculation, trichuriasis both sexes,

1990.......................................................................... 2709.11a Data for DALY calculation, hookworm, males, 1990.... 2719.11b Data for DALY calculation, hookworm, females, 1990 . 2729.12a Selected studies investigating the effects of parasitic

helminth infections on mental processing..................... 2749.12b Selected studies investigating the effects of parasitic

helminth infections on physical fitness......................... 279

Chapter 10

10.1 Review of available data on trachomatous blindness: population-based surveys after 1974 ........................... 305

10.2 Ratio of people with low vision (< 6/18 – 3/60) to people with blindness (< 3/60) ............................................... 312

10.3 Ratio of female prevalence of trachomatous blindness to male prevalence.......................................................... 313

10.4 Age distribution of the prevalence of trachomatous blindness ................................................................... 313

10.5 Prevalence of trachomatous blindness and low vision by region ........................................................................ 313

10.6 Age and sex distribution of the people with blindness or low vision attributable to trachoma, China, 1990 ........ 314

10.7 Age and sex distribution of the people with blindness or low vision attributable to trachoma, India, 1990.......... 314

x Global Epidemiology of Infectious Diseases

10.8 Age and sex distribution of the people with blindness or low vision attributable to trachoma, Middle Eastern Crescent, 1990 ........................................................... 315

10.9 Age and sex distribution of the people with blindness or low vision attributable to trachoma, Other Asia and Islands, 1990 ............................................................. 315

10.10 Age and sex distribution of the people with blindness or low vision attributable to trachoma, Sub-Saharan Africa, 1990.......................................................................... 316

10.11 Age and sex distribution of the people with blindness or low vision attributable due to trachoma throughout the world, 1990 ............................................................... 316

Chapter 11

11.1 Prevalence studies of human T. cruzi infection in Latin America .................................................................... 327

11.2 Prevalence of human T. cruzi infection in Latin America, 1975–1985 ................................................................ 328

11.3 Prevalence of Typarrosoma cruzi infected blood in blood banks of selected countries ......................................... 330

11.4 Incidence of cardiac lesions and T. cruzi infection, rates per 1000 person-years ...................................................... 331

11.5 Excess mortality rates with cardiac lesions, rates per 1000 person-years............................................................... 332

11.6 Efficacy of triatomine control tools: percentage of re-infested houses after different interventions, Argentina, Chile, Honduras and Paraguay, April 1994 .................. 335

11.7 Human infection by Trypanosoma cruzi and reduction of incidence, Southern Cone initiative for the elimination of Chagas disease: 1983–2000 ........................................ 336

11.8 Summary of control activities in Central America, 1999.......................................................................... 341

11.9 The time table towards the interruption of transmission of Chagas disease ........................................................... 343

Chapter 12

12.1 Diagnostic methods for schistosomiasis ....................... 35012.2 S. Japonicum empirical databases, China .................... 35712.3 S. japonicum empirical databases by region, Other Asia and

Islands ....................................................................... 36012.4 S. mansoni empirical databases, sub-Saharan Africa .... 36212.5 S. intercalatum empirical databases by region, sub-Saharan

Africa ....................................................................... 36512.6 S. mansoni empirical databases by region, Latin America

and the Caribbean ...................................................... 366

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12.7 S. haematobium empirical databases by region, Middle Eastern Crescent ....................................................... 368

12.8 S.mansoni empirical databases by region, Middle Eastern Crescent .................................................................... 369

12.9 Causes of death related to schistosomiasis ................... 37112.10 Studies of mortality rates associated with schistosomiasis,

World Bank regions .................................................... 37212.11 Epidemiological estimates for schistosomiasis,1990,

males ......................................................................... 37612.12 Epidemiological estimates for schistosomiasis,1990,

females ...................................................................... 380

xii Global Epidemiology of Infectious Diseases

List of Figures

Chapter 2

2.1 Percentage distribution of pertussis cases before (grey bars) and after (black bars) widespread use of pertussis vaccine, Poland (1971 versus 1991), United States (1918–21 versus 1980–89) .................................................................... 34

2.2 Reported annual incidence of pertussis, by WHO region, 1974–1994 .................................................................. 44

Chapter 3

3.1 Annual diphtheria incidence reported to the World Health Organization, by region, 1974–1994, based on reports received as of March 1996 ............................................ 61

3.2 Age-specific immunity of a hypothetical population before and after widespread use of diphtheria vaccine .............. 62

Chapter 4

4.1 Number of cases of measles and measles vaccine coverage reported globally, 1974–1996 ....................................... 76

4.2 Age of onset of measles in the pre-vaccine era ................ 87

Chapter 5

5.1 Global immunization coverage (per cent) of OPV3 for children in the first year of life.................................... 113

5.2 Reported incidence of indigenous poliomyelitis ............ 1145.3 Annual incidence of paralytic poliomyelitis, 1990 ........ 1265.4 Annual number of deaths due to poliomyelitis, 1990 .... 1335.5 DALYs lost due to paralytic poliomyelitis, 1990........... 1335.6 Immunization status of poliomyelitis cases in Shandong

Province, 1990 ........................................................... 1365.7 Reduction of polio incidence by region, 1990 .............. 1375.8 Anticipated reduction of polio incidence with full vaccine

coverage .................................................................... 138

Chapter 6

6.1 Incidence and mortality rates and case fatality ratios for neonatal tetanus, Denmark, 1920–1960....................... 156

6.2 Reported age-specific tetanus incidence rates, by 5-year intervals, United States, 1965–1994 ............................ 162

6.3 Number of tetanus cases and immunization coverage reported to WHO by national authorities, 1975–1995.. 169

6.4 Reported number of neonatal and non-neonatal tetanus cases by WHO region, 1974–1992 .............................. 170

xiiiTable of Contents

6.4 Reported number of neonatal and non-neonatal tetanus cases by WHO region, 1974–1992 (continued)............. 171

6.5 Estimated number of tetanus deaths occurring in the world by WHO region, 1990 ................................................ 183

6.6 Estimated neonatal tetanus mortality rate per 1000 live births, 1990 ............................................................... 184

6.7 Reported coverage with at least two doses of tetanus toxoid among pregnant women, 1995.......................... 187

Chapter 11

11.1 Southern Cone Initiative for the elimination of transmission of Chagas disease: incidence of infection 1980–2000 ... 336

Foreword to The GLOBAL BURDEN OF DISEASE AND INJURY SERIES

Ralph H. Henderson

The collection and use of timely and reliable health information in sup-port of health policies and programmes have been actively promoted by the World Health Organization since its foundation. Valid health statis-tics are required at all levels of the health system, ranging from data for health services support at the local community level, through to national statistics and information used to monitor the effectiveness of national health strategies. Equally, regional and global data are required to moni-tor global epidemics and to continuously assess the effectiveness of global public health approaches to disease and injury prevention and control, as coordinated by WHO technical programmes. Despite the clear need for epidemiological data, reliable and comprehensive health statistics are not available in many Member states of WHO, and, indeed, in many countries the ascertainment of disease levels, patterns and trends is still very uncertain.

In recent years, monitoring systems, community-level research and dis-ease registers have improved in both scope and coverage. Simultaneously, research on the epidemiological transition has increased our understanding of how the cause structure of mortality changes as overall mortality rates decline. As a consequence, estimates and projections of various epidemio-logical parameters, such as incidence, prevalence and mortality, can now be made at the global and regional level for many diseases and injuries. The Global Burden of Disease Study has now provided the public health community with a set of consistent estimates of disease and injury rates in 1990. The Study has also attempted to provide a comparative index of the burden of each disease or injury, namely the number of Disability-Adjusted Life Years (DALYs) lost as a result of either premature death or years lived with disability.

The fi ndings published in the Global Burden of Disease and Injury Series provide a unique and comprehensive assessment of the health of populations as the world enters the third millennium. We also expect that the methods described in the various volumes in the series will stimulate

xvForeword

Member States to improve the functioning and usefulness of their own health information systems. Nonetheless, it must be borne in mind that the results from an undertaking as ambitious as the Global Burden of Disease Study can only be approximate. The reliability of the data for cer-tain diseases, and for some regions, is extremely poor, with only scattered information available in some cases. To extrapolate from these sources to global estimates is clearly very hazardous, and could well result in errors of estimation. The methods that were used for some diseases (e.g. cancer) are not necessarily those applied by other scientists or institutions (e.g. the International Agency for Research on Cancer) and hence the results obtained may differ, sometimes considerably, from theirs. Moreover, the concept of the DALY as used in this Study is still under development, and further work is needed to assess the relevance of the social values that have been incorporated in the calculation of DALYs, as well as their applicabil-ity in different socio-cultural settings. In this regard, WHO and its vari-ous partners are continuing their efforts to investigate burden-of-disease measurements and their use in health policy decision-making.

Dr Ralph H. Henderson is former Assistant Director-General of the World Health Organization.

Foreword to The GLOBAL BURDEN OF DISEASE AND INJURY SERIES

Dean T. Jamison

Rational evaluation of policies for health improvement requires four basic types of information: a detailed, reliable assessment of epidemiological conditions and the burden of disease; an inventory of the availability and disposition of resources for health (i.e. a system of what has become known as national health accounts); an assessment of the institutional and policy environment; and information on the cost-effectiveness of available technologies and strategies for health improvement. The Global Burden of Disease and Injury Series provides, on a global and regional level, a detailed and internally consistent approach to meeting the fi rst of these information needs, that concerning epidemiological conditions and disease burden. It fully utilizes what information exists while, at the same time, pointing to great variation—across conditions and across countries—in data quality. In the Global Burden of Disease and Injury Series, Christo-pher Murray, Alan Lopez and literally scores of their collaborators from around the world present us with a tour de force: its volumes summarize epidemiological knowledge about all major conditions and most risk fac-tors; they generate assessments of numbers of deaths by cause that are consistent with the total numbers of deaths by age, sex and region provided by demographers; they provide methodologies for and assessments of aggregate disease burden that combine—into the Disability-Adjusted Life Year or DALY measure—burden from premature mortality with that from living with disability; and they use historical trends in main determinants to project mortality and disease burden forward to 2020. Publication of the Global Burden of Disease and Injury Series marks the transition to a new era of health outcome accounting—an era for which these volumes establish vastly higher standards for rigour, comprehensiveness and internal consistency. I fi rmly predict that the offi cial reporting of health outcomes in many countries and globally will increasingly embody the approach and standards described in this series.

The Global Burden of Disease and Injury Series culminates an evolution-ary process that began in the late 1980s. Close and effective collaboration

xviiForeword

between the World Bank and the World Health Organization initiated, supported and contributed substantively to that process.

Background

Work heading to the Global Burden of Disease and Injury Series proceeded in three distinct phases beginning in 1988. Intellectual antecedents go back much further (see Murray 1996, or Morrow and Bryant 1995); perhaps the most relevant are Ghana’s systematic assessment of national health problems (Ghana Health Assessment Project Team 1981) and the introduc-tion of the QALY (quality-adjusted life year)—see, for example Zeckhauser and Shepard (1976). My comments here focus on the three phases leading directly to the Global Burden of Disease and Injury Series.

Phase 1 constituted an input to a four-year long “Health Sector Priorities Review” initiated in 1988 by the World Bank; its purpose was to assess “…the signifi cance to public health of individual diseases for related clus-ters of diseases…and what is now known about the cost and effectiveness of relevant interventions for their control” (Jamison et al. 1993, p. 3; that volume provides the results of the review). Dr Christopher Murray of Har-vard University introduced the DALY as a common measure of effectiveness for the review to use across interventions dealing with diverse diseases, and Dr Alan Lopez of the World Health Organization prepared estimates of child deaths by cause that were consistent with death totals provided by demographers at the World Bank (Lopez 1993). At the same time, and in close coordination, a World Bank effort was preparing consistent estimates for adult (15-59) mortality by cause for much of the developing world (Feachem et al. 1992). Ensuring this consistency was a major advance and is a precondition for systematic attempts to measure disease burden. (Estimates of numbers of deaths by cause that are not constrained to sum to a demographically-derived total seem inevitably to result in substantial overestimates of deaths due to each cause.) Phase 1 of this effort, then, introduced the DALY and established important consistency standards to guide estimation of numbers of deaths by cause.

Phase 2 constituted the fi rst attempt to provide a comprehensive set of estimates not only of numbers of deaths by cause but also of total disease burden including burden from disability. This effort was commissioned as background for the World Bank’s World Development Report 1993: Investing in Health; it was co-sponsored by the World Bank and the World Health Organization; and it was undertaken under the general guidance of a committee chaired by Dr JP Jardel (then Assistant Director-General of WHO). The actual work was conceptualised, managed and integrated by Drs Murray and Lopez and involved extensive efforts by a large number of individuals, most of whom were on the WHO staff. First publication of the estimates of 1990 disease burden appeared in Appendix B of Investing in Health (World Bank 1993) and, more extensively, in Murray, Lopez and Jamison (1994). The World Health Organization subsequently published

xviii Global Epidemiology of Infectious Diseases

a volume containing a full account of the methods used and a somewhat revised and far more extensive presentation of the results (Murray and Lopez 1994).

Preparation and publication of the Global Burden of Disease and Injury Series constitutes Phase 3 of this sequence of efforts. As in the earlier phases, the Global Burden of Disease and Injury Series was undertaken to inform a policy analysis—in this case an assessment of priorities for health research and development in developing countries being guided by WHO’s Ad Hoc Committee on Health Research Relating to Future Intervention Options. The Committee sought updated estimates of disease burden for 1990, projections to 2020 and an extension of the methods to allow assessment of burden attributable to selected risk factors. The committee’s report (Ad Hoc Committee 1996) and the Global Burden of Disease and Injury Series appear as companion documents.

Chapters summarizing results from the Global Burden of Disease and Injury Series appear in volume I, The Global Burden of Disease; underly-ing epidemiological statistics for over 200 conditions appear in volume II, Global Health Statistics. The next two volumes of the Series provide, for the fi rst time, chapters detailing the data on each condition or cluster of conditions in the areas of reproductive health and infectious diseases.

Will there be a fourth phase? I am sure there will. Reporting of the dis-ease-specifi c and risk factor analysis in the Global Burden of Disease and Injury Series will provoke constructive and perhaps substantial criticism and improvements; country-specifi c assessments will multiply (over 20 are now under way) and they, too, will modify and enrich current estimates, see for example, Lozano et al. 1994. Estimates of trends in deaths by cause have recently been initiated, which will serve as the precursor for estimates of trends in disease burden. Methodologies will be criticized and, I would predict, constructively revised. Unfi nished elements of the agenda discussed in the next section will be completed. Phase 4, centred on the estimation of global and regional disease burden for 2000 and including a look at the past, will take us well beyond where we now are.

The Agenda

Disease burden (or numbers of deaths by cause) were initially partitioned in three separate ways for different age, sex and regional groupings (Mur-ray et al. 1994). One partition is by risk factor—genetic, behavioural, environmental and physiological. The second is by disease. The third is by consequence—premature mortality by consequence—premature mortality by consequence— at different ages and different types of disability (e.g. sensory, cognitive functioning, pain, affective state, etc.). A fourth partition, by reason for remaining burden, was later introduced (Ad Hoc Committee, 1996).

Disaggregation by risk factor helps guide policy concerning primary and secondary prevention, including development of new preventive measures. Disaggregation by disease helps guide policy concerning cure, secondary

xixForeword

prevention and palliation; and disaggregation by consequence helps guide policies for rehabilitation.

Work on the disease burden assessment agenda began with assessments of mortality and burden by disease; the Global Burden of Disease and Injury Series advances the agenda in that domain by revising and adding great detail on disease burden estimates. More recently, the World Health Report for 2002 (World Health Organization, 2002) provides an exten-sive assessment of the burden from a range of important risk factors; this extends usefulness of the work to the domain of prevention policy.

There remains, however, an important unfi nished agenda. The disease burden associated with different types of disability remains to be assessed; perhaps part of the reason for neglect of rehabilitation in most discussion of health policy is the lack of even approximate information on burden due to disability or on the DALY gains per unit cost of rehabilitative intervention.

A related agenda item—relevant to planning for curative and, particu-larly, rehabilitative intervention—is to present disease burden estimates from a current prevalence perspective. The dominant perspective of work so far undertaken, including in the Global Burden of Disease and Injury Series, is that of adding up over time the burden that will result from all conditions incident in a given year (here 1990); this well serves the devel-opment of primary prevention policy and of treatment policy for diseases of short duration. The prevalence perspective complements the incidence one by assessing how much burden is being experienced during a par-ticular year by chronic conditions or by disabilities; those conditions or disabilities will often have been generated sometime in the past. From an incidence perspective, disability in this year from, say, an injury occurring a decade ago would generate DALY loss in the year of incidence; but to guide investment in rehabilitation we need to know how much disability exists today, i.e., we need a prevalence perspective. Murray and Lopez in The Global Burden of Disease and in Global Health Statistics provide the basic estimates of prevalence of different disabilities and fi rst glimpses of the prevalence perspective.

A fi nal major agenda item is to establish for each condition and in the aggregate how much of the potential current burden is in fact being averted by existing interventions and how much of the remaining burden persists because of lack of any intervention, lack of cost-effective interventions, or because of ineffi ciency of the system.

Uses of DALY and Disease Burden Measurement

DALYs have six major uses to underpin health policy. Five of these relate to measurement of the burden of disease; the fi nal one concerns judging the relative priority of interventions in terms of cost-effectiveness.

Assessing performance. A country-specifi c (or regional) assessment of the

xx Global Epidemiology of Infectious Diseases

burden of disease provides a performance indicator that can be used over time to judge progress or across countries or regions to judge relative performance. These comparisons can be either quite aggregated (in terms of DALYs lost per thousand population ) or fi nely disaggregated to allow focused assessment of where relative performance is good and where it is not. The Global Burden of Disease and Injury Series with its burden assessments for eight regions in 1990—and with the increasing number of country-specifi c assessments that it will report—will provide, I predict, the benchmark for all subsequent work. The most natural comparison is to the development of National Income and Product Accounts (NIPAs) by Simon Kuznets and others in the 1930s, which culminated in 1939 with a complete NIPA for the United Kingdom prepared by James Meade and Richard Stone at the request of the UK Treasury. NIPAs have, in the subsequent decades, transformed the empirical underpinnings of economic policy analysis. One of the leading proponents of major changes in NIPAs has put in this way:

The national income and product accounts for the United States (NIPAs), and kindred accounts in other nations, have been among the major con-tributions to economic knowledge over the past half century…Several generations of economists and practitioners have now been able to tie theoretical constructs of income output, investment, consumption, and savings to the actual numbers of these remarkable accounts with all their fi ne detail and soundly meshed interrelations. (Eisner 1989).

My own expectation is that this series will, over a decade or two, initiate a transformation of health policy analysis analogous to that initiated for economic policy by the introduction of NIPAs in the late 1930s. Today most health policy work concerns only cost, fi nance, process and access; burden of disease (and risk factor) assessments should soon allow full incorporation of performance measures in policy analysis.

Generating a forum for informed debate of values and priorities. The assessment of disease burden in a country-specifi c context in practice involves participation of a broad range of national disease specialists, epidemiologists and, often, policy makers. Debating the appropriate values for, say, disability weights or for years of life lost at different ages helps clarify values and objectives for national health policy. Discussing the inter-relations among diseases and their risk factors in the light of local conditions sharpens consideration of priorities. And the entire pro-cess brings technically informed participants to the table where policy is discussed. The preparation of a well-defi ned product generates a process with much value of its own.

Identifying national control priorities. Many countries now identify a relatively short list of interventions, the full implementation of which

xxiForeword

becomes an explicit priority for national political and administrative atten-tion. Examples include interventions to control tuberculosis, poliomyelitis, HIV infection, smoking and specifi c micronutrient defi ciencies. Because political attention and administrative capacity are in relatively fi xed and short supply, the benefi ts from using those resources will be maximized if they are directed to interventions that are both cost-effective and aimed at problems associated with a high burden. Thus, national assessments of disease burden are instrumental for establishing this short list of control priorities.

Allocating training time for clinical and public health practitioners. Medical schools offer a fi xed number of instructional hours; training programmes for other levels and types of practitioners are likewise limited. A major instrument for implementing policy priorities is to allocate this fi xed time resource well—again that means allocation of time to training in interven-tions where disease burden is high and cost-effective interventions exist.

Allocating research and development resources. Whenever a fi xed effort will have a benefi t proportional not to the size of the effort but rather to the size of the problem being addressed, estimates of disease burden become essential for formulation of policy. This is the case with political attention and with time in the medical school curriculum; and it is likewise true for the allocation of research and development resources. Developing a vaccine for a broad range of viral pneumonias, for example, would have perhaps hundreds of times the impact of a vaccine against disease from Hanta virus infection. Thus information on disease or risk factor burden is one (of several) vital inputs to inform research and development resource allocation. Indeed, as previously noted, this series—with its disease burden assessments for 1990, its projections to 2020 and its initial assessment of burden due to risk factors—was commissioned to inform a WHO Com-mittee charged with assessing health research and development priorities for developing countries (Ad Hoc Committee 1996).

The Committee sought not only to know the burden by condition, but also to partition the burden remaining for each condition into several distinct parts refl ecting the importance of the reasons for the remaining disease burden. This division into four parts was undertaken for several conditions; a major agenda item for future analysis is to undertake such a partitioning systematically for all conditions so that there could be rea-sonably approximate answers to such questions as “How much of the remaining disease burden cannot be addressed without major biomedical advances?" Or, “How much of the remaining disease burden could be averted by utilizing existing interventions more effi ciently?” Arguably most of the spectacular gains in human health of the past century have resulted from advances in knowledge (although improvements in income and education have also played a role). If so, improving research and development policy in health may be more important than improving

xxii Global Epidemiology of Infectious Diseases

policy in health systems or fi nance; improved assessments and projections of disease burden will be critical to that undertaking.

Allocating resources across health interventions. Here disease burden assessment often plays a minor role; the task is to shift resources to inter-ventions which, at the margin, will generate the greatest reduction in DALY loss. When there are major fi xed costs in mounting an intervention—as is the case with political and managerial attention for national control priori-ties—burden estimates are indeed required to optimize resources allocation. But, typically, much progress can be made with only an understanding of how the DALYs gained from an intervention vary with the level of expen-diture on it; such assessments are the stuff of cost-effectiveness analysis. The DALY as a common measure of effectiveness allows comparison of cost-effectiveness across intervention addressing all conditions; such an initial effort was undertaken for the World Bank’s “Health Sector Priori-ties Review” (Jamison et al. 1993) in the late 1980s using a forerunner to the DALY utilized in this series.

———

The Global Burden of disease and Injury Series contains the only available internally consistent, comprehensive and comparable assessments of causes of death, incidence and prevalence of disease and injury, measures and projections of disease burden, and measures of risk factor burden. In that sense the authors’ contributions represent a landmark achievement and provide an invaluable resource for policy analyst and scholars. This effort dramatically raises the standard by which future reporting of health condi-tions will be judged. Yet, the very need for the ad hoc assessments that the volumes in this series report, points to important gaps in the international system for gathering, analysing and distributing policy-relevant data on the health of populations. Without information on how levels and trends in key indicators in their own countries compare with other countries, national decision-makers will lack benchmarks for judging performance. Likewise students of health systems will lack the empirical basis for forming outcome-based judgements on which policies work—and which do not. I hope, then, that one follow-on to the Global Burden of Disease and Injury Series will be the institutionalization of continued efforts to generate and analyse internationally comparable data on health outcomes.

Dean T. Jamison is Professor of Public Health and of Education at the University of California Los Angeles, and a Fellow at the Fogarty International Center of the National Institutes for Health. He recently served as Director, Economics Advisory Service, at the World Health Organization in Geneva, and is currently leading the preparation of the second edition of Disease Control Priorities in Developing Countries.

xxiiiForeword

References

Ad Hoc Committee on Health Research Relating to Future Intervention Options (1996) Investing in health research and development. World Health Organiza-tion. Geneva (Document TDR/Gen/96/1).

Eisner R (1989) The total incomes system of accounts. Chicago, University of Chicago Press.

Feachem RGA et al., eds. (1992) The health of adults in the developing world. New York, Oxford University Press for the World Bank.

Ghana Health Assessment Project team (1981) A quantitative method of assessing the health impact of different diseases in less developed countries. International Journal of Epidemiology, 10:73-80.

Goerdt A et al. (1996) Disability: defi nition and measurement issues. In: Murray CJL and Lopez AD, eds., The global burden of disease: a comprehensive assess-ment of mortality and disability from diseases, injuries, and risk factors in 1990 and projected to 2020. Cambridge, Harvard University Press.

Jamison DT et al., eds. (1993) Disease control priorities in developing countries. New York, Oxford University Press for the World Bank.

Lopez AD (1993) Causes of death in industrial and developing countries: estimates for 1985-1990. In: Jamison DT et al., eds. Disease control priorities in developing countries. New York, Oxford University Press for the World Bank, 35-50.

Lozano R et al. (1994) El peso de la enfermedad en México: un doble reto. [The national burden of disease in México: a double challenge.] Mexico, Mexican Health Foundation, (documentos para el análisis y la convergencia, No. 3).

Morrow RH, Bryant JH (1995) Health policy approaches to measuring and valuing human life: conceptual and ethical issues. American journal of public health, 85(10):1356-1360.

Murray CJL (1996) Rethinking DALYs. In: Murray CJL and Lopez AD, eds., The global burden of disease: a comprehensive assessment of mortality and disability from diseases, injuries, and risk factors in 1990 and projected to 2020. Cambridge, Harvard University Press.

Murray CJL and Lopez AD, eds. (1994) Global comparative assessments in the health sector: disease burden, expenditures and interventions packages. Geneva, World Health Organization.

Murray CJL, Lopez AD, Jamison DT (1994) The global burden of disease in 1990: summary results, sensitivity analysis and future directions. Bulletin of the World Health Organization, 72(3):495-509.

World Bank (1993) World development report 1993: investing in health. New York, Oxford University Press for the World Bank.

World Health Organization. World health statistics annual, various years. Geneva, WHO.

World Health Organization (2002). World health report 2002: reducing risks, promoting healthy life, Geneva, WHO.

Zeckhauser R, Shepard D (1976) Where now for saving lives? Law and contemporary problems, 40: 5-45.

This fourth volume of the Global Burden of Disease and Injuries Seriesprovides the reader with information on the epidemiology and burden of major infectious and parasitic diseases. As with previous volumes of the Global Burden of Disease study, the chapters in this book detail the situation as experienced in the year 1990. Since then the epidemiology of some of the conditions described has changed, and where this is the case the authors have added a brief paragraph acknowledging this. The chapters therefore do not provide a detailed update on the current burden current burden currentof disease, which is accommodated in the documentation of the Global Burden of Disease 2000 and published elsewhere.

In Chapter 1 Bern focuses on diarrhoeal diseases which were a major contributor to the global burden of infectious disease in the year 1990 and still account for high numbers of infections in childhood. This is followed by fi ve detailed and focussed chapters on the burden of vaccine-preventable diseases. In Chapters 2 and 3 Robertson and Galazka describe the epide-miology and burden of pertussis and diphtheria, respectively. In Chapter 4 Clemens and colleagues concentrate on the global epidemiology of measles which has undergone signifi cant change in recent years. While approxi-mately 4 million children died of measles in 1990, it is estimated that this number has fallen well below 1 million in 2000. In Chapter 5 Shibuya and Murray summarise the global burden of poliomyelitis, which has similarly been transformed by recent efforts in poliomyelitis eradication. Birmingham and Galazka give a detailed account of the epidemiology of tetanus in Chapter 6.

In Chapter 7 Daumerie informs the reader about the global situation of leprosy, followed by Chapter 8 in which LeDuc describes the epidemiology of dengue. Chapter 9 by Bundy and colleagues provides an overview of intestinal nematode infestations, which give rise to considerable disease burden world-wide. In Chapter 10 Thylefors and colleagues focus on the global burden of trachoma whose epidemiology has undergone some change in the recent past. Moncayo gives a detailed account of the burden

Preface

xxvPreface

of Chagas’ Disease in the Americas in Chapter 11 and provides a pertinent update on recent efforts to eliminate the disease. The volume concludes with Chapter 12 by the late Mott and fi nalised by Mathers who describe the epidemiology of schistosomiasis.

This volume summarises the burden of twelve major infectious and parasitic diseases. Volume 3 also contained chapters detailing the global epidemiology of HIV/AIDS and of other sexually transmitted diseases in 1990. These chapters provide information on the data sources and meth-odological approaches to measuring infectious disease burden that are still relevant today for analysis of current burden, as well as for interpreting time trends between 1990 and 2000 estimates of infectious disease burden. It is our hope that these chapters will also stimulate further debate about the availability and validity of the data, methods and assumptions used to arrive at disease estimates and spur efforts to improve the availability and quality of epidemiological data on these diseases.

This will be the fi nal volume of the original Global Burden of Disease and Injuries Series. The Global Burden of Disease study has stimulated further constructive debate, methodological developments and new analy-ses in summary measures of population health (Murray et al. 2002), in comparative risk assessment (Ezzati et al. 2004) and in the assessment of priorities for interventions (Tan Torres Edejer et al. 2003). Methods and data sources for the assessment of the burden of nutritional defi ciencies, non-communicable diseases and injuries have also evolved and are being progressively documented as part of the Global Burden of Disease 2000 project (draft documentation is available at www.who.int/evidence/bod). Substantial documentation of the Global Burden of Disease 2000 study has also been published in peer reviewed journals and books, and we anticipate that there will be further publications containing revised and more extensive presentation of the methods and results.

CJLMADLCDM

References

Ezzati M, Lopez A, Rodgers A, Murray CJL (2004) Comparative quantifi cation of health risks: global and regional burden of disease attributable to several major risk factors. Geneva, WHO.

Murray CJL., Salomon, JA, Mathers CD, Lopez AD (2002) Summary measures of population health: concepts, ethics, measurement and applications. Geneva, WHO.

Tan-Torres Edejer T, Baltussen R, Adam T, Hutubessy R, Acharya A, Evans DB, Murray CJL (2003) Making choices in health: WHO guide to cost-effectiveness analysis. Geneva, WHO.

Numerous people have contributed to bring this fourth volume of the 1990 Global Burden of Disease and Injuries Series to conclusion. First and foremost we thank Claudia Stein and Christina Bernard, our editorial managers who were instrumental in ensuring the completion of this task. They pursued chapter submissions with dogged determination, edited the manuscripts, critically reviewed them for consistency with the numbers published in Volumes 1 and 2, and organised the editorial process. Their efforts have been invaluable in achieving the production of this book and are very gratefully acknowledged. We are grateful to David Bramley for expert legal advice, Kai Lashley for excellent editorial assistance, and Kenji Shibuya and Lara Wolfson for much valued scientifi c input. We gratefully acknowledge the efforts of Emmanuela Gakidou in pursuing chapter submissions in the earlier stages of the process and Marie-Claude von Rulach and Susan Piccolo for superb secretarial support. We also thank Soma Ganguli, Michaela Herinkova, Petra Schuster for additional secretarial support.

This volume has been in preparation for some time, and where authors were unable to fi nalise their chapters others have completed the task, where possible. Former authors who were unable to conclude their work are acknowledged as co-authors in this volume. We are particularly grate-ful for the pioneering manuscripts of those who sadly passed away while preparing this publication: A Galazka and K Mott. To acknowledge their invaluable contribution to this volume and burden of disease epidemiology at large, Maureen Birmingham and Susan Robertson have kindly taken on the task to complete the chapters by A Galazka, and the editors that of K Mott.

CJLMADLCDM

Acknowledgments

Diarrhoeal DiseasesCaryn Bern

Chapter 1

Introduction

Diarrhoea remains a leading cause of morbidity and mortality in the world, predominantly affecting children in developing countries. Each child in the world experiences an average of one to three episodes of diarrhoea per year, with incidence rates as high as 10 per year for children in some areas (Bern et al. 1992b). During the 1990s diarrhoea was estimated to cause 20 to 25 per cent of mortality among children younger than 5 years in the developing world (Bern et al. 1992b). Effective interventions, including correct case management (oral rehydration therapy, continued feeding and antibiotics in cases of dysentery), promotion of breastfeeding, and better weaning practices, have the potential to reduce the burden of diarrhoeal disease substantially in the future.

This chapter reviews the global burden of morbidity and mortality from infectious diarrhoea, especially dysentery and persistent diarrhoea, as well as examining the issues involved in reducing that burden of disease through existing interventions.

Aetiology And Clinical Patterns

While non-infectious causes of diarrhoea may play a role, for example among the hospitalized elderly (Lew et al. 1991), the most important aetiological agents of diarrhoea are viral and bacterial, with rotavirus and enterotoxigenic E. coli generally identifi ed most frequently among children E. coli generally identifi ed most frequently among children E. coliin developing countries, and viral aetiologies playing a proportionately greater role in industrialized settings (Bern & Glass 1994, Huilan et al. 1991). Even among the elderly, infectious diarrhoea may be an important contributing cause of mortality (Lew et al. 1991).

Diarrhoea causes morbidity and mortality through several mechanisms. Acute watery diarrhoea can lead to dehydration severe enough to require hospitalization and to cause death. Rotavirus is the agent most frequently associated with acute dehydrating diarrhoea, and primarily affects children

2 Global Epidemiology of Infectious Diseases

younger than 2 years (Kapikian & Chanock 1990). Vibrio cholerae can cause epidemics of dehydrating diarrhoea affecting all age groups, and may lead to high case-fatality rates in the absence of rapid public health intervention, as in the recent epidemic among Rwandan refugees in Goma, Zaire (Goma Epidemiology Group 1995). Dysentery, most often associated with Shigella species, may cause death through bacteraemia or hypogly-caemia (Bennish 1991), but also is associated with a more marked effect on growth (Black, Brown & Becker 1984a). Dysentery may present a refractory problem in that case management depends upon treatment with antibiotics, and resistance is a widespread problem in areas with high rates of dysenteric morbidity and mortality (Salam & Bennish 1991).

Persistent diarrhoea, defined as diarrhoea lasting at least 14 days (World Health Organization 1988), has been recognized recently as an entity which carries a risk of both nutritional compromise and of mortal-ity in excess of that for acute diarrhoea (Bhan et al. 1989, Victora et al. 1993). While enteroaggregative E. coli and cryptosporidium have been associated with persistent diarrhoea (Bhan et al. 1989, Baqui et al. 1992a, Henry et al. 1992), often no specifi c pathogen can be implicated (Lanata et al. 1992), and serial infection with different organisms may play a role (Baqui et al. 1992a).

Definitions and codes

Diarrhoea is a symptom complex defi ned by an increased number of stools of a looser consistency than usual per 24-hour period. In a comparison of the defi nitions commonly used in epidemiological studies, Baqui et al. (1991) reported that those with the best balance of sensitivity and specifi city were 3 or more loose stools, or any number of stools containing blood, in a 24-hour period, while the optimal defi nition of the end of an episode was 3 diarrhoea-free days. The authors concluded that differences in defi nitions, especially of the end of the episode, made a substantial difference to the fi nal estimate of diarrhoeal incidence, and that validation of the defi nition of diarrhoea was important to the overall validity of a study.

The ninth and tenth revisions of the International Classifi cation of Diseases (ICD-9 and ICD-10) classify diarrhoea according to aetiological agent, rather than symptom complex. Because a number of agents may cause either watery or bloody diarrhoea, and because persistent diarrhoea is defi ned by duration of illness rather than aetiology, the ICD codes do not correspond neatly to the symptom complexes described in this chapter. An approximate mapping of symptom complexes and codes is, however, possible (Table 1.1). Persistent diarrhoea, which is discussed below, has been associated with a variety of aetiological agents which also cause acute watery diarrhoea and dysentery. Thus it is not included in the table, but may fall under any of several ICD classifi cations, depending on what agent, if any, is identifi ed.

3Diarrhoeal Diseases

Methods for the measurement of diarrhoeal morbidity and mortality

Community longitudinal studies provide the most reliable data for diar-rhoeal disease incidence and, if the study size is large enough, mortality estimates. Even for longitudinal studies, however, morbidity estimates can be shown to vary with the intensity of surveillance, with twice-weekly surveillance resulting in higher estimates than less frequent surveillance (Bern et al. 1992b). For example, in one study that made regional estimates for diarrhoeal morbidity, the reported number of episodes per child per year was consistently higher in studies in Latin America than in studies in India or Bangladesh, but the frequency of surveillance in the Latin American studies was also consistently higher (Bern et al. 1992b). How-ever, in a more recent study conducted in India with home visits every 3 days, the incidence of diarrhoea was found to be similar to that in the most frequently surveyed Latin American communities (Bhandari, Bhan & Sazawal 1994). This suggests that among children in the poorest com-munities, diarrhoeal disease incidence is remarkably similar around the world, and that in studies with less frequent surveillance, the shorter or less severe episodes are likely to be missed. At the same time, several stud-ies which monitored diarrhoeal morbidity among children from different socioeconomic strata in the same locality have demonstrated substantial variation in incidence rates, with poorer children experiencing from 2 to 6 times the number of annual episodes as more affl uent children (Araya et al. 1986, Guerrant et al. 1983).

While longitudinal studies are best for measurement of incidence of disease, the number of individuals followed is generally too small to allow measurement of mortality. Hence active surveillance, survey data and vital registration are the principal methods used for mortality assess-ment. For developing countries, where nearly all mortality from diarrhoea occurs, vital registration is unreliable or incomplete, and a so-called “gold

Table 1.1 International Classifi cation of Diseases (ICD) codes corresponding to watery diarrhoea and dysentery

Symptom complex Aetiological agent ICD-8 and 9 ICD-10

Watery diarrhoea CholeraSalmonella gastroenteritisBacterial food poisoningOther bacteriaGiardiasisViral gastroenteritisGastroenteritis, presumed infectious

001003005008.2–008.5007.1008.6009.1, 009.3

A00A02A05A04.0–A04.9A07.1A08A09

Dysentery ShigellaCampylobacterYersiniaAmoebiasisDysentery, aetiology unspecifi ed

004008.43008.44006009.0, 009.2

A03A04.5A04.6A06A09


standard” does not exist for its assessment. In addition, where vital regis-tration is incomplete or absent, cause of death is ascertained on the basis of verbal autopsy methods, and the sensitivity and specifi city of those methods for the diagnosis of diarrhoea and of dehydration have varied substantially in different evaluations (Snow et al. 1992, Kalter et al. 1990). In one study, verbal autopsy identifi ed diarrhoeal deaths with a specifi c-ity greater than 80 per cent, but a sensitivity less than 50 per cent (Snow et al. 1992), while in another, the performance of verbal autopsy for the diagnosis of diarrhoea was adequate, but the identifi cation of deaths from severe dehydration was problematic (Kalter et al. 1990). Nevertheless, estimates based on these methods refl ect the best available data on the magnitude of diarrhoeal mortality, and are useful for comparison to the estimates published by the Global Burden of Disease Study (World Bank 1993, Murray & Lopez 1996).

Review of past attempts to quantify disease burden

Morbidity from diarrhoea disproportionately affects children younger than 5 years, and mortality from diarrhoea is overwhelmingly a problem of infants and young children in developing countries. Thus, most attempts to quantify disease burden from diarrhoea have focused on these age groups, and on developing countries. Three methods have been used to estimate global disease burden (Table 1.2).

Snyder & Merson (1982) developed estimates based primarily on lon-gitudinal studies of children for morbidity, and included vital registration data for mortality estimates. These estimates were recently updated, using more recent longitudinal studies to estimate morbidity and including stud-ies employing a wider range of methodologies, including vital registration and cross-sectional surveys, to estimate mortality (Bern et al. 1992b). For each of these studies, the empirical database was reviewed, and a median diarrhoeal incidence and mortality rate calculated for each region for which data were available, and for all developing countries excluding China. This

Table 1.2 Previous estimates of diarrhoeal disease burden for children younger than 5 years in developing countries

Authors (reference) YearDeaths per year

(millions)Deaths per

1000 per yearEpisodes per child per year Methods

Snyder & Merson (1982)

1982 4.6 13.6 2.2 Longitudinal cohorts and active surveillance

Bern et al. (1992b) 1992 3.3 7.6 2.6 Longitudinal cohorts and active surveillance

Institute of Medicine (1986)

1986 3.5 7.0 3.5 Estimated incidence plus case fatality rate

Martines et al. (1993)

1990 3.2 6.5 3.5 Data from surveys using WHO methods


method requires extrapolation from available longitudinal studies, which may not be entirely representative of the country or region.

The Institute of Medicine (1986), for the purpose of establishing priori-ties for vaccine development, published estimates of morbidity and mortal-ity derived by a committee of expert researchers in the fi eld. Based on a review of the literature and personal fi eld experience, the committee made estimates of incidence by region and age group, which were combined with estimates of distribution of diarrhoeal episodes by severity (mild, moderate, severe, death), to yield fi gures for each of four regions of the developing world. This approach depends on the accuracy of estimates by a small group of experts, and is not derived directly from individual studies.

The third approach to estimating disease burden (Martines et al. 1993) is based on data from 276 surveys of diarrhoeal morbidity and mortality in 60 countries conducted between 1981 and 1986. From these data, a median and range were calculated for each region. The methodology for these surveys involved two-stage cluster sampling, and a standardized questionnaire to ascertain two-week prevalence and deaths from diarrhoea among children younger than 5 years (World Health Organization 1989) (Table 1.3). These studies represent the source of data with the broadest available coverage. The reliability of some national survey results have, however, been questioned, in part because of the inadequate training or supervision of fi eld staff. In addition, the method used to estimate mortality, a one-year recall by the household head, is thought to result in underes-timates (Martines et al. 1993). Thus, estimates made by these methods include an inherent uncertainty.

Table 1.3 Diarrhoeal morbidity and mortality in 276 surveys in children younger than 5 years, using WHO methodology, 1981–1986

Region

Number of

surveys

Number of

countries

Episodes/child/year

Deaths per 1000 children

per year

Diarrhoeal deaths as a percent-

age of total

(median)Median Range Median Range

Latin America and Caribbean

12 8 4.9 0.8–10.4 4.2 1.2–9.20 35

Sub-Saharan Africa 67 22 4.4 1.6–9.9 10.60 3.1–54.9 38Middle East and

North Africa 47 10 2.7 2.1–10.8 5.8 1.0–25.3 39

Asia and the Pacifi c

150 20 2.6 1.1–5.7 3.2 0.0–17.2 29

India — 1 2.7 — 3.2 — — China — 1 1.2 — 0.0 — — Other — 18 2.6 — 3.3 — —

All regions 276 60 3.5 0.8–10.8 6.5 0.0–54.9 36

Source: Martines 1993


Review of empirical databases

Children in developing countries

Because community-based studies of morbidity require intensive surveil-lance, the number of persons studied is generally insuffi cient to allow mor-tality measurements. Thus, the groups of empirical studies which examine morbidity (Table 1.4) and mortality (Table 1.5) are different. With two exceptions for which surveillance was monthly (Yang et al. 1990, Chen et al. 1991), the diarrhoeal morbidity studies presented in these tables are all longitudinal, community-based studies of children in developing coun-tries, in which follow-up was at least one year, and surveillance occurred at least every two weeks.

Mortality data from studies employing active surveillance or cross-sectional ascertainment are sparse, especially for Latin America, but vital registration data support the observation that diarrhoeal mortality rates have declined substantially in Latin America (World Health Organization 1982, Pan American Health Organization 1991) (Table 1.6).

Many of the more recent studies presented here for Africa and Asia were studies of interventions for acute respiratory disease (Bang et al. 1990, Pandey et al. 1989, Roesin et al. 1990, de Francisco et al. 1993, Khan et al. 1990) or vitamin A defi ciency (Daulaire et al. 1992, West et al. 1991, Herrera et al. 1992), which included longitudinal surveillance for cause-specifi c mortality. For these studies, as well as for diarrhoeal case management intervention studies, the rates shown are for the non-intervention group or area.

Older age groups

The Institute of Medicine (1986) has estimated that 60 per cent of overall morbidity and 90 per cent of mortality occur among children younger than 5 years. The few studies that have directly measured incidence of diarrhoea demonstrate that older children and adults experience about 0.1 to 0.5 episodes per year, and that the incidence rises to approximately 1 episode per year among the elderly. The results of some of these studies are seen in Table 1.7. Mortality rates for older children and adults are substantially lower than for children younger than 5 years (Table 1.8).

Morbidity and mortality by type of diarrhoea

Recently, persistent diarrhoea has been identifi ed as the cause of a substan-tial proportion of diarrhoeal mortality (Table 1.9), although the percentage differs by location, with a range from 23 to 70 per cent. Differences in prevalent pathogens are likely to contribute to the variation in morbidity and mortality by type of diarrhoea. In addition, Victora et al. (1993) suggest that the differences in mortality may in part be attributable to differential access to oral rehydration therapy. When properly applied, oral rehydra-tion therapy is highly effective in treating acute watery diarrhoea (Duggan,


Tab

le 1

.4

R

evie

w o

f em

piri

cal d

atab

ases

on

mor

bidi

ty fr

om d

iarr

hoea

: lon

gitu

dina

l stu

dies

mea

suri

ng in

cide

nce

Episo

des

of d

iarr

hoea

per

per

son

per

year

Loca

tion

Perio

d

Age

grou

p (m

onth

s)Ag

e gr

oup

(yea

rs)

All a

ges

0–5

6–11

12

34

0–4

Indi

a

Rur

al U

ttar

Pra

desh

(Bh

an e

t al

. 19

89)

1985

–86

1.6

1.3

0.8

0.6

0.6

0.4

0.7

Urb

an C

alcu

tta

(Sir

car

et a

l. 19

84)

1985

–86

—1.

7—1.

7—1.

72.

00.

80.

50.

41.

1

Rur

al A

ndhr

a Pr

ades

h (M

athu

r et

al.

1985

)ea

rly

1980

s3.

1—

1.6—

1.6—

1.6

1.6

Rur

al N

orth

ern

Indi

a (K

umar

, Kum

ar

& D

atta

198

7)ea

rly

1980

s—

1.8—

2.7

2.4

2.0

1.7

2.2

Urb

an U

ttar

Pra

desh

(Bh

anda

ri, B

han

& S

azaw

al 1

994)

1993

—9.

9—

9.9

——

9.9—

9.9

Chin

a

Heb

ei (

Yang

et

al. 1

990)

1986

–87

—4.

2—

4.2

——

3.8

2.3

1.6

1.7

2.5

Fujia

n (C

hen

et a

l. 19

91)

1986

-87

2.3

0.73

Oth

er A

sia a

nd Is

land

s

Bang

lade

sh (

Hut

tly e

t al

. 198

9)19

84–8

72.

44.

45.

04.

3

Bang

lade

sh (B

lack

et a

l. 198

2a, 1

982b

, Bl

ack,

Bro

wn

& B

ecke

r 19

84a)

1978

–79

—7.

0—7.

0—7.

06.

05.

54.

5 4

.55.

6

Bang

lade

sh (

Che

n et

al.

1981

)19

78–7

9—

——

——

4.1

—4.

1—

——

——

—4.

1

cont

inue

d


Sub-

Saha

ran

Afric

a

Gam

bia

(Row

land

et

al. 1

985)

1981

–84

—7.

3—

Nig

eria

(O

yejid

e &

Fag

bam

i 198

8a,

1988

b)2.

24.

01.

7

Nig

eria

(H

uttly

et

al. 1

990,

Blu

m e

t al

. 199

0)19

82–8

62.

75.

05.

03.

83.

02.

83.

7

Zai

re (

Man

un’e

bo e

t al

. 199

4)19

87–8

86.

3

Gha

na (

Biri

twum

et

al. 1

986)

1982

–85

2.7

3.3

2.4

1.6

0.7

0.6

1.3

Mid

dle

East

ern

Cres

cent

Egyp

t (E

l Ala

my

et a

l. 19

86)

1982

–84

5.3

5.9

—2.

1—

2.1

——

3.1

1.0

Latin

Am

erica

and

the

Carib

bean

Peru

(La

nata

et

al. 1

989)

1984

–86—

10.6—

10.6—

10.6

Peru

(Lo

pez

de R

oman

a et

al.

1989

, Bl

ack

et a

l. 19

89)

1982

–84

9.3

10.3

Mex

ico

(Cra

viot

o et

al.

1988

)19

82–8

5—

3.0—

3.0—

3.0

3.0

Mex

ico

(Cra

viot

o et

al.

1990

)19

85–8

7—

4.0

—4.

0—

—4.

0—4.

0

Braz

il (G

iugl

iano

et

al. 1

986)

1978

–79

3.2

1.8

1.9

1.1

Braz

il (G

uerr

ant

et a

l. 19

83)

1978

–80

7.6

9.6

7.7

—5.

3—

5.3

—a —

6.4

4.5

7.3

6.4

—4.

0—

4.0

—b —

4.9

0.5

1.5

1.3

—1.

2c —1.

2

Tab

le 1

.4

R

evie

w o

f em

piri

cal d

atab

ases

on

mor

bidi

ty fr

om d

iarr

hoea

: lon

gitu

dina

l stu

dies

mea

suri

ng in

cide

nce

(con

tinue

d)

Episo

des

of d

iarr

hoea

per

per

son

per

year

Loca

tion

Perio

d

Age

grou

p (m

onth

s)Ag

e gr

oup

(yea

rs)

All a

ges

0–5

6–11

12

34

0–4


Santosham & Glass 1992), but has limited impact on persistent or dysenteric diarrhoea.

Developed countries

Diarrhoeal disease continues to cause sub-stantial morbidity among children in devel-oped countries, with an estimated incidence of 1.3 to 2.3 episodes per year for children younger than 5 years (Glass et al. 1991), an estimate based on a review of the only four longitudinal studies which provide relevant data (Gurwirth & Williams 1977, Dingle, Badger & Jordan 1964, Hughes et al. 1978, Rodriguez et al. 1987). It is estimated that perhaps 10 per cent of diarrhoeal episodes in the United States entail a physician visit, and 1 per cent a hospital admission (Glass et al. 1991).

Lew et al. (1991) examined diarrhoeal mortality using vital registration data from the United States. Mortality rates ranged from <0.1 per 100 000 for persons 5–24 years, to 2 per 100 000 for children younger than 5 years, and 14 per 100 000 for per-sons 75 years or older. The only age group in the United States for which the diarrhoeal mortality rate increased from 1978 to 1987 were males 25–54 years old, and this increase appeared to be associated with acquired immunodefi ciency syndrome (AIDS). These estimates were based on fi nding one of the ICD-9 codes for diarrhoea in the underly-ing cause (45 per cent) or in one of the top three positions (55 per cent) in the death certifi cate. However, 51 per cent of child-hood deaths and 86 per cent of those among the elderly were coded using the ICD-9 code 558 (diarrhoea, presumed non-infectious), despite indirect evidence based on the season-ality of deaths that a substantial proportion were attributable to an infectious agent. This suggests that even good vital registration data may underestimate the contribution of infectious diarrhoea to mortality, because in most cases no aetiological agent is identifi ed before death.Br

azil

(Lin

hare

s et

al.

1989

)19

82–8

6—

2.6

—2.

6—

—

Braz

il (S

chor

ling

et a

l. 19

90)

1984

–86

9.4

14.1

15.1

12.2

8.7

7.2

11.3

Cos

ta R

ica

(Sim

hon

et a

l. 19

85)

1981

–84

0.7

0.8

0.6

Chi

le (

Ferr

ecci

o et

al.

1991

)19

86–8

9—

2.3

—2.

3—

—2.

11.

51.

30.

91.

5

Chi

le (

Ara

ya e

t al

. 198

6)19

83 0

.4c

0.8

b

Arg

entin

a (G

rins

tein

et

al. 1

989)

1983

–86

2.0

5.6

3.0

4.0

4.0

3.9

3.7

a.Po

or r

ural

chi

ldre

n.

b.Po

or u

rban

chi

ldre

n.

c. M

ore

affl u

ent

urba

n ch

ildre

n.


Tab

le 1

.5

R

evie

w o

f em

piri

cal d

atab

ases

on

mor

talit

y fr

om d

iarr

hoea

: stu

dies

mea

suri

ng a

nnua

l dea

ths

per

1000

chi

ldre

n

Loca

tion

Stud

y ch

arac

teris

tics

Dia

rrho

eal d

eath

s pe

r 10

00 b

y ag

e gr

oup

(yea

rs)

Dia

rrho

eal d

eath

s as

per

cent

age

of

tota

l 0–4

yea

r m

orta

lity

Perio

dPo

pula

tion

Type

of s

tudy

< 1

1–

40–

4

Indi

a

Eigh

t st

ates

(Ta

ndon

et

al. 1

987)

1984

–85

5 35

0A

ctiv

e su

rvei

llanc

e 9

.2

Har

yana

(Bh

anda

ri, B

han

& S

azaw

al

1992

)19

82–8

41

467

Act

ive

surv

eilla

nce

16.0

Mah

aras

htra

(Ba

ng e

t al

. 199

0)19

876

176

Act

ive

surv

eilla

nce

8.4

20

Tam

il N

adu

(Rah

mat

hulla

h et

al.

1990

)19

897

655

Act

ive

surv

eilla

nce

4.3

41

Oth

er A

sia a

nd Is

land

s

Mat

lab,

Ban

glad

esh

(Che

n, R

ahm

an &

Sa

rder

198

0)19

75–7

742

000

Act

ive

surv

eilla

nce

19.6

15.1

16.0

27

Mat

lab,

Ban

glad

esh

(Sha

ikh

et a

l. 19

90)

1978

–87

28 0

00A

ctiv

e su

rvei

llanc

e 5

.710

.4 9

.5

Jum

la, N

epal

(D

aula

ire

et a

l. 19

92)

1989

3 41

1A

ctiv

e su

rvei

llanc

e97

.577

Kat

man

du V

alle

y, N

epal

(Pa

ndey

et

al. 1

989)

19

84–8

51

019

Act

ive

surv

eilla

nce

70.0

12.0

23.0

39

Tera

i, N

epal

(W

est

et a

l. 19

91)

1990

12 2

64A

ctiv

e su

rvei

llanc

e 4

.628

Sum

atra

, Ind

ones

ia (

Naz

ir, P

arde

de &

Is

mai

l 198

5)19

8397

4N

atio

nal s

urve

y18

.8 9

.2

11.3

22

Ked

iri,

Indo

nesi

a (R

oesi

n et

al.

1990

)19

86–8

78

624

Act

ive

surv

eilla

nce

9.9

23


Sub-

Saha

ran

Afric

a

Cen

tral

Afr

ican

Rep

ublic

(G

eorg

es e

t al

. 198

7)19

836

584

One

-tim

e cl

uste

r su

rvey

5.6

19

Tanz

ania

(M

tang

o &

Neu

vian

s 19

86)

1984

9 91

5A

ctiv

e su

rvei

llanc

e6.

8 1

4.4

Gam

bia

(Gre

enw

ood

et a

l. 19

90)

1982

–83

1 06

4A

ctiv

e su

rvei

llanc

e11

.419

1984

–86

3 14

615

.931

Ken

ya (

Om

ondi

-Odh

iam

bo, v

an

Gin

aeke

n &

Voo

rhoe

ve 1

990)

1975

–78

29 0

00

(tot

al

popu

latio

n)

Act

ive

surv

eilla

nce

11.2

0.9

3.0

20

Ethi

opia

(Sh

ameb

o et

al.

1991

)19

86–8

85

067

Act

ive

surv

eilla

nce

7.6

3.1

4.0

9

Nig

eria

(Jin

adu

et a

l. 19

91)

1987

1 92

8R

etro

spec

tive

surv

ey

(1 y

ear

reca

ll)20

.033

Suda

n (H

erre

ra e

t al

. 199

2)19

88–9

014

149

6-m

onth

ly s

urve

ys

3.5a

44

Gui

nea-

Biss

au (

Mol

bak

et a

l. 19

92)

1987

–90

1 42

6A

ctiv

e su

rvei

llanc

e18

.934

Gam

bia

(de

Fran

cisc

o et

al.

1993

)19

88–8

925

000

Act

ive

surv

eilla

nce

11.0

4.5

5.8

17

Mid

dle

East

ern

Cres

cent

Yem

en (

Bage

nhol

m a

nd N

ashe

r 19

89)

1982

–84

2 07

16-

mon

thly

asc

erta

inm

ent

27.7

0.8

(1

–2 y

ears

)21

Egyp

t (N

atio

nal C

ontr

ol o

f Dia

rrhe

al

Dis

ease

s Pr

ojec

t 19

88)

1980

10 4

18Lo

cal r

egis

trat

ion

15.3

85

1986

12 1

56 4

.671

Egyp

t (E

l-Rafi

e e

t al

. 199

0)19

8410

739

Nat

ionw

ide

clus

ter

surv

eys

—10

.9—

(0–2

yea

rs)

62

cont

inue

d


1986

8 70

4—

5.5—

(0–2

yea

rs)

50

Egyp

t (E

l Ala

my

et a

l. 19

86)

1980

–81

2 55

6Fa

mily

coh

ort

stud

y w

ith

activ

e su

rvei

llanc

e27

.5 4

.411

.2

Paki

stan

(K

han

et a

l. 19

90)

1986

1 19

4A

ctiv

e su

rvei

llanc

e 9

.022

Latin

Am

erica

and

the

Carib

bean

Nic

arag

ua (

Prof

amili

a &

Cen

ters

for

Dis

ease

Con

trol

199

3)19

82–9

3C

hild

ren

of 7

150

w

omen

Nat

iona

l dem

ogra

phic

su

rvey

(re

tros

pect

ive

asce

rtai

nmen

t)

12.0

15.0

14.4

31

El S

alva

dor

(Sal

vado

ran

Dem

ogra

phic

A

ssoc

iatio

n &

Cen

ters

for

Dis

ease

C

ontr

ol a

nd P

reve

ntio

n 19

94)

1988

–93

Chi

ldre

n of

5 7

52

wom

en

Nat

iona

l dem

ogra

phic

su

rvey

(re

tros

pect

ive

asce

rtai

nmen

t)

7.0

3.0

3.8

20

Ecua

dor

(Min

istr

y of

Hea

lth, E

cuad

or

& C

ente

rs fo

r D

isea

se C

ontr

ol

and

Prev

entio

n 19

92)

1979

–89

Chi

ldre

n of

7 9

61

wom

en

Nat

iona

l dem

ogra

phic

su

rvey

(re

tros

pect

ive

asce

rtai

nmen

t)

7.0

5.0

5.4

23

Pelo

tas,

Braz

il (B

arro

s et

al.

1987

, V

icto

ra e

t al

. 198

7)19

835

914

Birt

h co

hort

with

one

-tim

e as

cert

ainm

ent

4.5

Cea

rá, B

razi

l (Ba

iley

et a

l. 19

90)

1985

1 67

7Bi

rth

coho

rt w

ith 6

-mon

thly

as

cert

ainm

ent

21.8

a.9–

72 m

onth

s. O

vera

ll m

orta

lity

unex

pect

edly

low

.

Tab

le 1

.5

R

evie

w o

f em

piri

cal d

atab

ases

on

mor

talit

y fr

om d

iarr

hoea

: stu

dies

mea

suri

ng a

nnua

l dea

ths

per

1000

chi

ldre

n (c

ontin

ued)

Loca

tion

Stud

y ch

arac

teris

tics

Dia

rrho

eal d

eath

s pe

r 10

00 b

y ag

e gr

oup

(yea

rs)

Dia

rrho

eal d

eath

s as

per

cent

age

of

tota

l 0–4

yea

r m

orta

lity

Perio

dPo

pula

tion

Type

of s

tudy

< 1

1–

40–

4


Tab

le 1

.6

R

evie

w o

f dat

abas

es o

n m

orta

lity

from

dia

rrho

ea: e

stim

ated

from

vita

l reg

istr

atio

n da

ta in

Lat

in A

mer

ica

and

the

Car

ibbe

an

1975

–197

919

80–1

984

1985

–90

Coun

try

Dea

ths

per

1000

ch

ildre

n 0–

4 ye

ars

Dia

rrho

eal d

eath

s as

% o

f tot

al fo

r ch

ildre

n 0–

4 ye

ars

Dea

ths

per

1000

ch

ildre

n 0–

4 ye

ars

Dia

rrho

eal d

eath

s as

% o

f tot

al fo

r ch

ildre

n 0–

4 ye

ars

Dea

ths

per

1000

ch

ildre

n 0–

4 ye

ars

Dia

rrho

eal d

eath

s as

% o

f tot

al fo

r ch

ildre

n 0–

4 ye

ars

Dia

rrho

eal d

eath

s as

% o

f tot

al fo

r al

l age

s

Arg

entin

a0.

98 9

.80.

50 6

.70.

31 4

.50.

5Be

lize

2.86

26.8

1.11

13.5

0.86

12.9

3.8

Braz

il4.

8226

.63.

0220

.71.

9417

.23.

8C

olom

bia

3.98

23.6

1.56

16.7

——

—C

osta

Ric

a1.

1613

.70.

37 7

.30.

27 6

.11.

5C

uba

0.37

7.1

0.24

5.4

0.18

4.9

0.6

Chi

le1.

1910

.40.

31 5

.20.

17 3

.40.

8D

omin

ican

Rep

ublic

4.73

22.8

3.01

17.4

——

—Ec

uado

r7.

5429

.44.

8525

.73.

5323

.68.

7El

Sal

vado

r—

—4.

0921

.6—

——

Gua

tem

ala

9.35

28.1

7.46

27.3

——

—H

ondu

ras

8.57

38.4

6.56

36.1

——

—Ja

mai

ca1.

9926

.11.

3228

.5—

——

Mex

ico

4.25

28.3

2.69

25.5

2.17

24.7

7.7

Nic

arag

ua9.

8344

.6—

——

——

Pana

ma

1.45

14.3

0.70

9.5

0.66

9.4

2.8

Para

guay

4.50

32.3

2.95

24.4

2.35

23.0

7.0

Peru

7.80

24.6

5.50

19.9

——

—U

rugu

ay1.

0310

.00.

61 8

.40.

31 5

.20.

6Ve

nezu

ela

2.27

20.1

1.55

17.2

1.08

13.6

3.5

Sour

ce: P

an A

mer

ican

Hea

lth O

rgan

izat

ion

1991


Disease Burden

Morbidity

Table 1.10 highlights the burden of diarrhoeal disease globally: 4 bil-lion episodes of diarrhoea were estimated to occur each year (Murray & Lopez 1996). More than 90 per cent of the morbidity occurs in develop-ing countries. Based on our review of empirical data, it seems likely that some of the regional fi gures in Table 1.10 are underestimates of the true scale of morbidity. For children in the poorest socioeconomic strata, it is likely that incidence rates are similar in India, Latin America and Africa, and that complete ascertainment of all episodes of diarrhoea would yield rates in the order of 8–14 episodes per year for children between 6 and 24 months, and 5–8 episodes per year for all children younger than 5 years. The overall incidence for a region would be dependent on its socioeconomic mix. It is therefore probable that morbidity is actually somewhat higher than presented in Table 1.10 for Africa, India, the Middle Eastern Crescent and Other Asia and Islands. In Africa, especially, the burden of diarrhoeal disease for adults is undoubtedly increasing because of the magnitude of the AIDS epidemic there.

Mortality

Table 1.11 presents summary estimates for mortality attributable to diar-rhoea (Murray & Lopez 1996). Nearly 3 million people were estimated to die each year from diarrhoeal diseases. More than 99 per cent of the deaths occurred in developing countries and 84 per cent of all diarrhoeal deaths were among children under 5 years in developing countries. The highest diarrhoeal mortality rates on a regional basis were found in sub-Saharan Africa, followed by India, the Middle Eastern Crescent, and Other Asia and Islands. Latin America achieved an impressive decrease in diarrhoeal mortality rates over the past 20 years, a fi nding corroborated by both empirical and vital registration data.

Table 1.7 Review of empirical databases on morbidity from diarrhoea: morbidity in various age groups

Age group (years) and morbidity

China (Chen et al. 1991) 0–4 all ages Episodes per person per year 2.3 0.73

Indonesia (El Alamy et al. 1986) 0–4 5–12 >12 2 week prevalence (%) 35% 2% 2%

Egypt (Nazir, Pardede & Ismail 1985) 0–4 5–14 >14 Episodes per person per year 3.1 0.3 0.1

United States (Rodriguez et al. 1985) 0–4 5–14 >14 Episodes per person per year 1.0 0.4 0.4


Tab

le 1

.8

R

evie

w o

f em

piri

cal d

atab

ases

on

mor

talit

y fr

om d

iarr

hoea

: var

ious

age

gro

ups

Age

grou

p (y

ears

) and

mor

talit

y

Bang

lade

sh (

Shai

kh e

t al

. 199

0)0–

4 5–

9 >

9

Dea

ths

per

1000

per

yea

r (P

erce

ntag

e of

tot

al

mor

talit

y)1.

2 (2

7%)

1.7

(20%

)

Bang

lade

sh (

Fauv

eau

et a

l. 19

89)

(Wom

en o

nly)

15–2

425

–34

35–4

4D

eath

s pe

r 10

00 p

er y

ear

(Per

cent

age

of t

otal

m

orta

lity)

0.12

(5%

)0.

4 (1

3%)

0.5

(14%

)

Ken

ya (

Brad

ley

& G

illes

198

4)0–

4 5–

14

>14

Perc

enta

ge o

f tot

al m

orta

lity

25%

28%

21%

Egyp

t (E

l Ala

my

et a

l. 19

86)

0–4

5–14

>

14D

eath

s pe

r 10

00 p

er y

ear

11.2

1.3

0

Uni

ted

Stat

es (

Lew

et

al. 1

991)

0–4

5–24

25–5

455

–74

> 7

4al

l age

sD

eath

s pe

r 10

00 p

er y

ear

0.02

< 0

.001

0.00

30.

020.

140.

014


Tab

le 1

.9

Stu

dies

of p

ersi

sten

t di

arrh

oea

and

dist

ribu

tion

of m

orta

lity

by t

ype

of d

iarr

hoea

Loca

tion

(ref

eren

ces)

Type

of s

tudy

Per

siste

nt d

iarr

hoea

(e

piso

des

per

year

)

Perc

enta

ge o

f dia

rrho

eal d

eath

s at

trib

utab

le to

:

Oth

er fi

ndin

gsAc

ute

wat

ery

diar

rhoe

aPe

rsist

ent

diar

rhoe

aD

ysen

tery

Bang

lade

sh (

Fauv

eau

et a

l. 19

92)

Cas

e-co

ntro

l stu

dy o

f de

aths

49Pe

ak m

orta

lity

for

pers

iste

nt d

iarr

hoea

with

m

alnu

triti

on 2

4–35

mon

ths

Bang

lade

sh (

Baqu

i et

al. 1

992b

)Lo

ngitu

dina

l N

= 7

050.

34

(age

0–4

yea

rs)

Ris

k fa

ctor

s fo

r pe

rsis

tent

dia

rrho

ea: b

lood

in

stoo

l, de

hydr

atio

n

Bang

lade

sh (

Baqu

i et

al. 1

993)

Sam

e co

hort

as

Baqu

i et

al. 1

992b

Mal

nutr

ition

and

imm

une

defi c

ienc

y in

depe

nden

t ri

sk fa

ctor

s fo

r pe

rsis

tent

dia

rrho

ea

Bang

lade

sh (

Hen

ry

et a

l. 19

92)

Ret

rosp

ectiv

e N

= 3

630.

8 (a

ge 6

–11

mon

ths)

Ris

k fa

ctor

s fo

r pe

rsis

tent

dia

rrho

ea: b

lood

or

muc

us in

sto

ol

Bang

lade

sh (

Fauv

eau

et a

l. 19

89)

Popu

latio

n-ba

sed

surv

eil-

lanc

e: w

omen

15–

44

year

s

2459

1710

per

cen

t of

mor

talit

y at

rrib

utab

le t

o di

arrh

oea;

pers

iste

nt d

iarr

hoea

may

be

impo

rtan

t in

adu

lts

Bang

lade

sh (

Vic

tora

et

al.

1993

)Po

pula

tion-

base

d23

6 de

aths

3423

42

Braz

il (V

icto

ra e

t al

. 19

92)

Popu

latio

n-ba

sed

stud

y of

227

infa

nt d

eath

s62

99 p

er c

ent

of c

hild

ren

seen

in h

ealth

car

e fa

cilit

y du

ring

fata

l illn

ess

Braz

il (S

chor

ling

et

al. 1

990)

Long

itudi

nal

N =

175

1.5

(age

0–4

yea

rs)

135

diar

rhoe

a da

ys p

er y

ear

for

thos

e w

ith a

nd

22 fo

r th

ose

with

out

pers

iste

nt d

iarr

hoea

Braz

il (L

ima

et a

l. 19

92)

Ret

rosp

ectiv

e st

udy

of

deat

hs70

Braz

il (V

icto

ra e

t al

. 19

93)

Popu

latio

n-ba

sed

227

infa

nt d

eath

s28

6210

Gui

nea

Biss

au (

Mol

-ba

k et

al.

1992

)Lo

ngitu

dina

lN

= 1

426

42b

58


Disability calculations

In longitudinal studies of diarrhoeal morbidity, the median duration of watery diarrhoea has been observed to be 4 to 5 days, while dysentery lasts longer, 6 to 11 days (Baqui et al. 1991, Black et al. 1982a, Lopez de Romana et al. 1989, Black et al. 1989, Baqui et al. 1992b). Persistent diarrhoea, by defi nition, lasts at least 14 days (World Health Organiza-tion 1988).

For the purpose of calculating dis-ability, the distribution of episodes by category (watery, persistent or dysen-teric) was assumed to be constant for developing countries and was estimated by WHO based on an average derived from published sources (Bhan et al. 1989, Victora et al. 1993, Schorling et al. 1990, Bhan et al. 1986, Baqui et al. 1992b, Lanata et al. 1991, Henry 1991). Disability weights were assigned according to type of diarrhoea (Tables 1.12 and 1.13). As discussed above, the distribution of types of diarrhoea varies widely in the developing world. In addi-tion, persistent diarrhoea may be a more important cause of mortality among adults than is reflected in the World Development Report disability estimates. Active surveillance data from Bangladesh suggest that diarrhoea may cause up to 10 per cent of mortality among women of child-bearing age, more than half of that mortality being attributable to persistent diarrhoea (Fauveau et al. 1989).

Diarrhoea, both persistent and acute, is associated with malnutrition. In par-ticular, severe malnutrition is a signifi cant risk factor for mortality from acute diar-rhoea (Bern et al. 1992a) and, more strik-ingly, from persistent diarrhoea (Bhan et al. 1986, Baqui et al. 1993). Pre-existing malnutrition has also been shown to lead to increased duration (Black, Brown & Becker 1984b) and severity (Tomkins In

dia

(Bha

n et

al.

1986

)Lo

ngitu

dina

l N

= 1

467

CFR

a 0.

7C

FRa

14R

isk

fact

ors

for

mor

talit

y: se

vere

mal

nutr

ition

, pe

rsis

tent

dia

rrho

ea

Indi

a (B

han

et a

l. 19

89)

Long

itudi

nal

N =

963

0.31

(a

ge <

1 y

ear)

Ris

k fa

ctor

s fo

r pe

rsis

tent

dia

rrho

ea: b

lood

in

stoo

l, ag

e 3–

5 m

onth

s

Indi

a (V

icto

ra e

t al

. 19

93)

Popu

latio

n-ba

sed

146

deat

hs35

5114

Peru

(La

nata

et

al.

1991

)Lo

ngitu

dina

l N

= 6

770.

25

(age

0–3

yea

rs)

Ris

k fa

ctor

s fo

r pe

rsis

tent

dia

rrho

ea:

age

< 6

mon

ths,

≥ 6

sto

ols/

day

Sene

gal (

Vic

tora

et

al. 1

993)

Popu

latio

n-ba

sed

531

deat

hs

4647

8

a.C

ase-

fata

lity

rate

.

b.In

clud

es d

ysen

tery

last

ing

< 1

4 da

ys.


1981) of diarrhoea. Diarrhoeal disease can affect growth in the short term (Henry et al. 1987) and long term (Black, Brown & Becker 1984a, Guerrant et al. 1983). This may depend on the type of diarrhoea, with dysentery having a more marked effect on linear growth (Black, Brown & Becker 1984a). It has been shown that sustained nutritional supple-mentation can obviate the nutritional consequences of diarrhoea in young children (Lutter et al. 1989), but that without supplements, there may be lifelong consequences for growth (Rivera & Martorell 1988).

Table 1.10 Regional summary estimates for morbidity from diarrhoeal disease

Diarrhoeal episodes (millions)Episodes of diarrhoea per person

per year

Region All ages < 5 years All ages < 5 years

Established Market Economies

167.2 92.6 0.21 1.8

Former Socialist Econo-mies of Europe

93.8 61.9 0.27 2.3

India 787.9 524.1 0.93 4.5China 1010.3 318.2 0.89 2.3Other Asia and Islands 496.7 301.0 0.73 4.0Sub-Saharan Africa 653.1 444.4 1.28 5.0Latin America and the

Caribbean434.5 225.6 0.98 4.0

Middle Eastern Crescent 430.3 307.7 0.86 4.0

World 4073.9 2275.4 0.77 3.6

Source: Murray & Lopez 1996.

Table 1.11 Regional summary estimates for mortality from diarrhoeal disease

Diarrhoeal deaths (thousands)

Mortality rate from diar-rhoea (deaths per 1000)

Diarrhoeal deaths as percentage of total

mortality

Region All ages < 5 years All ages < 5 years All ages < 5 years


3 <1 0.003 0.007 <0.1 0.4

Former Socialist Econo-mies of Europe

4 4 0.01 0.1 0.1 3.5

India 922 733 1.1 6.3 9.8 22.6China 93 50 0.1 0.4 1.0 4.7Other Asia and Islands 397 352 0.6 4.1 7.2 21.8Sub-Saharan Africa 950 809 1.9 8.6 11.6 20.1Latin America and the

Caribbean153 130 0.4 2.3 5.1 18.4

Middle Eastern Crescent 424 402 0.8 5.0 9.3 21.6

World 2946 2480 0.6 3.9 5.8 19.4

Source: Murray & Lopez 1996.


Conclusion

Oral rehydration therapy (ORT) is the major intervention that has been promulgated globally for control of morbidity and mortality from diar-rhoeal disease. ORT is not a primary intervention, in that it does not affect incidence of diarrhoeal disease, but it has been shown to be effective in reducing hospitalizations and mortality from diarrhoea in intensive studies (Oberle et al. 1980, Rahaman et al. 1979, Heymann et al. 1990). It has been more diffi cult to demonstrate an effect of ORT diarrhoeal control programmes on a larger scale (Santosham & Greenough 1991). Data from the Egyptian national programme have demonstrated a decrease in mortality over the 1970s and 1980s (National Control of Diarrheal Dis-eases Project 1988), but the decrease in mortality had begun before the programme was in place, suggesting that other changes, such as socioeco-nomic development with attendant improvements in nutrition, sanitation and water, may have been at least partly responsible.

WHO estimates suggest that increased global access to ORT coupled with methods to improve usage have the potential to decrease global mor-tality from diarrhoea (World Health Organization 1992). The extent to which this will be effective will depend upon the proportion of mortality resulting from acute watery diarrhoea in the locality in question (Victora

Table 1.13 Assignment of disability weights according to type of diarrhoea; classifi cation used for calculation of disability-adjusted life years

Percentage assigned to severity classa

Type of diarrhoea I II III IV

Acute watery 70 20 10Persistent 50 40 10Dysentery 40 40 20

a. Severity classes based on limited ability to perform activities in the following areas: recreation, education, procreation or occupation. Class I denotes limited ability to perform at least one activity in one of these areas. Class II denotes limited ability to perform most activities in one area. Class III denotes limited ability to perform most activities in two or more areas. Class IV denotes limited ability to perform most activities in all areas.

Table 1.12 Estimates for distribution of episodes by type of diarrhoea according to age

Percentage of episodes attributable to Percentage of mortality attributable to

Age (years)Watery

diarrhoeaPersistent diarrhoea Dysentery

Watery diarrhoea

Persistent diarrhoea Dysentery

0–4 80 10 10 50 35 155–14 89 1 10 75 5 2015–44 90 0 10 80 0 2045–59 90 0 10 80 0 20≥ 60 85 0 15 85 0 15

Source: WHO.


et al. 1993). Recent data on diarrhoeal mortality attributable to persistent diarrhoea and dysentery suggest that once ORT use is high, further reduc-tion of diarrhoeal mortality will depend upon additional interventions such as improved case management, hygiene education, encouragement of breast-feeding, improved sanitation, and general socioeconomic develop-ment (Feachem, Hogan & Merson 1983, Esrey, Feachem & Hughes 1985, Feachem 1984, Ashworth & Feachem 1985, Feachem & Koblinsky 1984, Ronsmans et al. 1991), all of which are more diffi cult to implement. Thus, in areas where diarrhoeal mortality is very high and ORT access is low, such as sub-Saharan Africa, a large fraction of deaths may be preventable through improved ORT access and education, while areas such as Brazil may already be at the point where further reduction will require other interventions in addition to the maintenance of ORT promotion.

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PertussisArtur M Galazka, Susan E Robertson

Chapter 2

Introduction

“The severity of whooping cough…is much underrated, both in the direct and the indirect damage it causes to the health, growth and resistance of young children…. Deaths are inordinately frequent among infants aged less than one year. As a world problem of pre-school children, whooping cough is in the front rank of acute infec-tions…. Despite all this, the disease continues to be lightly regarded by the public, and also by many physicians.”

This situation analysis was reported by Gordon & Hood in 1951, but it remains for the most part true today. Over the past three decades, immu-nization programmes have been implemented successfully in most coun-tries of the world, and morbidity and mortality attributable to pertussis have declined dramatically (Galazka 1992). Since the 1970s, however, six developed countries (Germany, Italy, Japan, Sweden, United Kingdom, and United States of America) have grappled with low levels of pertussis vaccination, leading to substantial problems with this disease in places where it had previously been well controlled. The underlying causes of this situation include apathy and complacency on the part of physicians and parents, negative attitudes toward immunization spread by anti-immu-nization pressure groups, and litigation over liability for alleged vaccine related injuries (Galazka 1992, Mortimer 1988).

In developing countries, coverage with a primary series of three doses of diphtheria-pertussis-tetanus (DPT) vaccine in infants reached 81 per cent in 1995 (Expanded Programme on Immunization 1996). There were, however, considerable differences in coverage rates between WHO regions (58 per cent in Africa compared with 92 per cent in the Western Pacifi c) and, likewise, between and within countries. Failure to reach and main-tain high immunization coverage in developing countries is the result of multiple factors, including weak management of immunization services,


inadequate resources, missed opportunities to immunize eligible children, and ineffective motivation of mothers to return to complete immunization series for their infants.

In developing countries, pertussis has not received the epidemiological attention given to measles or to infections with the other major respiratory viral and bacterial pathogens (Wright 1991). In countries where condi-tions predispose to early acquisition of disease, where malnutrition and concomitant diseases worsen early infections, and where preventive and curative interventions remain unsatisfactory, the burden from pertussis is still signifi cant.

Causative agent

The majority of classic pertussis cases result from infection with Borde-tella pertussis, a pathogenic organism with marked tropism for ciliated cells of the respiratory epithelium. B. pertussis is a natural pathogen for humans only. Pertussis-like illness can also be seen with infection by B. parapertussis and adenovirus types 1, 2, 3, and 5.

Characteristics of pertussis

Clinically, pertussis is unrecognizable in the fi rst, catarrhal stage and becomes a real disease only afterwards, when temperature is normal and the patient is not so much sick as affl icted.

Pathologically, changes in the respiratory tract are neither deep-seated nor general since the primary infection attacks superfi cial mucous mem-branes. Yet deaths occur and resistance to a second attack continues for a long time. In spite of its being a bacterial infection, pertussis resembles a superfi cial mucosal viral infection such as those with infl uenza and respiratory syncytial viruses (Wright 1991).

Epidemiologically, the age distribution of deaths is different from that of other communicable diseases of childhood; deaths from pertussis in the fi rst year of life are inordinately frequent because of lack of passive protection acquired from the mother.

Clinical aspects

Phases of disease

Pertussis is an exhausting illness that can persist for several months. The incubation period lasts for 7 to 13 days. This is followed by the catarrhal (or prodromal) phase, which lasts for one to two weeks. Patients in the catarrhal phase exhibit only mild symptoms of an uncomplicated upper respiratory infection with rhinorrhoea, conjunctivitis, lacrimation, mild cough, and low-grade fever. This phase is indistinguishable from a viral infection, making it virtually impossible to diagnose pertussis clinically at

31Pertussis

this point, except in the setting of an epidemic or known exposure. The catarrhal stage is the most infectious period and transmission occurs by airborne droplets.

The paroxysmal phase, which follows, usually lasts for 2 to 4 weeks, but occasionally persists as long as 20 weeks. It is characterized by a repetitive series of paroxysmal coughs during a single expiration, followed by a sudden massive inspiratory effort that produces a “whoop” as air is inhaled forcefully against the narrowed glottis. Facial redness or cyanosis, bulging eyes, protruding tongue, lacrimation, and salivation are commonly seen during paroxysms. Haemoptysis, subconjuctival haemorrhages, and hernias may result from severe paroxysms. Young infants may experience apnoea. The coughing is so severe that the patient is commonly unable to eat or sleep. The coughing paroxysm may lead to vomiting of suffi cient severity to result in weight loss and malnutrition, especially in young infants with borderline nutritional status (Morley, Woodland & Martin 1966).

The fi nal phase of pertussis is the convalescent phase, when paroxys-mal episodes gradually decrease in frequency and severity. Coughing may persist for months, especially in association with subsequent respiratory infections. With each such infection the cough may return, although it will not be as severe as in the initial stage.

The course of the disease may be infl uenced by immunization against pertussis. Among 100 Finnish children with culture-confi rmed pertussis, all unimmunized patients showed typical pertussis with paroxysmal cough and whoops, while among immunized patients, 43 per cent developed typical pertussis, 49 per cent had atypical disease (with paroxysmal cough but no whoops), 6 per cent had an abortive form of pertussis with sore throat, slightly elevated temperature and transient coughing, and 2 per cent were asymptomatic carriers (Huovila 1982). The disease is more severe in unimmunized individuals, as judged by rates of admission to hospital. Among 1265 children aged 1–4 years, 1.8 per cent of immunized children required hospital admission compared with 7.3 per cent of unimmunized children (Ramsay, Farrington & Miller 1993).

Diagnosis

Typical cases of pertussis with characteristic cough are easily diagnosed on clinical grounds by health workers and parents who have had previous experience with pertussis manifestations. However, in young infants the presentation of pertussis may be atypical, without the distinctive whoop (Cherry et al. 1988, Walker 1981). Symptoms may be milder in partially immunized individuals and in fully immunized older children or adults with waning immunity.

Problems in laboratory diagnosis of pertussis contribute to the substan-tial underreporting of cases (Halperin, Bortolussi & Wort 1989, Onorato & Wassilak 1987). Isolation of B. pertussis from nasopharyngeal swabs remains the gold standard for the diagnosis of pertussis infection. Isola-tion of the organism is, however, fraught with potential diffi culties. To


ensure a reasonable chance of bacterial identifi cation, special care must be taken with preparation of culture plates, transport of specimens, and identifi cation of colonies (Wright 1991). Under ideal conditions, 80 per cent of suspected cases can be confi rmed by culture, but in most clinical situations isolation rates are much lower (Onorato & Wassilak 1987). The isolation rate of the organism from the respiratory tract is greatest during the catarrhal phase. The frequency of positive culture diminishes when specimens are taken more than two weeks after onset of symptoms or when patients are receiving antibiotics or have been previously immu-nized (Onorato & Wassilak 1987).

Fluorescent antibody staining has been used for the identifi cation of B. pertussis in direct smears from nasopharyngeal swabs and for identifi cation of organisms growing on plates. Fluorescent antibody testing offers the advantage of more rapid laboratory identifi cation; however, this method is less sensitive and less specifi c (Halperin, Bortolussi & Wort 1989).

Serological methods involve measurement of IgG and IgA antibodies to pertussis toxin (PT) and fi lamentous haemagglutinin (FHA) using the ELISA method. There is a signifi cant rise of ELISA IgG titres to PT and FHA during the pertussis infection. In unimmunized children, a combi-nation of these two determinations and the ELISA IgA for FHA seems to be the most sensitive method for serological diagnosis of pertussis. In immunized persons, however, the interpretation of serological test results is complicated since it is not possible to distinguish between antibodies produced in response to natural infection and antibodies produced fol-lowing immunization.

Treatment

The treatment of pertussis is mainly supportive. In severe cases it is criti-cal to prevent hypoxia and pulmonary complications. Delivery of oxygen and gentle suction to remove profuse, viscid secretions may be required, particularly in infants with pneumonia and signifi cant respiratory distress. Maintenance of hydration and nutrition is important.

The effi cacy of antibiotic therapy with erythromycin depends on the time of its administration. When given during the incubation period, it can prevent the disease or modify its course. When given early in the catarrhal stage, erythromycin can reduce symptoms and/or shorten the course of the disease. Initiation of erythromycin treatment within 7 days after cough onset may be associated with a shorter duration of cough and fewer whoops (Bergquist et al. 1987, Farizo et al. 1992, Steketee et al. 1988). Among children under 12 months of age, those who received erythromycin (irrespective of timing of therapy) were signifi cantly less likely to have pneumonia than those who did not receive such therapy (Farizo et al. 1992). Erythromycin treatment shortens the period of com-municability and thus may be useful in an epidemic situation (Bergquist et al. 1987, Huovila 1982).

33Pertussis

Epidemiological aspects

Communicability

Pertussis is a highly communicable disease. It is likely that no one escapes pertussis in the absence of immunization. By the age of 16 years, almost 100 per cent of children have suffered an episode of pertussis but about 25 per cent of episodes are unrecognized (Thomas 1989). This has been demonstrated by data from epidemic investigations, studies of secondary spread within families, and serological surveys. In pertussis epidemics, attack rates in unimmunized children are high, ranging between 11 per cent and 81 per cent depending on age (Table 2.1). The high degree of communicability has been repeatedly demonstrated by secondary attack rates of 70 to 100 per cent among susceptibles within families (Gordon & Hood 1951).

In Sweden, one study of 372 unvaccinated children showed how the cumulative proportion with clinically typical pertussis increases with age: 12 per cent by age 2 years, 35 per cent by age 4 years, 55 per cent by age 6 years, and 61 per cent by age 10 years. Furthermore, an additional 25 per cent of children who did not experience clinical disease had a mild or atypical disease, as evidenced by IgG antibody against pertussis toxin (Isacson et al. 1993).

Age distribution of pertussis cases

The epidemiological pattern of pertussis is infl uenced by the age-specifi c proportions of susceptible and resistant individuals in the community. Although no specific antibody against B. pertussis antigens has been

Table 2.1 Pertussis attack rates, by age, during pertussis outbreaks in Côte d’Ivoire, Guatemala, and Indonesia

Age in years

Attack rate (percentage), by country and year of outbreak

Côte d’Ivoire 1982 Guatemala 1968 Indonesia 1983

<1 59 35 501 46 40

762 77 45

3 71 47

814 63 20

5 61

11

636 40

7 63

658 —9 —10–14 — 1 —

Total 62 19 68

Sources: Côte d’Ivoire: Sokal, Soga & Imboua-Bogui 1986, Guatemala: Mata 1978, Indonesia: Expanded Programme on Immunization 1984


convincingly shown to be responsible for immunity against the disease, the antibody prevalence at different ages may be a valuable index of the exposure to pertussis antigens. The proportion of persons with measur-able IgG antibodies against pertussis toxin (PT), considered an important antigen in the pathogenesis of the disease, increases with age, refl ecting contact with B. pertussis organisms. The rate of this increase seems to be more rapid in developing countries than in developed countries. In Cam-eroon, 82 per cent of children were seropositive by 10–11 years of age (Stroffoloni et al. 1991), compared with 67 per cent of Italian children 11–12 years of age (Stroffolini et al. 1989). In New Zealand only 39 per cent were seropositive by 15 years of age (Lau 1989).

Before the introduction of pertussis immunization, the peak of the reported incidence was in children 1–4 years of age (Figure 1). In Sweden, where pertussis vaccination was discontinued in 1979, 69 per cent of cases in 1980–1985 occurred in children 1–6 years of age (Romanus, Jonsell & Bergquist 1987). In Kenya during 1974–1977 prior to widespread introduction of pertussis vaccine, 87 per cent of pertussis cases occurred in children 6 years of age or younger, with a median age of 3.5 years, and highest attack rates in children 3–4 years of age (167 cases per 1000) and infants (159 per 1000) (Voorhoeve et al. 1978).

The introduction of widespread immunization against pertussis has changed the pattern of the disease (Figure 2.1). Apart from a consider-able reduction in the number of cases and abolishing the endemic pattern

0% 10% 20% 30% 40% 50% 60%

>10 years

5–9 years

1– 4 years

<1 year

5–14 years

1–4 years

<1 yearPoland

USA

Figure 2.1 Percentage distribution of pertussis cases before (grey bars) and after (black bars) widespread use of pertussis vaccine, Poland (1971 versus 1991), United States (1918–21 versus

1980–89)

Sources: Gordon & Hood (1951), Adonajlo (1975,1993), Farizo et al. (1991).

35Pertussis

of the disease, there has been a clear change in the age distribution of pertussis morbidity.

The scope of these changes differs depending on the schedule of vaccine delivery and the coverage rates achieved. In Poland, for example, the most noticeable reduction of pertussis morbidity has been among children 1–4 years of age and the peak incidence has shifted to infants. Infants repre-sented only 12 per cent of all pertussis cases in Poland 1973, compared with 49 per cent in 1993 (Adonajlo 1975, 1993). In the United States of America during 1980–1989, children under one year of age accounted for nearly 50 per cent of all cases; the incidence rate among infants was nearly 10 times higher than that among children of 1–4 years of age, and more than one hundred times higher than that among adolescents or adults (Farizo et al. 1992).

There is a lack of reliable information from developing countries on the infl uence of pertussis immunization on age-specifi c pertussis morbid-ity. Data from pertussis epidemics during the pre-vaccine era in Côte d’Ivoire (Sokal, Soga & Imboua-Bogui 1986), Guatemala (Mata 1978) and Indonesia (Expanded Programme on Immunization 1984) show that incidence rates were highest in children aged 1–4 years (Table 2.1). These fi ndings are similar to the situation observed in developed countries in the pre-vaccine era.

Death rates

Before the mid-20th century, pertussis was a major cause of childhood mortality. Uttley (1960) has compared the evolution of pertussis mortal-ity under the age of 15 years in England and Wales with the mortality in Antigua, a small Caribbean island with relatively accurate mortality statistics going back more than 100 years. In the latter half of the 19th century, pertussis death rates were about the same in England and Wales, and in Antigua; in both places nearly 1 in 1000 children under 15 years of age died from pertussis. In England and Wales, death rates began to decline by the end of the 19th century and had fallen to 20 per million by the 1960s. In contrast, the rates in Antigua did not show signifi cant changes until the mid-20th century. In the 1950s, death rates in Antigua were still ten times higher than in England and Wales. Improved economic conditions, better nutrition, decreasing family size and falling birth rates were probable factors contributing to these decreases in pertussis mortality (Gordon & Hood 1951).

Age is an important determinant of pertussis severity and prognosis. The case fatality rate (CFR) is highest in infants (Table 2.2). Infants under 6 months and children born prematurely or with congenital disorders are especially vulnerable to pulmonary complications and suffer higher fatality rates than other groups.

In the United States of America, the pertussis CFR declined from high levels in the 1920s (Gordon & Hood 1951) to 0.4 per cent in the


1980s (Farizo et al. 1992), although the rate remained above 1 per cent in infants under 2 months of age (Table 2). In England and Wales, the overall CFR was 0.02 per cent in 1980–1991 (Miller, Vurdien & White 1992). In Sweden, where routine immunization against pertussis was stopped in 1979, three deaths were reported among 2282 hospitalized patients in 1981–1982, yielding a CFR of 0.13 per cent (Romanus, Jonsell & Bergquist 1987).

Data on hospitalized patients in developing countries show a high CFR, ranging from 3.3 per cent in South Africa (Ramkissoon, Coovadia & Loening 1989) to 9 to 16 per cent in Kenya (Fendall & Grounds 1965), Nigeria (Omololu 1965, Morley Woodland & Martin 1966), and Uganda (Bwibo 1971). In these studies, CFR was dependent on age, with the high-est rates among infants.

Hospital data may be biased since young and more severely ill patients and those with complications are those more likely to be hospitalized, infl uencing the high CFR reported. Thus, the CFR is lower in commu-nity-based surveys and in outbreak data. CFRs have ranged from 0.3 per cent in an urban outbreak in the immunized population in South Africa (Strebel et al. 1991) to 1–3 per cent in rural areas of Kenya (Mahieu et al. 1978, Voorhoeve et al. 1978), Côte d’Ivoire (Sokal, Soga & Imboua-Bogui 1982) and among Mexican Indians (Heimgartner 1977). In 1968

Table 2.2 Pertussis case fatality rates, by age, United States of America 1927–1989, England and Wales 1980–1991, and Kenya 1974–1976

Fatality rate (percentage)

Age group

Hospital data, Detroit, USA

National surveil-lance system,

USA

National surveil-lance system,

England and Wales

Biweekly house-hold visits, rural

community, Kenya

1927–1929 1950 1980–1989 1980–1991 1974–1976

0 months — — 1.3

0.5

—1 month — — —2 months — — 0.3 —3 months — —

0.17

—4 months — — 0.3 —5 months — — —6–11 months — — 0.3 0.07 —< 1 year 42.3 3.3 0.6 0.3 3.21–4 years 19.2 2.2 0.3 0.007 1.55–9 years 2.9 5.3 <0.1 0 0.005 0.0510–14 years — — 015–19 years — — 0 0.01 —20+ years — — 0.1 —

Total 22.2 3.1 0.4 0.02 1.3

Sources: United States, Detroit: Gordon & Hood (1951), United States, national: Farizo et al. (1992), England and Wales: Miller, Vurdien & White (1992), Kenya: Mahieu et al. (1978)

37Pertussis

there was a pertussis outbreak with high mortality in one community in Guatemala, with a CFR approaching 15 per cent for children less than 15 years of age (Mata 1978).

Only a few countries report the number of deaths attributable to pertus-sis. In countries that report mortality data, there is evidence that pertussis may be responsible for many more deaths than offi cial mortality statistics show (Miller & Farrington 1988). Analysis of trends in infant mortality rates from infectious respiratory illness has shown an excess of 460 to 700 deaths in England and Wales coinciding with pertussis outbreaks over the period 1977–1982; this amounts to 14 to 22 times the number of pertussis deaths reported during this period (Nicoll & Gardner 1988).

Complications following pertussis

There are three major categories of complications following pertussis: respiratory, neurological, and nutritional.

Respiratory complications

The most frequent complications are respiratory (Table 2.3). Pulmonary involvement may be suffi ciently severe to compromise respiratory function and cause death. The majority of full-blown cases of pertussis exhibit atel-ectasis or bronchopneumonia or both. Bronchopneumonia was reported in 14 to 15 per cent of hospitalized cases in Sweden (Romanus, Jonsell & Bergquist 1987) and the United States of America (Farizo et al. 1992), 26 to 37 per cent in the United Kingdom (Miller & Fletcher 1976, Walker et al. 1981) and 74 per cent in South Africa (Ramkissoon, Coovadia & Loening 1989). Pulmonary complications were clearly age-dependent and ranged from 22 to 32 per cent in infants, to 4 to 17 per cent in children over 5 years of age (Farizo et al. 1992, Walker et al. 1981). Apnoea was noted in 2 to 5 per cent of hospitalized cases (Swansea Research Unit of the Royal College of General Practitioners Unit 1987, Walker et al. 1981).

Controversy surrounds the issue of whether children who have had pertussis may have long term respiratory sequelae. One study found that children who had experienced pertussis under 5 years of age showed long term respiratory sequelae, such as deterioration of lung function, increase in respiratory symptoms, and increased admission to hospital for both upper and lower respiratory conditions (Swansea Research Unit of the Royal College of General Practitioners 1985). In another study, children who had been hospitalized for pertussis when younger than one year, approximately 9 years previously, showed more respiratory symptoms than controls, although the differences were not statistically signifi cant, and there were no signifi cant differences between cases and controls in lung function indices or in bronchial reactivity (Johnston et al. 1986).

Neurological complications

There may be a wide variety of neurological manifestations, most com-mon of which are convulsions and altered consciousness. Acute neuro-


logical manifestations may also include hemiplegia, paraplegia, ataxia, aphasia, blindness, deafness, and decerebrate rigidity. Central nervous system complications are apparently secondary to anoxia and/or cerebral haemorrhages caused by raised intracranial pressure during episodes of paroxysmal coughing or encephalitis.

The risk of neurological complications is markedly age dependent

Table 2.3 Complication rates attributable to pneumonia, seizures, and encephalopathy among pertussis patients in seven studies

Country, study period Reference Type of study Age group

Percentage of patients with

Pneu-monia Seizures

Encepha-lopathy

South Africa1982–1987

Ramkissoon, Coovadia & Loening 1989

Hospital study

All ages 74.0 — 6.9

Sweden1981–1983

Romanus, Jonsell & Bergquist 1987

Hospital study

All ages 14.0 3.2 0.5

UK1977–1979

Swansea Research Unit 1981

Telephone survey of general prac-titioners

All ages 0.8 0.6 0.1

UK1969–1980

Walker et al. 1981

Hospital study

< 3 months 32.0 — —3–5 months 26.0 — —6–11 months 27.0 — —1–4 years 26.0 — —5 years 17.0 — —0–5 years 26.0 4.0 —

USA1980–1989

Farizo et al. 1992

National surveillance system

0–1 month 24.7 4.1 1.42–3 months 22.5 2.7 1.04–5 months 18.8 1.8 0.56–11 months 19.3 3.1 0.7< 12 months 21.7 3.0 0.91–4 years 12.3 2.1 0.45–9 years 5.0 0.9 0.410–19 years 4.0 0.5 0.220+ years 2.9 0.8 0.5All ages 14.6 2.2 0.7

USA 1985–1989

Sutter & Cochi 1992

Hospital study using national surveillance system

All ages 31.0 3.7 1.2

USA1985–1989

Sutter & Cochi 1992

Hospital discharge database

All ages 20.0 2.1 0.2

39Pertussis

(Table 2.3). It is higher in young infants and negligible in older children. Occasionally, cases of neurological complications after pertussis have been reported in adults (Halperin & Marrie 1991). Estimates of the risk of encephalopathy associated with pertussis are not precise because they are based on hospital cases and do not include in the denominator the much larger number of pertussis cases that do not require hospitalization (Mortimer 1992). In hospitalized series, convulsions were noted in 3.7 to 4 per cent (Miller & Fletcher 1976, Walker et al. 1981, Sutter and Cochi 1992) and encephalopathy in 1.2 to 6.9 per cent (Ramkissoon, Coovadia & Loening 1989, Sutter & Cochi 1992). Data from routine reporting systems or outbreak investigations indicate a frequency of encephalopathy between 0.1 and 0.7 per cent (Swansea Research Unit 1981, Romanus, Jonsell & Bergquist 1987, Farizo et al. 1992) and a frequency of convul-sions between 0.08 and 3.2 per cent (Swansea Research Unit 1981, 1987, Farizo et al. 1992, Romanus, Jonsell & Bergquist 1987).

Complications involving the central nervous system may result in permanent sequelae. Zellweger (1959) estimated that among patients with pertussis encephalopathy, one-third will survive and appear normal, one-third will survive with sequelae, and the remaining one-third will die. Early studies, largely in the pre-vaccination era, suggested an association between pertussis and mental retardation or behavioural disturbance. The prognosis of pertussis encephalopathy depends on the severity of the symp-toms. Although simple seizures may have no sequelae, mental retardation or residual sensory and motor defi cit may occur after more severe disease (Halperin & Marrie 1991). A large longitudinal cohort study in Britain found that children who had been hospitalized for pertussis were three times more likely to be intellectually abnormal (Butler et al. 1982). Another study in the United Kingdom suggested that convulsions or apnoea as a complication of pertussis may be associated with subsequent intellectual impairment; the study group of children had a signifi cantly lower median intelligence quotient and poorer school attainment than control groups of children who had never had pertussis or who had pertussis without complications (Swansea Research Unit 1987).

Nutritional complications

Nutritional problems related to repeated vomiting are occasionally of major importance. Inability to maintain adequate caloric intake is a severe problem in previously malnourished children who develop pertussis, a frequent experience in the least developed countries (Morley, Woodland & Martin 1966).

Hospitalization rates

The likelihood of hospitalization in pertussis cases depends on various fac-tors. Younger patients with more severe pertussis illness are hospitalized more frequently and for longer periods than those who are older and have


less severe disease. Infants less than 6 months of age have the highest rate of hospitalization. In the United States of America during 1980–1989, the reported hospitalization rate for pertussis cases was 43 per cent overall, with 69 per cent among infants, 26 per cent in children 1–4 years of age and 6 to 9 per cent in persons over 5 years of age (Farizo et al. 1992). Outbreak investigation data found lower hospitalization rates of 46 per cent for infants and 4 per cent for patients older than one year (Sutter & Cochi 1992). In Sweden, the hospitalization rate attributable to pertussis was 12 to 18 per cent for all ages (Romanus, Jonsell & Bergquist 1987). In the United Kingdom, almost 10 per cent of patients were admitted to hospital and this proportion ranged from 60 per cent in children less than 6 months of age compared with 3 per cent in those over 3 years of age (Miller & Fletcher 1976).

Other reasons for hospitalization included additional medical factors, such as congenital heart disease, prematurity, asthma or social reasons (Miller & Fletcher 1976). In the United States of America, the average length of inpatient stay was 7 days in 1980–1989 (Farizo et al. 1992). In Sweden, the mean duration of hospital stay was 8 days for infants younger than 6 months, 6 days for children 6–11 months of age, and 4 days for patients older than 12 months (Romanus, Jonsell & Bergquist 1987). In the United Kingdom, the mean duration of hospital stay was 15.2 days, ranging from 17.8 days in children under 6 months of age to 13.8 days in children over 5 years of age (Miller & Fletcher 1976). In South Africa, the average duration of hospital stay was 13 days (Ramkissoon, Coovadia & Loening 1989).

Impact of pertussis on child and family health

Even today, pertussis may be a prolonged, severe and frightening disease occasionally resulting in serious sequelae. The disease causes considerable distress to both child and family (Johnston et al. 1985). Because of the long-lasting course of the disease, pertussis patients are exhausted, lose appetite and weight, and have disturbed sleeping habits. Eight weeks following onset about one-third of children still have symptoms affecting their behaviour. Behavioural changes observed in pertussis patients include irritability, anxiety, and setbacks in development (Mark & Granstrom 1992).

Pertussis becomes a “family affair” (Mortimer 1990) because of social and economic consequences for the affl icted families. Episodes of choking, apnoea or cyanosis in ill children are distressing events for the entire fam-ily. One study reported disturbed sleep for 78 per cent of parents, with 53 per cent having to attend to the child 4 times or more each night (Mark & Granstrom 1992). The economic consequences of the disease include expenses for medical visits and drugs, and the need to stay at home from work for a prolonged period to take care of the ill child.

41Pertussis

Reported pertussis morbidity

Case defi nitions

The ninth revision of the International Classifi cation of Diseases (ICD-9) codes related to pertussis are listed in Table 2.4 (World Health Organization 1975). The ICD-9 has a major category for “whooping cough” (ICD-9 033) which includes diseases caused by all three species of the bacterial genus Bordetella. The subcategories are as listed in Table 2.4. B. pertussis(ICD-9 033.0) causes pertussis, which is the disease entity described in this chapter. B. parapertussis (ICD-9 033.1) usually causes milder respiratory disease and is much less common than pertussis. B. bronchiseptica (ICD-9 033.8) causes tracheobronchitis, and is uncommon.

The International Nomenclature of Diseases gives the following syn-onyms for pertussis: chin cough, morbus cucullaris, and whooping cough; however, it is noted that the term “whooping cough” applies to a clinical manifestation that is not always present (Council for International Orga-nizations of Medical Sciences & World Health Organization 1985). The International Nomenclature of Diseases indicates that the term “pertussis” should be reserved for disease caused by B. pertussis, and should not be used for disease caused by B. parapertussis or B. bronchiseptica.

For purposes of surveillance, the following case defi nitions have been recommended by the World Health Organization (Strassburg 1984):

A suspect case of pertussis arises when an individual with a history of severe cough also has a history of any one of the following:

• cough persisting 2 or more weeks; • fi ts of coughing; cough followed by vomiting.

A probable case of pertussis is a suspect case with any one of the fol-lowing:

• typical fi ndings on physical investigation by a qualifi ed health worker: in young infants prolonged coughing (sometimes without

Table 2.4 Ninth Revision of the International Classifi cation of Diseases (ICD-9) codes for pertussis

Code Description

033 Whooping coughIncludes: pertussisUse additional code, if desired, to identify any associated pneumonia

033.0 Bordetella pertussis [B. pertussis]033.1 Bordetella parapertussis [B. parapertussis]033.8 Whooping cough attributable to other specifi ed organism

Bordetella bronchiseptica [B. bronchiseptica]033.9 Whooping cough, unspecifi ed organism483.4 Pneumonia in whooping cough

Code also underlying disease (033.0–033.9)

Source: World Health Organization (1975).


whoop) is followed by a period of apnoea and cyanosis; in older children the paroxysm is often followed by choking and sometimes vomiting and the production of sticky and stringy mucus; parox-ysmal coughing is usually followed by a typical breath intake and “whoop”;

• subconjunctival haemorrhages; • exposure to a suspect case in the previous 2–4 weeks; • epidemic of pertussis in the area; • white blood cell count with 15 000 lymphocytes per ml or more.

A confi rmed case of pertussis is a probable case with positive culture or immunofl uorescence of nasopharyngeal secretions for B. pertussis.

Weakness of pertussis surveillance

Reported pertussis incidence is likely to be grossly underestimated for many reasons. The disease is frequently underdiagnosed, particularly if the classic symptoms of paroxysmal cough and whoop have not occurred. Diffi culties in laboratory confi rmation also contribute to underdiagnosis. These problems are compounded by reliance on a passive reporting system with its inherent weakness of underreporting. Reported data based on hos-pitalized cases may suffer from disproportionate representation of severe cases in younger children and infants. During outbreaks, reporting rates may increase because of temporarily enhanced awareness of physicians, anxiety in the community, and media attention (Crombie 1983).

Only an estimated 5 to 25 per cent of all pertussis cases are reported in the United Kingdom and the United States of America (Jenkinson 1983, Hinman & Koplan 1984, Clarkson & Fine 1985, Thomas 1989). Reporting is disproportionately higher for hospitalized patients with classic, labora-tory-confi rmed disease (Centers for Disease Control 1990). In the United States of America, the completeness of reporting pertussis hospitalizations was highest in infants (34 per cent), declining to 28 per cent for children aged 1 to 4 years, 14 per cent for children aged 5 to 9 years, and 9 per cent for persons 10 years of age and above (Sutter & Cochi 1992). In Canada, there was a nine-fold increase in the number of reported pertussis cases when an active enhanced pertussis surveillance system was introduced in Nova Scotia Province (Halperin et al. 1989).

Limitations in the available data on pertussis cases and deaths make comparisons between different regions or countries diffi cult. Such com-parisons are also hampered by differences in the reliability of surveillance data, differences in completeness of reporting of pertussis, and differences in the quality of clinical and bacteriological diagnosis in different coun-tries. In some developing countries, pertussis is still not notifi able, and in others, statistics on pertussis incidence are not reliable. In many countries, the reported numbers refl ect only hospitalized cases, reporting is consider-ably delayed, and available data cannot serve as an operational tool for

43Pertussis

controlling the disease. As of March 1996, only 82 per cent, 69 per cent and 60 per cent of countries had provided data on pertussis incidence for 1993, 1994, and 1995, respectively, to the World Health Organization (Expanded Programme on Immunization 1996).

Global trends

The worldwide total number of cases reported to the World Health Orga-nization ranged from 2.1 to 2.8 million cases per year at the end of the 1970s, and 600 000 to 800 000 cases at the end of the 1980s (Expanded Programme on Immunization 1996). A further decline in reported cases of pertussis was noted by the beginning of the 1990s when 200 000 to 440 000 cases were reported annually. This represents a global decrease of pertussis morbidity by 85 to 90 per cent over a 15-year period. Obvi-ously, these data represent only a small proportion of the real pertussis morbidity. With an estimated number of pertussis cases in the world of about 30 million in 1990 (see estimates, below), the global completeness of reporting is in the range of 1 to 2 per cent.

Regional trends

Although existing surveillance data cannot be considered qualitatively accurate, World Health Organization data show substantial decreases in the number of reported cases from 1980 to 1990 (Expanded Programme on Immunization 1996). Data from China show a striking 97 per cent decline during this period. Declines of 75 per cent or more were seen in develop-ing countries of Asia, Latin America, the Middle Eastern Crescent, and sub-Saharan Africa (Table 2.5). India experienced a 65 per cent decrease in number of reported cases. No clear trend is apparent in the Established Market Economies and Formerly Socialist Economies of Europe.

Table 2.5 Number of pertussis cases reported to WHO, by demographic region, 1980, 1985 and 1990

Demographic region

Number of reported pertussis cases(in thousands)

Change from 1980 to 1990 1980 1985 1990

Established Market Economies 66.1 129.1 70.3 6% increaseFormerly Socialist Economies

of Europe32.7 60.2 34.1 4% increase

India 320.1 184.4 112.4 65% decreaseChina 613.6 147.3 20.0 97% decreaseOther Asia and Islands 289.7 136.2 57.7 80% decreaseSub-Saharan Africa 395.9 245.5 90.0 77% decreaseLatin America and the Caribbean 116.7 48.6 24.5 79% decreaseMiddle Eastern Crescent 145.3 104.8 31.1 79% decrease

World 1980.1 1 065.1 440.1 78% decrease

Source: Expanded Programme on Immunization 1996


Similar conclusions can be drawn from the analysis of reported pertussis morbidity by World Health Organization regions (Figure 2.2). The most acute downward trends are seen in the Eastern Mediterranean and Western Pacifi c. More gradual declines are seen in Africa, the Americas, and South-East Asia. No clear trend is apparent in the European Region.

Regional data summarize cases from surveillance systems of varying quality, and real trends may be clouded by mixing reliable and unreliable data. The analysis of pertussis incidence at the country level indicates an obvious downward trend in many countries. However, some countries, especially in Europe, have had consistently high or increasing pertussis morbidity, and this is cause for concern. Several European countries continue to have high incidence rates, including Italy, which has had low coverage (Binkin et al. 1992), Germany where vaccine coverage has been spotty, and Sweden, where the immunization programme was interrupted in the mid-1980s (Dittmann 1996).

Figure 2.2 Reported annual incidence of pertussis, by WHO region, 1974–1994

74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94

AfricaAmericasEastern MediterraneanEuropeSouth-East AsiaWestern Pacific

100

1 000

10 000

100 000

1 000 000

10 000 000

Year

Num

ber

of R

epor

ted

Cas

es

Source: Expanded Programme on Immunization (1996).

45Pertussis

Estimated pertussis morbidity and mortality

Methods for estimating morbidity and mortality

Since 1985, the WHO EPI Information System has published the estimated number of pertussis cases and deaths occurring and prevented through immunization. Since 1992, the method used in the estimation process has involved the following four steps (Table 2.6):

The number of pertussis cases without immunization is estimated for each country. The underlying assumption is that 80 per cent of surviv-ing newborns will acquire pertussis in the fi rst 5 years of life.

The impact of immunization on the number of cases is assessed by the use of the protection factor (the result of vaccination coverage with 3 primary doses of DPT vaccine in infants and 80 per cent assumed vac-cine effi cacy).

The number of deaths without or with immunization is estimated by using estimated CFRs of 0.04 per cent for developed countries and 1 per cent for developing countries (Galazka 1991).

The estimated numbers of cases and deaths are summarized, forming regional and global totals.

For this chapter we have developed a second method for estimating per-tussis cases, and deaths is based on the following two steps (Table 2.7):

Table 2.6 World Health Organization EPI Information System method for estimating number of cases and deaths attributable to pertussis

Cases or deathsPertussis immuni-

zation status Country status Formula for estimation

Number of cases attributable to pertussis

Without Any 80% of all newbornsWith Any No. cases without immunization

× protection factor a

Number of deaths attributable to pertussis

Without Developing No. cases without immunization × 0.01b

Without Developed No. cases without immunization × 0.0004 c

With Developing No. cases with immunization × 0.01b

With Developed No. cases with immunization × 0.0004 c

a. Protection factor = (1 – coverage with 3 doses of DPT vaccine in infants × 80 per cent vaccine effi cacy).

b. Case fatality rate for developing countries, 1 per cent.

c. c. c. Case fatality rate for developed countries, 0.04 per cent.

Source: Galazka (1991).


The number of pertussis cases is estimated by multiplying the number of reported cases by arbitrarily allocated reporting completeness rates for different World Development Report regions.World Development Report regions.World Development Report

The number of pertussis deaths is estimated by multiplying the number of estimated cases by arbitrarily allocated CFRs for different World Development Report regions. Development Report regions. Development Report

Estimated global number of pertussis cases and deaths

Global estimates obtained for 1990 by using the two methods differ somewhat in the number of cases (Table 2.8), amounting to 39 million with the WHO EPI Information System method compared with 30 million based on the reported cases method. With both methods, the estimated number of pertussis deaths was about 350 000. Thus, for 1990, pertus-sis occupies the third place among vaccine preventable diseases after the two main killers, measles and neonatal tetanus. For practical reasons, we have used the reported cases method as the basis for further calculations in this chapter.

Estimated number of pertussis cases and deaths by age

To estimate the number of pertussis cases by age, we assumed that in developing countries 30 per cent, 50 per cent and 20 per cent of pertus-sis cases occur among children in age groups < 1, 1–4 and 5–14 years (Table 2.9). For developed countries, we assumed that 50 per cent, 25 per cent, 20 per cent and 5 per cent of pertussis cases occur among age groups

Table 2.7 Assumptions concerning completeness of reporting and case fatality rates used in estimating the number of pertussis cases and deaths by demographic region, 1990

Demographic region

No. cases reported in

1990

Assumed reporting

completeness (%)

Estimated number of cases in 1990

Assumed case fatality

rate (%)

Estimated number of deaths in

1990


70 300 12.500 562 000 0.04 225

Formerly Socialist Economies of Europe

34 100 6.25 546 000 0.06 328

India 112 400 1.89 5 947 000 1.35 80 000China 20 000 0.52 3 860 000 0.44 17 000Other Asia and

Islands57 700 1.71 3 382 000 0.62 21 000

Sub-Saharan Africa 90 000 1.04 8 638 000 1.62 140 000Latin America and

the Caribbean24 500 0.85 2 870 000 0.33 17 000

Middle Eastern Crescent

31 100 0.69 4 511 000 0.33 15 000

World 440 100 30 316 000 347 000

47Pertussis

< 1, 1–4, 5–14, and > 15 years, respectively. Pertussis deaths in different age groups were estimated by applying various CFRs to numbers of cases in particular age groups (Table 2.10). For 1990, worldwide there were estimated to be around 230 000 pertussis deaths in infants and 88 000 in children 1 to 4 years of age.

Estimated number of pertussis complications

We estimate that the frequency of bronchopneumonia, convulsions and encephalopathy is 15 per cent, 1 per cent and 0.5 per cent, respectively, of all estimated pertussis cases (30 million in 1990). Thus, we estimate that in 1990, pertussis caused 4.5 million cases of bronchopneumonia and 300 000 cases of convulsions. An estimated 150 000 children suffered

Table 2.8 Estimated global number of pertussis cases and deaths in 1990, based on two methods of estimation

WHO EPI Information System method Reported cases method

Estimated number of pertussis cases in 1990

39 200 000 30 316 000

Estimated number of pertussis deaths in 1990

348 800 347 000

Table 2.9 Estimated number of pertussis cases, by age, in developing countries, developed countries, and worldwide, 1990

Age in years

Developing countries Developed countries World

Estimated age distribution (%)

Estimated num-ber of cases

Estimated age distribution (%)



< 1 30 8 762 000 50 554 000 9 316 0001–4 50 14 604 000 25 277 000 14 881 0005–14 20 5 842 000 20 222 000 6 064 00015+ 0 0 5 55 000 55 000

Total 100 29 208 000 100 1 108 000 30 316 000

Table 2.10 Estimated number of pertussis deaths, by age, developing countries, developed countries, and worldwide, 1990

Age in years


Estimated case fatality rate (%)

Estimated num-ber of deaths

Estimated case fatality rate (%)



< 1 2.6 229 000 0.10 550 229 5501–4 0.6 88 000 0.05 140 88 1405–14 0.5 29 000 0.02 40 29 04015+ 0.0 0 0.02 10 10

Total 346 000 740 346 740


pertussis encephalopathy in 1990, with about 50 000 of these resulting in long-lasting sequelae.

Impact of immunization against pertussis

Immunization is the key to preventing pertussis. Whole cell pertussis vaccines, widely used in industrialized countries since the late 1950s and 1960s, and introduced in developing countries within the WHO Expanded Programme on Immunization in the 1970s and 1980s, are of proven effi cacy. Experience in Japan, Sweden and the United Kingdom has provided additional evidence of vaccine effi cacy. Stopping immunization with pertussis vaccine (Sweden) or a decline of pertussis vaccine coverage (Japan, United Kingdom) in a previously highly immunized population resulted in the resurgence of the disease (Mortimer 1988). By 1994, an estimated 71 million pertussis cases and 626 pertussis deaths were being prevented worldwide each year through immunization (Ivanoff & Rob-ertson 1997).

Current killed, whole cell pertussis vaccines are combined with diph-theria and tetanus toxoids and adsorbed onto aluminium salt, comprising DPT vaccine. The World Health Organization recommends three doses of DPT vaccine in infancy (Expanded Programme on Immunization 1995). Many countries have added a booster dose approximately one year later, and some countries schedule another dose at school entry.

The immunization coverage with three doses of DPT vaccine in infants is very heterogeneous by region (Table 2.11), and even more varied by country and within countries. Of note, coverage with three doses of DPT vaccine has consistently remained much lower in the African Region, and remains below 50 per cent in some African countries.

To effectively control pertussis in the world, all countries should use

Table 2.11 Regional and global levels of coverage with three doses of diphtheria-pertussis-tetanus (DPT) vaccine among children by age 12 months for 1985, 1990 and 1995

Region

Percentage of infants with three doses of DPT vaccine, by yearaPercentage of infants with three doses of DPT vaccine, by yearaPercentage of infants with three doses of DPT vaccine, by year

1985 1990 1995

Africa 20 58 58Americas 52 70 83Eastern Mediterranean 45 81 71Europe 77 80 83South-East Asia 35 82 91Western Pacifi c 66 93 91

Global 45 83 81a Based on routine reporting systems data reported to the World Health Organization as of March 1996.


49Pertussis

available pertussis vaccines in child immunization programmes. Since acellular pertussis vaccines are not generally available, the widespread use of DPT vaccine containing the whole-cell pertussis component should be continued. Efforts should be directed to increase or maintain coverage of infants with three doses of DPT vaccine at 90 per cent or higher in all districts. Surveillance of pertussis morbidity should be strengthened in all countries and, ideally, pertussis should be a reportable disease. More information on the epidemiological pattern of pertussis, especially the age distribution of pertussis cases in developing countries, is needed to develop recommendations on booster doses for children above one year of age.

Discussion

Based on data presented in this chapter, we estimate that in 1990 pertussis was responsible for 30 million cases and almost 350 000 deaths. Assum-ing that bronchopneumonia, convulsions and encephalopathy occur in 15 per cent, 1 per cent and 0.5 per cent of pertussis cases, respectively, we estimate that 4.5 million, 300 000, and 150 000 children suffered from these complications in 1990.

There have been a number of previous attempts to quantify the burden of disease attributable to pertussis, but most estimates have referred to methods developed by the World Health Organization Expanded Pro-gramme on Immunization. A Rockefeller Foundation strategy paper on selective primary health care estimated that in 1977–1978 for developing countries alone pertussis accounted for 70 million infections and 250 000 to 450 000 deaths (Walsh & Warren 1979). During the late 1970s less than 5 per cent of children in developing countries were immunized against pertussis, so the Rockefeller Foundation estimates represent disease bur-den largely in the absence of vaccination. Their fi gures were based on World Health Organization estimates modifi ed by extrapolations from published epidemiological studies performed in well defi ned populations. The Rockefeller Foundation strategy paper classifi ed pertussis as a high priority for disease control because of its high morbidity, high mortality, and the availability of effective control with vaccines. By the early 1980s, the World Health Organization estimated that there were 60 million cases of pertussis worldwide each year with half a million to a million deaths (Muller, Leeuwenburg & Pratt 1986). These estimates took account of pertussis vaccine coverage, which was increasing gradually during this period, as well as work suggesting that in the absence of an immunization programme 80 per cent of surviving newborns would acquire pertussis in the fi rst fi ve years of life (Fine & Clarkson 1984).

Conclusion

Although in many countries pertussis has been successfully controlled by routine immunization of infants and children, it continues to cause exten-


sive morbidity and mortality throughout the world. The disease burden is not suffi ciently recognized because pertussis incidence and mortality are grossly underreported. Although we estimate some 30 million cases and 350 000 deaths occurred because of pertussis in 1990, very few of these cases and deaths were offi cially reported through routine surveil-lance systems.

The number of pertussis cases reported annually to the World Health Organization decreased from between 2.1 and 2.8 million at the end of the 1970s to between 200 000 and 400 000 at the beginning of the 1990s. Although these numbers represent only a small proportion of the real morbidity attributable to pertussis, they indicate a genuine downward trend refl ecting the increased delivery of pertussis vaccine to children around the world.

Over the past 30 years, successful immunization programmes have been implemented in most countries of the world. In developing countries, immunization coverage of infants with a primary series of three doses of DPT vaccine reached 81 per cent in 1990, but there were considerable differences in coverage rates between regions and between and within countries.

It is hoped that even higher levels of DPT vaccine coverage can be achieved; however, problems in reaching this goal have arisen in both developed and developing countries. In some developed countries pertussis vaccine coverage has dropped because of apathy and complacency on the part of physicians and parents, negative attitudes toward immunization spread by anti-immunization pressure groups, and litigation over liability for alleged vaccine-related injuries. In a number of developing countries, failure to reach and maintain high immunization coverage results from multiple factors, including weak management of immunization services, missed opportunities to immunize eligible children, and ineffective informa-tion and motivation of mothers to return to complete the immunization series.

Pertussis is an exhausting illness that can last for several months. The disease is characterized by several immunological and epidemiological peculiarities compared with other communicable diseases of childhood. The newborn infant has little or no maternally transferred passive pro-tection, and deaths from pertussis in the fi rst year of life are inordinately frequent. Mortality rates are highest in infancy, especially in children under 6 months of age. Overall CFRs have been reported from 0.02 per cent to 0.4 per cent in developed countries and from 0.3 per cent to 16 per cent in developing countries.

Among the major complications that follow pertussis illness, the most frequent are those affecting the respiratory tract. Bronchopneumonia has been reported in 14 to 31 per cent of pertussis cases. Young infants are especially vulnerable to pulmonary complications. Other major complica-tions of pertussis include convulsions and encephalopathy. We estimate

51Pertussis

that in 1990 nearly 5 million children suffered from one of the serious complications of pertussis.

To effectively control pertussis in the world, all countries should use available pertussis vaccines, aiming to achieve and sustain at least 90 per cent coverage of infants with three vaccine doses.

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Romanus V, Jonsell R, Bergquist SO (1987) Pertussis in Sweden after the cessation of general immunization in 1979. Pediatric Infectious Disease Journal, 6:364–371.

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Strebel P et al. (1991) An outbreak of whooping cough in a highly vaccinated urban community. Journal of Tropical Pediatrics, 37:71–76.

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DiphtheriaArtur M Galazka, Susan E Robertson

Chapter 3

Introduction

Before the advent of routine immunization, diphtheria was a common cause of morbidity and mortality among preschool-aged children. In temperate climates, more than 1 in 20 inhabitants suffered from clinical diphtheria during their lifetime and 5 to 10 per cent of these died of the disease (Griffi th 1979). In developing countries, the disease appeared to be endemic. These countries have rarely reported highly visible outbreaks and epidemics, as were characteristic of the pre-vaccine era in industrial-ized countries. Recent epidemics of diphtheria in several eastern European countries have again drawn attention to this forgotten disease. Reports from developing countries suggest changes in the epidemiological pat-terns of the disease so that it now occurs in outbreaks, resulting in high case fatality rates and a large proportion of patients with complications (Galazka & Robertson 1995b).

Causative agent

Diphtheria is caused by the potent toxin produced by Corynebacterium diphtheriae, a gram-positive bacillus. C. diphtheriae strains may be either toxigenic or nontoxigenic. Toxin production results when bacteria are infected by a special phage (corynebacteriophage) carrying the toxin’s structural gene. Human beings are the only reservoir of infection. Trans-mission occurs via contact with a patient or a carrier, usually via airborne droplets. Untreated patients are infectious for 2–3 weeks, while antibiotic treatment usually renders patients noninfectious within 24 hours (Begg 1994). Immunization does not always prevent asymptomatic carriage of the organism. Less commonly, transmission has been documented by articles soiled by patient discharges and by milk products (Jones et al. 1985, Benenson 1995).


Clinical features

Forms of diphtheria

There are fi ve main forms of diphtheria:

tonsillar (faucial);

pharyngeal;

laryngeal or laryngotracheal;

nasal;

nonrespiratory forms (cutaneous and other).

Classical respiratory diphtheria is characterized by a gradual onset after an incubation period of 2 to 5 days. The patient develops pharyngitis, with a red throat slowly becoming covered with a patchy exudate. The exudate gradually spreads and coalesces into a membrane that may cover the tonsils and/or the pharynx. The membrane is distinctly gray, tough, and adherent; it can lead to mechanical obstruction of the airway, requir-ing tracheostomy or intubation. Attempts to lift a mature membrane may lead to local bleeding. There is a low-grade fever, and enlarged and tender cervical lymph nodes. Cervical node swelling may become so prominent that the patient develops a “bull neck” appearance. Laryngeal diphtheria occurs when the membrane extends into the larynx, and the patient exhibits hoarseness and stridor. Nasal diphtheria presents like a common cold and is characterized by unilateral or bilateral nasal discharge, which is initially clear and later purulent and bloody. The nasal discharge makes it diffi cult to see the underlying diphtheritic membrane. Cutaneous diphtheria results when C. diphtheriae infects a skin lesion, such as an abrasion, laceration, insect bite, or burn. Cutaneous diphtheria is more common in tropical areas, but is also found in temperate climates and among the homeless and other persons with poor hygiene. Rarely, diphtheria can infect the conjunctiva, ear, or genitalia.

Diagnosis

The clinical diagnosis of diphtheria is diffi cult, particularly in countries where the disease has largely been eliminated. The differential diagnosis includes bacterial and viral pharyngitis, infectious mononucleosis, can-didiasis, oral syphilis, and ingestion of caustic chemicals (Begg 1994, Strass burg 1984). The presence of a smooth gray membrane should trig-ger suspicion of diphtheria. The clinical diagnosis should be confi rmed by bacteriological examination. Guidelines on laboratory diagnosis of diphtheria have been issued by the World Health Organization (Brooks 1981, Efstratiou & Maple 1994). Swabs should be obtained from the throat, nasopharynx, and from the edge of the membrane, if it is present. These should be rapidly transported to the laboratory for inoculation

57Diptheria

onto the appropriate media. If specimens cannot be transported to the laboratory immediately, use of a transport medium should be considered. Diagnosis of diphtheria should not be made on direct microscopy of the smear, because of problems with false positives and false negatives. All laboratory isolates should be submitted for toxigenicity testing and strain confi rmation at a qualifi ed laboratory.

Major complications of diphtheria

The most common and most serious complications from diphtheria are those caused by the dissemination and effects of diphtheria toxin on the heart (myocarditis) and nervous system (polyneuritis).

Myocarditis

Cardiac manifestations usually appear in the second week of the disease. The greater the delay in instituting antitoxin therapy, the greater the likeli-hood of myocarditis (Begg 1994). Diphtheria toxin causes electrocardio-graphic (ECG) aberrations in 33 to 65 per cent of cases, and these are clinically signifi cant in 10 to 20 per cent of cases (Boyer & Weinstein 1948, Morgan 1963, Desphande, Patel & Shetty 1970, Stockins et al. 1994). Myocarditis may present acutely with congestive failure and circulatory collapse, or more insidiously with progressive dyspnoea, weakness, dimin-ished heart sounds, cardiac dilatation, and a galloping rhythm.

Myocarditis is an important complication of diphtheria because it is responsible for approximately half of the mortality from the disease (Mor-gan 1963, Salih, Suliman & Hassan 1981). The number of deaths rises steadily with the increasing degree of ECG aberrations. In a large series of diphtheria cases, the case fatality rate (CFR) rose from 6 per cent in cases with slight ECG changes to 71 per cent in cases with marked ECG abnormalities (Boyer & Weinstein 1948). A patient with diphtheria may appear to be recovering from pharyngitis only to develop toxic myocar-ditis, which may result in congestive heart failure. Although the majority of patients who survive myocarditis recover completely, occasionally there may be permanent damage to the heart. Individuals who have apparently recovered from mild myocarditis have died suddenly several weeks later (Tillman 1980).

Neurological complications

Polyneuritis may involve cranial and peripheral nerve palsies. Peripheral nerve involvement is manifested primarily as a motor defect, usually bilat-eral. The severity may vary from mild weakness to complete paralysis. Soft-palate paralysis, which occurs during the third week, is the most common manifestation of diphtheritic neuritis. Other manifestations of neuritis include ocular palsy (paralysis of the muscle of accommodation, causing blurring of vision), paralysis of the diaphragm, and limb paralysis indistinguishable from the Guillain-Barré syndrome.

The incidence of neurological complications is proportional to the


severity of infection. Mild cases have a complication rate of 2 per cent while the rate in severe infections can be as high as 75 per cent (Hoeprich 1994). Although neuritis may persist for months, total resolution of all diphtheritic nerve damage is usual. In Sweden, during an outbreak of diphtheria in the 1980s, 6 out of 17 patients (35 per cent) had reversible paralysis (Rappuoli, Perugini & Falsen 1988). Studies of hospitalized patients in Sudan and the United States of America found a frequency of neurological complications between 8 and 10 per cent (Dobie & Tobey 1979, Salih, Suliman & Hassan 1981).

Reported diphtheria morbidity and mortality

Case defi nitions

The ninth revision of the International Classifi cation of Diseases (ICD-9) codes related to diphtheria are listed in Table 3.1 (World Health Organiza-tion 1977). The ICD-9 has a major category for diphtheria (032) which includes all types of infection by Cornybacterium diphtheriae. Subcatego-ries code the anatomical location of the infection.

In the early 1980s, the World Health Organization Expanded Pro-gramme on Immunization produced guidelines for investigation and control of outbreaks of the diseases targeted by immunization, including diphtheria (Strassburg 1984). This document recommended the following case defi nitions:

Suspected diphtheria: • Acute pharyngitis, • Acute nasopharyngitis, or with a pseudomembrane• Acute laryngitis

Probable diphtheria: • Suspected case and• Any one of the following:

– typical fi ndings on physical examination by a qualifi ed health worker;

Table 3.1 Ninth revision of the International Classifi cation of Diseases (ICD-9) codes for diphtheria

Code Description

032 Diphtheria (infection by Corynebacterium diphtheriae)032.0 Faucial diphtheria (diphtheritic membranous angina)032.1 Nasopharyngeal diphtheria032.2 Anterior nasal diphtheria032.3 Laryngeal diphtheria (diphtheritic laryngotracheitis)032.8 Other, cutaneous diphtheria032.9 Diphtheria, unspecifi ed

Source: World Health Organization (1977).

Acute nasopharyngitis, or

59Diptheria

– airway obstruction;– myocarditis or neuritis (paralysis) 1–6 weeks after onset; – exposure to a case of diphtheria in the previous 2 weeks;– epidemic of diphtheria currently in the area;– death;– common alternative diagnoses excluded by appropriate tests

(for example; negative throat culture for group A streptococci or negative blood; tests for mononucleosis).

Confi rmed diphtheria: • Probable case; and• Positive culture of Corynebacterium diphtheriae. Demonstration

of toxin production is recommended since there are nontoxigenic strains, but not required in typical cases. Microscopic examina-tion of a smear of a clinical specimen is not suffi ciently accurate to substitute for a culture.

Global trends

Since 1974, countries have submitted offi cial reports of their annual inci-dence of diphtheria to the World Health Organization (Expanded Pro-gramme on Immunization 1996). In 1990, the total number of diphtheria cases reported was 22 624, with 21 442 from developing countries and 1182 from developed countries. The worldwide total number of reported cases fell from between 74 000 and 94 000 per year in the 1970s to an all-time low of between 20 000 and 25 000 per year in 1990–1992. This represents a global decrease in diphtheria morbidity of about 70 per cent over a 20-year period. The vast majority (95 per cent or more) of reported diphtheria cases were from developing countries during the period 1974 to 1990 (Table 3.2). However, the contribution of developing countries to the global total declined to 87 per cent in 1991 and fell further to 13 per cent in 1994. Since 1992, the global number of reported diphtheria cases has risen steeply, with totals of 31 953 in 1993 and 54 718 in 1994 (Expanded Programme on Immunization 1996). This is the result of a massive outbreak, which began in the Russian Federation and Ukraine and eventually spread to nearby countries.

Regional trends

There are notable differences in trends in reported diphtheria incidence among the World Health Organization regions (Figure 3.1). Since the mid-1980s, signifi cant declines in diphtheria morbidity have occurred in the Region of the Americas and the Eastern Mediterranean and Western Pacifi c Regions. A less noticeable decline occurred in the South-East Asia Region. No clear change is apparent in the African Region, refl ecting the later start of immunization programmes and the lower vaccine coverage levels achieved. In the European Region, diphtheria morbidity was stable for many years, but has increased dramatically since 1992.


Diphtheria incidence in developed countries

Historical records document that severe epidemics of diphtheria have occurred in a cyclical manner since the 16th century (Table 3.3). In the mid-18th century, an epidemic raged in England, France, the New England colonies, and the West Indies. In the 19th century, diphtheria returned to America and Europe in a great pandemic. During and after the Second World War, a huge diphtheria epidemic occurred in Europe, with incidence rates higher than 100 per 100 000 population (Galazka, Robertson & Oblapenko. 1995a). In 1943 alone there were an estimated 1 million cases and 50 000 deaths attributable to diphtheria in Europe, excluding the USSR (Stowman 1945).

The implementation of large-scale diphtheria immunization programmes has led to marked decreases in diphtheria—and in some countries its virtual elimination—over the past three decades. At the beginning of the 1980s, many developed countries were progressing towards the elimination of the disease. In some European countries, not a single case of diphtheria has been reported for more than 10 years. By 1995, coverage of infants

Table 3.2 Number of diphtheria cases reported to the World Health Organization from developing and developed countries, and percentage of total cases occurring in developing countries, 1974 –1994, based on reports received as of March 1996

Year

Number of cases reportedPercentage of cases

from developing countriesDeveloping countries Developed countries World

1974 75 318 1 827 77 145 981975 92 767 1 549 94 310 981976 72 008 1 646 73 654 981977 85 612 1 141 86 753 991978 78 302 953 79 255 991979 76 911 822 77 733 991980 97 155 656 97 811 991981 73 922 725 74 647 991982 59 919 1 040 60 959 981983 49 652 1 545 51 197 971984 45 146 1 704 46 850 961985 41 954 1 637 43 591 961986 28 957 1 256 30 213 961987 27 883 1 163 29 046 961988 28 461 966 29 427 971989 29 728 887 30 615 971990 21 442 1 182 22 624 951991 21 553 3 210 24 763 871992 14 609 5 835 20 444 711993 12 388 19 565 31 953 391994 6 910 47 808 54 718 13


61Diptheria

with three doses of diphtheria-pertussis-tetanus (DPT) vaccine reached 88 per cent among the developed countries (Expanded Programme on Immunization 1996).

Widespread immunization has resulted not only in a considerable reduc-tion of diphtheria incidence, but also in profound changes in the immune status of different age groups. Children acquire a high level of diphtheria immunity as the result of infant immunization. The level of immunity declines in late childhood and adolescence. High levels of immunity in children result in reduced incidence of the disease, and, as diphtheria has become rare, opportunities for acquiring or reinforcing natural immunity have also been reduced. In many industrialized countries, adults become susceptible to diphtheria as a consequence of reduced opportunities to boost immunity through subclinical infection. The changes in immunity profi les by age after introduction of routine immunization are presented schematically in Figure 3.2.

Diphtheria cannot be considered a disease that has already been con-

74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94

AfricaAmericasEastern MediterraneanEuropeSouth-East AsiaWestern Pacific

100

1 000

10 000

100 000

Year

Num

ber

of R

epor

ted

Cas

esFigure 3.1 Annual diphtheria incidence reported to the World Health

Organization, by region, 1974–1994, based on reports received as of March 1996



quered. Since the 1990s, there has been a striking resurgence of diphtheria in several countries of Eastern Europe (Expanded Programme on Immu-nization 1993, 1994a, 1994c, Galazka, Robertson & Oblapenko 1995a, Hardy, Dittmann & Sutter 1996). In the Russian Federation, the number of reported cases of diphtheria increased dramatically from 1211 in 1990 to 39 703 in 1994; in Ukraine, reported cases increased from 109 in 1990 to 2990 in 1994 (Expanded Programme on Immunization 1996). The main reasons for the return of diphtheria in these countries were: decreasing immunization coverage among infants and children; waning immunity to diphtheria in adults; mass movements of the population secondary to economic and political changes; and an irregular supply of vaccines. By 1994, this outbreak had spread to nearby countries, including Azerbaijan,

Figure 3.2 Age-specifi c immunity of a hypothetical population before and after widespread use of diphtheria vaccine

0 5 10 15 20 25 30 35 40 45 50 55 600

20

40

60

80

100

Age (years)

Per

cent

imm

une

Pre-vaccine era

Post-vaccine era

Table 3.3 Cyclic occurrence of diphtheria in the world, 16th–20th centuries

Century Place, period Forms and extent

16th–17th Spain, 1583–1613, 1630, 1645, 1666 “Garotillo” or “morbus suffocans”

18th England, France, New England, West Indies, 1735–1740

“Throat distemper” with high case fatality rates

19th Europe and the Americas, 1857–1899 Pandemic with mortality up to 100 per 100 000 population

20th Europe during and after Second World War

Virulent form of diphtheria, with incidence > 200 per 100 000 population

Russian Federation and Ukraine, 1990–1994

Next round in the diphtheria cycle?

63Diptheria

Belarus, Georgia, Kazakhstan, Kyrgyzstan, Latvia, Lithuania, the Republic of Moldova, Tajikistan, and Uzbekistan.

Diphtheria incidence in developing countries

To date, diphtheria has not been a major problem in most developing countries. Immunization for infants and children was introduced with the Expanded Programme on Immunization in the late 1970s. Coverage of infants in developing countries with three doses of DPT vaccine rose gradu-ally from less than 10 per cent in 1974 to 81 per cent in 1995 (Expanded Programme on Immunization 1996). In these countries, the process of maintaining immunity still operates through natural mechanisms, includ-ing frequent skin infections caused by C. diphtheriae.

Socioeconomic changes, especially rapid urbanization with migration from rural areas, and sociocultural changes, including improved hygiene and different lifestyles, are changing the epidemiological patterns of diph-theria, so that in some developing countries epidemics are occurring, with more serious faucial and laryngeal forms. Algeria, China, Ecuador, Jordan, Lesotho, and Yemen have reported diphtheria outbreaks which occurred following a 5 to 10 year period of high immunization coverage. These outbreaks have been characterized by high case fatality rates (CFRs), a large proportion of patients with complications, and occurrence in both young and older age groups (Galazka & Robertson 1995).

Death rates

Before the era of immunization and modern treatment, diphtheria was a highly lethal disease. During a severe diphtheria outbreak in the New England colonies of the Americas in the mid-18th century, most families lost at least one child (English 1985). Statistics from Hampton Falls, New Hampshire, in 1735 show that the CFR was nearly 40 per cent in children younger than 10 years of age (Table 3.4).

In 1881 in New York City, more than 1 per cent of children under 10 years of age died from diphtheria (Doull 1952). From 1880 to 1888, the annual diphtheria CFR in a large hospital in Boston ranged from 40 to 52 per cent (Kass 1993). In Europe during the late 19th century, Hamburg and London reported diphtheria mortality rates as high as 50 to 100 deaths

Table 3.4 Mortality attributable to diphtheria, by age groups, Hampton Falls, New Hampshire, 1735

Age group in years

PopulationNumber of

deathsCase fatality rate

(%)Number Percentage

< 10 404 32.1 160 39.610–20 310 24.6 40 12.9> 20 546 43.3 10 1.8

Total 1 260 100.0 210 16.7

Source: English (1985).


per 100 000 population, and the average mortality rate in Europe was approximately 40 per 100 000 population (Kostrzewski 1964).

A high risk of death continues to be associated with diphtheria. CFRs of 5 to 10 per cent for noncutaneous diphtheria have changed little in 50 years (Benenson 1995). In the United States of America, from 1971 to 1981, more than 1000 cases of diphtheria were reported, with a relatively stable CFR close to the historically prevailing 10 per cent (Chen et al. 1985). In Poland, the CFR was 13.8 per cent in 1970 (Kostrzewski & Abgarowicz 1973). In the recent epidemic of diphtheria in the Russian Federation and Ukraine, CFRs ranged from 1.5 per cent to 4.8 per cent (Expanded Programme on Immunization 1993, 1994a). Late reporting of diphtheria cases to medical services and delays in diagnosis, hospitaliza-tion and treatment are important factors infl uencing the outcome of the disease. In St Petersburg, only 12 per cent of diphtheria cases were hos-pitalized during the fi rst 3 days of the disease; the majority of cases were hospitalized 4 to 10 days after the onset of the disease (Rachmanova et al. 1993a). Among six patients who died from diphtheria, all were admitted later than the third day after onset, and three patients were hospitalized at 8, 10, and 40 days after onset (Rachmanova et al. 1993b). During the 1992–1993 epidemic in Ukraine, CFRs were several times higher in rural areas, where the access to medical services was limited and the quality of care was lower than in urban areas (Expanded Programme on Immuniza-tion 1994a) (Table 3.5).

In developing countries in the 1960s to the 1980s, diphtheria CFRs were high among hospitalized cases. CRFs ranged from 6 to 20 per cent in India (Bhargava & Bhatt 1960, Basappa 1963, Garg & Sharma 1964, Desphande, Patel & Shetty 1970, Tibrewala et al. 1975), to 14 to 39 per cent in African countries (Bwibo 1969, Chintu, Bathirunathan & Patel 1978) and Yemen (Jones et al. 1985).

CFRs depend on age. Hospital reports from developing countries reveal high rates (11 to 50 per cent) in infants, moderate rates (8 to 18 per cent)

Table 3.5 Diphtheria case fatality rates in urban and rural areas, Ukraine, 1992 and 1993

Part of country 1992 1993

Urban Number of cases 1 239 2 497Number of deaths 35 46Case fatality rate (%) 2.8 1.8

Rural Number of cases 314 490Number of deaths 33 32Case fatality rate (%) 10.5 6.5

Total Number of cases 1 553 2 987Number of deaths 68 78Case fatality rate (%) 4.4 2.6

Source: Expanded Programme on Immunization (1994a).

65Diptheria

in preschool children, and low rates (0 to 5 per cent) in schoolchildren (Bassapa 1963, Bharghava & Bhatt 1960, Desphande, Patel & Shetty 1970, Garg & Sharma 1964, Tibrewala et al. 1975). Data for the United States for 1959–1970 showed the highest CFR (16 per cent) in children under fi ve years of age (Munford et al. 1974).

Completeness of routine reporting

The true numbers of diphtheria cases and deaths are unknown. In devel-oped countries, where diphtheria occurs in the form of single imported cases or, as recently in the Russian Federation and Ukraine, in defi nite outbreaks, the reporting may be assumed to be good. In developing coun-tries, however, where the disease is usually endemic, reporting systems are weak and the impact of immunization on disease incidence is monitored primarily through national incidence fi gures. Such statistics are often inac-curate because they are based on incomplete data gathered by the routine surveillance systems, which are usually hospital-based.

Completeness of reporting depends mainly on two elements. First, the public must have access to health services and use them. Second, the health services must report cases accurately and regularly to the appro-priate public health authorities. A study in 13 developing countries that compared survey data with reported data found that only 2 to 5 per cent of tetanus cases and 1 to 26 per cent of poliomyelitis cases were detected and reported through routine surveillance systems (Expanded Programme on Immunization 1982). Overall reporting effi ciency for the vaccine pre-ventable diseases is estimated to be less than 10 per cent, although this estimate does not specifi cally address diphtheria case reporting (Expanded Programme on Immunization 1994b). Further efforts are needed to estab-lish highly effi cient surveillance systems capable of detecting most cases of targeted diseases.

Estimated diphtheria morbidity and mortality

Estimated total number of diphtheria cases and deaths

The number of diphtheria cases reported from developed countries can be assumed to be relatively accurate; thus, we estimate that reporting was 60 per cent complete for developed countries in 1990. For develop-ing countries, we estimate that reporting was much lower, with no more than 20 per cent of diphtheria cases reported. Thus, the total number of diphtheria cases worldwide in 1990 can be estimated to be about 106 000, with 104 000 from developing countries and about 2000 from developed countries.

Assuming a case fatality rate of about 10 per cent for all parts of the world, the total number of deaths attributable to diphtheria in 1990 would be about 11 000.


Estimated number of diphtheria cases and deaths by age

In estimating the number of cases and deaths attributable to diphtheria by age, it is important to consider the differing age distributions of this disease in developing countries (mostly young children) and in developed countries (mostly adolescents and adults). Table 3.6 shows the estimated number of cases by age group occurring in 1990 in developing countries, developed countries, and worldwide.

In estimating the number of diphtheria deaths by age, we applied dif-ferent case fatality rates reported for different age groups. With these assumed rates, the number of estimated deaths attributable to diphtheria in 1990 is about 9000 in children under the age of 5 years and nearly 1600 in school-aged children (Table 3.7).

Estimated number of diphtheria cases and deaths by region

The estimated number of diphtheria cases and deaths by region is shown in Table 3.8. The highest estimated numbers of diphtheria cases in 1990 were from India, other Asian countries, and sub-Saharan Africa.

Estimated number of diphtheria complications

Assuming that clinically signifi cant myocarditis occurs in 10 per cent of patients, we estimate that approximately 11 000 cases of myocarditis occurred in 1990. Most of these occurred in children under 5 years of

Table 3.6 Estimated number cases of diphtheria, and proportion, by age group, in developing countries, developed countries, and worldwide, 1990

Age group in years


Number of cases Proportion (%)

Number of cases Proportion (%)

Number of cases

0–4 62 530 60 178 10 62 7085–14 31 260 30 446 25 31 70615–49 10 420 10 1 069 60 11 489>50 0 0 89 5 89

Total 104 210 100 1 782 100 105 992

Table 3.7 Estimated number of diphtheria cases and deaths, by age group, worldwide, 1990

Age group in yearsEstimated no.

casesEstimated case fatality

rate (%)Estimated no.

deaths

0–4 62 708 14 8 7795–14 31 706 5 1 58515–49 11 489 2 230>50 89 5 4

Total 105 992 10 10 598

67Diptheria

age and schoolchildren. About half of the myocarditis cases would end in death; only a small portion of the surviving patients would suffer from permanent heart damage.

Neurological complications may be expected to occur in about 20 per cent of patients. This would amount to about 21 000 patients worldwide with neurological complications secondary to diphtheria in 1990.

Prevention, treatment, and epidemic preparedness

Routine immunization

Diphtheria toxoid is one of the three components of diphtheria-pertussis-tetanus (DPT) vaccine. A primary series of three doses of DPT vaccine is given to children in their fi rst year of life in all countries around the world. Global coverage of infants with three doses of DPT vaccine was 45 per cent in 1985, 83 per cent in 1990, and 81 per cent in 1995 (Expanded Programme on Immunization 1996). It needs to be emphasized, however, that overall coverage fi gures mask regional variations and intra-country variations in coverage (see Table 2.11, Chapter 2, Pertussis).

Diphtheria toxoid is a formaldehyde-inactivated preparation of diph-theria toxin, adsorbed on aluminium salts to increase its antigenicity. This toxoid protects against the action of toxin, so when an immunized individual is infected by a toxin-producing strain of diphtheria, the sys-temic manifestations of diphtheria will not occur. There are no data from randomized controlled trials of the clinical effi cacy of diphtheria toxoid, but outbreak investigations have shown a protective effi cacy of over 87 per cent (Jones et al. 1985). After a primary series of three doses of DPT vaccine, diphtheria antitoxin levels wane gradually. In industrialized coun-tries, more than half of all adults may lack immunity and many of these countries therefore recommend booster doses of diphtheria toxoid. The same situation does not appear to be true in developing countries, and

Table 3.8 Estimated number of diphtheria cases and deaths, by World Development Report region, 1990Development Report region, 1990Development Report

Region Estimated number of cases Estimated number of deathsa

Established Market Economies 40 4Formerly Socialist Economies of Europe 1 400 140India 42 130 4 213China 2 100 210Other Asia and Islands 24 000 2 400Latin America and the Caribbean 5 000 500Sub-Saharan Africa 19 300 1 930Middle Eastern Crescent 12 000 1 200

Total 105 970 10 597

a. Assumed case fatality rate of 10 per cent for all regions.


it is thought that this may result from ongoing exposure to persons with cutaneous diphtheria. Thus, most developing countries do not recommend booster doses of diphtheria toxoid. This situation needs careful monitoring, and serosurveys may be appropriate as immunization programmes in these countries mature (Expanded Programme on Immunization 1995).

Treatment

When a case of diphtheria is identifi ed, strict isolation procedures need to be instituted, including disinfection of all articles in contact with the patient (Benenson 1995). The outcome, including complications and mortality, depends on the speed with which antitoxin treatment is initi-ated. Antitoxin will only neutralize circulating toxin that is not yet bound to tissue. If diphtheria is strongly suspected, treatment with diphtheria antitoxin should be given immediately after bacteriologic specimens are taken, without waiting for laboratory results (Begg 1994, Farizo et al. 1993). Antibiotic therapy, consisting of intramuscular procaine penicillin G or parenteral erythromycin, should also be instituted, to prevent the patient from transmitting diphtheria to others. Once the patient can swal-low, oral therapy with penicillin V or erythromycin should be continued for two weeks. During convalescence, the patient should receive a dose of diphtheria toxoid, because clinical diphtheria does not always confer immunity (Begg 1994).

The risk of infection is directly related to the closeness and duration of contact. Anyone who has been in close contact with a case of diphtheria attributable to toxigenic C. diphtheriae in the previous seven days should be considered at risk. This includes household members, sexual contacts, school classroom contacts, those people with diphtheria. Close contacts should have a throat culture taken and receive a dose of intramuscular benzethine penicillin. They should be clinically assessed daily, including a check for pharyngitis, until seven days after their last contact with the case. If a positive culture is obtained in a close contact, they should receive antibiotic treatment with penicillin or erythromycin for two weeks, fol-lowed by another throat culture (Begg 1994).

Epidemic preparedness

Epidemic preparedness is an ever-important issue, brought to attention dur-ing the 1990s by the massive diphtheria epidemic affecting most countries of the former Soviet Union. Management of diphtheria outbreaks requires careful public health planning. In the outbreak situation, emphasis must be placed on rapid delivery of vaccine to the affected population, prompt diagnosis and management of diphtheria cases, and appropriate investiga-tion and management of close contacts (Begg & Balraj 1995). In outbreaks with large numbers of adult cases, mass diphtheria immunization should be carried out for adult groups at highest risk, including health care workers,

69Diptheria

teachers, and military personnel. Detailed guidelines have been developed for immunization of adults (Galazka & Robertson 1996).

Discussion

Based on data presented in this chapter, we estimate that in 1990 diphtheria was responsible for a total of some 106 000 cases worldwide. Assuming a case fatality rate of about 10 per cent for all parts of the world, the total number of deaths attributable to diphtheria in 1990 would be about 11 000. Major complications of diphtheria result from the damaging effects of the bacterial toxin on heart and nerve tissues. For 1990, we estimate that 11 000 individuals suffered from myocarditis, with half of these cases ending in death. In the same year, an estimated 21 000 persons developed neurological complications of diphtheria, but most of these cases can be expected to have resolved spontaneously within a few months. These esti-mates take account of the disease reduction through vaccination, which had become widespread in both developing and developed countries by 1990.

There have been few previous attempts to quantify the burden of dis-ease due to diphtheria. A Rockefeller Foundation strategy paper on selec-tive primary health care estimated that in 1977 for developing countries alone diphtheria accounted for 700 000 to 900 000 cases of disease and 50 000 to 60 000 deaths (Walsh & Warren 1979). During the late 1970s less than 5 per cent of children in developing countries were immunized against diphtheria, so the Rockefeller Foundation estimates represent dis-ease burden largely in the absence of vaccination. A 1980 World Health Organization report estimated that worldwide diphtheria caused at least 100 000 deaths each year among children under fi ve years of age (World Health Organization 1980).

One medical textbook chapter on diphtheria published in 1992 states that in developing countries there are estimated 1 million deaths a year caused by diphtheria (Willett 1992). We believe this fi gure represents an extreme overestimate, which is nearly 100 times greater than our estimate of 11 000 deaths attributable to diphtheria in 1990. Unfortunately the author of this chapter provides no justifi cation and no references for the estimate. The same textbook chapter states that DPT vaccine coverage of infants in developing countries was only 10 per cent (Willett 1992); however, based on offi cial reports by governments to the World Health Organization, coverage of infants in developing countries with three doses of DPT vaccine reached 81 per cent worldwide by 1990 (Expanded Pro-gramme on Immunization 1996).

Conclusion

Diphtheria is still present in many parts of the world. The most effective preventive measure against diphtheria is active immunization of children


and an adequate programme to maintain immunity against diphtheria throughout life. Many countries that have implemented an effective immunization programme report a continuous decline in the incidence of diphtheria or its virtual elimination.

Despite this, countries cannot become complacent about this disease. In 1990, more than 90 per cent of diphtheria cases occurred in develop-ing countries. After 1992, this pattern, seen for three decades, changed abruptly when a massive diphtheria outbreak surged in eastern Europe. This was the largest diphtheria epidemic since 1950 and it was declared by the World Health Organization to be a public health emergency. The history of diphtheria has been marked by sudden unexpected fl ares, which cause fear and panic because of the high mortality associated with this disease. Many of these epidemic surges have occurred during wars or peri-ods of turmoil, thus exacerbating already diffi cult situations. The Eastern European outbreak of the 1990s serves as a reminder to all countries to be vigilant. There is a need to improve surveillance for diphtheria and maintain the laboratory capability to diagnose diphtheria even when the disease has declined to very low levels. In addition, diphtheria should be included as part of public health planning for epidemic preparedness.

References

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Begg N (1994) Manual for the management and control of diphtheria in the European Region. Copenhagen, Expanded Programme on Immunization, World Health Organization Regional Offi ce for Europe (ICP/EPI/038).

Begg N, Balraj V (1995) Diphtheria: are we ready for it? Archives of Disease in Childhood, 73:568–572.

Benenson AS, ed. (1995) Control of communicable diseases in man, 16th ed.Washington, DC, American Public Health Association.

Bhargava HS, Bhatt AN (1960) A study of 275 cases of diphtheria. Journal of the Indian Medical Association, 35:243–248.

Boyer NH, Weinstein L (1948) Diphtheritic myocarditis. New England Journal of Medicine, 239:913–919.

Brooks R (1981) Guidelines for the laboratory diagnosis of diphtheria. Geneva, World Health Organization (LAB/81.7).

Bwibo NO (1969) Diphtheria in African children (report of 13 cases seen at Mulago Hospital). Journal of Tropical Pediatrics, 15:15–17.

Chen RT et al. (1985) Diphtheria in the United States, 1971–81. American Journal of Public Health, 75:1393–1397.

Chintu C, Bathirunathan N, Patel JM (1978) Diphtheria at the University Teaching Hospital Lusaka. East African Medical Journal, 55:36–38.

71Diptheria

Deshpande RS, Patel JI, Shetty SV (1970) Clinical features of diphtheria in Bombay. Journal of Postgraduate Medicine, 16:5–11.

Dobie RA, Tobey DN (1979) Clinical features of diphtheria in the respiratory tract. Journal of the American Medical Association, 242:2197–2201.

Doull JA (1952) The bacteriological era (1876–1920). In: The history of American epidemiology. Top FH, ed. St Louis, Mosby, pp 74–133.

English PC (1985) Diphtheria and theories of infectious disease: centennial appre-ciation of the critical role of diphtheria in the history of medicine. Pediatrics, 76:1–9.

Efstratiou A, Maple PAC (1994) Laboratory diagnosis of diphtheria. Copenhagen, Expanded Programme on Immunization, World Health Organization Regional Offi ce for Europe (ICP/EPI/038C).

Expanded Programme on Immunization (1982) The use of survey data to supple-ment disease surveillance. Weekly Epidemiological Record, 57:361–362.

Expanded Programme on Immunization (1993) Outbreak of diphtheria, update, Russian Federation. Weekly Epidemiological Record, 68:134–140.

Expanded Programme on Immunization (1994a) Diphtheria epidemic. Weekly Epidemiological Record, 69:253–258.

Expanded Programme on Immunization (1994b) Poliomyelitis in 1993. Weekly Epidemiological Record, 69:169–175.

Expanded Programme on Immunization (1994c) Diphtheria outbreak. Weekly Epidemiological Record, 69: 349–352.

Expanded Programme on Immunization (1995) Immunization policy. Geneva, World Health Organization (WHO/EPI/GEN/95.3).

Expanded Programme on Immunization (1996) EPI information system global summary. Geneva, World Health Organization. (WHO/EPI/CEIS/96.07).

Farizo KM et al. (1993) Fatal respiratory disease due to Corynebacterium diph-theriae: case report and review of guidelines for management, investigation, and control. Clinical Infectious Diseases, 16:59–68.

Galazka AM, Robertson SE (1995) Diphtheria: changing patterns in the develop-ing world and the industrialized world. European Journal of Epidemiology, 11:107–117.

Galazka AM, Robertson SE (1996) Immunization against diphtheria with special emphasis on immunization of adults. Vaccine, 14:845–857.

Galazka AM, Robertson SE, Oblapenko GP (1995) Resurgence of diphtheria. European Journal of Epidemiology, 11:95–105.

Garg BK, Sharma BK (1964) Diphtheria in Kanpur. Indian Pediatrics, 1:436–444.

Griffi th AH (1979) The role of immunization in the control of diphtheria. Devel-opments in Biological Standardization, 43:3–13.

Hardy IRB, Dittmann S, Sutter RW (1996) Current situation and control strategies for resurgence of diphtheria in newly independent states of the former Soviet Union. Lancet, 347:1739–1744.


Hoeprich PD (1994) Diphtheria. In: Hoeprich PD, Jordan MC, Roland AR, eds. Infectious diseases: a treatise of infectious processes. Philadelphia, JB Lippincott Company, pp. 373–380.

Jones EE et al. (1985) Diphtheria: a possible foodborne outbreak in Hodeida, Yemen Arab Republic. Bulletin of the World Health Organization, 63:287–293.

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Kostrzewski J, Abgarowicz A (1973) Blonica (Diphtheria). In: Infectious diseases in Poland and their control in 1961–1970 [in Polish]. Warsaw, Panstwowy Zaklad Wydawnictw Lekarskich, pp. 41–52.

Morgan BC (1963) Cardiac complications of diphtheria. Pediatrics, 32:549–557.

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Rappuoli R, Perugini M, Falsen E (1988) Molecular epidemiology of the 1984–1986 outbreak of diphtheria in Sweden. New England Journal of Medicine, 318:12–14.

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Strassburg MA (1984) Guidelines for the investigation and control of outbreaks of EPI target diseases. Geneva, World Health Organization. (EPI/GEN/84.7/rev1).

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73Diptheria

World Health Organization (1977) Manual of the International Statistical Classifi cation of Diseases, Injuries, and Causes of Death, Ninth Revision, Volume 1. Geneva, World Health Organization.

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MeaslesCJ Clements, GD Hussey

Chapter 4

Introduction

Measles has been called the greatest killer of children in history. Over the centuries, it has been responsible for severe epidemics throughout the world. Before measles vaccine became available, virtually all children con-tracted measles —an estimated 135 million cases and around 7–8 million deaths globally each year (assuming a case fatality rate of 7 per cent in the pre-immunization era in developing countries).

Mortality rates from measles fell when socioeconomic conditions improved in industrial countries. Further gains were made against the disease when a vaccine was developed in the 1960s. However, despite its availability, the vaccine has not always been used to its full potential, and measles remains a major preventable cause of childhood mortality in developing countries.

Towards the end of the 1970s, the Expanded Programme on Immu-nization (EPI) adopted measles vaccine as one of its six infant antigens. This resulted in a dramatic increase in immunization coverage, which has contributed signifi cantly to reducing both measles morbidity and mortal-ity. Even though developing nations did not all introduce measles vaccine into their routine immunization programmes until 1984–1985, many were quick to reach high coverage levels.

Despite excellent progress, the World Health Organization estimated that as of August 1994, 45 million cases of measles still occurred in the world each year. Notwithstanding the severe underreporting of the disease, data received by the World Health Organization clearly demonstrated a dramatic downward trend in the number of measles cases (Figure 4.1).

Some countries (both developed and developing) have experienced more than 99 per cent reduction in the incidence of reported cases. In recent years, however, the number of reported cases in some of those countries has temporarily increased, although still remaining far below pre-vaccine era levels. In developing countries, measles remains endemic in most areas,


with the largest proportion of cases reported in children under 5 years, and over a quarter of all cases involving children under 9 months of age (Taylor et al. 1988).

Defi nitions

A case of measles. Until 1996, the World Health Organization used the following clinical case defi nition:

• generalized maculopapular rash; and

• history of fever 38°C (101°F) or more, (if not measured, “hot” to touch); and

• at least one of the following: cough, coryza, or conjunctivitis.

The current WHO case defi nition is:

• any person in whom a clinician suspects measles infection; or

• any person with fever and maculopapular rash and cough, coryza, or conjunctivitis.

A measles death. A working defi nition of a measles death is “a death which occurs within one month of onset of measles.”

The International Classifi cation of Diseases (ICD) codes for measles are 055 (ICD-9) and B05 (ICD-10).

It is probable that some measles deaths may occur beyond one month from onset of the disease. Decreased survival can be recognized epide-miologically following an outbreak of measles. Unless ways are devised of recognizing this phenomenon on a case-by-case basis, however, it is not realistic to count such cases as measles deaths. Wherever possible, a secondary cause of death is defi ned, such as diarrhoea, acute respira-

Figure 4.1 Number of cases of measles and measles vaccine coverage reported globally, 1974–1996

Source: WHO Expanded Programme on Immunization (1996)

20

0

40

60

80

100

73 75 77 79 81 83 85 87 89 91 93 95

YearYearY

Cov

erag

e (%

)

0

1

2

3

4

5

6

7

Num

ber

of c

ases

(m

illio

ns)

Number of cases % immunization coverage

77Measles

tory infection or malnutrition. Even though a death may appear to be from other causes (e.g. diarrhoea, trauma), it is counted as a measles death if it occurs within one month of onset of measles.

Case fatality rate (CFR). The number of individuals who contract mea-sles and die within one month of the attack, divided by the total number of individuals who contract measles, expressed as a percentage.

Acute measles complication. The presence of a sign or symptom of a recognized complication of measles occurring within one month of the onset of measles illness.

Delayed measles complication. A number of studies have indicated that children who have had measles have signifi cantly increased morbidity and mortality in the ensuing months when compared with community controls. This is characterized by failure to thrive, recurrent infections, persistent pneumonia, and diarrhoea. Vitamin A defi ciency will aggra-vate these problems. The survival rate of children during this phase is also signifi cantly reduced (Aaby & Clements 1989, Hull, Williams & Oldfi eld 1983).

Measurement of incidence

Past attempts by the World Health Organization at measuring disease burden have been twofold. First, the number of cases reported through the routine surveillance system has been collected. These data suffer from gross incompleteness in that only 3–5 per cent of cases that are estimated to occur are actually reported. Sentinel sites reporting more complete data for their catchment area still provide incomplete national data. The very nature of measles means many cases are subclinical or so mild that they never come to the notice of health workers. Thus, recording the number of cases reported to health systems is not likely to provide an accurate picture of the situation, but may, over time, refl ect a real trend.

Second, the World Health Organization bases estimates of the number of cases occurring on coverage levels of measles vaccine. One of the assump-tions made in calculating the estimate (see below) is that all children not immunized will eventually contract measles. This may have been near the truth in the pre-vaccine era, but is clearly not so in situations where little or no measles virus is circulating. For all its potential weaknesses, this method has provided a global estimate that has received general acceptance.

Measurement of complication rates

Complications from measles are listed in Table 4.1. Of these, respiratory complications and diarrhoea are undoubtedly the most frequent. Uncom-mon complications include acute encephalitis, nephritis, pneumomedias-tinum, myocarditis, pericarditis, hepatitis, ileocolitis, and appendicitis. Subacute sclerosing panencephalitis (SSPE) is a rare, long-term complica-tion of measles. It is a degenerative disease of the brain attributable to a


persistent measles virus infection and is the result of an inability of the immune system to clear the viraemia.

Studies from fi ve countries (Table 4.2) show that at least three-quarters of cases might be expected to have at least one complication, some with multiple system involvement. The frequency of complications varies in different parts of the world. For instance, a study from the United States of America in 1989 reported complications in 17.4 per cent of cases, including diarrhoea (6.4 per cent), otitis media (6 per cent), pneumonia (4.9 per cent), and encephalitis (0.2 per cent) (Centers for Disease Con-trol 1990). The frequency of complications in developing countries is less well known because of less effective surveillance systems. Hospital-based surveys have nevertheless shown that the three major problems associated with a signifi cantly higher mortality than others are pneumonia, diarrhoea, and croup.

Table 4.1 Complications of measles

Common Uncommon

Pneumonia

Diarrhoea

Laryngotracheobronchitis (croup)

Eye disease

Malnutrition

Otitis media

Severe stomatitis

Nosocomial infections

Encephalitis

Myocarditis

Pericarditis

Pneumomediastinum

Nephritis

Appendicitis

Subacute sclerosing panencephalitis (SSPE)

Source: Authors

Table 4.2 Studies from fi ve countries on the frequency of complica-tions in measles (as a percentage)

Country India South Africa Tanzania Thailand Zambia

Cases < 12 months

Unimmunized

Malnutrition

Pneumonia

Diarrhoea

Croup

Deaths

Deaths < 12 months

Number of cases

28

NR

47

50

15

NR

NR

NR

150

69

NR

53

76

78

32

10

12

97

26

65

61

75

21

22

8

11

931

15

NR

51

75

19

NR

10

19

522

17a

47

68

21

88

NR

15

67a

41

NR – not reported in this study.

a. Less than 9 months.

Sources: India: Raote & Bhave 1992, Tanzania: Burgess, Mduma & Josephson 1986, Thailand: Varavithya et al. 1985, South Africa: Hussey & Klein 1990, Zambia: Ministry of Health 1993.

79Measles

Measurement of deaths

As with cases, enumerating measles deaths reported to health authorities is problematic. When deaths are recorded, they are frequently incorrectly attributed to diarrhoea, chest infection, or malnutrition when they are actually primarily measles deaths. This is because the underlying cause may have been measles, but complications did not set in for more than two weeks. At this time, those looking after the child may not have considered that measles itself was the cause of death, but rather a complication such as chest infection. In addition, measles causes increased mortality for up to a year after the illness, presumably from an altered immune system. Reports of such deaths are likely to ignore measles as the cause.

Because reporting of measles deaths is subject to so much variation, the World Health Organization estimates measles deaths based on the number of cases estimated to occur multiplied by the case fatality rate (CFR). Even using this technique, both the CFR and the number of estimated cases may be largely unsubstantiated in some countries, leaving a measure of uncertainty as to the actual number of deaths attributable to measles.

While the actual number of deaths remains uncertain, a number of well documented community and hospital studies reveal the complications from which measles patients die. These are principally acute lower respiratory infections (ALRI), diarrhoea, and others, many of which represent an extremely small percentage of the total. Markowitz & Nieberg (1991) reviewed published articles reporting ALRI-associated measles deaths. In an unpublished revision of these data, Gindler et al. extended the study to include deaths from all complications (see Table 3). In 17 studies reviewed, there were 3515 measles deaths. ALRI deaths reported in community stud-ies were 10 per cent lower than in hospital studies, but it was not possible to draw any conclusions from community versus hospital-based diarrhoea deaths because of the small numbers. A child may have more than one complication from measles and, in the same way, death may be linked with more than one major pathology. From the review in Table 3, it is reasonable to make a general statement about the distribution of deaths. Around 67 per cent are associated with ALRI, 27 per cent with diarrhoea, and 5 per cent with another complication. Data on the prevalence of malnutrition are scant, but we estimate that up to 40 per cent of measles deaths are attributable to some level of malnutrition.

Measurement of case fatality rates

Diffi culties related to measurement of case fatality rates (CFRs) include unreliable civil registration, poorly applied defi nition of a measles death, and the fact that many measles deaths occur at home, unrecorded by health facilities. Reported CFRs may be subject to bias, in that most information is usually obtained from sources that have an unrepresentative caseload. For example, hospitals tend to admit and report the most serious cases. Such hospitalized cases are at increased risk of dying compared to non-hospitalized cases.


Recognizing that many countries are uncertain of an accurate value for measles CFR, the World Health Organization/EPI reviewed published community studies of CFRs. Based on this review and on negotiation with countries, the World Health Organization now allocates CFRs to countries. This value ranges from 5 per cent in high-risk countries to 0.1 per cent in most industrialized countries. Such values must be viewed with caution in the light of some community studies which suggest that underestima-tion may occur (Aaby & Clements 1991) and that further work is needed to refi ne how CFRs should be calculated. For instance, an outbreak in Afghanistan resulted in a recorded CFR of 28 per cent for all ages and a CFR of 42 per cent for children aged 0–4 years (Wakeman 1978).

Tables 4.4–4.6 list studies of case fatality rates, many of which were car-ried out before signifi cant immunization began. The age-specifi c incidence of measles in these locations (and hence the CFR) will certainly have altered since then. Many countries have greatly improved their treatment capabili-ties over recent years and have reduced CFRs accordingly. Nonetheless, recently reported outbreaks confi rm that alarmingly high CFRs continue

Table 4.3 Distribution of measles deaths by cause

Country of region (study)Type of studyastudyastudy

Number of deathsb

Percentage of deaths attributable for

ALRIc Diarrhoea OtherdOtherdOther

Bangladesh (Koster et al. 1981) C 10 40 60 0Bangladesh (Spika et al. 1989) C 122 25 — —Burma (Han, Khin & Hlaing 1990) H 28 50 7 43England (Ellison 1932) H 37 89 11 0Kenya (O’Donovan 1971) H 66 79 42 NEGKenya (Hayden 1974) C 469 72 6 22Latin America (Puffer & Serano

1973)C 2 106 80 50 NEG

Nigeria (Obi 1979) H 36 81 14 6Nigeria (Fagbule & Orifunmishe

1988)H 70 71 44 NEG

Nigeria (Adedoyin 1990) H 71 73 37 NEGNigeria (Ibia & Asinda 1990) H 80 70 29 1Papua-New Guinea (Riley et al.

1986) C 22 64 — —

Tanzania (Barclay, Foster & Sommer 1987)

H 29 48 14 38

West Africa (Morley, Martin & Allen. 1967)

H 266 74 56 NEG

Zaire (Markowitz et al. 1989) H 71 66 — —Zimbabwe (Kambarami et al. 1991) H 20 55 30 15

a Type of study: C = Community, H = Hospital.

b Data collected from death registries at 13 sites in 8 countries.

c ALRI = acute lower respiratory infections.

d Deaths not attributable to ALRI or diarrhoea. For studies where the total of ALRI and diarrhoea deaths exceeds 100 per cent, this is designated as “NEG.”

81Measles

Tab

le 4

.4

M

easl

es c

ase

fata

lity

rate

s in

pro

spec

tive

com

mun

ity s

tudi

es,

Afr

ica

Coun

try

or R

egio

n (a

utho

r)Ty

pe o

f stu

dyIm

mun

izat

ion

(per

cen

t)M

edia

n ag

e at

in

fect

ion

(yea

rs)

0–4

year

sAl

l age

s

Case

fata

lity

rate

(p

er c

ent)

Num

ber

of c

ases

Case

fata

lity

rate

(p

er c

ent)

Num

ber

of c

ases

Rura

l Afr

icaBo

tsw

ana

(Ose

i & M

agan

u 19

87)

Pros

pect

ive

com

mun

ity

stud

y0

135

Cam

eroo

n (W

orld

Hea

lth

Org

aniz

atio

n 19

79b)

Hou

seho

ld S

urve

y4

865

Ethi

opia

(Li

ndtjø

rn 1

986)

Out

brea

k in

vest

igat

ion

Non

e27

63G

ambi

a (H

eyw

orth

197

3)O

utbr

eak

inve

stig

atio

nN

one

1072

Gam

bia

(Hul

l et

al. 1

983)

Out

brea

k in

vest

igat

ion

Som

e3.

59

775

132

Gam

bia

(Lam

b 19

88)

Pros

pect

ive

com

mun

ity

stud

y90

026

054

Gam

bia

(McG

rego

r 19

64)

Pros

pect

ive

com

mun

ity

stud

yN

one

5.0

2225

9

Gui

nea-

Biss

au (

Aab

y et

al.

19

84a)

Pros

pect

ive

com

mun

ity

stud

yN

one

3.5

3410

124

162

Ken

ya (

Burs

tröm

et

al. 1

992)

Out

brea

k in

vest

igat

ion

604.

713

134

825

2K

enya

(Bu

rstr

öm e

t al

. 199

2)O

utbr

eak

inve

stig

atio

n29

2.8

1298

913

9K

enya

(Le

euw

enbu

rg e

t al

. 19

84)

Out

brea

k in

vest

igat

ion

202.

58

331

642

4

Ken

ya (

Leeu

wen

burg

et

al.

1984

)O

utbr

eak

inve

stig

atio

nSo

me

2.5

253

22

665

Ken

ya (

Mul

ler

et a

l. 19

77)

Out

brea

k in

vest

igat

ion

561

734

Mal

i (M

orle

y 19

73)

Out

brea

k in

vest

igat

ion

Non

e38

123

Mal

i (Im

pera

to 1

975)

Out

brea

k in

vest

igat

ion

Non

e50

256

Nig

eria

(O

gbei

de 1

967)

Out

brea

k in

vest

igat

ion

Non

e25

Nig

eria

(M

orle

y et

al.

1967

) Pr

ospe

ctiv

e co

mm

unity

st

udy

Non

e7

222

Sene

gal

(Sy

1967

)O

utbr

eak

inve

stig

atio

nN

one

979

516

0 cont

inue

d


Sene

gal (

Gar

enne

& A

aby

1990

)Pr

ospe

ctiv

e co

mm

unity

st

udy

Non

e3.

610

966

715

00

Sene

gal (

Lang

aney

& P

ison

19

79)

Pros

pect

ive

com

mun

ity

stud

yN

one

2716

0

Sene

gal (

Piso

n 19

82)

Pros

pect

ive

com

mun

ity

stud

yN

one

2710

6

Sene

gal (

Piso

n &

Bon

neui

l 19

88)

Pros

pect

ive

com

mun

ity

stud

yN

one

3.5

2044

1368

Sene

gal (

Satg

e et

al.

1965

)Pr

ospe

ctiv

e co

mm

unity

st

udy

Non

e5.

022

8710

221

Sene

gal (

Step

hens

198

6)Pr

ospe

ctiv

e co

mm

unity

st

udy

Non

e18

537

Sene

gal (

Sy 1

967)

Out

brea

k in

vest

igat

ion

Non

e26

119

926

6So

mal

ia (

Wor

ld H

ealth

Org

a-ni

zatio

n 19

80)

Hou

seho

ld S

urve

yN

one

260

0

Urb

an A

frica

Gui

nea-

Biss

au (

Aab

y et

al.

1984

b)Pr

ospe

ctiv

e co

mm

unity

st

udy

Som

e2.

015

124

1416

1

Gui

nea-

Biss

au (

Aab

y et

al.

1988

)Pr

ospe

ctiv

e co

mm

unity

st

udy

Non

e2.

521

356

1745

9

Nig

eria

(H

ondi

us &

Sut

oriu

s 19

79)

Out

brea

k in

vest

igat

ion

Som

e0

78

Nig

eria

(R

ea 1

968)

Out

brea

k in

vest

igat

ion

Non

e4

68Z

aire

(K

ason

go P

roje

ct T

eam

19

81)

Pros

pect

ive

com

mun

ity

stud

ySo

me

610

69

Zam

bia

(Rol

fe 1

982)

Out

brea

k in

vest

igat

ion

Som

e1.

52

360

Not

e: O

nly

deat

hs w

ere

regi

ster

ed. T

he c

ase

fata

lity

rate

is b

ased

on

the

assu

mpt

ion

that

all

non-

imm

uniz

ed c

hild

ren

in t

he a

ge g

roup

cau

ght

mea

sles

.

Sour

ce: d

eriv

ed f

rom

Aab

y &

Cle

men

ts (

1991

)

Tab

le 4

.4

M

easl

es c

ase

fata

lity

rate

s in

pro

spec

tive

com

mun

ity s

tudi

es,

Afr

ica

(con

tinue

d)

Coun

try

or R

egio

n (a

utho

r)Ty

pe o

f stu

dyIm

mun

izat

ion

(per

cen

t)M

edia

n ag

e at

in

fect

ion

(yea

rs)

0–4

year

sAl

l age

s

Case

fata

lity

rate

(p

er c

ent)

Num

ber

of c

ases

Case

fata

lity

rate

(p

er c

ent)

Num

ber

of c

ases

83Measles

Tab

le 4

.5

M

easl

es c

ase

fata

lity

rate

s in

pro

spec

tive

com

mun

ity s

tudi

es,

Am

eric

as

Coun

try

or r

egio

n (s

tudy

)Ty

pe o

f stu

dyIm

mun

izat

ion

(per

cen

t)

Med

ian

age

at in

fect

ion

(yea

rs)

0–4

year

sAl

l age

s

Case

fata

lity

rate

(per

cen

t)N

umbe

r of

ca

ses

Case

fata

lity

rate

(per

cen

t)N

umbe

r of

ca

ses

Gua

tem

ala

(Gor

don,

Jans

en &

Asc

oli 1

965)

Pros

pect

ive

com

mun

ity

stud

yN

one

3.5

529

24

449

Gua

tem

ala

(Mat

a 19

78)

Pros

pect

ive

com

mun

ity

stud

yN

one

2.0

423

12

267

Mex

ico

(C

uauh

tli, R

uiz-

Mat

us &

Nei

burg

19

90)

Out

brea

k in

vest

igat

ion

546

882

Mex

ico

(San

chez

-Var

gas,

Lope

z-O

rtiz

&

Bust

aman

te-H

erna

ndez

199

0)O

utbr

eak

inve

stig

atio

n39

5.0

1070

423

0

Not

e: O

nly

deat

hs w

ere

regi

ster

ed. T

he c

ase

fata

lity

rate

is b

ased

on

the

assu

mpt

ion

that

all

non-

imm

uniz

ed c

hild

ren

in t

he a

ge g

roup

cau

ght

mea

sles

.

Sour

ce: d

eriv

ed f

rom

Aab

y &

Cle

men

ts (

1991

).


Tab

le 4

.6

M

easl

es c

ase

fata

lity

rate

s in

pro

spec

tive

com

mun

ity s

tudi

es,

Asi

a

Coun

try

or R

egio

n (a

utho

r)Ty

pe o

f stu

dyIm

mun

izat

ion

(per

cen

t)M

edia

n ag

e at

in

fect

ion

(yea

rs)

0–4

year

sAl

l age

s

Case

fata

lity

rate

(p

er c

ent)

Num

ber

of c

ases

Case

fata

lity

rate

(p

er c

ent)

Num

ber

of c

ases

Rura

l Asia

Afg

hani

stan

(W

akem

an 1

978)

Out

brea

k in

vest

igat

ion

Non

e6.

042

214

728

327

Bang

lade

sh (

Bhui

ya e

t al

. 198

7)Pr

ospe

ctiv

e co

mm

unity

st

udy

Non

e2

3 45

8

Bang

lade

sh (

Kos

ter

et a

l. 19

81)

Pros

pect

ive

com

mun

ity

stud

yN

one

3.5

451

04

896

Bang

lade

sh (

Wor

ld H

ealth

O

rgan

izat

ion

1986

)H

ouse

hold

sur

vey

3.4

22

354

23

026

Burm

a (C

hin

& T

haun

g 19

85)

Out

brea

k in

vest

igat

ion

Non

e5.

012

918

182

Indi

a (A

garw

al e

t al

. 198

6)O

utbr

eak

inve

stig

atio

nN

one

3.0

579

411

2In

dia

(Bha

tia 1

985)

Out

brea

k in

vest

igat

ion

Non

e3

515

Indi

a (C

hava

n, N

atu

& P

ratin

i-dh

i 198

6)Pr

ospe

ctiv

e co

mm

unity

st

udy

Non

e3

103

Indi

a (C

heri

an, J

osep

h &

John

19

84)

Out

brea

k in

vest

igat

ion

Non

e10

78

Indi

a (D

hano

a &

Cow

an 1

982)

Out

brea

k in

vest

igat

ion

Non

e4

78In

dia

(Indi

an C

omm

unic

able

D

isea

se B

ulle

tin 1

985)

Out

brea

k in

vest

igat

ion

Non

e24

46

Indi

a (In

dian

Com

mun

icab

le

Dis

ease

Bul

letin

198

6)O

utbr

eak

inve

stig

atio

nN

one

2.9

2677

2110

2

Indi

a (Jo

hn e

t al

. 198

0)O

utbr

eak

inve

stig

atio

nN

one

3.0

1850

1465

Indi

a (L

akha

npal

& R

atho

re

1986

)O

utbr

eak

inve

stig

atio

n2.

61

182

124

1

Indi

a (L

obo

et a

l. 19

87)

Pros

pect

ive

com

mun

ity

stud

yN

one

232

22

436

Indi

a (N

arai

n et

al.

1989

)O

utbr

eak

inve

stig

atio

nN

one

7.0

1229

27

771

85MeaslesIn

dia

(Per

eira

& B

enja

min

19

72)

Out

brea

k in

vest

igat

ion

Non

e2.

54

80

Indi

a (R

eddy

et

al. 1

986)

Non

e0

318

Indi

a (S

alun

ke &

Nat

u 19

77)

Out

brea

k in

vest

igat

ion

Non

e4.

021

7314

114

Indi

a (S

harm

a et

al.

1984

)O

utbr

eak

inve

stig

atio

nN

one

2.6

490

410

2In

dia

(Sin

ha 1

977)

Pros

pect

ive

com

mun

ity

stud

yN

one

4.0

372

118

1

Indi

a (S

wam

i et

al. 1

987)

Pros

pect

ive

com

mun

ity

stud

yN

one

173

1

Indo

nesi

a (W

orld

Hea

lth

Org

aniz

atio

n 19

79a)

Out

brea

k in

vest

igat

ion

3.5

1674

1210

4

Indo

nesi

a (W

orld

Hea

lth

Org

aniz

atio

n 19

82)

Surv

eySo

me

14

760

Mar

shal

l Isl

ands

(M

cInt

yre

et

al. 1

982)

Out

brea

k in

vest

igat

ion

Non

e3.

01

252

134

0

Papu

a (Jü

ptne

r &

Qui

nnel

l 19

65)

Out

brea

k in

vest

igat

ion

Non

e6.

00

1 07

20

2 61

2

Phili

ppin

es (

Alm

oira

die-

Javo

-ni

llo &

Javo

nillo

198

4)O

utbr

eak

inve

stig

atio

nN

one

5.5

Sri L

anka

(W

orld

Hea

lth O

rga-

niza

tion

1985

b)H

ouse

hold

sur

vey

Som

e1

2 38

6

Tha

iland

(W

orld

Hea

lth O

rga-

niza

tion

1985

a)O

utbr

eak

inve

stig

atio

nN

one

5.0

3324

2450

Urb

an A

siaBu

rma

(Chi

n &

Tha

ung

1985

)O

utbr

eak

inve

stig

atio

nN

one

4.0

378

72

1 34

0In

dia

(Sat

path

y &

Cha

krab

orty

19

90)

Out

brea

k in

vest

igat

ion

Non

e0

581

Indi

a (S

iddi

qi, G

hosh

& B

erry

19

74)

Out

brea

k in

vest

igat

ion

Non

e3

67

Indi

a (V

elha

f et

al. 1

989)

Out

brea

k in

vest

igat

ion

Som

e2.

51

359

Not

e: O

nly

deat

hs w

ere

regi

ster

ed. T

he c

ase

fata

lity

rate

is b

ased

on

the

assu

mpt

ion

that

all

non-

imm

uniz

ed c

hild

ren

in t

he a

ge g

roup

cau

ght

mea

sles

.

Sour

ce: d

eriv

ed f

rom

Aab

y &

Cle

men

ts (

1991

).


to occur in some parts of the world during outbreaks. One outbreak in Niger in 1992 recorded CFRs of 18.2 per cent in children under 5 years of age (World Health Organization 1993b) while an earlier outbreak in Afghanistan resulted in CFRs between 28 and 42 per cent (Wakeman 1978). CFRs may vary during outbreaks, and may differ between studies in the community and those in hospitals.

Outbreak investigations and retrospective community studies or “verbal autopsies” have been the most common methods used by researchers to measure CFRs. These have been used partly because routine data were not adequate, and partly because events, such as outbreaks, stimulated researchers to undertake the studies. There are diffi culties and biases inher-ent in both these approaches, however. Retrospective surveys, for example, are likely to underreport deaths.

Outbreak investigations are likely to be biased in two different ways. First, outbreaks with high mortality are probably more likely to be inves-tigated. Second, medical intervention in the outbreak may tend to reduce the associated mortality. Investigations of measles outbreaks, especially in Africa, have generally reported surprisingly high CFRs. The most reliable estimates of CFRs for measles should therefore come from areas with exist-ing longitudinal studies of child mortality. The World Health Organization has developed a standard protocol for use in the community to measure the CFR during an outbreak (World Health Organization 1993a).

More refi ned estimates of acute measles mortality may not necessarily raise the global estimate of measles deaths signifi cantly. The precise size of the burden of acute deaths from measles, however, remains uncertain.

Risk factors for dying

The burden of measles deaths falls on the very young and those children already weakened by malnutrition, especially vitamin A defi ciency. The risk of dying is higher the younger the age of onset of measles. In the pre-vaccine era, the burden of cases (and therefore deaths) fell on the very young (Figure 4.2), with resulting high overall CFRs. As immunization programmes have taken effect, the age of onset of the disease has been pushed higher, helping to lower CFRs.

Hospital studies indicate that the patient’s state of nutrition appears to be a major risk factor, as mortality during hospitalization is related to the weight-for-age at admission. In contrast, no community study with information on state of nutrition prior to infection has documented this to be a risk factor for outcome (Aaby 1988b). The correlation found in hospital studies may therefore refl ect that children with the most severe and potentially fatal infections have lost more weight prior to admission.

Whereas anthropometric indices may be of limited value in predicting the case fatality rate in measles infection, studies have implicated vitamin A defi ciency as an important determinant of measles mortality (Markowitz et al. 1989). In Indonesia, even mild optical indicators of vitamin A defi ciency, such as night blindness and Bitot’s spots, have been associated with mark-

87Measles

edly increased morbidity and mortality in childhood. The incidence of both respiratory infection and diarrhoeal disease, two of the most debilitating complications of measles, were also considerably increased in children who were vitamin A defi cient (Sommer, Katz & Tarwotjo 1984).

Sex difference

Garenne (1994) reported an excess of female measles mortality from birth to age 50. This is contrary to what might be expected in that males gener-ally have higher mortality. Studies of the effect of high-titre measles vaccine used in children under 9 months of age revealed an unexpected and, as yet, unexplained lower survival in females compared with controls (Aaby et al. 1994). It is not clear at this point whether there is a link. Nor is it clear whether reported sex differences are a consistent phenomenon, are biologically or genetically based, or whether local social differences may account for some of the difference.

Review of empirical databases by World Bank Region

The World Health Organization estimates that by 1995 there were 2.4 million deaths annually from vaccine-preventable diseases and 1.16 million deaths from measles in the developing world. The degree to which measles virus infl icts death on a region or population (Table 4.7) varies widely between countries, between regions within countries, and even between epidemics in the same district. This is partly a result of the difference in age-specifi c attack rates, the underlying level of nutrition, the presence or absence of supportive treatment services, and other environmental and sociological factors.

Figure 4.2 Measles deaths in the Americas, 1971–1980, by age group

0

10

20

30

40

50

60

70NorthCaribbeanCentralTropical SouthTemperate South

Dea

ths

(per

cent

age)

<1 1–4 5–9 10–14 15–19 20+

Age group


Tab

le 4

.7

T

he e

stim

ated

bur

den

of m

easl

es b

y W

orld

Ban

k R

egio

n

Wor

ld B

ank

Regi

on

Num

ber

of in

fant

s su

rvivi

ng to

12

mon

ths

of a

ge

(thou

sand

s)

Num

ber

of

repo

rted

ca

ses

CFRa

(per

cen

t)

Imm

uniz

atio

n co

vera

ge b

y va

ccin

e (p

erce

ntag

e)

BCG

bD

PT-3

cPo

lio-3

dM

easle

sTT

2+e

CH

I24

389

85 7

050.

3093

9595

94 2

EME

10 6

8014

003

0.10

8886

8578

—FS

E 4

805

19 4

180.

4593

9293

92—

IND

23 6

1589

612

3.00

9290

9085

78LA

C10

985

37 9

391.

6891

7887

8347

MEC

17 7

85 8

921

1.51

8479

7976

57O

AI

18 8

6537

959

2.14

9083

8884

68SS

A22

280

37 0

314.

6462

4949

4936

Sour

ce: W

orld

Hea

lth O

rgan

izat

ion,

WH

O/E

PI in

form

atio

n sy

stem

, as

of O

ctob

er 1

994.

a.C

ase

fata

lity

rate

b.Ba

cillu

s C

alm

ette

-Gué

rin

c.D

ipht

heri

a-pe

rtus

sis-

teta

nus,

3 do

ses

d.Po

lio, 3

dos

es

e.Te

tanu

s to

xoid

, 2 d

oses

89Measles

Using the number of cases reported is one method of assessing how many cases of measles are occurring. Table 4.7 shows the number of cases reported by World Bank Region. Although it is not obvious from the table, in general it can be said that developing countries with the highest immu-nization coverage rates experience the lowest incidence of cases.

Assumptions made in calculating the burden of measles

As previously mentioned, reported numbers of cases and deaths may be highly unreliable for a variety of reasons. The World Health Organization estimates cases and deaths using a number of assumptions. It is assumed that all susceptible members of the birth cohort will eventually contract measles by one year of age. Because the highest death rate in childhood is under one year of age, and because measles vaccine is generally adminis-tered in developing countries between 9 and 11 months of age, the number of children surviving to one year of age (SI) is taken as a component of the numerator. For the purposes of the calculation, measles vaccine effi cacy (VE) is taken as 85 per cent (although when administered after one year of age, it may be 95 per cent or more).

The following formulae are used:

Estimated number of cases per year

= [1 – (Coverage × VE)] × SI

and

Estimated number of deaths occurring per year

=Estimated number of

cases per year× CFR .

These formulae have been used to estimate the numbers of cases and deaths shown in Table 4.8.

China region

As a result of China’s strong immunization programme, well over 90 per cent of children are immunized against measles. The surveillance system is able to detect a far greater proportion of cases than in many countries, resulting in a high number of reported cases. The burden of disease in this country, is, however, probably not as great as Table 4.8 would suggest, bearing in mind the size of its child population. Of those cases occurring, the CFR is only 0.3 per cent, indicating a strong health infrastructure that is able to treat cases successfully.

Established market economies

At 78 per cent, measles vaccine coverage is not as high as it could be. Limited resources and diffi cult access to services are not obstacles to immunization in these countries. Parental choice, is, however, a feature


of the immunization programmes in many of these nations; when combined with mediocre promotional activities, the result is that too many children are not immunized. Signifi cant numbers of cases continue to occur in pockets of the population, especially in the lower socioeconomic groups, and epidemics continue to be a feature of the disease. Largely excellent treatment services ensure a very low mortality rate.

Former Socialist Economies of Europe

An expectation that every child will be processed by child health services results in a high coverage in these countries. A strong reporting system means that a higher than average proportion of cases is reported. Never-theless, treatment services are not quite as successful at preventing deaths as are some of the established market economies that are their European neighbours.

India

Given that India began using measles vaccine in its national programme only in 1985, the progress is truly impressive. The 85 per cent coverage rate for measles vaccine highlights the enormous numbers of children success-fully immunized and protected to date. Higher case fatality rates suggest pockets of low coverage and areas with inadequate treatment facilities, poor access to treatment services and a high level of background ill health and malnutrition including vitamin A defi ciency.

Latin America and the Caribbean

Following mass vaccination campaigns against measles in the past decade, the Latin American and Caribbean countries have been successful in reduc-ing measles. This provides a model for other countries and regions to strive to emulate over the coming years.

Table 4.8 Annual estimated burden of measles by World Bank Region, 1990, unadjusted for background mortality

RegionEstimated incidence of

measles casesaEstimated CFR (percentage)b

Estimated number of measles deathsa

CHI 4 902 189 0.30 14 707EME 3 559 160 0.10 3 559FSE 4 233 124 0.45 19 049IND 6 553 162 3.00 196 595LAC 3 235 082 1.68 54 349MEC 6 295 890 1.51 95 068OAI 5 395 390 2.14 115 461SSA 12 993 696 4.64 602 907

a. Formula used for the calculation is explained in the text.

b. Case fatality rates (CFRs) are estimated based on the World Health Organization's review of published studies and country information, summarised in Tables 4.4, 4.5 and 4.6.

91Measles


While a few countries have average coverage and measles still occurs, some countries in this region have attained very high coverage and reduced measles cases and deaths close to zero. It is to be anticipated that these high-performance countries will be in a position to eliminate measles in the near future. Countries performing less well have the potential to improve performance rapidly and are expected to reduce the burden of disease accordingly over the next 5 years.

Other Asia and Islands

Some of the larger nations in this region are still suffering from a consider-able amount of circulating measles virus, with signifi cant morbidity and mortality. Other countries, particularly the smaller Pacifi c Island nations, have been able to reduce measles to very low levels. As with strongly per-forming countries in the Middle Eastern Crescent, such nations are in an excellent position to consider elimination in the next few years.

Sub-Saharan Africa

Children in the countries of this region suffer the greatest burden from measles. Underlying ill-health and malnutrition interact with measles infection to produce a high caseload and high CFR. Tragically, this is also the region where measles vaccine coverage is lowest and the health infrastructure is least able to cope with providing immunization and cura-tive services.

Administration of measles vaccine is one of the most cost-effective pub-lic health tools. A World Bank study calculated the cost-effectiveness of immunization in disability-adjusted life years (DALYs). The cost of gaining one DALY is less than US$10 for measles vaccine, to date the most cost-effective of all public health interventions studied (World Bank 1993).

Other considerations in calculating the burden of measles

Crowded conditions have been found to be associated with higher case fatality rates (Aaby 1988a). Large urban agglomerations typically present ideal conditions for measles transmission, especially among the poor who live in close proximity to each other and are under-immunized. They also experience high rates of other infectious conditions as well as reduced access to medical care. Even in recent outbreaks in such conditions, the CFR can be as high as 20 per cent (World Health Organization 1993b).

Transmission also occurs in both urban and rural areas in age groups below the recommended age of immunization. It was previously thought that the achievement of high coverage in older children would protect young children by herd immunity, but this has not always been observed because of the highly infectious nature of measles virus.

The age at which children contract measles depends on a variety of local circumstances. Because maternal antibodies decay at variable rates in different parts of the world, different proportions of infants are protected


against measles in the fi rst few months of life. As maternal antibodies wane, the attack rates for measles increase each month to a maximum between one and two years of age in developing countries. A hospital-based study in Afghanistan reported a typical picture of the age distribution of cases, with 74 per cent of all cases occurring between 4 months and 3 years of age (Arya et al. 1987).

Even so, measles is still responsible for more deaths than any other EPI target disease. Measles ranks as one of the leading causes of childhood mortality in the world. In one community study in Kenya (Spencer et al. 1987), measles accounted for 35 per cent of reported deaths in infants 1 to 12 months of age and for 40 per cent of deaths in children 1 to 4 years old. The impact of measles on the lives of millions of young children every year, particularly in developing countries, indicates the urgent need for further reduction in measles incidence. The risk of becoming ill or dying from measles is not evenly distributed in a population but occurs in high-risk groups which include the urban poor, school children (who represent cohorts from previous years when coverage was lower and who may not have been exposed to measles infection), ethnic minorities (who may have been underserved or may have rejected immunization for cultural reasons), hospitalized children (who are at high risk of nosocomial transmission), and children in refugee camps (where crowding facilitates the spread of the virus).

A number of studies suggest that measles is more severe and is more likely to result in death in situations where intense exposure occurs, such as “secondary” transmission (transmission from an index case to other children in the same household), crowding and outbreaks. A study in the Machakos District, Kenya (Aaby & Leeuwenburg 1990), showed that in families with several cases of measles, secondary cases had a higher risk of dying than those who were infected from outside. Older children, with their increased mobility, appear to have an increased opportunity for acquiring infection outside the home but lower case fatality rates because of a lower infecting dose and a more mature immune system. Another study from the Gambia showed that measles mortality was strongly associated with more than 5 measles cases in a household (Hull 1988).

This dynamic does not seem to affect the severity of disease in the same way in industrialized countries. Sutter et al. (1991) found no difference in severity between primary and secondary cases in a setting where the overall severity of measles was much less and mortality was minimal.

Measles as a risk factor for other diseases

As mentioned earlier, there are a number of potent co-factors which may act in synergy with measles infection to produce serious disease and com-plications. Among these are malnutrition (especially vitamin A defi ciency) and high background morbidity and mortality from other infections such

93Measles

as diarrhoeal disease. Measles may cause a number of acute complications, described in detail below.

Pneumonia

Measles is a major cause of pneumonia in children. It has been estimated that measles accounts for 6–21 per cent of all cases of pneumonia and for 8–93 per cent of pneumonia-related deaths (Markowitz & Nieberg 1991). Studies done in the past two decades indicate that pneumonia is a major complication in hospitalized cases, occurring in about 60–80 per cent of cases, with CFRs varying from 5 per cent to 20 per cent (Table 4.9) (Tidstrom 1968, De Buse, Lewis & Mugerwa 1970, Commey & Richardson 1984, Burgess, Mduma & Josphson 1986, Hussey & Klein 1990, Lamabadusuriya & Jayantha 1992, Samsi et al. 1992). Rates during outbreaks may rise dramatically, as illustrated in the report by Narain et al. (1989) describing a measles outbreak in an unimmunized rural com-munity in India. The reported incidence of pneumonia was 39.4 per cent and the case fatality rate was an exceptional 46.3 per cent.

There are few published data on the etiology of measles-associated pneumonia. Results from three descriptive studies are shown in Table 4.10, indicating that Streptococcus pneumoniae and Staphylococcus aureus were the predominant isolates (Wesley, Sutton & Widrich 1971, Dover et al. 1975, Morton & Mee 1986). Ristori et al. (1962) reported that about 50 per cent of the fatal cases of pneumonia seen in Santiago in 1962 were attributable to S. aureus. Additional evidence for the impor-tant role of bacterial superinfection comes from postmortem studies that reported this problem in 25–50 per cent of fatal cases (Kaschula, Druker & Kipps 1983).

The study from Nigeria (Morton & Mee 1986) showed that a higher bacterial isolation rate was found in severe cases of pneumonia (94.7 per cent) compared to milder cases (37.8 per cent, p < 0.01), and in more malnourished children (65 per cent) than in better nourished children (42 per cent, p = 0.07).

Limited studies suggest that viruses are also a signifi cant cause of mea-sles-associated pneumonia. Postmortem studies (histology and virology) from Cape Town indicate that measles virus, herpes virus or adenovirus are each responsible for approximately 25 per cent of cases (Kipps & Kaschula 1976). Serological studies from Nigeria (Morton & Mee 1986) and Colombia (Dover et al. 1975) found respectively, that 3 out of 7 cases (42.9 per cent) and 5 out of 21 cases (23.8 per cent) were positive for adenovirus.

Croup

Recent data from both the United States of America and Africa indicate that croup occurs in approximately 10 to 25 per cent of hospitalized cases of measles (Table 4.9) (Tidstrom 1968, De Buse, Lewis & Mugerwa 1970, Hancock 1972, Commey & Richardson 1984, Burgess, Mduma &


Tab

le 4

.9

In

cide

nce

rate

s of

pne

umon

ia, c

roup

and

dia

rrho

ea a

nd r

espe

ctiv

e ca

se fa

talit

y ra

tes

in h

ospi

taliz

ed p

atie

nts

with

mea

sles

Pneu

mon

iaCr

oup

Dia

rrho

ea

Coun

try

or c

ityYe

arIR

a (%

)CF

Rb (%

)IR

a (%

)CF

Rb (%

)IR

a (%

)CF

Rb (%

)

Bang

kok

(El

Beha

iry

et a

l. 19

86)

1980

–81

——

——

79—

Cap

e To

wn

(Hus

sey

& K

lein

199

0)19

87–8

877

713

780

0H

oust

on (

Ros

s et

al.

1992

)19

88–8

9—

—22

7—

—Ja

kart

a (

Sam

si e

t al

. 199

2)19

82–8

675

10—

— 3

8Li

ma

(Gre

enbe

rg e

t al

. 199

1)

1985

–87

——

——

71 8

Los A

ngel

es (

Han

cock

197

2)19

90—

—19

1—

—D

enm

ark

(Tid

stro

m 1

968)

19

48–6

226

1

4.1

——

—G

hana

(C

omm

ey &

Ric

hard

son

1984

) 19

73–8

263

2211

20 9

21In

dia

(R

aote

& B

have

199

2)19

86–8

716

——

——

—K

enya

(La

bay

et

al. 1

985)

19

72—

—10

39—

—Sr

i Lan

ka (

Lam

abad

usur

iya

& Ja

yant

ha 1

992)

1990

68 4

——

13 0

Tanz

ania

(Bu

rges

s, M

dum

a &

Jose

phso

n 1

986)

19

81–8

375

818

2313

0U

gand

a (D

e Bu

se L

ewis

& M

uger

wa

1970

) 19

67–6

879

2014

21—

—

a. IR

= in

cide

nce

rate

.

b.C

FR =

cas

e fa

talit

y ra

te.

95Measles

Josephson 1986, Hussey & Kelin 1990, Fortenberry et al. 1992, Ross et al. 1992). Case fatality rates vary from about 1 per cent in the United States of America (Ross et al. 1992) up to an exceptional 40 per cent in some areas of Africa (Hancock 1972). There are no recently published data on the incidence of measles-associated croup from Asia or South America.

There are few data on the aetiology of measles-associated croup. Many children with measles present with croup early in the clinical course, this complication probably being caused by the measles virus itself. Unpub-lished data from Cape Town suggest that herpes virus is a common cause of post-measles croup. Some cases may be associated with oropharyngeal lesions. Herpes virus (from the oropharynx) and adenovirus (from the lung) were cultured in 2 of 6 patients with croup in one study from the United States of America (Ross et al. 1992).

In the Cape Town study, 13 of 189 children (6.9 per cent) were presumed to have early onset measles-croup and none required airway intervention. In contrast, late onset croup, presumed to be herpes-associated, occurred in 40 of 189 patients (21.2 per cent) and 12.5 per cent required intubation (Hussey & Klein 1990).

Bacterial tracheitis is an uncommon cause of stridor and is usually due to S. aureus, S. pneumoniae or Haemophilus infl uenzae infection (Dover et al. 1975, Labay et al. 1985). Its presentation in measles is not much different from that in non-measles cases (Conley, Beste & Hoffman 1993). Experience indicates that it should be considered in patients whose symptoms, in addition to stridor, include toxicity, purulent sputum, or associated pneumonia.

Table 4.10 Frequency of bacterial isolates and complications following lung and tracheal aspirates in measles-associated pneumonia

Country (study):Colombia

(Dover et al. 1975)

Colombia (Dover et al.

1975)

Nigeria (Morton & Mee

1986)

South Africa (Wesley, Sutton & Widrich, 1971)

Aspirate Lung aspirate Tracheal aspirate Lung aspirate Tracheal aspirate

Number 21 21 56 22

Bacterial isolates (percentage)Positive culturesS. pneumoniaeS. aureusH. infl uenzaeS. pyogenesS. viridansKlebsiella sppE. coli

10505————

62291019————

55551293—3—

680460014027

Complications (percentage)Pneumothorax

Case fatality rate

—

15

—

—

21

18

23

41


Diarrhoea

It has been estimated that measles-associated diarrhoea accounts for 1–7 per cent of all diarrhoeal episodes and 9–77 per cent of diarrhoeal deaths (Feachem & Koblinsky 1983). The proportion of measles cases presenting with diarrhoea varies greatly as does the CFR (Table 4.9). In a measles out-break in an unimmunized rural community in India the reported incidence (and CFRs) of diarrhoea and dysentery were, respectively, 32.2 per cent (4.8 per cent), and 10.8 per cent (13.3 per cent) (Narain et al. 1989).

Few studies have evaluated the role of measles in persistent diarrhoea. A prospective, community-based study from Bangladesh (Koster et al. 1981) reported that 25 per cent of measles-associated diarrhoea lasted for 7 or more days. The CFR was signifi cantly higher when associated with prolonged diarrhoea (i.e. lasting 7 or more days); 11.9 per cent compared to 1 per cent in those with diarrhoea lasting less than 7 days. In addition, in children with acute diarrhoea, those with measles-associated diarrhoea had a higher case fatality rate (1 per cent) than those without measles (0.1 per cent).

In contrast, a prospective hospital-based study (Dutta et al. 1991) on persistent diarrhoea reported that no such cases occurred in children who had reported having had measles in the previous 6 months.

The aetiology of measles-associated diarrhoea has been well defi ned in four case-controlled studies (Varavithya et al. 1985, 1989, Greenberg et al. 1991, Sang et al. 1992). A few distinct trends are noted when comparing the cases (measles-associated diarrhoea) and controls (non-measles-associ-ated-diarrhoea). The frequency with which no pathogen was identifi ed was higher in cases than in controls in all of the studies. This would suggest that many cases of measles-associated diarrhoea (varying from 8 to 46 per cent) were attributable to measles virus per se. Rotavirus was isolated in 16 to 30 per cent of controls in three studies where it was looked for, while it was virtually never isolated in cases of measles (Varavithya et al. 1989, Greenberg et al. 1991, Sang et al. 1992). Parasitic infections were more common in the two studies (Varavithya et al. 1989, Greenberg et al. 1991) where this was looked for. The reason for this phenomenon may be related to the immune suppression of measles. No difference was noted in bacterial isolation rates, except for one study (Greenberg et al. 1991) indicating a higher rate of campylobacter isolation.

Additional support for the belief that measles virus may be a cause of mild diarrhoea comes from a descriptive study from Egypt (El Behairy et al. 1986) which reported that the bacterial stool cultures of children with mild diarrhoea (n = 33) were negative in 42 per cent of cases compared to 27 per cent in children with moderate diarrhoea (n = 11) and none in severe diarrhoea (n = 6).

Malnutrition

Malnutrition has generally been held to be the major predictor of mortal-ity in cases of measles. Data derived mainly from hospital surveys show

97Measles

that children who are signifi cantly malnourished have a higher morbidity and mortality rate (Table 4.11) (Burgess, Mduma & Josephson 1986, Samsi et al. 1992, Alwar 1992). This, however, does not necessarily imply a causal relationship. It has been shown that measles is an extremely catabolic event and that children lose a signifi cant proportion of weight following infection. The amount of weight loss may be related to severity of infection (infecting dose). The presence of dehydration resulting from diarrhoea and reduced fl uid intake exacerbates weight loss and complicates the assessment of nutritional status. Most studies have not controlled for dehydration. An exception is a study from Kenya (Sang et al. 1992) which also reported a longer hospital stay for severely malnourished children. If malnutrition is a risk factor, then the effects are probably mediated via immune suppression.

In a review of risk factors for measles, Aaby (1991) reported that no difference in mortality was noted in relation to nutritional status in com-munity based studies (except for one in Bangladesh).

Conjunctivitis and keratitis

Conjunctivitis and keratitis are hallmarks of measles and mild cases usually resolve within a few days of onset. Treatment is supportive and topical antibiotics are frequently prescribed, although their effi cacy in preventing secondary bacterial infections has not been tested.

Signifi cant corneal damage in children with measles can result in blind-ness (Foster & Sommer 1987). The causes of corneal damage include measles virus infection, secondary herpes or bacterial infection, and chemical conjunctivitis as a result of harmful eye practices such as herbal remedies and vitamin A defi ciency (xerophthalmia).

Table 4.11 Association between nutritional status and complications

Percentage of expected weight

Country of city (study) All >80 60–80 <60

MorbidityJakarta (Samsi et al. 1992)

Pneumonia

Diarrhoea

Convulsions

Otitis media

74.9

18.6

7.5

5.9

61.9

13.7

8.2

6.7

84.6

19.9

7.7

5.9

100.00

39.2

2.2

2.2

MortalityJakarta (Samsi et al. 1992)

Kenya (Foster & Sommer 1987)

Tanzania (Burgess, Mduma & Josephson 1986)

10.3

1.8

8.0

5.9

0.8

3.6

12.7

1.4

7.3

23.1

4.0

24.5


Xerophthalmia

The association between infections and xerophthalmia is a well-recognized observation. In a global review of xerophthalmia, Oomen, McLaren & Escapani (1964) stated that “there appears to be a universal relationship between infectious diseases and xerophthalmia. This relates especially to measles….” The results from case control studies, however, are confl icting. Studies from Ethiopia (De Sole, Belay & Zegeye 1987) and Malawi (Tielsch et al. 1986) reported signifi cant risk ratios (4.6 and 1.6 respectively) but studies from the Philippines (Solon et al. 1978) and Bangladesh (Stanton et al. 1986) found no signifi cant association.

A prospective study from India (Reddy et al. 1986) reported that con-junctival signs of xerophthalmia developed in 1.1 per cent of children (3 out of 281) in the 6-month period following measles, compared to 0.5 per cent of children (4 out of 819) without measles. The relative risk of developing xerophthalmia was 2.19 times greater following measles, although the 95 per cent confi dence intervals were wide, 0.49 to 9.71, p= 0.25. Children presenting with acute corneal xerophthalmia during the early stage of measles (10 of 318) were excluded from the analysis.

Acute encephalitis

Central nervous system (CNS) manifestations may be a consequence of a number of measles-associated complications including hyperpyrexia, hypoxaemia associated with pneumonia and croup, and dehydration and electrolyte disturbance associated with diarrhoea. In a 1963 community-based survey in the United Kingdom (Miller 1964), neurological distur-bances, which include a range of CNS problems including encephalitis, were reported in 0.4 per cent of cases; and 0.1 per cent were regarded as having encephalitis. In a subsequent hospital-based study in Denmark (Tidstrom 1968), encephalitis was seen in 1.4 per cent of patients with a CFR of 9 per cent. At follow-up, 32 per cent of survivors had some neuro-logical dysfunction. The epidemiology of this complication in developing countries has not been well described. Reported CNS complications in developing countries (Varavithya et al. 1985, Wahab et al. 1988, Samsi et al. 1992, Raote & Bhave 1992, Lamabadusuriya & Jayantha 1992) are shown in Table 4.12. The major area of concern relates to the diagnostic criteria for encephalitis in developing countries. The lack of standard case defi nitions makes comparison of data diffi cult.

Otitis media and stomatitis

Although otitis media and severe stomatitis are well recognized complica-tions of measles, there are very few publications dealing with their aetiol-ogy, natural history, complications, and management. A study from South Africa reported that herpes virus infection was detected in 43 per cent of hospitalized cases and 37 per cent of outpatient children with measles (Orren et al. 1981).

99Measles

Nosocomial infections

Children with measles are prone to secondary infections, particularly when hospitalized. Data are, however, lacking on the subject. A retrospective case-controlled study in South Africa reported that nosocomial bacterae-mia was six times more common in children with measles than in general paediatric patients (Hussey & Simpson 1990). The predominant organisms were gram-negative ones (Klebsiella and Salmonella), accounting for 86.5 per cent of the isolates, and 23 per cent were multiple drug resistant.

Morbidity from delayed complications

A number of studies have indicated that children who have had measles have signifi cantly increased morbidity and mortality in the ensuing months when compared with community controls.

A case-controlled study in Lima (Greenberg et al. 1991) reported that the number of episodes of diarrhoea in the month following measles was signifi cantly greater than in the absence of measles, as was the duration of episodes. No differences in weight gain pattern were, however, observed, which may be ascribed to good home-based follow up. A prospective, community-based study in Bangladesh (Koster et al. 1981) reported that children with measles complicated by diarrhoea for 7 days or more failed to improve their nutritional status compared to controls with diarrhoea or to children with measles complicated by a brief attack of diarrhoea.

In India, in a follow-up study of children for a period of 6 months after hospitalization, Bhaskaram et al. (1984) found that children gained hardly any weight in the fi rst month but thereafter they gained weight, although more slowly than the controls. In addition, the frequency of other infec-tions was 10 times that of the controls during the period.

In a prospective, community-based study of 281 cases of measles and 819 controls, Reddy et al. (1986) found that 34 per cent of the children with measles developed chest infections in the 6 months following infection,

Table 4.12 Frequency of central nervous system complications in measles

Location (study) Year Clinical criteria Percentage

Bangkok (Varavithya et al. 1985 1980–81 Encephalitis 13.9

Ghana (Commey & Richardson 1984) 1973–82 Coma or convulsions 3.2

India (Raote & Bhave 1992) 1986–87 EncephalitisMeningitisConvulsions

8.0 3.3 2.6

Sri Lanka (Lamabadusuriya & Jayantha 1992) 1990 Encephalitis 4.3

Sudan (Wahab et al. 1988) 1988 Convulsions 7.2

Thailand (Samsi et al. 1992) 1982–86 ConvulsionsEncephalopathy

17.0


compared to 6 per cent of the control children. In addition, the incidence of hospitalization was, respectively, 2.9 per cent versus 0.4 per cent.

It has generally been believed that measles predisposes people to the development of tuberculosis or its reactivation as a consequence of immune suppression. A comprehensive review by Flick (1976) concluded that the evidence for this assumption was not very strong. Decreased tuberculin skin reactivity should not be equated with reduced tuberculosis immunity or increased risk of tuberculosis. No recent data support or refute the hypothesis.

Measles has been associated with recurrent chest infections and bronchi-ectasis. The magnitude of the problem has, however, not been quantifi ed. In South Africa, a number of cases have been shown to follow measles (Kaschula, Druker & Kipps 1983).

Studies in West Africa have reported that children with measles had a fi vefold to tenfold greater risk of dying in the year following an attack of measles, compared to community controls (Hull 1988). The effect was most noticeable in those under one year of age. A recent study in Kenya (Burström et al. 1992) reported a mortality rate of 4.3 per cent in children aged 8–35 months living in compounds where there was a measles outbreak the previous year. The mortality rate in the compounds where there was no measles was much lower (1.1 per cent), but this was not statistically signifi cantly because of the small numbers.

The reasons for the increased morbidity and mortality following mea-sles are unclear, but may theoretically be attributable to viral persistence (although this has never been demonstrated), persistent immune suppres-sion or vitamin A defi ciency, or more likely a combination of these.

Certain conditions are known to result from measles infection and cause long term disability. These include blindness, mental retardation, brain damage (including brain abscess, deafness, and fi ts), and vitamin defi ciencies.

Conclusion

Case fatality rates have dropped dramatically over the past 20 years, especially in countries with good primary health care facilities. Simple inexpensive treatments for complications prevent death. These include the administration of oral rehydration fl uids, antibiotics, nutritional manage-ment, and vitamin A. Case fatality rates remain high in areas where these measures are not available, where communities are not provided with the services, not educated to avail themselves of the services or are unable to afford them, or where there is an underlying problem of malnutrition or vitamin A defi ciency.

Burden with no intervention

If there were no immunization with measles vaccine, no administration of vitamin A and no treatment of complications, measles would remain

101Measles

one of the greatest killers of children. Virtually every child in the world would eventually contract measles. At least 90 per cent of children under 5 years of age could be expected to contract the disease. In industrialized countries, at least 10 per cent of children would develop complications, but only about 0.1 per cent of those would die (mostly from encephalitis). In developing countries, however, with high transmission rates in very young children, complication rates could be as high as 70–90 per cent, with case fatality rates at 6 per cent, and as high as 25 per cent in some outbreaks. A conservative estimate would be 16 million deaths; but tak-ing into account very high local case fatality rates and the possibility of delayed mortality, that fi gure could easily be doubled.

Cost of interventions

High measles vaccine coverage throughout a population, followed by mass campaigns, has been shown capable of eliminating measles in the Americas. In the early 1990s, measles vaccines were inexpensive at about US$0.15 a dose and were at least 85 per cent effective when administered correctly. There is strong evidence suggesting that the measles virus could be eliminated from large portions of the world with existing technologies. Global eradication will be a greater challenge but is considered by many to be at least theoretically possible. In the meantime, properly applied simple treatments could reduce deaths to as low as 0.1 per cent of cases (complications such as encephalitis are likely to prevent case fatality rates from reaching zero).

Measles immunization is probably the most cost-effective public health intervention in the world. Estimates suggest that the cost per life-year gained for expanding measles coverage in a routine programme from 50 per cent to 80 per cent is US$2.53 (at a discounted rate) in areas with high disease incidence and high measles case fatality rates.

The cost of immunizing a child against measles in a mass campaign is assumed to be in the order of US$0.60 if conducted jointly with a poliomyelitis national immunization day, or US$1.20 for a stand-alone measles campaign. These fi gures can be combined with modelling results to calculate the cost per death prevented. This suggests that adding mass measles campaigns to a strategy of improving routine coverage is highly cost-effective. For a baseline campaign aimed at children aged 9–59 months, the cost per death prevented is US$40 if measles vaccine is given as part of a poliomyelitis national immunization day activity. The overall cost per death prevented by a campaign aimed at children aged 9 months to 14 years is still excellent value at around US$166.

Update

Following the assessment of the burden of measles in the 1980s, global measles vaccine coverage fl attened out at around 80 per cent. This overall


fi gure conceals many areas and districts with much lower coverage and proportionately higher risks of measles virus circulation. A supreme effort will clearly be needed if coverage is to be raised above this level globally, and especially in some trailing countries.

In the late 1990s, when stagnation in coverage levels seemed likely, countries in the Americas stepped up their efforts at measles control by achieving high coverage for routine vaccination, following this up with mass campaigns for children aged 9 months to 14 years. Island nations such as Cuba showed that it was possible to interrupt measles virus transmission in this way. Following this example, mass campaigns aimed at elimination were held in all countries of Latin America. Indigenous measles has now been eliminated from the Americas.

In other parts of the world, mass campaigns are now being carried out in many countries and situations. As well as drives towards elimination, campaigns are being conducted in situations where there are epidemiologi-cal grounds for thinking that an outbreak is expected. Studies show that mass campaigns performed after an outbreak is under way have virtually no impact and are expensive (Aylward, Clements & Olivé 1997). Preventive campaigns using measles-containing vaccines (such as measles-rubella or measles-mumps-rubella vaccines) have been implemented in, for instance, the United Kingdom with great success. In addition, mass campaigns have been used in high-risk situations such as refugee populations or in the urban environment when intense transmission is anticipated.

In more than one hundred countries, vitamin A supplementation has been provided with national immunization days for poliomyelitis eradica-tion. While not yet eliminating vitamin A defi ciency, this has undoubtedly reduced the burden of disease from lack of the micronutrient, and it is anticipated that a major impact will be demonstrable over the long term in reducing the mortality and morbidity from measles infection as a result.

The latter part of the 1990s saw a dramatic change in the epidemiology and control of measles. The successes of the smallpox and the poliomyelitis eradication initiatives have demonstrated the human capacity for control-ling infectious diseases. It will soon become clear whether the global com-munity is prepared to pay the price to eradicate measles from the globe.

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Aaby P, Clements CJ (1989) Measles immunization research: a review. Bulletin of the World Health Organization, 67:443–448.

103Measles

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107Measles

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PoliomyelitisKenji Shibuya, Christopher JL Murray

Chapter 5

Introduction

Poliovirus is an enterovirus in the family of Picornaviridae and consists of three antigenic types, 1, 2, and 3. All three types cause paralysis and the poliomyelitis vaccine is intended to be antigenic for all of these. Poliovirus type 1 causes paralysis most often and is responsible for most epidem-ics in unvaccinated populations (Assaad & Ljungars-Esteves 1984, Sen, Sharma & Sarthanam 1985, Kadi et al. 1988, Khare et al. 1991). Some outbreaks due to poliovirus type 1 have been reported among unimmunized populations in regions with high vaccine coverage (Kim-Farley et al. 1984, Sutter et al. 1991, Otten et al. 1992). In contrast, the poliomyelitis cases in vaccinated populations are usually caused by types 2 and 3 (Assaad & Ljungars-Esteves 1984).

Immunity to poliovirus is lifelong. Poliovirus infections occur only in humans and there is no animal reservoir. This is one of the key charac-teristics for possible eradication of poliomyelitis. Spread of infection by faecal–oral routes is most common in developing countries with poor hygiene and sanitation, while oral–oral (respiratory) infection may be more common in industrialized countries and during outbreaks. Perinatal transmission from mothers to newborn infants also occurs. After oral ingestion of poliovirus, the virus fi rst multiplies in the lymph nodes in the pharynx and gastrointestinal tract. The incubation period is 4 to 35 days, most cases occurring 1–3 weeks after exposure. Once the virus enters the human body, it invades local lymphoid tissues, enters the bloodstream, and then may invade anterior horn cells of the spinal cord. As it multiplies intracellularly, poliovirus may cause temporary or permanent damage of the nerve cells due to the infl ammation process. Other areas of both the spinal cord and brain may be affected as well.

Most poliovirus infections are asymptotic. Non-septic illness with low-grade fever and sore throat (minor illness) occurs in 4 to 8 per cent of infections. Aseptic meningitis occurs in 1 to 5 per cent of patients a few


days after the minor illness has resolved. Severe illness with rapid onset of asymmetric, acute fl accid paralysis (AFP) resulting from damage of lower motor neurons, with arefl exia of the involved limb and without loss of sensation occurs in 0.1 to 2 per cent of infections. Bulbar paralysis and paralysis of respiratory muscles may occur. Incidence of residual paralytic disease ranges from 1 per 1000 to 1 per cent of infections, and thus most cases are asymptomatic. Although cases are rarely recognized (Ledinko 1951, Debre & Thieffery 1955, Melnick & Nathanson & Martin 1979), incidence is known to be higher among older patients (Halstead et al. 1985). Despite the fact that, of those who survive an acute attack, most will recover some degree of function in the affected muscles, the true burden of paralytic poliomyelitis is that the affected patients may suffer from disability and handicap for the rest of their life and only a minority will recover completely. Patients with a history of paralytic poliomyelitis, in particular those who were older at the onset of polio infection and had an initially severe presentation of poliomyelitis, may present years later with complaints of muscle pain and increased weakness in the previously affected limb: late effects or post-paralytic-poliomyelitis syndrome (Hal-stead, Wiechers & Rossi 1985). Although it has a good prognosis, it may alter the sequelae of the disease burden.

It is well known that there are temporal and epidemiological changes in the pattern of transmission of poliovirus (Anderson & May 1993, Horst-mann 1982, Melnick 1990, Nathanson & Martin 1979, Paul et al. 1952). Melnick (1990) has suggested that poliomyelitis can be viewed as having three major phases: endemic, epidemic, and vaccine-era. Because of poor sanitation and hygiene in most developing countries, polioviruses circulate freely among infants and young children. Therefore, almost all children develop antibodies to at least one of the three poliovirus types before 5 years of age. Consequently, clinical poliomyelitis in tropical developing countries is almost exclusively an infantile disease, with more than 90 per cent of cases occurring under the age of 5 years because of age-dependent acquisition of immunity (Babaniyi & Parakoyi 1991, Heymann et al. 1983, Mahadevan et al. 1989, Ofosu-Amaah, Kratzer & Nicholas 1977, Onadeko & Familusi 1990, Prabhakar et al. 1981, Sabin & Silva 1983, Thuriaux 1982). As hygiene and sanitation improve, paralytic poliomyelitis will become epidemic and affect young adolescents and the older popula-tion, where it is more likely to cause severe illness (Anderson & May 1993, Nathanson & Martin 1979, Paul 1955). It has been shown that the age distribution of reported cases during 1944–1950 in England and Wales moved towards an older age group, with 30 per cent of reported cases occurring over 15 years of age (Table 5.1) (Freyche & Nielsen 1955). A similar age shift in the incidence of poliomyelitis was observed in a review of cases in the United States from 1969 to 1981 (Moore et al. 1982). These two phases sometimes coexist and are seen in developing countries where vaccine coverage has not been adequate.

113Poliomyelitis

Review of past attempts at measuring the burden of poliomyelitis

Paralytic poliomyelitis causes signifi cant lifelong disability and handicap in affected persons. Since the early 1970s, lameness surveys to determine the prevalence of residual paralysis resulting from poliomyelitis have been carried out, particularly in developing regions (a detailed list of lameness surveys and their poliomyelitis prevalences is available from the authors on request). As a consequence of high immunization coverage and specifi c programmes to eradicate poliomyelitis, the global incidence of poliomyelitis has fallen dramatically since the initiation of the poliomyelitis eradica-tion initiative in 1988 (Figures 5.1 and 5.2). It is suggested, however, that under the current reporting system, actual prevalence or incidence of poliomyelitis in the world is still underreported, particularly in developing countries (Tangermann et al. 1997, World Health Organization 1994). The reported cases in the African Region in 1990 was initially only 572, but was revised and given as 4408 cases in the offi cial fi gure. WHO estimated that the actual incidence of poliomyelitis in the world was approximately

Table 5.1 Percentage distribution of notifi ed cases of poliomyelitis by age-group and median age of notifi ed cases: England and Wales, 1912–19 and 1944–50

Year Sex

Percentage distribution by age-group (years)Total

(per cent)Median age

(years) 0–5 5–14 15 and over

1912–19 Male 64 28 8 100 3.93Female 66 28 6 100 3.90

1944–50 Male 34 37 29 100 8.46Female 33 33 34 100 9.15

0

10

20

30

40

50

60

70

80

90

1993199219911990198919881987198619851984

Perc

enta

ge

Year

Figure 5.1 Global immunization coverage (per cent) of OPV3 for children in the fi rst year of life


148 000 in 1990, based on the assumption of a vaccine effi cacy of 80 per cent and a paralysis rate of 5 per 1000 infections (Expanded Programme on Immunization 1993). Similarly, although a total of 7898 cases of polio-myelitis were reported in 1993, WHO estimated that 110 000 cases of poliomyelitis occurred, suggesting that reporting effi ciency was less than 10 per cent (World Health Organization 1994).

It is well known that indirect estimates of incidence derived from lame-ness surveys have suggested a much heavier disease burden than reported cases would suggest. There is a considerable difference between low inci-dence of reported cases and the relatively high incidence derived from lame-ness surveys (Table 5.2) (Evans 1984, Melnick 1990). The prevalence of paralytic poliomyelitis in lameness surveys ranges from less than 1 per 1000 to more than 20 per 1000 and is 3–4 cases per 1000 on average among

Table 5.2 Annual incidence of poliomyelitis per 100 000 total population during the period 1976–1980

Country Reported Incidence Estimate from lameness survey

Burma 1.1 18Cameroon 1.2 24Côte d’Ivoire 1.2 34Egypt 1.8 7Ghana 2.3 31India 2.1 18Indonesia 0.1 13Malawi 1.2 28Thailand 1.7 7Yemen 3.3 14

0

10

20

30

40

50

60

70

1993199219911990198919881987198619851981 1982 1983 1984

Perc

enta

ge

Year

Figure 5.2 Reported incidence of indigenous poliomyelitis

115Poliomyelitis

school-age children in most developing countries (Bernier 1984). There is some variation within countries (urban or rural) and between regions. A review of surveys reveals considerable variation in both the choice and use of survey methods and in the assumption made in the analysis and interpretation of fi ndings (Bernier 1984). The true magnitude of the burden of poliomyelitis in 1990, just before the wide dissemination of the key strategies for global poliomyelitis, was thus not well documented.

Definition and Measurement

The incidence of poliomyelitis can be estimated in a variety of ways: sur-veillance of clinical diagnoses, such as diagnosis of acute fl accid paralysis (AFP); laboratory confi rmation of poliovirus isolated from cases; indirect estimation through lameness surveys of prevalence; and serosurveys for poliomyelitis neutralising antibodies (Pan American Health Organization 1993). A defi nitive diagnosis is made by laboratory confi rmation. Virus isolation from stool culture is the most reliable, and is thus a standard for diagnosis of poliomyelitis incidence. At the population level, poliomyelitis incidence has been estimated either by lameness surveys to identify cases with residual paralysis or by AFP surveillance of acute cases. AFP surveil-lance has been proposed as one of the key strategies for the eradication of poliomyelitis and implemented more widely since the early 1990s (Hull et al. 1994). Before the use of AFP surveillance became widespread, indirect estimation of poliomyelitis incidence from lameness surveys was more common (Bernier 1983). In serosurveys for poliomyelitis, antibodies are of little use for estimating incidence since it is almost impossible to distinguish antibodies formed in response to vaccination from those formed in response to wild poliovirus (Pan American Health Organization 1993).

Surveillance and reporting by health care providers is most often used in many countries, but the standardized and systematic surveillance of poliomyelitis was not feasible until the 1990s in most developing coun-tries with relatively poor information systems, with the exception of Latin America and the Caribbean (de Quadros et al. 1997, Pan American Health Organization 1993). It is suggested that, in the early 1990s, many cases of paralytic poliomyelitis were not reported (Robertson et al. 1990, Ward et al. 1993, World Health Organization 1994). The process of develop-ing a highly effi cient surveillance system capable of detecting all cases of poliomyelitis is one of the critical steps leading to eradication. The World Health Organization has recommended using standardized case defi nitions for active surveillance of AFP (Andrus et al. 1992, Biellik et al. 1992, de Quadros et al. 1991, Hull et al. 1994, Pan American Health Organization 1988).

Whether the surveillance is effective or not depends largely upon the sensitivity and specifi city of the case defi nition. In the early years of efforts to eradicate the poliomyelitis when wild poliovirus was prevalent, AFP cases were “confi rmed” as poliomyelitis if they met one of the following


criteria: laboratory confi rmation, epidemiological linkage to another case of AFP or to a confi rmed case of poliomyelitis, residual paralysis 60 days after onset of symptoms, death or lack of appropriate investigation of a reported AFP case (de Quadros et al. 1997, Pan American Health Organi-zation 1993). Therefore, AFP surveillance to detect paralytic poliomyelitis had relatively high sensitivity but its specifi city was low, resulting in a large number of false positives. In 1990, of 2497 cases of AFP that were reported, only 18 had wild poliovirus isolates from the stool (Dietz et al. 1992). In the AFP surveillance in China during the early 1990s, Chiba et al (1992) showed that 25 of 130 AFP cases were actually poliomyelitis, which 40 per cent of cases were attributable to either Guillain-Barré syndrome or transverse myelitis. In contrast, it has been suggested that, among children with AFP, the use of criteria such as age under 6 years and either presence of fever at the onset of paralysis or a less than four-day period for com-plete development of paralysis, result in a sensitivity of 96 per cent and an increase in specifi city to 49 per cent (Andrus et al. 1992, Dietz et al. 1992). Even though data may be comparable and internally consistent, a relatively small number of reported cases might be attributable to biases in selection and observation attributable to qualifi cation of health personnel and other social, cultural and economic factors.

As the programme for the eradication of poliomyelitis progresses, with increasing vaccine coverage and reported AFP cases, the criteria for confi rmation have become more specifi c (de Quadros et al. 1997). In 1990, the defi nition of confi rmed cases was modifi ed and the criteria for fi nal classifi cation were shifted from a clinical classifi cation scheme to greater reliance on the virological investigation (World Health Organiza-tion 1998). Accordingly, an AFP case is confi rmed only if it is associated with wild poliovirus isolation from either the patient’s stool or a specimen obtained from a contact of the patient. Under this classifi cation system, AFP cases that resulted in residual paralysis or death or that could not be fully investigated or neither be confi rmed nor discarded are classifi ed as “compatible” cases with poliomyelitis. Such cases indicate a failure of the AFP surveillance system to collect adequate specimens in a timely manner (de Quadros et al. 1997). Following successful use in Latin America and the Caribbean, the experiences and the success in the LAC Region, AFP surveillance emerged as one of the key strategies for polio eradication and was more widely used in developing countries during the 1990s (Pan American Health Organization 1988, 1994). The effi ciency of surveillance is, however, higher in countries with a low incidence of poliomyelitis, and lower in countries with high levels of this disease. This was true, in particular during the early years of AFP surveillance around 1990. Thus, data on incidence of AFP cases are inadequate for the estimation of inci-dence of poliomyelitis in 1990 in established market economies and in Latin America and the Caribbean (Birmingham et al. 1997b, Centers for Disease Control and Prevention 1994).

Before the introduction of AFP surveillance, indirect estimation of

117Poliomyelitis

incident cases from lameness surveys was more widely used, particularly in the endemic regions. The case defi nition used in the lameness surveys includes: acute onset of the disease; no progression; intact sensation; atro-phy of muscle; and fl accid paralysis (Singh & Kumar 1991). In paralytic poliomyelitis, muscles in the proximal lower limbs are usually involved. Clinical data from several developing countries, where more than 95 per cent of poliomyelitis cases occurred in children under 5 years of age, showed evidence of involvement of the lower limbs in 78 to 86 per cent of cases (LaForce et al. 1980). La Force and colleagues (1980) have sug-gested that any prevalence study of poliomyelitis in developing countries that uses a lameness survey as a criterion for diagnosis would identify approximately 80 per cent of cases and the total prevalence of residual paralysis attributable to poliomyelitis could be estimated by multiplying the prevalence by 1.25 or

Total casesLower limb cases

= 10080

.

In contrast, studies in the established market economies have shown a slightly higher rate of residual paralysis because of the difference in age-composition of cases (Nathanson & Martin 1979). For example, 203 paralytic poliomyelitis cases were reported from 1969 to 1981 in the United States, and lower limb involvement was present in 180 patients (93 per cent) among 193 patients for whom the site of spinal paralysis was specifi ed (Moore et al. 1982).

To estimate incidence from prevalence in a lameness survey, it must be assumed that the region is in a stable, endemic condition. Under this assumption, and if, as in most developing countries, most cases occur in children under 5 years of age, the paralysis attributable to poliomyelitis in the 5–9 year age group may refl ect the residual paralytic cases which occurred in the 0–4 year age group from 1 to 5 years ago. The following simple formula can be used to estimate the incidence of paralytic polio-myelitis from 1 to 5 years of age:

IP= ×5 9P5 9P −5 9− 1 25

5.1 2.1 2

where I is the annual incidence of paralytic poliomyelitis and I is the annual incidence of paralytic poliomyelitis and I P5–9 is the prevalence of lameness in the 5–9 year age group (LaForce et al. 1980). Some studies show that majority of cases occur before 4 years of age. Therefore, the denominator here should be altered according to the epi-demiological pattern of the region (Bernier 1984). This case defi nition assumes that the sequelae of residual paralytic poliomyelitis are observ-able and distinctive enough to be reliably attributed to poliomyelitis. But, the assumption may not hold, since it is diffi culty to make an accurate etiological diagnosis long after the onset of illness (Pan American Health Organization 1993). The problems of sensitivity and specifi city of case


defi nition and sample size of a lameness survey still remain as in AFP surveillance.

First, there are a number of possible outcomes after poliomyelitis infec-tion. These outcomes are important since it is only the child with residual paralysis who can be identifi ed at a later date as having had poliomyelitis. According to the study conducted in Greater Bombay, India, from 1971 to 1975 (Table 5.3), 74 per cent of the cases showed residual effects when assessed 2 months after the initial onset of paralysis and 26 per cent of the cases, including deaths and patients who recovered completely, would not have been detected in a later clinical survey (Chodankar & Dave 1979, LaForce et al. 1980). Thus, prevalence surveys of residual paralysis due to poliomyelitis will always underestimate the true incidence of the disease, ignoring fatal cases and complete recovery cases. A rough estimate of all clinical cases of poliomyelitis could be made by multiplying the prevalence rate of residual paralysis attributable to poliomyelitis by 1.33 (LaForce et al. 1980).

Second, schoolchildren have often been selected as the sample for lame-ness surveys because of the feasibility of such studies in terms of cost and time (Belcher et al. 1979, Joseph et al. 1983). The population of school-age children in the catchment area might, however, not be representative of the population at risk since not all school-age children attend school, particularly lame children, children living in remote rural areas, or female children in certain societies. Consequently, it is diffi cult to generalize the results to other populations. As demonstrated in the surveys in several developing countries (Belcher et al. 1979, Heymann et al. 1983, Heymann 1984), the sensitivity of school-based surveys is not always as high as that of community-based surveys with house-to-house case fi nding and may lead to underestimation of the true magnitude of the burden of poliomy-elitis. House-to-house surveys, although expensive and time-consuming, are a sensitive method of identifying lame children in both urban and rural regions. School surveys and reviews of hospital and clinic registers, while equally sensitive in urban regions, are less sensitive in rural regions and may signifi cantly underestimate the annual incidence of paralytic poliomyelitis (Heymann et al. 1983). Moreover, as mentioned above, the prevalence of lameness attributable to poliomyelitis is always an underestimation of the true total morbidity and mortality associated with poliomyelitis.

Finally, the sensitivity of lameness survey varies signifi cantly among

Table 5.3 Poliomyelitis cases in Greater Bombay: clinical outcome

Outcome Number Percentage

No recovery 342 11Partial recovery 1 895 63Complete recovery 506 17Death 255 9

Total 2 898 100

119Poliomyelitis

surveys and is often lower than that of AFP surveillance, ranging from 34 per cent in Bangladesh to 86 per cent in Madagascar (Snyder et al. 1981, World Health Organization 1982, Bernier 1984). For example, a survey in Ghana showed that poliomyelitis was the leading cause of lameness (63.3 per cent) and motor neuron disorders of the central nervous system, such as cerebral palsy; and encephalitis was second (11.7 per cent) (Nicholas et al. 1977). In most lameness surveys, the specifi city of the survey has not been fully evaluated. Box 5.1 lists the major limitations encountered in lameness surveys, which may lead to biases in the estimation of annual incidence of paralytic poliomyelitis.

International Classifi cation of Diseases (ICD) codes for poliomyelitisICD-9 codes for poliomyelitis

In the basic tabulation of the ICD-9, acute poliomyelitis (045) is classi-fi ed in the category of poliomyelitis and other non-arthropod-borne viral diseases of the central nervous system (045–049), and its four-digit codes are defi ned based on the clinical and anatomical diagnosis of poliomyeli-tis. It should be noted that the code 045 excludes the late effects of acute poliomyelitis, which are classifi ed in one of the additional codes for late effects of infectious and parasitic diseases (137–139). Encephalitis attribut-

Box 5.1 Limitations of lameness surveys

Unreliable case fi ndings because of:

lack of sensitivity or specifi city of case defi nition

inter-observer variations

Restricted study population:

school

catchment area

house-to-house survey

Sample size considerations

Potential biases:

change of epidemiological patterns in the past

extent of vaccine coverage

change in population

Inadequate information concerning:

age distribution

sex differences

baseline mortality rate

remission rate

case-fatality rate

vaccine coverage and effi cacy

Source: Heymann (1984)


able to poliovirus infection is also listed under encephalitis, myelitis and encephalomyelitis (323.2*). The ICD-9 codes are:

045 Acute poliomyelitis (323.2*)

045.0 Acute poliomyelitis specifi ed as bulbar (323.2*)Infantile paralysis (acute) specifi ed as bulbarPoliomyelitis (acute) (anterior)Polioencephalitis (acute) (bulbar)Polioencephalomyelitis (acute) (anterior) (bulbar)

045.1 Acute poliomyelitis with other paralysis (323.2*)Paralysis:– acute atrophic, spinal– infantile, paralyticPoliomyelitis (acute)– anterior – epidemic

with paralysis except bulbar

045.2 Acute nonparalytic poliomyelitis (323.2*)Poliomyelitis (acute)– anterior – epidemic

specifi ed as nonparalytic

045.9 Acute poliomyelitis, unspecifi ed (323.2*)–Infantile paralysisPoliomyelitis (acute)– anterior – epidemic

unspecifi ed whether paralytic or nonparalytic

138 Late effects of acute poliomyelitis The late effects include conditions specifi ed as such, or as sequelae,

or as attributable to old or inactive poliomyelitis, without evidence of active disease.

ICD-9 codes consistent with acute fl accid paralysis

Acute fl accid paralysis (AFP) surveillance has become a crucial strategy since the late 1980s. The fact that AFP includes various types of diseases sometimes reduces the specifi city of AFP surveillance for poliomyelitis cases. The possible ICD-9 codes for AFP other than poliomyelitis include:

094.1 General paresis 323.0–323.9 Encephalitis, myelitis and encephalomyelitis335.2 Motor neurone disease342.0 Flaccid hemiplegia344.0–344.9 Arm or leg paralytic syndromes355.0–355.9 Mononeuritis of lower limb357.0 Acute infective polyneuritis (Guillain-Barré Syndrome)

121Poliomyelitis

781.2 Gait disorders 781.4 Transient paralysis of limb

ICD-10 codes for poliomyelitis

In accordance with the rapid decline in global incidence of poliomyelitis and the substantial progress toward its eradication, the emphasis of the classifi cation scheme in the ICD-10 for poliomyelitis (A80) shifted from the clinical and anatomical diagnosis in ICD-9 to the source of poliovirus infection. The late effects of poliomyelitis are now classifi ed in the category of sequelae of poliomyelitis (B91). The ICD-10 codes are as follows:

A80 Acute poliomyelitisA80.0 Acute paralytic poliomyelitis, vaccine-associatedA80.1 Acute paralytic poliomyelitis, wild virus, importedA80.2 Acute paralytic poliomyelitis, wild virus, indigenousA80.3 Acute paralytic poliomyelitis, other and unspecifi edA80.4 Acute nonparalytic poliomyelitisA80.9 Acute poliomyelitis, unspecifi ed

B91 Sequelae of poliomyelitis

Estimation of Disability-Adjusted Life Years (DALYs)

To calculate the burden of disease attributable to poliomyelitis requires detailed estimates of the age-specifi c and sex-specifi c epidemiology of poliomyelitis (Murray & Lopez 1996). Valid community-based epide-miological studies that could inform these estimates do not exist for many of the variables in many regions. For this reason, the burden of paralytic poliomyelitis was calculated by age, sex, and region from various sources of available data.

Incidence

Annual incidence rates of paralytic poliomyelitis were estimated from information on prevalence of residual paralysis, since comparable incidence data based on acute fl accid paralysis (AFP) surveillance were not available before 1990, except from the Latin America and Caribbean (LAC) region. A signifi cant amount of information on the prevalence of residual paralysis has been reported to WHO and is available for India (IND), Other Asia and Islands (OAI), and sub-Saharan Africa (SSA) regions. To estimate annual incidence of paralytic poliomyelitis in 1990 in these regions, the most recent and representative house-to-house lameness surveys, or school-based surveys in some cases, were selected. China, where there have been several epidemics in the southern provinces, has improved its reporting system of the AFP cases; but AFP surveillance before 1990 was incom-plete and the assessment of residual paralysis was not reported. In these


circumstances, the estimate of prevalence in China in 1990 was based on regions that have similar epidemiological profi les, including neighbouring OAI countries where poliomyelitis was endemic.

For other regions, especially those with lower incidence, such as Estab-lished Market Economies (EME), Former Socialist Economies of Europe (FSE) and LAC regions, lameness surveys have not been conducted recently because of the low incidence of residual paralysis and because AFP sur-veillance of sporadic cases is more important for the eradication process. The estimation of incidence in EME and FSE was primarily based on the number of poliomyelitis cases reported to the World Health Organization. These reported cases included a sporadic outbreak in EME among the unvaccinated population and a slight increase in paralytic poliomyelitis cases in FSE because of social instability and vaccine shortage, although the number of such cases was small. For the LAC region, data both from lameness surveys in the 1980s and AFP surveillance around 1990 can be used to estimate the annual incidence in 1990. Since our main focus is the residual paralysis attributable to poliomyelitis, and there was a large discrepancy between the relatively high incidence of paralytic poliomy-elitis and the low numbers of reported cases, lameness surveys are a more appropriate method to estimate the burden in 1990 than the reported cases of AFP.

Since lameness surveys are most often aggregated for the children aged 5 to 9 years, age-specifi c- and sex-specifi c estimation of annual incidence for developing regions should be made by incorporating information on sex differences and age distributions. Some epidemiological studies have reported the male-to-female ratio in prevalence of paralytic poliomyelitis. In general, the ratio varies signifi cantly from one study to another, even in the same region. Since such variations could be attributable to potential biases or chance alone, we apply a ratio of 1.4 to 1 of males to females, which is an average ratio in the selected studies when excluding extreme values (Jamison et al. 1993).

In developing regions, the majority of poliomyelitis cases occurred among children under 5 years of age, following the classical endemic pat-tern poliomyelitis infection ( Nicholas et al. 1977, Nathanson & Martin 1979, LaForce et al. 1980, Thuriaux 1982, Heymann et al. 1983, Khajuria et al. 1989, Onadeko & Familusi 1990, Mandke et al. 1991) from the prevalence data on residual paralysis of the specifi c age-group studied. The age distribution of incidence was estimated. First, using the formula proposed by LaForce et al. (1980), the prevalence of lameness in the age group 5–9 years, obtained from relatively large house-to-house surveys in the 1980s, was converted to the incidence rates of the age group 0–4 in the study years. Since the age-patterns of incidence by age group were not available in all regions, where necessary all the rates for a region were estimated from other regions with similar epidemiological patterns by adjusting for the vaccine coverage, as described below. Second, the age-specifi c incidence rates of paralytic poliomyelitis were assumed to follow

123Poliomyelitis

a polynomial distribution function which fi tted well the endemic pattern of poliomyelitis in developing regions ( Paul et al. 1952, Nathanson & Martin 1979, Anderson & May 1993). The fi tted polynomial function for developing regions has the following distribution fraction by age group: 97 per cent for age 0–4 years; 5.4 per cent for age 5–14 years; 1.6 per cent for age 15–44 years; 0.8 per cent for age 45–59 years; and 0.06 per cent for age 60 years and over. To estimate age-specifi c incidence for each age group in developing regions, the estimated incidence of age 0–4 was then multiplied by the factor derived from the ratio of the distribution fraction of each age group to that of age 0–4: 1.0000 for age 0–4; 0.056 for 5–14; 0.0165 for 15–44; 0.0082 for 45–59; 0.0006 for 60 and over. The estimated age-specifi c and sex-specifi c incidence rates in the refer-ence years of lameness surveys in developing regions, which were used to compute internally consistent epidemiological parameters, are described in the following section.

The estimated age- and sex-specifi c incidence will thus pertain to a specifi c time period with a particular level of coverage with the vaccine (Table 5.4). To derive incidence in 1990 from data in the study years of lameness surveys, adjustment for the change in vaccine coverage over the previous decade was made using the exponential change in incidence rate for each year. Suppose we want to estimate the incidence in year (t + t + t n) but we only have the incidence of year (t) and vaccine coverage of both years. Then the rate of change (r) can be calculated using the formula:

r

CCt n

t

= −−

t n+t nln100100

where Ct and t and t Ct+n are the percentages of vaccine coverage in years t and (t + t + t n), respectively. Then, using this rate, the incidence in year (t + t + t n) is written in the form:

I I et nI It nI Inrn

t n+t nI It nI I+I It nI II I=I I

where It+n is the incidence in year (t + t + t n) and In is the incidence in year t.

Table 5.4 Change in OPV coverage (percentage) by region

Region 1981 1985 1989 1990

CHI 90 NA 95 98IND 7 35 82 93OAI 35 39 73 86SSA 21 30 58 69FSE 95 88 94 93EME 83 88 88 85LAC 45 70 82 87MEC 45 60 87 88

Global 53 59 82 87


Finally, internal consistency between incidence, remission, case-fatality rates, duration of paralysis and prevalence estimates was ascertained by the DisMod software specifi cally developed for the Global Burden of Disease Study (Murray & Lopez 1996). For incidence data on paralytic poliomyelitis estimated from lameness surveys, we assume that remission and case-fatality rates of those with residual paralysis are zero because deaths and patients with complete recovery would not have been detected in later clinical surveys.

Mortality

To estimate the burden of premature deaths from paralytic poliomyelitis, both vital registration data and an epidemiological model based on case-fatality rates were employed. For the regions where a vital registration system is established (i.e. EME, FSE and LAC), the reported number of deaths attributable due to poliomyelitis was used. For most developing regions where vital data are not available or incomplete (China, India, MEC, OAI, and SSA), mortality was estimated from incidence of paralytic poliomyelitis, multiplied by the correction factor of 1.33 for total cases (LaForce et al. 1980), and case-fatality rates. There are some variations in the reported case-fatality rates of poliomyelitis among studies, but most very from 5 per cent to 15 per cent ( Freyche and Nielsen 1955, Chodankar & Dave 1979, LaForce et al. 1980, Moore et al. 1982, Hajar et al. 1983, Mahadevan et al. 1989, Khare et al. 1991, Jamison et al. 1993).

In general, mortality data are infl uenced by the extent and completeness of notifi cation and registration of deaths. The differences in study years, treatment facilities and results, and the time interval between onset of the disease and death in fatal cases may explain these variations as well as true differences in case-fatality rates. Since age-specifi c and sex-specifi c mortality data were not available, and since, as reported in most studies, most cases occur under 5 years of age in developing regions, for the main analysis we used a case-fatality rate of 10 per cent as a plausible value in developing regions and employed a constant case-fatality rate for all age groups. Case-fatality rates may be affected by the age composition of the study population because poliovirus infection in older people is more likely to produce serious illness. Case-fatality rates in older patients may be higher than those of young children in developed regions, but the bias would be minimal in developing regions since the majority of cases and deaths occur among children under 5 years of age, and samples of the epidemiological studies on poliomyelitis in developing regions most often include children aged under 15 years (Basu & Sokhey 1984, Chodankar & Dave 1979, Hajar et al. 1983, Khare et al. 1991, LaForce et al. 1980, Mahadevan et al. 1989, Maru et al. 1988).

Disability Weights

In the calculation of disability-adjusted life years (DALYs) of poliomyelitis, the disability weights were derived from studies on the distribution of dis-

125Poliomyelitis

abilities associated with poliomyelitis in developing regions that report on the severity of disabilities within each age group ( Nicholas et al. 1977, Basu 1981, Basu & Sokhey 1984, Heymann 1984, Deivanayagam & Nedunche-lian 1992). We assume that all patients affected by paralytic poliomyelitis become disabled to some extent, since the estimated incidence was derived from the lameness surveys of residual paralysis. Furthermore, the percent-age distribution of the degree of disability, adjusted to be consistent with the lameness surveys and their defi nition of disability, is assumed to be constant among lame patients over each age group, even though serious illness more likely results when infection occurs in older individuals.

Other Considerations in Calculating Disease Burden

To estimate incidence from prevalence of residual paralysis of poliomyelitis, it is assumed that each region is in a stable, epidemic or poliomyelitis free situation. Lameness surveys most often target children 5 to 9 years of age in developing countries where poliomyelitis is endemic. As a consequence, residual paralysis in children of 5 to 9 years of age refl ects the paralytic poliomyelitis cases that occurred from 1 to 10 years before the survey. Therefore, if a sudden increase in incidence (poliomyelitis outbreaks) occurred some years prior to the lameness survey, the actual incidence would be underestimated. In contrast, if a reduction of poliomyelitis incidence had been achieved through effective interventions, such as vac-cination and improvement of sanitation, the actual incidence would be overestimated.

Although changes in vaccine coverage and subsequent changes in inci-dence have been taken into account in our estimation, some of the limita-tions of the original surveys should be noted. Since our estimate of the incidence of residual paralysis is based on lameness surveys for developing regions, sporadic cases other than indigenous poliomyelitis cases including imported and vaccine-associated cases are not captured in our calculation of the burden of poliomyelitis in those regions.

Disability weights for paralytic poliomyelitis were derived from the studies in developing regions. It is suggested that disability attributable to poliomyelitis in developed regions is more severe, refl ecting the increase in mean age of infection (Nathanson & Martin 1979). For example, in the review of the poliomyelitis cases in the United States, the proportion of severe paralysis was high: 11 per cent of patients had minor paralysis whereas 79 per cent had signifi cant or severe residual paralysis that required mechanical aids (Moore et al. 1982). Although the application of the same disability weights to all regions would underestimate the burden in developed regions, the bias would be minimal since the number of reported incident cases in developed regions (EME and FSE) was quite small.

Neither late effects of paralytic poliomyelitis (post-paralytic poliomye-litis syndrome) nor partial remission resulting from an effective rehabili-tation programme that might alter the sequelae of disease are taken into


account in our calculation of the disease burden. It is assumed that the severity of residual paralysis remains constant over the rest of life.

Burden of Poliomyelitis in 1990

Tables 5.5a and 5.5b represent the detailed epidemiological estimates (incidence, prevalence, number of deaths, years of life lost, years lived with disability, and disability adjusted life years) for poliomyelitis by age, sex, and region in 1990.

The distribution of estimated incidence of poliomyelitis by region is given in Figure 5.3. Among the estimated global total of 212 000 para-lytic poliomyelitis cases including complete recovery and fatal cases, India accounted for 47 000 cases, or 39 per cent of the global total in 1990. It was followed by SSA with 38 000 cases (18 per cent), MEC with 30 000 cases (14 per cent), OAI with 26 000 cases (12 per cent), China with 24 000 cases (11 per cent), and LAC with 12 000 cases (6 per cent). The majority of reported incidence in FSE were the outbreak cases in several southern former Soviet republics. The two poliomyelitis-endemic regions—India and SSA—accounted for more than half of the global incidence of polio-myelitis in 1990.

The estimated number of deaths attributable to poliomyelitis in 1990 was approximately 27 000, with a range of 20 000 to 35 000 depending on the case-fatality rate used in the analysis. The burden of disease, mea-sured by years of life lost (YLLs), years lived with disability (YLDs) and disability-adjusted life years (DALYs), shows a similar pattern. The global burden of poliomyelitis was 3 360 000 DALYs, which amounted to 0.24 per cent of the global burden of disease from all causes in 1990. The pro-portion of burden from poliomyelitis was highest in India (0.5 per cent), followed by MEC, OAI and SSA. On average, YLDs accounted for 75 per

0

50 000

100 000

150 000

200 000

250 000

TotalCHIINDOAISSAMECLACFSEEME

Ann

ual I

ncid

ence

WDR Region

Figure 5.3 Annual incidence of paralytic poliomyelitis, 1990

127Poliomyelitis

Tab

le 5

.5a

Ep

idem

iolo

gica

l est

imat

es fo

r po

liom

yelit

is, 1

990,

mal

es

Age

grou

p (y

ears

)

Incid

ence

Prev

alen

ce

Avg.

Age

at

Ons

et (y

ears

)

Aver

age

Dur

atio

n (y

ears

)

Dea

ths

YLLs

(’000

s)

YLD

s

(’000

s)

DAL

Ys

(’000

s)N

umbe

r (’0

00s)

Rate

per

10

0 00

0N

umbe

r (’0

00s)

Rate

per

10

0 00

0N

umbe

r (’0

00s)

Rate

per

10

0 00

0

Esta

blish

ed M

arke

t Eco

nom

ies

(EM

E)0

–4

00.

00

0.0

——

00.

00

00

5–14

00.

00

0.0

——

00.

00

00

15–

440

0.0

00.

0—

—0

0.0

00

145

–59

00.

00

0.0

——

00.

00

00

60+

00.

00

0.0

——

00.

21

01

All

Age

s0

0.0

00.

0—

—0

0.0

20

2

Form

erly

Socia

list E

cono

mie

s (F

SE)

0–

40

0.0

00.

0—

—0

0.0

00

05–

140

0.0

00.

0—

—0

0.0

00

015

–44

00.

00

0.0

——

00.

00

00

45–5

90

0.0

00.

0—

—0

0.0

00

060

+0

0.0

00.

0—

—0

0.0

00

0A

ll A

ges

00.

00

0.0

——

00.

00

00

Indi

a (IN

D)

0–

446

77.5

014

123

5.8

2.5

58.7

610

.40

208

531

739

5–14

00.

269

067

8.1

9.7

56.4

00.

01

34

15–

441

0.7

1 50

074

8.0

29.8

38.7

00.

01

1415

45–5

90

0.3

362

760.

052

.220

.00

0.0

01

160

+0

0.0

227

762.

669

.7 9

.80

0.0

00

0A

ll A

ges

4811

.00

2 92

066

4.0

3.5

58.0

61.

421

054

975

8

cont

inue

d


Chin

a (C

HI)

0–

413

20.8

032

53.

1 2

.564

.51

2.3

4714

819

55–

140

0.1

106

109.

310

.059

.00

0.0

01

215

–44

10.

335

511

5.9

29.9

40.5

00.

01

1112

45–5

90

0.2

8912

2.5

52.3

20.7

00.

00

11

60+

00.

060

123.

069

.6 9

.60

0.0

00

0A

ll A

ges

142.

464

210

9.7

5.1

62.3

10.

249

160

209

Oth

er A

sia a

nd Is

land

s (O

AI)

0–

414

31.2

037

83.

0 2

.560

.82

4.2

6115

821

95–

140

0.2

180

214.

010

.057

.80

0.0

12

315

–44

10.

537

623

4.0

29.8

40.1

00.

03

911

45–5

90

0.3

8324

3.1

52.3

21.2

00.

00

01

60+

00.

050

245.

070

.110

.10

0.0

00

0A

ll A

ges

154.

372

521

1.4

4.4

59.4

20.

665

169

234

Sub–

Saha

ran

Afric

a (S

SA)

0–

421

45.1

058

122.

1 2

.450

.63

5.6

9023

232

35–

140

0.2

213

303.

2 9

.850

.90

0.0

12

315

–44

10.

533

932

6.0

29.5

36.1

00.

02

57

45–5

90

0.3

6833

6.0

52.2

19.7

00.

00

00

60+

00.

036

339.

069

.5 9

.50

0.0

00

0A

ll A

ges

228.

871

428

3.0

3.2

50.2

31.

193

240

335

Tab

le 5

.5a

Ep

idem

iolo

gica

l est

imat

es fo

r po

liom

yelit

is, 1

990,

mal

es (c

ontin

ued)

Age

grou

p (y

ears

)

Incid

ence

Prev

alen

ce

Avg.

Age

at

Ons

et (y

ears

)

Aver

age

Dur

atio

n (y

ears

)

Dea

ths

YLLs

(’000

s)

YLD

s

(’000

s)

DAL

Ys

(’000

s)N

umbe

r (’0

00s)

Rate

per

10

0 00

0N

umbe

r (’0

00s)

Rate

per

10

0 00

0N

umbe

r (’0

00s)

Rate

per

10

0 00

0

129Poliomyelitis

Latin

Am

erica

and

the

Carr

ibea

n (L

AC)

0–

47

25.8

020

69.

6 2

.564

.01

3.1

3087

117

5–14

00.

187

166.

9 9

.859

.50

0.0

01

115

–44

00.

218

617

8.4

29.8

41.8

00.

00

23

45–5

90

0.1

4118

2.0

52.3

23.0

00.

00

00

60+

00.

026

182.

770

.910

.90

0.0

00

0A

ll A

ges

83.

536

016

2.4

3.5

63.1

10.

430

9012

0

Mid

dle

East

ern

Cres

cent

(MEC

)0

–4

1740

.30

4510

9.3

2.5

61.6

25.

272

192

264

5–14

00.

217

226

3.2

9.8

58.8

00.

00

12

15–

441

0.5

321

281.

829

.840

.80

0.0

06

645

–59

00.

265

291.

052

.321

.50

0.0

00

060

+0

0.0

4029

3.0

70.1

10.1

00.

00

00

All

Age

s18

6.7

643

250.

8 3

.560

.82

0.8

7320

027

3

Wor

ld0

–4

118

36.7

033

310

3.0

2.5

58.9

150

4.7

508

1 34

81

857

5–14

10.

11

448

262.

7 9

.856

.60

0.0

311

1415

–44

50.

43

076

246.

129

.839

.50

0.0

946

5545

–59

00.

270

722

6.3

52.3

20.7

00.

01

23

60+

00.

043

920

0.6

69.8

9.9

00.

11

01

All

Age

s12

44.

76

002

226.

2 3

.858

.015

00.

652

11

408

1 92

9


Tab

le 5

.5b

Ep

idem

iolo

gica

l est

imat

es fo

r po

liom

yelit

is, 1

990,

fem

ales

Age

grou

p (y

ears

)

Incid

ence

Prev

alen

ce

Avg.

Age

at

Ons

et

(yea

rs)

Aver

age

Dur

atio

n (y

ears

)

Dea

ths

YLLs

YLD

sD

ALYs

Num

ber

(’000

s) R

ate

per

100

000

Num

ber

(’000

s)Ra

te p

er

100

000

Num

ber

(’000

s)Ra

te p

er

100

000

Num

ber

(’000

s)N

umbe

r (’0

00s)

Num

ber

(’000

s)

Esta

blish

ed M

arke

t Eco

nom

ies

(EM

E)0

–4

00.

00

0.0

——

00.

00

00

5–14

00.

00

0.0

——

00.

00

00

15–

440

0.0

00.

0—

—0

0.0

00

045

–59

00.

00

0.0

——

00.

00

00

60+

00.

00

0.0

——

00.

10

01

All

Age

s0

0.0

00.

0—

—0

0.0

00

1

Form

erly

Socia

list E

cono

mie

s (F

SE)

0–

40

0.0

00.

0—

—0

0.0

00

05–

140

0.0

00.

0—

—0

0.0

00

015

–44

00.

00

0.0

——

00.

00

00

45–5

90

0.0

00.

0—

—0

0.0

00

060

+0

0.0

00.

0—

—0

0.0

00

0A

ll A

ges

00.

00

0.0

——

00.

00

00

Indi

a (I

ND

)0

–4

340

59.8

010

318

1.0

2.5

59.6

58.

316

038

954

95–

140

0.2

498

525.

0 9

.757

.80

0.0

12

315

–44

10.

51

056

576.

329

.840

.70

0.0

010

1145

–59

00.

327

058

6.0

52.3

21.5

00.

00

11

60+

00.

017

058

7.7

70.1

10.1

00.

00

00

All

Age

s35

08.

620

9651

1.1

3.5

58.9

51.

216

140

256

4

131Poliomyelitis

Chin

a (C

HI)

0–

49

16.0

024

41.4

2.5

67.5

11.

835

110

146

5–14

00.

176

84.1

10.0

62.3

00.

00

11

15–

441

0.3

253

89.1

29.9

43.6

00.

00

89

45–5

90

0.1

6194

.052

.423

.30

0.0

00

060

+0

0.0

4994

.870

.610

.60

0.0

00

0A

ll A

ges

101.

946

384

.4 5

.065

.41

0.2

3612

015

6

Oth

er A

sia a

nd Is

land

s (O

AI)

0–

410

024

.00

2764

.3 2

.564

.91

3.0

4311

916

25–

140

0.1

132

164.

610

.061

.40

0.0

11

215

–44

10.

428

717

9.8

29.8

43.3

00.

02

79

45–5

90

0.2

6618

7.0

52.4

23.6

00.

00

01

60+

00.

043

189.

070

.810

.80

0.0

00

0A

ll A

ges

110

3.2

555

163.

4 4

.563

.41

0.4

4612

717

3

Sub–

Saha

ran

Afric

a (S

SA)

0–

416

034

.70

4493

.6 2

.453

.82

4.1

6518

124

75–

140

0.1

163

234.

0 9

.853

.50

0.0

11

215

–44

00.

426

725

1.3

29.5

38.2

00.

12

46

45–5

90

0.2

5725

9.0

52.3

21.1

00.

00

00

60+

00.

033

261.

070

.010

.00

0.0

00

0A

ll A

ges

170

6.5

565

219.

0 3

.353

.32

0.8

6818

725

5

Latin

Am

erica

and

the

Carr

ibea

n (L

AC)

0–

45

19.9

018

65.0

2.5

68.2

12.

220

6586

5–14

00.

111

923

4.5

9.8

63.4

00.

00

00

15–

440

0.2

280

269.

029

.945

.00

0.0

02

245

–59

00.

163

269.

752

.425

.30

0.0

00

060

+0

0.0

4627

1.0

71.6

11.6

00.

00

00

All

Age

s6

2.6

526

236.

2 3

.667

.31

0.3

2168

89

cont

inue

d


Mid

dle

East

ern

Cres

cent

(MEC

)0

–4

120

31.0

033

84.0

2.5

64.4

24.

054

145

198

5–14

00.

112

520

1.6

9.8

61.7

00.

00

11

15–

440

0.4

233

217.

329

.943

.60

0.0

04

545

–59

00.

250

224.

352

.423

.70

0.0

00

060

+0

0.0

3522

5.0

70.8

10.8

00.

00

00

All

Age

s13

05.

247

619

3.0

3.5

63.6

20.

754

150

205

Wor

ld0

–4

870

28.3

024

980

.0 2

.561

.211

3.6

378

1 01

01

388

5–14

10.

11

114

212.

0 9

.859

.20

0.0

28

1015

–44

30.

32

377

198.

329

.842

.50

0.0

735

4145

–59

00.

156

618

2.0

52.4

22.7

00.

01

23

60+

00.

037

613

9.7

70.5

10.5

00.

00

01

All

Age

s92

03.

54

682

179.

1 3

.860

.312

0.4

388

1 05

51

442

Tab

le 5

.5b

Ep

idem

iolo

gica

l est

imat

es fo

r po

liom

yelit

is, 1

990,

fem

ales

(con

tinue

d)

Age

grou

p (y

ears

)

Incid

ence

Prev

alen

ce

Avg.

Age

at

Ons

et

(yea

rs)

Aver

age

Dur

atio

n (y

ears

)

Dea

ths

YLLs

YLD

sD

ALYs

Num

ber

(’000

s) R

ate

per

100

000

Num

ber

(’000

s)Ra

te p

er

100

000

Num

ber

(’000

s)Ra

te p

er

100

000

Num

ber

(’000

s)N

umbe

r (’0

00s)

Num

ber

(’000

s)

133Poliomyelitis

cent of total disease burden from poliomyelitis. As shown in Figures 5.4 and 5.5, India and SSA accounted for approximately 60 per cent of total deaths and disability-adjusted life years from poliomyelitis in 1990.

Burden and Intervention

The global incidence of paralytic poliomyelitis was dramatically reduced with the introduction of the Salk inactivated poliomyelitis vaccine (IPV) in 1955 and the Sabin live-attenuated oral vaccine (OPV) in 1961. Mass campaigns in addition to routine immunization with OPV in the 1960s

0

3 000

6 000

9 000

12 000

15 000

TotalCHIINDOAISSAMECLACFSEEME

Num

ber

of D

eath

s

WDR Region

Figure 5.4 Annual number of deaths due to poliomyelitis, 1990

0

1 000 000

2 000 000

3 000 000

4 000 000

5 000 000

GlobalCHIINDOAISSAMECLACFSEEME

DA

LYs

Lost

WDR Region

Figure 5.5 DALYs lost due to paralytic poliomyelitis, 1990


virtually eliminated paralytic poliomyelitis from developed regions. Both vaccines have advantages and limitations for developing countries, as summarized in Box 5.2 (Melnick 1978,1990). Because of its low cost, ease of administration, superiority in inducing secretory immunity in the

Box 5.2 Advantages and disadvantages of poliomyelitis vaccines

Advantages Disadvantages

Inactivated Poliomyelitis Vaccine (IPV)

Confers humoral immunity in vaccinees if suffi cient numbers of doses of potent vaccine are given.

Can be incorporated into regular immu-nization programme, such as diphtheria-pertussis-tetanus

Absence of living virus excludes po-tential for mutation and reversion to virulence.

Absence of living virus permits its use in immunodefi cient or immunosuppressed individuals and their households.

Has greatly reduced the spread of po-lioviruses in some regions where it has been properly used.

May prove useful in certain tropical areas where live virus vaccine has failed to take in some young infants.

Early studies indicated a disappointing record in percentage of vaccines devel-oping antibodies after three doses (but more immunopotent antigens are now produced).

Generally, repeated boosters have been required to maintain detectable antibody levels.

Does not induce appreciable local in-testinal immunity in the vaccinee; hence vaccines do not serve as a block to transmission of wild polioviruses by the faecal–oral route

More expensive than live virus vaccine.

Use of virulent polioviruses as vaccine seed creates potential for tragedy. This problem can, however, be overcome by use of attenuated strains for production.

Oral Poliomyelitis Vaccine (OPV )

Like the natural infection, confers both humoral and intestinal immunity.

Immunity induced appears to be lifelong. Induces antibody very quickly in a large proportion of vaccinees.

Oral administration is more acceptable to vaccinees than injection, and easier to accomplish.

Administration does not require use of highly trained personnel.

When properly stabilized, can retain potency under diffi cult fi eld conditions with little refrigeration and no freezing.

Under epidemic conditions, not only induces antibody quickly, but also rapidly infects the alimentary tract, blocking epidemic spread of virus.

Is relatively inexpensive, both to produce and to administer, and does not require continuing booster doses.

Vaccine virus may mutate, and in very rare instances has reverted toward neurovirulence suffi cient to cause para-lytic poliomyelitis in recipients and their contacts.

Vaccine progeny virus spreads to house-hold contacts.

Vaccine virus also spreads to people in community.

In certain tropical countries, induction of antibodies in a satisfactorily high propor-tion of vaccinees has been diffi cult to accomplish.

Contraindicated in those with immuno-defi ciency diseases, and in their house-hold associates, as well as in people undergoing immunosuppresive therapy and their households.

Source: Melnick (1978, 1988).

135Poliomyelitis

intestines, and ability to infect household and community contacts, OPV has been used by WHO for the purpose of eradicating wild poliovirus (Wright et al. 1991, Hull et al. 1994, 1997).

Initially, the WHO Expanded Programme on Immunization (EPI) promoted three doses of OPV for all children in the fi rst year of life as the routine immunization programme. Since the foundation of the EPI programme, WHO, UNICEF, and other international donors have con-tributed to establishing an effective routine immunization system. Vaccine coverage for poliomyelitis with OPV has increased and reported incidence has substantially decreased (Figures 5.1 and 5.2). Although the primary strategy of EPI was to raise the vaccine coverage of OPV and sustain the higher level, it has been suggested that poliomyelitis eradication may not be achieved through a routine immunization programme alone (Sutter et al. 1991) and three doses of OPV have proven inadequate in some endemic countries (Montefi ore et al. 1963, John 1976, Bottiger et al. 1981, Chopra, Kundu & Chowdhury 1989, Patriarca 1993). Some studies have shown that the seroconversion rate and the effi cacy are lower in the trop-ics (Patriarca, Wright & John 1991, Sutter et al. 1991) and an additional fourth dose at birth (or fi ve doses) has been recommended in these areas ( John 1976, Dong et al. 1986, Chopra, Kundu & Chowdhury 1989, Hull & Ward 1992). For example, despite the relatively high vaccine coverage rates, several outbreaks among children fully immunized with three doses of OPV have been reported in India, China, Other Asia and Islands (OAI), Middle East Crescent (MEC) and Former Socialist Economies of Europe (FSE) regions (Expanded Programme on Immunization 1993, Lasch et al. 1984, Samuel, Sutter et al. 1991, Hull & Ward 1992, Balraj & John1993). Extremely high routine immunization coverage has failed to prevent epi-demics in China, which reported epidemics of poliomyelitis in 1989 and 1990 despite the 98 per cent coverage with three doses of OPV achieved in 1990 (Expanded Programme on Immunization 1993). In some developing regions where OPV alone would not decrease incidence of poliomyelitis further, combined OPV/IPV regimens have been used and proven successful (Magnus & Peterson 1984, Melnick 1988, Tulchinsky et al. 1989). The vaccines do not interfere with each other and each compensates for some of the other’s limitations.

It has been suggested that failure to vaccinate is much more critical than vaccine failure for an outbreak to take place (Anderson & May 1985, Kim-Farley et al. 1984, Patriarca, Sutter & Oostovogel 1997). In fact, in China, most of the paralytic poliomyelitis cases occurred in unimmunized or incompletely immunized children as shown in Figure 5.6 (Expanded Programme on Immunization 1993). Routine vaccination may not reach unregistered populations, certain religious groups, ethnic minorities, illegal immigrants or migratory populations. Other factors, such as false contra-indication, poor access, and attitude and knowledge of health personnel, may lead to missed opportunities (Pan American Health Organization 1994). Although a role for IPV deserves further exploration, especially in


developed regions where transmission has been interrupted, improving vaccine delivery rather than changing immunization regimen should be the priority for poliomyelitis eradication since many cases are attributable to missed opportunities (John 1976, Wright et al. 1991, Hull et al. 1994).

WHO currently recommends implementation of mass campaigns in addition to maintaining a high coverage rate of routine vaccination with four doses of OPV (Hull et al. 1994, 1997). In Brazil, a policy of holding a national immunization day, when all children under 5 years of age are vaccinated regardless of prior immunization status, has led to the cessa-tion of poliovirus transmission (Expanded Programme on Immunization 1993). This policy was implemented to compensate for the failures of routine vaccination, such as thermal inactivation and lower seroconversion rate. The success of the approach has made it the model for poliomyelitis eradication in the Latin America and Caribbean (LAC) Region. WHO has endorsed this strategy and recommends that all children under 5 years of age receive an additional two doses of OPV during the national immu-nization days (NIDs), preferably during the low season for poliovirus transmission (Wright et al. 1991, Hull & Ward 1992, Centers for Disease Control and Prevention 1993, Ward et al. 1993). There was a substan-tial increase in the number of countries with endemic poliomyelitis that conducted national immunization days from 16 countries in 1988 to 62 countries in 1995, resulting in tremendous successes in LAC and China, and some parts of OAI, MEC and sub-Saharan Africa (SSA) regions (Hull et al. 1994, Birmingham et al. 1997a, Cochi et al. 1997).

What would be the current burden attributable to paralytic poliomyelitis

Figure 5.6 Immunization status of poliomyelitis cases in Shandong Province, 1990

0

30

60

90

120

150

UnknownFullyimmunized

(3+)

Partiallyimmunized

(1–2)

Notimmunized

(0)

Num

ber

of C

ases

Immunization Status

137Poliomyelitis

if immunization coverage were zero? We have estimated the current bur-den of poliomyelitis in the absence of immunization for polio. Before the introduction of OPV, in the early 1950s, poliomyelitis was highly endemic all over the world. Figures for the incidence of poliomyelitis at that time were available only in EME (Nathanson & Martin 1979) and some parts of today’s FSE (Freyche & Nielsen 1955). Lameness survey data before dis-semination of OPV, before 1980, are available for some developing regions, including India, LAC, MEC, SSA, and OAI, with some studies reporting vaccine coverage (Foster et al. 1984, Khajuria et al. 1989, Nicholas et al. 1997). Where data for the 1950s were not available, indirect methods were used, based on the historical trend of epidemiological and demographic transition, and including lameness surveys and vaccine coverage. Because of the epidemiological shift of disease occurrence in developed regions (EME and FSE), the following age-distribution proportions of poliomyelitis incidence were used for developed regions: 47 per cent for 0–4, 24 per cent for 5–14, 28 per cent for 15–44, 0.06 per cent for 45–59 and 0.02 per cent for 60 and over ( Paul 1955, Moore et al. 1982). For developing regions, where the majority of cases occur under 5 years of age, the age-distribution proportions for each age group were assumed to follow the endemic pattern: 97 per cent for age 0–4; 5.4 per cent for age 5–14; 1.6 per cent for age 15–44; 0.8 per cent for age 45–59; and 0.06 per cent for age 60 and over. Figure 5.7 illustrates that over 800 000 cases would have occurred annually in the absence of current vaccination programmes, and over half a million cases could be prevented with current immunization coverage (Figure 5.8). It should be noted, however, that an improved stan-dard of living, including better sanitation and hygiene, might have reduced the incidence of poliomyelitis during this period. Nonetheless, the result illustrates the signifi cant impact of immunization programmes, especially in developing regions where these programmes, along with case manage-

Figure 5.7 Reduction of polio incidence by region, 1990

0

100 000

200 000

300 000

400 000

500 000

600 000

700 000

800 000

900 000

GlobalCHNINDOAISSAMECLACFSEEME

Ann

ual I

ncid

ence

WDR Region

1990 (vaccine available)1990 (no vaccine)


ment and surveillance systems, have been implemented and improved both through the commitment of governments and with the fi nancial and technical support of international community.

The lessons learned from smallpox eradication suggest that poliomyeli-tis eradication depends on effective disease surveillance to guide vaccine strategy, verify outcome and certify success, particularly in the fi nal stage toward eradication (Pan American Health Organization 1993). Based on the experiences in the LAC Region, the focus of EPI shifted in the 1990s from monitoring vaccine coverage to assessing disease incidence through surveillance (Birmingham et al. 1997b). WHO has recommended the strengthening of the following elements in the poliomyelitis eradication programme in addition to the routine OPV vaccination and mass cam-paigns (Hull et al. 1994, 1997):

improve the acute fl accid paralysis (AFP) surveillance system to the point where each country can detect all cases of paralysis which might be poliomyelitis;

build a global network of laboratories with the technical competence to reliably identify poliovirus from specimens collected from these cases; and

conduct supplemental immunization activities including outbreak response immunization and mopping-up immunization.

As discussed earlier in this chapter, AFP surveillance was widely used during the 1990s as a critical component of poliomyelitis eradication strategies (Box 5.3) (de Quadros et al. 1997, Hull et al. 1997). Since there are no absolute criteria that will permit poliomyelitis to be identifi ed on a clinical basis, WHO recommends laboratory-based AFP surveillance

Figure 5.8 Anticipated reduction of polio incidence with full vaccine coverage

0

50 000

100 000

150 000

200 000

250 000

GlobalCHNINDOAISSAMECLACFSEEME

Ann

ual I

ncid

ence

WDR Region

1990 (100% coverage)1990 (actual coverage)

139Poliomyelitis

for the purpose of poliomyelitis eradication. The performance of AFP surveillance in each country is evaluated by the following fi ve indicators: at least 80 per cent of representative health units within the reporting network should report regularly (weekly or monthly); at least one case of non-poliomyelitis AFP should be detected annually per 100 000 popula-tion under 15 years of age; at least 80 per cent of all AFP cases reported should be investigated within 48 hours and have two stool specimens taken for virus culture within two weeks of onset of acute paralysis; at least 80 per cent of all AFP cases should have a follow-up examination of residual paralysis at 60 days after the onset of paralysis; and all virological studies on AFP cases must be performed in a laboratory of certifi ed competence that is part of the WHO’s global poliomyelitis laboratory network (Hull & Dowdle 1997, World Health Organization 1998).

Many endemic countries, including China, India, and countries in the SSA, MEC, and OAI regions, started national immunization days and AFP surveillance in the 1990s. It is suggested, however, that the effi ciency and quality of surveillance vary considerably within and between countries (Centers for Disease Control and Prevention 1994). For example, the assessment of performance of AFP surveillance in SSA, MEC, and FSE in the early 1990s showed great variations between countries and evidence of underreporting of AFP cases in these regions (Birmingham et al. 1997b). For example, the non-poliomyelitis AFP rate, which is an indicator of AFP surveillance sensitivity, varies signifi cantly among regions, from less than 0.1 in SSA to 1.2 in LAC, CHN and a part of OAI (Tangermann et al. 1997). Developing a surveillance system is a long-term commitment that must be maintained until global eradication is certifi ed (Eichner &

Box 5.3 Key interventions for poliomyelitis eradication

Interventions Indicators

High routine immunization coverage At least 90 per cent of infants should be vaccinated against poliomyelitis by one year of age through routine four doses of OPV immunization.

National immunization days All children under 5 years of age should be immunized regardless of prior immunization status during two rounds of mass campaign.

Laboratory-based surveillance of acute fl accid paralysis (AFP) surveillance

All AFP cases in children under 15 years of age should be reported immediately; clinical and epidemiological investigation should begin within 48 hours; two stool samples should be collected; stool from contacts of cases should also be tested.

Mopping-up immunization All children under 5 years of age should be immunized, regardless of prior immunization status, in the targeted district.

Source: (Hull et al. 1994, 1997).


Dietz 1996), and AFP surveillance poses special diffi culties in countries with inadequate health infrastructure (Hull & Dowdle 1997). In countries where poliovirus circulation has been limited to focal areas, and surveil-lance is adequate, the next step towards eradicating the transmission of wild poliovirus completely and permanently from the region is a mopping-up campaign (Pan American Health Organization 1993). A mopping-up campaign comprises a response to an additional outbreak by immunizing children living in a community where a case of suspected poliomyelitis has occurred and carrying out a localized immunization campaign targeting high-risk population.

As shown in World development report 1993: investing in health (World Bank 1993), immunization is one of the most cost-effective health interven-tions. In a study of poliomyelitis immunization in Brazil, intensifi cation strategies such as mass campaigns had lower average costs than routine immunization programmes (Creese 1984). Although Shepard (1989) has suggested that most studies do not report the incremental cost-effective-ness of additional expenditures on routine vaccination, mass campaign programmes are likely to have a greater impact per dollar spent than are routine vaccination since they have lower incremental costs for additional vaccines and their effi cacy has been proven to be greater (Richardson et al. 1995, Reichler et al. 1997). Moreover, such a comprehensive effort could be extended to combine other interventions, such as vitamin A supplementation, that are considered to be cost-effective.

A particular feature of the economic analysis of the health interventions for poliomyelitis is the assessment of benefi ts of eradication. If an eradi-cation programme is feasible and its benefi t is discounted at low rates, it yields almost infi nite benefi ts, from a cost-effectiveness viewpoint, and any amount of fi nite costs can be undertaken to eradicate a disease (Acharya & Murray 1998). Such a calculation nevertheless depends on the timespan of the global poliomyelitis eradication processes in different regions. In countries where immunization and surveillance are inadequate, extending the implementation of additional strategies for poliomyelitis eradication would be quite costly in the short run and the current expenditure for poliomyelitis eradication would be cost-effective only when benefi ts in the distant future were taken into account.

In contrast, in countries where poliovirus transmission has been inter-rupted and active surveillance has been established, immediate eradica-tion rather than delayed eradication proves more cost-effective (Musgrove 1988, Bart, Foulds & Patriarca 1996). Furthermore, since the eradication of poliomyelitis in a region also depends on poliovirus transmission in other regions, it is more cost-effective for such a region to have oth-ers engaged in intensive strategies to prevent the reintroduction of wild poliovirus (Hall et al. 1998). Therefore, global poliomyelitis eradication programmes should be cost-effective from a global viewpoint, even though they may not be cost-effective for a single country in the short run. Since poliomyelitis eradication strategies would impose a heavy fi nancial burden

141Poliomyelitis

on the health care resources of many endemic countries, the international community has a signifi cant role to play in providing resources to sustain global poliomyelitis eradication efforts ( Hull et al. 1997, Satcher 1999, Aylward et al. 2000).

Conclusions

Reported cases of poliomyelitis have been dramatically decreased since the global poliomyelitis eradication initiative in 1988. We expect that progress will continue until the eradication of poliomyelitis early in the 21st century. As our estimates for 1990 have shown, however, paralytic poliomyelitis still causes more burden than would be expected from the reported incidence, especially in India and sub-Saharan Africa. The rela-tively low effi cacy of the surveillance and reporting systems in developing regions, in which poliomyelitis is still endemic, may underestimate the true magnitude of paralytic poliomyelitis in past decades.

Although rising coverage of routine oral poliomyelitis vaccination (OPV) has contributed to the signifi cant decline in the incidence of paralytic poliomyelitis, it is suggested that polio eradication may not be achieved through the current vaccination programme alone. Implementation and establishment of mass campaigns and laboratory-based surveillance are critical to the fi nal stage of the eradication. The benefi ts of eradicating poliomyelitis include: reduction in the burden of life-long disability and premature death; savings in costs of prevention, treatment and rehabilita-tion, and other non-medical costs; and gains in productivity. Such benefi ts could exceed the additional costs for expanding the key strategies, not only for countries free from poliovirus in the short run, but even for endemic poor countries in the long run. Under the WHO initiative, national and international fi nancial and technical support for the endemic countries is essential to sustain the vaccine supply and to improve the surveillance system.

Update: Epidemiological trends in the 1990s

Since the adoption of the global poliomyelitis eradication initiative in 1988, WHO has been leading a global partnership of international organiza-tions and governments to implement strategies to eradicate poliomyelitis for poliomyelitis eradication in all remaining endemic countries. This chapter estimates the global burden of paralytic poliomyelitis in 1990; but there has subsequently been substantial progress towards eradication. The number of known or suspected poliomyelitis-endemic countries has decreased from over 120 to less than 50 and is expected to continue to decline (World Health Organization 1999). The reported incidence of paralytic poliomyelitis declined from 35 251 in 1988 to 6349 in 1998, more than 85 per cent reduction over the decade. Nevertheless, the esti-mated incidence was approximately 80 000, assuming that less than 10 per


cent of cases were reported (Hull et al. 1997). Tremendous achievements were observed in the Americas, where eradication of wild poliovirus was announced in 1994 (Robbins & de Quadros 1997). The Western Pacifi c Region, which includes the world’s most populous country, China, was recently certifi ed free of indigenous wild poliovirus transmission (World Health Organization 2000).

Success in these regions has proved the effectiveness of the strategies recommended by WHO, and the number of countries implementing the strategies has increased rapidly since the mid-1990s. Global routine OPV coverage peaked in 1990 at 85 per cent and stabilized at around 80 per cent thereafter (Figure 5.1). The number of countries conducting national immunization days (NIDs), often coupled with other primary health care interventions, has increased to over 100 including many endemic countries in Africa and South-East Asia (Aylward et al. 2000). AFP surveillance has been implemented in many countries in which poliomyelitis is or recently was endemic (Tangermann et al. 1997).

Despite these efforts, poliomyelitis is still endemic in some 50 coun-tries, including India, sub-Saharan Africa, and parts of the MEC and OAI Regions (Satcher 1999). In order to achieve the goal of eradication, the rapid development of complete and timely AFP surveillance and the continuation of national immunization days are a priority (Hull et al. 1998). Compared to implementation of national immunization days, the establishment of AFP surveillance has been delayed. In 1998, the global average rate for non-poliomyelitis AFP exceeded the targeted level at 1.15 per 100 000 population but the rates in endemic areas were still much lower. Eradication efforts should now focus on the remaining poliomyelitis-endemic countries, especially those in sub-Saharan Africa and the Indian Subcontinent that are affected by war or are politically isolated. From the remaining reservoirs in those countries wild poliovirus can continue to spread into bordering or even distant poliomyelitis-free regions (Centers for Disease Control and Prevention 1995, Tangermann et al. 1997, 2000, Wise 1999). The major obstacle facing eradication is inadequate political and fi nancial commitment, the success of the initiative rests on political commitment within the endemic countries together with support from international organizations and donor countries (Centers for Disease Control and Prevention 1998, Hull et al. 1998, Satcher 1999). Although the goal of eradicating of poliomyelitis by the year 2000 was not achieved, enough resources should continue to be mobilized through international cooperation until poliomyelitis is eradicated. The Global Alliance for Vac-cines and Immunizations (GAVI), which aims to mobilize enough resources to reach children who are currently missed in immunization efforts, has been launched to that end.

143Poliomyelitis

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TetanusA Galazka, M Birmingham, M Kurian, FL Gasse

Chapter 6

Introduction

Tetanus, although vaccine-preventable, remains a common disease in many developing countries. In these countries, tetanus affects mainly younger persons, especially newborns. Neonatal tetanus can be considered as a paradigm of underdevelopment: each case demonstrates multiple failures in the health system. Each is a result of failure to protect the mother with tetanus toxoid, coupled with unhygienic practices which bring tetanus spores into contact with the umbilical stump. For a long time, the persis-tence of this disease was attributable, at least in part, to a lack of aware-ness by health authorities about the true magnitude of this problem. In industrialized countries, the incidence of tetanus decreased considerably with rising standards of living and effective primary health care services that include routine immunization services for children, adolescents and adults, and modern midwifery. However, elderly persons not vaccinated during their youth are still victims of tetanus.

In this chapter we outline the extent of tetanus in developing and industrialized countries, and discuss relevant clinical and epidemiologi-cal aspects of this disease. Such knowledge is essential for adjusting and strengthening control strategies.

Causative agent and pathogenesis of tetanus

The tetanus bacillus, Clostridium tetani, is the causative agent of tetanus. C. tetani is an obligate anaerobic bacillus which has the ability to form spores resistant to various disinfectants and to heat. Boiling for 20 minutes does not destroy it. For practical purposes, autoclaving at 120ºC for 15 minutes is the best method of sterilizing contaminated materials. Spores are ubiquitous; they are present in soil samples, house and operating room dust, fresh and salt water, and the gastrointestinal tract of humans and other animals.


C. tetani produces disease through a potent neurotoxin, tetanospasmin. C. tetani produces disease through a potent neurotoxin, tetanospasmin. C. tetaniThe clinical syndrome is caused entirely by tetanospasmin produced by the vegetative forms of C. tetani. The bacillus is usually introduced into an area of injury in the form of spores. Spores convert to the vegetative forms, multiply and produce toxin only when they fi nd anaerobic conditions—i.e. when they are placed in an area of low oxygen availability —which are produced by necrosis, or bacterial or chemical changes in a wound. This explains the association of non-neonatal tetanus with puncture wounds, lacerations and burns contaminated with soil, street dust, or animal or human faeces. Tetanus can also follow induced abortions, chronic otitis (common in India), administration of non-sterile injections (particularly with necrotizing materials such as intramuscular quinine), body pierc-ing, scarification rituals, insect bites (bees, scorpions, etc.) and other unnoticed, minor and trivial injuries. It can also occur as a postoperative complication.

Neonatal tetanus may occur during delivery, through the introduction of tetanus spores by cutting the umbilical cord with an unclean instrument, or after delivery, by dressing the umbilical stump with substances heavily contaminated with tetanus spores. Contaminated by dirt or other foreign substances, the necrotized and infected umbilical stump is an ideal place for the growth of C. tetani and the production of tetanus toxin.

Toxin produced in the place of injury travels along nerves towards the central nervous system (CNS) by retrograde intra-axon transport. The severity of the disease is determined by the amount of tetanospasmin produced. In the CNS, tetanus toxin becomes fi xed in the ganglion cells of the anterior horn of the spinal and cranial nerves. Tetanus toxin causes increased irritability of the CNS and exaggerated motor activity. It dis-inhibits spinal cord refl ex arcs, presumably by interfering with release of inhibitory neurotransmitters. Freed from inhibition, excitatory refl exes lead to multiple spasms.

Clinical manifestations, diagnosis and treatment

There are considerable differences in the epidemiology, clinical picture, morbidity and mortality rates of the two main age groups of tetanus (neonatal and non-neonatal), as well as their predisposing causes and prevention.

Clinical course of neonatal tetanus

The clinical course of neonatal tetanus is well known to people in areas where the disease is prevalent. As early as 1764, the Reverend Kenneth MacAuley of St Kilda, a remote island off the Atlantic coast of Scotland, whose population was progressively decimated by neonatal tetanus in the 18th and 19th centuries, gave an excellent description of the disease (Collacot 1981, Woody & Ross 1989). In some developing countries, the disease is so common it has descriptive names such as “sickness with

153Tetanus

inability to breast feed,” “convulsion sickness,” or “stiff body sickness” (Marshall 1968). Numerous reports have described the clinical course of the disease (Jellife 1950, Ogbeide 1966, Athavale et al. 1975, Handalage & Wickramasinghe 1976). The fi rst symptom noticed by mothers on the 3rd to 10th day of life is the child’s excessive crying and inability to suck at the breast after developing normally for the few fi rst days. The baby wants to feed but cannot because of trismus (or “lockjaw”), a spasm of the jaw muscles (masseters) that prevents the proper positioning of the baby’s lips and the rhythmic contraction of the appropriate muscles necessary for effective suckling.

Within hours after the fi rst symptoms the baby develops generalized stiffness of the body and begins to have spasms. Trismus and risus sardoni-cus are the symptoms most often noted upon hospital admission of neo-natal tetanus cases. These two symptoms are characterized by a clenched jaw, raised eyebrows and lips drawn laterally and upwards—the whole appearance producing the risus sardonicus facial expression. In neonates, sometimes the lips are pursed in a whistling expression (Ogbeide 1966). Tetanus spasms are infrequent at fi rst, but increase in frequency and often are precipitated by a stimulus such as touch, light or noise. Spasms may last from a few seconds to over a minute. During spasms breathing is affected and the child may become cyanotic or pale. Children may die from severe apnoea during spasms, or 2 to 4 days later as a result of aspiration pneumonia or acute gastroenteritis.

During spasms, both arms are fl exed at the elbows and held in the front of chest. The legs are drawn up and fl exed at the knees. The feet are dorsi-fl exed and the toes acutely fl exed. This hyperfl exion of toes, a very marked feature, is indicative of severe generalized rigidity and of hypertonia in the small muscles of the soles of the feet (Athavale & Pai 1965). The neck is somewhat retracted and there is a marked stiffness of abdominal and back muscles. In severe cases, spasms of the erector muscles of the spine cause the baby’s back to be arched backward (opisthotonos).

Clinical course of non-neonatal tetanus

The incubation period of non-neonatal tetanus varies from 3 to 21 days with extremes of 1 day to several months and a median of seven days (Wassilak, Orenstein & Sutter 1997). Tetanus may appear in one of three clinical forms: localized, cephalic, or generalized.

In the localized form, there is persistent, painful rigidity of the group of muscles in close proximity to the site at which C. tetani was introduced. Symptoms may persist for several weeks or months and fi nally disappear, without leaving any sequelae, or progress to generalized tetanus. Local tetanus is usually mild, and has a case-fatality ratio of about 1 per cent.

Cephalic tetanus is rare and is usually associated with injury of the head, eye, face, ear (e.g. chronic otitis media), or neck. Clinical features are palsies of cranial nerves III, IV, VII, IX, X, and XI. The disease has a short incubation period and may progress to generalised tetanus.


Generalized tetanus is the most common form of the disease. It is char-acterized by painful muscular contractions, primarily of the masseters (i.e. trismus) and neck muscles. A common fi rst sign is abdominal rigidity, although other groups of muscles may be involved, usually accompanied by severe pain. Generalized spasms occur, frequently induced by external stimuli such as touch, light or noise. The case fatality ratios are highest in infants and the elderly, and vary inversely with the length of the incubation period and the quality of medical care received (Einterz & Bates 1991).

Diagnosis

The diagnosis of tetanus is established primarily on clinical grounds and secondarily on epidemiological grounds. A history of a wound contami-nated by soil or other material, or a history of unhygienic delivery are helpful in the diagnosis. Usually diagnosis is made clinically by excluding other possibilities. Attempts at laboratory confi rmation are of little help; the organism is rarely recovered from the site of infection and usually there is no detectable antibody response.

Treatment

Management of generalized tetanus aims to:

Neutralize any toxin still present in the blood before it comes into contact with the nervous system. This is accomplished by the prompt administration of tetanus antitoxin.

Prevent further toxin production by eliminating the organism at the infected site. This can be done by the thorough debridement of wounds, excising all devitalised tissue and removing all foreign bodies. Antibacte-rial therapy with antibiotics is routinely used to reduce the number of vegetative forms of the organism.

Provide constant and meticulous nursing and medical care. Along with assisted ventilation, many tetanus patients are managed with heavy sedation, muscle relaxants and curare-like drugs, and drugs that reduce the hyperactivity of the autonomic nervous system.

Closely monitor fl uid, electrolyte, and caloric balance, especially in neonates and other patients with repeated seizures or inability to take food or liquids because of severe trismus, dysphagia or hydrophobia.

Prevent recurrence through vaccination. Since the disease does not stimulate the development of immunity against further attacks, every patient should be given an injection of tetanus toxoid followed by a second dose after at least 4 weeks and a third dose 6 to 12 months after the second dose.

155Tetanus

Mortality related to tetanus

Case-fatality ratios

The prognosis of tetanus is infl uenced by various factors, including dura-tion of incubation or onset (a function of the amount and rapidity of tetanus toxin production), age, immunization status, underlying illness, delay-time from onset to treatment and quality of supportive care (Marshal 1968, Sutter, Overstein & Wassilak 1994). The highest case-fatality ratios (CFRs) occur at extreme ages: neonates and elderly persons (Table 6.1). Three main causes of death from tetanus include: deaths that occur from asphyxiation attributable to a muscle spasm resulting in prolonged hypoventilation (57 per cent); deaths attributable to metabolic troubles such as dehydration, hypoglycaemia, hyponatriaemia and hypocalcaemia (20 per cent); and deaths related to superinfection (23 per cent) (Sow, Coll & Diop-Mar 1985).

Case fatality ratios for tetanus reported through national surveillance systems in industrialized countries are varied. In the past, CFRs for general tetanus exceeded 40 per cent, but have declined over time to as low as 10 per cent as a result of improved care (Edmonston & Flowers 1979). In Denmark, CFRs for non-neonatal tetanus decreased from 80 per cent in the early 1900s to 38 per cent in the 1930s to 13–27 per cent in the 1960s to 9–11 per cent during the 1970s and early 1980s (Simonsen, Block & Heron 1987) (Figure 6.1). Data from other national tetanus surveillance systems indicate CFRs of 11 per cent in Finland (Luisto 1989), 17–30 per cent in Spain, Switzerland (Zuber et al. 1993) and the United States of America (Prevots et al. 1992); and 39–43 per cent in France (Pelletier & Roure 1991) and Poland (Kuszewski & Dutkiewicz 1994). The large majority of tetanus cases reported from these surveillance systems were non-neonatal.

Table 6.1 Case fatality ratios in tetanus patients by age, India 1954–1968 and 1975, Nigeria 1974–1984

Age India 1954–68a India 1975b Nigeria 1974–84c

< 1 month 86.4 74.4 —1 month–4 years 32.8 50 —5–9 years — 37.8 —10–19 years 33.7 50 46.720–29 years 61.5 52.9 35.830–39 years 45.9 56.7 30.940–49 years 46.8 46.2 43.650–59 years 49.3 70.6 66.7> 60 years 53.4 — 85.7

a. Patel and Mehta (1975)

b. Ghosh (1984)

c. Bandele, Akinyan & Bojowoye et al. (1991)


Reported CFRs associated with neonatal tetanus from commmu-nity-based studies in developing countries range from 25–100 per cent (Table 6.2). Neonatal tetanus CFRs reported from health facilities ranged from 11–100 per cent. Facility-based data are, however, diffi cult to interpret since they are affected by health care seeking behaviour, and hospital-ized patients, particularly those who are moribund, may be discharged or removed from the hospital by family members before their outcome is recorded. Modern therapeutic methods such as artifi cial respirators and neuromuscular blocking agents are often unavailable in health facilities in developing countries; nevertheless, implementation of simple therapeutic schemes and good basic nursing care have been reported to reduce neonatal tetanus CFRs to between 24 per cent and 63 per cent (Daud, Mohammad Ahmad 1981, Einterz & Bates 1991).

Maternal tetanus is associated with unhygienic conditions primarily dur-ing home deliveries and abortion procedures, and is estimated to account for 5 per cent of all maternal mortality (Faveau et al. 1993). Maternal tetanus is mentioned as the cause in 1–15 per cent of all non-neonatal tetanus illness or death (La Force, Young & Bennet 1969, Patel & Mehta 1999, Yadav, Kala & Yadav 1990, World Health Organization 1991). In an urban hospital in South Africa, 35 per cent of all tetanus patients among women between the ages of 15 and 50 years were admitted after abortions; the incidence of post-abortion tetanus was 1 in 800 cases of abortion (Bennett 1976). In Lagos Teaching Hospital in Nigeria, 82 per cent of 27 maternal tetanus cases were post-abortal (Adadevoh & Akinla 1970). In a series of 503 adult tetanus cases seen at a hospital in Ibaden, Niger,

Figure 6.1 Incidence and mortality rates and case fatality ratios for neo-natal tetanus, Denmark, 1920–1960

Year

1920–1924

1925–1929

1930–1934

1935–1939

1940–1944

1945–1949

1950–1954

1955–1959

1960–1964

1965–1969

Neo

nata

l tet

anus

inci

denc

e an

d m

orta

lity

rate

(per

10

000

live

birt

hs)

0

1

2

3

4

5

6

7

8 97%* 97%*

87%* 87%* 67%* 63%*

40%*

40%*

42%*25%*

* case fatality ratio

Mortality rateIncidence rate

Source: Simonsen, Block & Heron, 1987

157Tetanus

Table 6.2 Case fatality ratios associated with tetanus, 1920–1995

Country

Year(s) to which data

pertainType of tetanusa

Case fatality

ratio (%) Reference

Community-based studiesColombia 1961 NT 95 Newell et al. 1966Mexico 1988–1989 NT 25 Ayala et al. 1995Nigeria 1991–1992 NT 50 Abuwa et al. 1997 Nigeria 1988 NT 80 Babaniyi & Parakoyi 1991Nigeria 1990 NT 40–90 Eregie 1993Pakistan 1986–1987 NT 1000 Khan & Hardjotanajo 1989Sudan 1981 NT 74 Olive, Gadir El Sid & Abbas 1982Viet Nam 1989 NT 80 Thanh et al.1990

Facility-based studiesIndia 1984–1987 MT, PA 70 Yadav, Kala & Yadav 1991Nigeria, Lagos 1963–1967 MT, PA 50 Adadevoh & Akinla 1970South Africa, Cape Town 1965–1972 MT, PA 16 Bennett, 1976India 1984–1987 MT, PP 47 Yadav, Yadav & Kala 1991Nigeria, Lagos 1963–1967 MT, PP 20 Adadevoh & Akinla 1970Senegal, Dakar 1982–1983 MT, PP 50 Diop-Mar et al. 1985

Denmark 1978–1982 NNT 9 Simonsen, Block & Heron 1987Finland 1969–1985 NNT 11 Luisto 1989France 1990 NNT 43 Pelletier & Roure 1991Greece 1966–1977 NNT 32 Teknetzi, Manios S & Katsouya no-

poulos V 1983Haiti 1959–1966 NNT 30 Marshall 1968India 1985–1987 NNT 31 Yadav YR, Kala & Yadav 1990India, Bombay 1954–1962 NNT 33 Vakil BJ, Tulpule TH & Rananvare

MM 1965India, Bombay 1954–1968 NNT 86 Patel & Mehta 1975Italy 1956–1960 NNT 72 Rosmini et al. 1987Italy 1961–1965 NNT 52 Rosmini et al. 1987Italy 1966–1970 NNT 47 Rosmini et al. 1987Italy 1971–1975 NNT 64 Rosmini et al. 1987Italy 1976–1980 NNT 70 Rosmini et al. 1987Switzerland 1980–1989 NNT 30 Zuber et al. 1993Tanzania, Dar es Salam 1970 NNT 20 Ayim 1972Turkey 1977–1991 NNT 28 Tutuncuoglu et al. 1994United Kingdom,

Leeds1961–1977 NNT 10 Edmonsen & Flowers 1979

United States 1965–1966 NNT 68 La Force, Young & Bennett 1969United States 1947 NNT 91 Prevots et al. 1992United States 1976 NNT 44 Prevots et al. 1992United States 1989–1990 NNT 24 Prevots et al. 1992

Bangladesh 1994–1995 NT 55 Kalter et al.1999Benin 1977–1986 NT 29 Ayivi et al. 1992

continued


Brazil 1964 NT 77 Pinheiro 1964Denmark 1930–1950 NT 85 Christensen 1970Denmark 1920–1930 NT 97 Simonsen, Block & Heron 1987Denmark 1930–1940 NT 87 Simon, Block & Heron 1987Denmark 1940–1945 NT 67 Simonsen, Block & Heron 1987Denmark 1945–1950 NT 63 Simonsen, Block & Heron 1987Denmark 1950–1955 NT 46 Simonsen, Block & Heron 1987Denmark 1955–1960 NT 40 Simonsen, Block & Heron 1987Denmark 1960–1965 NT 42 Simonsen, Block & Heron, 1987Denmark 1965–1970 NT 25 Simonsen, Block & Heron 1987Egypt 1988 NT 66 El-Sherbini 1991Egypt 1980 NT 78 Riyad & El Gereidy 1983Germany, Dresden 1957 NT 60 Marshall 1968Ghana 1971–1974 NT 64 Blankson 1977Haiti, rural 1953 NT 53 Marshall 1968Haiti, rural 1967 NT 1000 Berggren, Ewbank & Berggren

1981India 1987–1988 NT 82 Deivanayagam, Nedunchelian &

Kamula 1991India 1989 NT 63 Deivanayagam, Nedunchelian &

Kamula 1991India 1985–1986 NT 97 Verma, Dhanwade & Singh 1989India 1973–1974 NT 72 Bhat, Joshi & Kandoth 1979India 1970 NT 57 Mazumdar & Chakraborthy 1974India 1964–1970 NT 88 Phatak & Shah 1973India 1967–1970 NT 57 Majumdar & Kaur S 1971India, Bikaner 1945–1965 NT 91 Saxena & Saxena 1965India, Bombay 1956–1963 NT 73 Athavale & Pai 1965India, Bombay 1959–1972 NT 77 Athavale et al. 1975India, Bombay 1954–1968 NT 86 Patel & Mehta 1975India, Hyderabad 1961–1964 NT 59 Jaffari, Pandit & Ismail 1966Indonesia 1960–1973 NT 39 Barten 1973Iran 1973–1982 NT 43 Hasanabadi 1987Iraq 1984–1985 NT 51 Al Mukhtar 1987Japan 1940–1982 NT 80 Ebisawa & Homma 1986Malaysia, Kuala Lumpur 1974–1977 NT 11 Khoo, Lee & Lam 1978Malaysia, west 1968–1972 NT 21 Chen 1974Mexico 1970–1979 NT 47 Simental et al. 1993Mexico 1980–1990 NT 13 Simental et al. 1993Mexico 1970–1990 NT 25 Simental et al. 1993Mozambique, Maputo 1976–1982 NT 65 Cliff 1985Nigeria 1989 NT 33 Antia-Obong & Ikpatt 1991Nigeria 1983–1986 NT 51 Antia-Obong & Ikpatt 1991

Table 6.2 Case fatality ratios associated with tetanus, 1920–1995 (continued)

Country



Case fatality

ratio (%) Reference

continued

159Tetanus

Nigeria 1986–1988 NT 43 Owa & Makinde 1990Nigeria 1975–1977 NT 63 Okoro & Okeahialam 1987Nigeria 1978–1980 NT 34 Okaro & Okeahialam 1987Nigeria 1962–1964 NT 68 Ogbeide 1966Nigeria 1953–1956 NT 89 Tompkins 1958Nigeria 1953–1956 NT 90 Miller 1972Nigeria 1950 NT 96 Jelliffe 1950Nigeria, Benue 1984–1989 NT 65 Einterz & Bates 1991Pakistan 1979–1980 NT 48 Daud, Mohammad & Ahmad 1981Pakistan 1979–1980 NT 44 Akbar 1981Pakistan 1982 NT 38 Waheed et al. 1981Senegal 1980 NT 69 Sow et al.1985 Senegal 1984 NT 62 Sow, Coll & Diop-Mar 1985 Senegal 1992–1993 NT 53 Sow, Coll & Diop-Mar 1995Sierra Leone 1955–1960 NT 73 Wilkinson 1961Singapore 1946–1949 NT 91 Miller 1972Singapore 1960–1970 NT 77 Chen 1973Singapore 1946–1950 NT 90 Gek 1951South Africa 1953–1955 NT 97 Klenerman & Scragg 1955South Africa 1956–1959 NT 83 Wright 1960South Africa 1967–1972 NT 21 Smythe, Bowie & Voss 1974Sri Lanka 1971–1974 NT 60 World Health Organization 1977Sudan, Juba 1983 NT 84 Woodruff et al. 1984Turkey 1977–1991 NT 53 Tutuncuoglu et al. 1994Turkey 1978–1988 NT 42 Gurses & Aydin 1993Uganda 1985–1989 NT 78 Bwire & Kawuma 1992United States 1953–1961 NT 62 Bytchenko 1966United States 1965–1966 NT 77 La Force, Young & Bennett 1969United States, New

Orleans1946–1951 NT 77 Spivey, Grulee & Hickman 1953

United States, Southern Region

1957 NT 77 Axnick & Alexander 1957

United States, Texas 1954 NT 42 Box 1964Venezuela 1971–1975 NT 42 World Health Organization 1978Venezuela 1971–1975 NT 42 World Health Organization 1978Venezuela 1970–1992 NT 61 World Health Organization 1993a

a. NT = neonatal tetanus; NNT = non-neonatal tetanus; MT = maternal tetanus, PA = post-abortal, PP = post-partum

Table 6.2 Case fatality ratios associated with tetanus, 1920–1995 (continued)

Country



Case fatality

ratio (%) Reference

the uterus was the portal of entry in 72 (14 per cent) cases of which 20 (28 per cent) were post-abortal (Adeuja & Osuntokun 1971).

High CFRs have been reported for maternal tetanus (Bennett 1976, Adadevoh & Akinla 1970, La Force, Young & Bennett 1969, Patel &


Mehta 1999, Yadav, Yadav & Kala 1991). In a review of 1 101 cases of maternal tetanus from 60 studies in developing countries between 1958 and 1990, a median CFR of 52 per cent (range: 16–80 per cent) was found in Africa and 54 per cent (range: 42–64 per cent) in Asia (Faveau et al. 1993). An earlier review of seven studies of postpartum and post-abortal tetanus reported CFRs ranging from 65–72 per cent (Bytchen ko 1966). CFRs were generally higher for post-abortal tetanus than for postpartum tetanus in developing countries. Reviews of maternal tetanus (both post-partum and post-abortal) in Europe and the USA before 1960 showed CFRs between 57 per cent and 100 per cent (Adams & Morton 1955, Weinstein & Beacham 1941).

Complications and sequelae after tetanus

It is generally thought that patients who recover from tetanus do not have sequelae and that neurological complications are rare (Marshall 1968). However, a careful analysis of the literature shows that residua after teta-nus may have an important practical signifi cance when follow-up periods cover several months to several years after the acute phase of the disease. The complications of tetanus may be divided into two categories—those induced by the toxin itself and those resulting from debility (Sutter, Oren-stein & Wassilak 1994).

Toxin-related complications

Spasm-related complications include fractures of the long bones and ver-tebrae, asphyxia from obstruction of the glottis, spontaneous rupture of muscles, intramuscular haematomas, and traumatic glossitis.

Vertebral fractures should be considered among the most common complications of tetanus. They are recognized rarely because of their poor clinical expression; local signs and symptoms are uncommon even when the vertebral injury is extensive (Chaubey 1965, Januszkiewicz 1975, Veronesi, Vitule Filho & Ferrarceto 1975). In some cases there may be some mobility limitations (Yurchuk & Luchko 1989) but even in the presence of some pain, movements of the spine (fl exion, extension and rotation) are often impaired very little. The diagnosis is based mainly on X-ray examination. Vertebral fractures are not seen after neonatal tetanus but they are frequent in children and adults.

The extent of vertebral injury is directly related to the severity of tetanus, and especially to the degree of rigidity of dorsal muscles (Chaubey 1965, Januszkiewicz 1975). The fourth, fi fth and sixth thoracic vertebrae are most commonly affected; multiple fractures are common (Chaubey 1965, Patel, Mehta & Goodluck 1965, Januszkiewicz 1975, Veronesi, Vitule Filho & Ferraceto 1975). The vulnerability of these three vertebrae may be attributable to the powerful muscles operating in an area of minimal fl exibility, causing excessive outward curvature of the spine (i.e. kyphosis). The reported frequency of post-tetanus vertebral fractures varies: from 48

161Tetanus

per cent (Januszkiewicz 1975), to 51 per cent (Chaubey 1965) to 57 per cent (Patel, Mehta & Goodluck 1965) to 78 per cent (Veronesi, Vitule Filho & Ferraceto 1975).

Vertebral fractures may lead to kyphosis, “pectum carinatum,” and gibbous dorsal deformity (i.e. humpback) (Chaubey 1965, Veronesi, Vitule Folho & Ferraceto 1975). In one study, 16 patients (13 per cent) with degeneration-dystrophic changes in the spine (osteochondrosis, spondylitis) experienced diffi culties in their jobs and had to be transferred to easier work; four of them were offi cially declared as invalids (Yurchuk & Luchko 1989). Bilateral anterior dislocation of the temporomandibular joint was reported as a direct effect of toxin-induced spasms (Thachil, Philip & Sridhar 1993). Tetanus toxin may also induce urinary retention, cardiac arrhythmia, hypotension, and hypertension (Sutter, Orenstein & Wassilak 1994). Cardiovascular, gastric, and renal complications usually worsen the prognosis. All these complications can be minimized by paying strict attention to supportive care and by instituting appropriate therapy.

The effects of tetanus toxin on the autonomic nervous system are prob-ably the main causes of different conditions seen in post-tetanus follow-up. Among 25 adult tetanus survivors who were followed up for 3 months to 11 years, various proportions of them had symptoms of irritability, sleep disturbances, seizures, clonic spasms, decreased libido, postural hypoten-sion, and electroencephalographic abnormalities (Illis & Taylor 1971), but these symptoms were generally self-limiting.

Complications attributable to debility

Pneumonia, probably as a result of aspiration of the contents of the stom-ach during a spasm, occurs often in neonates. Pneumonia may also occur in the third or fourth week of the illness, possibly as a result of general debility.

Other complications may include pulmonary embolism, decubitus ulcers, faecal impaction, catheter-associated infections, and muscle con-tracture (Sutter, Orenstein & Wassilak 1994).

Neurological defects observed in survivors of neonatal tetanus, espe-cially in those who suffered frequent and prolonged bouts of spasms and apnoea, have been attributed to brain damage caused by anoxia at a vulner-able period of brain growth and development (Anlar et al. 1989, Khoo et al. 1978, Teknetzi et al. 1983, Tutuncuoglu et al. 1994). In many of these children, mental or growth retardation and behavioural disturbances were observed from 2 to 15 years after recovery.

Age distribution of tetanus

There are considerable differences in the epidemiology, clinical picture, and the morbidity and mortality rates of neonatal and non-neonatal tetanus, as well as in their predisposing causes and prevention.

The overall age distribution of tetanus has changed considerably,


particularly in age groups covered by routine immunization. Figure 6.2shows the progressive impact of tetanus immunization in the United States according to age. After 30–40 years of routine immunization, tetanus virtually disappeared in infants, children and teenagers and its incidence greatly decreased in adults, with the highest incidence rate among adults of 60 years of age and older.

In other industrialized countries, tetanus has also become a rare disease in children and young adults, the age groups that were most frequently affected before the introduction of immunisation services. In the industrial-ized world, persons under 20 years of age constitute only 2–9 per cent of all tetanus cases, and the majority of tetanus cases occur in persons over 50 years of age (Table 6.3). In France, of the 30 cases reported in 1990, 22 cases (73 per cent) were over 70 years of age; the median age of patients was 77 years (Pelletier & Roure 1991). In the United States, by 1985, 70 per cent of reported tetanus cases occurred in persons aged 50 years and older (Centers for Disease Control and Prevention 1985). In England and Wales, 60 per cent of 123 reported tetanus cases between 1984 and 1992 were patients over the age of 65 years (Anonymous 1993).

The age-specifi c shift in tetanus incidence parallels changes in tetanus immunity; the level of tetanus antibody is highest in persons under 30 years of age. Then immunity decreases with increasing age and falls to the lowest levels in the over-50 age group (Christenson and Bottiger 1987, Galazka and Kardymowicz, 1989, Bourleaud and Huet 1985, Misra and Rao 1988,

Figure 6.2 Reported age-specifi c tetanus incidence rates, by 5-year intervals, United States, 1965–1994

0

0.05

0.15

0.10

0.20

0.25

0.30

0.35

0.70

5–19< 1 20–39 40–49 50–59 60+

1965–19691970–19741975–19791980–19841985–19891990–1994

Age group (years)

Ave

rage

ann

ual r

ate

per

100

000

Source: Wassilak, Orenstein & Sutter 1997

163Tetanus

Table 6.3 Age distribution of tetanus cases (percentage of cases < 20 and > 50 years of age), 1954–1992

Country Year Type of Study< 20 years

> 50 years Reference

Developing countriesCameroon,

Yaounde1971–72 Hospital study 23 18 Ancelle et al. 1974

Chile 1975–76 National surveillance 56 19 de la Fuente, Gonzalez & Guevara 1986

Chile 1982–83 National surveillance 28 27 de la Fuente, Gonzalez & Guevara 1986

India, Bombay 1954–68 Hospital study 71 4 Patel & Mehta 1975Jamaica 1980–86 Hospital study 49 32 Figueroa & Clarke 1988Nigeria, Ibaden 1963–69 Hospital study 28 12a Adeuja & Osuntokun 1971Nigeria, Lagos 1967–70 Hospital study 48 8a Afonja 1973Senegal 1960–67 Hospital study 68 6 Rey & Tikhomorov 1989Senegal 1985–86 Hospital study 65 9 Rey & Tikhomorov 1989Upper Volta 1968–72 Hospital study 62 4 Galazka & Gasse 1995Upper Volta 1972–75 Hospital study 69 3a Cosnard, Joullie & Davin 1977

Industrialized countriesDenmark 1978–82 National surveillance 0 85 Simonsen, Block & Heron

1987England, Wales 1970 National surveillance 27b 50c Galbraith, Forbes & Tillett

1981England, Wales 1979 National surveillance 0b 55c Galbraith, Forbes & Tillett

1981Finland 1969–85 Hospital study 9d 54 Luisto 1989France 1969–79 Hospital study 1 69e Lamisse, Sonneville &

Choutet 1981France 1990 National surveillance 93f Pelletier & Roure 1991France 1991–92 National surveillance 93f Lombard & Lepoutre 1993Poland 1960 National surveillance 46 26 Galazka & Abgarowicz 1973Poland 1970 National surveillance 15 53 Galazka & Abgarowicz 1973Poland 1980 National surveillance 3 81 Galazka & Gasse 1995Poland 1990 National surveillance 2 86 Galazka & Gasse 1995Switzerland 1968–89 Hospital study 0 64 Jolliet et al. 1990Switzerland 1980–89 National surveillance 3 81 Zuber et al. 1993United States 1982–84 National surveillance 4 71a Centers for Disease Control

and Prevention CDC 1985United States 1985–86 National surveillance 5 71 Centers for Disease Control

and Prevention CDC 1985United States 1987–88 National surveillance 6 68 Centers for Disease Control

and Prevention CDC 1985United States 1989–90 National surveillance 6 64 Prevots et al. 1992

a. includes 50-year-olds

b. < 14 yearsc. > 45 yearsd. includes 20-year-oldse. < 15 yearsf. > 60 years


Crossley et al. 1979, Lau 1987). Serosurveys from industrialized countries since 1977 indicate that 49–68 per cent of elderly persons lack protective immunity against tetanus (Beytout et al. 1988, CDC 1985, Crossley et al. 1979, Simonsen et al. 1987b, Kjeldsen et al. 1988).

In developing countries, tetanus affects the younger segment of the population. A major portion of the burden is among neonates, and children or young adults up to the age 20 years (Table 6.3). Before implementation of routine immunization of pregnant women against tetanus and improve-ment of delivery conditions, neonatal tetanus was responsible for about half of all neonatal deaths (ranging from 23 per cent to 72 per cent) and for about 25 per cent of infant mortality (Stanfi eld & Galazka 1984, Gala-zka, Kardymowicz 1989). Four decades ago, a similar situation existed in what are now industrialized countries; in Denmark, neonatal tetanus accounted for more than 50 per cent of all tetanus deaths until the mid-1950s (Simonsen, Block & Heron 1987) and in the 1930s and 1940s the incidence of neonatal tetanus was about fi ve cases per 10 000 live births with an average case-fatality ratio of 80 per cent (Figure 6.1).

As tetanus immunity levels increase in target groups covered by routine immunization—infants or young children of both sexes and women of child-bearing age—one may expect a considerable drop in incidence and a shift in age distribution of tetanus cases (Misra & Rao 1988, Morgan et al. 1981, Mya et al. 1985, Vernacchio et al. 1993). Data from Sri Lanka show a 36-fold and 4-fold decline in neonatal tetanus and non-neonatal tetanus incidence, respectively, over a 10-year period beginning in 1978 when national immunization services were introduced for both pregnant women and infants (Galazka & Kardymovicz 1989).

Sex distribution of tetanus

During the pre-immunisation era, reports from all regions of the world indicated a male predominance of tetanus cases, with the exception of the child-bearing age group (Ebisawa 1971, Wassilak, Orenstein, K Sutter 1997). A review of several studies indicated a male:female ratio of approxi-mately 2:1 (Bychentko 1966). A male predominance is also reported for neonatal tetanus from many community-based studies (Table 6.4), sug-gesting that the male predominance of reported neonatal tetanus is not just a function of health care seeking practices (i.e. male babies are more likely to be brought to hospital than female babies). Although the male predominance of adult tetanus is considered to be largely related to occu-pation (e.g. agricultural practices), some authors have suggested that there may be biological factors; males may be more sensitive to tetanus toxin than are females (Bychentko 1966, Ebisawa 1971). Animal studies offer further evidence of a male predominance for tetanus (Bychentko 1966). Systematic immunzation of children and military recruits has been shown in many countries to reduce the incidence among children and adult males,

165Tetanus

respectively, resulting in a relative increase in the proportional morbidity among women (Bychentko 1966, Ebisawa 1971).

Table 6.4 Gender ratios of tetanus cases and deaths, 1944–1990

Country Year

Male:Female Ratio Outcome Reference

Community-based studiesBangladesh 1990 1.5 cases Hlady et al. 1992Ethiopia 1988–89 2.5 cases Alemu 1993Pakistan 1988 1.4 cases Traverso et al. 1989

Columbia 1961–66 0.9 deaths Newell et al. 1966Egypt 1981 2.6 deaths World Health Organization 1982bIndia 1957–59 3.2 deaths Gordon, Singh & Wyon 1961Côte d’Ivoire 1981–82 1.1 deaths World Health Organization 1983Pakistan 1981 1.6 deaths Suleman 1982Sudan 1981 1.4 deaths Olive, Gadir El Sid & Abbas 1982

Facility-based studiesEgypt 1980 2.5 cases Riyad & El Geneidy 1983Egypt 1988 2.3 cases El-Sherbini 1991Ghana 1971–74 1.1 cases Blankson 1977Greece 1966–77 3.3 cases Teknetzi, Manios & Katsouyanopou-

los 1983India 1956–63 1.4 cases Athavale & Pai 1965India 1967–71 2.0 cases Mazumder & Chakraborthy 1974India 1970–71 2.5 cases Parija & Mohanta 1973India 1975 3.7 cases Seghal, Gupta & Sidhu 1980India, Bikaner 1945–65 2.7 cases Saxena & Saxena 1965Iran 1967–76 2.5 cases Salimpour 1978Mexico 1970–90 2.1 cases Simmental et al. 1993Mozambique 1976–82 1.3 cases Cliff 1985Nepal 1975–77 2.2 cases Shreshta 1978Nepal 1975–77 3.0 cases Manandhar 1978Nigeria 1953–56 1.4 cases Tompkins 1958Singapore 1960–70 2.2 cases Chen 1973Sri Lanka 1972–74 1.5 cases Handalage & Wickramasinghe 1976Syrian Arab Republic 1982–84 2.5 cases World Health Organization 1988 United States 1965–66 1.0 cases La Force, Young & Bennett 1969United States, New

Orleans1946–51 1.0 cases Spivey, Grulee & Hickman 1953

India 1966–77 4.0 deaths Bildhaiya 1983Japan 1967 2.0 deaths Ebisawa 1971Nigeria 1953–56 0.9 deaths Tompkins 1958


Weakness of tetanus surveillance

Reporting of neonatal tetanus separatelyUntil recently, many countries did not provide data to WHO on neonatal tetanus separately from tetanus in other age groups. However, following WHO recommendations to do so, separate reporting of neonatal tetanus by countries increased from 18 per cent in 1974 to 89 per cent in 1995.

Notifi cation effi ciencies

Both forms of tetanus, neonatal and non-neonatal, are grossly underre-ported diseases. Neonatal tetanus especially, with its “peculiar quietness” is often overlooked by public health authorities and is hidden within the community (Stanfi eld & Galazka 1984). The neonate often dies at home or fails to reach a hospital. Table 6.5 presents the estimated notifi cation effi ciency of tetanus reporting from the published literature. The WHO estimated that at the beginning of the 1980s routine reporting systems identifi ed no more than 5 per cent of tetanus cases occurring worldwide (Stanfi eld & Galazka 1984).

When notifi cations of tetanus cases to health authorities were com-pared with results of a survey of tetanus cases admitted to nine hospitals in Jamaica between 1980 and 1986, it was found that only 32 per cent of tetanus admissions were offi cially reported to health authorities (Figueroa & Clarke 1988). The level of underreporting was underestimated by this study as it excluded most of the small rural and private hospitals. In Swit-zerland, through a capture-recapture method, only 6–13 per cent of tetanus cases were reported to the Federal Offi ce of Public Health; by contrast, mortality data reported by physicians on death certifi cates to the Swiss Federal Statistical Offi ce were more complete at 81–100 per cent (Zuber et al. 1993). In a review of all tetanus cases from 1969–1978 in England and Wales, it was estimated that only 25 per cent of all tetanus cases were notifi ed (Galbraith Forbes & Tillett 1981). A review of surveillance data from 1979–1984 in the United States showed that only 40 per cent of all tetanus deaths were reported to the US Centers for Disease Control and 60 per cent to the US National Center for Health Statistics, with a combined notifi cation effi ciency of 76 per cent by a capture-recapture method (Sutter et al. 1990). In Denmark, only 66 per cent of hospitalized tetanus cases were reported (Simonsen, Block & Heron 1987).

Trends in tetanus morbidity reported to WHO

Despite the poor notification efficiency of tetanus in most countries, the case reports are still useful to monitor trends. The global number of reported cases of tetanus decreased from 114 000 in 1980 to 64 000 in 1990, representing a 44 per cent decline in a 10-year period during which national immunization services were expanding rapidly in most developing countries (Figure 6.3). When neonatal tetanus and non-neonatal tetanus are presented separately, inverse patterns can be seen (Figure 6.3). The number of cases of reported non-neonatal tetanus was more than halved, from 101

167Tetanus

Tab

le 6

.5

N

otifi

catio

n ef

fi cie

ncie

s of

tet

anus

cas

es, 1

969–

1992

Coun

try

Year

(s) t

o w

hich

da

ta p

erta

inSt

udy

type

Not

ifi ca

tion

effi c

ienc

y (%

)Re

fere

nce

Neo

nata

l tet

anus

cas

esBu

rund

i19

81–1

986

Com

mun

ity-b

ased

sur

vey

<10

0W

orld

Hea

lth O

rgan

izat

ion

1987

aC

amer

oon

1981

–198

6C

omm

unity

-bas

ed s

urve

y10

–22

Wor

ld H

ealth

Org

aniz

atio

n 19

87a

Cot

e d’

Ivoi

re19

81–1

982

Com

mun

ity-b

ased

sur

vey

2So

kal e

t al

. 198

8Eg

ypt,

Ale

xand

ria

1980

Com

bine

d ac

tive/

pass

ive

case

fi nd

ing

94R

iyad

& E

l Gen

eidy

198

3Eg

ypt

1981

–198

6C

omm

unity

-bas

ed s

urve

y45

Wor

ld H

ealth

Org

aniz

atio

n 19

87a

Egyp

t19

88H

ospi

tal r

ecor

d re

view

10El

-She

rbin

i et

al. 1

991

Ethi

opia

1981

–198

6C

omm

unity

-bas

ed s

urve

y<

100

Wor

ld H

ealth

Org

aniz

atio

n 19

87a

Gam

bia

1981

–198

6C

omm

unity

-bas

ed s

urve

y<

100

Wor

ld H

ealth

Org

aniz

atio

n 19

87a

Indi

a19

89–1

992

Com

mun

ity-b

ased

sur

vey

10Si

ngh,

Dat

ta &

Fos

ter

1997

Indi

a19

81C

omm

unity

-bas

ed s

urve

y 8

Sing

h, D

atta

& F

oste

r 19

97In

dia

1989

Com

mun

ity-b

ased

sur

vey

11Si

ngh,

Dat

ta &

Fos

ter

1997

Indi

a19

92C

omm

unity

-bas

ed s

urve

y13

Sing

h, D

atta

& F

oste

r 19

97In

dia

1992

Com

mun

ity-b

ased

sur

vey

15Si

ngh,

Dat

ta &

Fos

ter

1997

Iran

1986

Com

mun

ity-b

ased

sur

vey

5H

asan

abad

i 198

7K

enya

1981

–198

6C

omm

unity

-bas

ed s

urve

y<

100

Wor

ld H

ealth

Org

aniz

atio

n 19

87a

Mal

awi

1983

Com

mun

ity-b

ased

sur

vey

6W

orld

Hea

lth O

rgan

izat

ion

1987

aM

exic

o19

88–8

9C

omm

unity

-bas

ed s

urve

y 0

Aya

la e

t al

. 199

5So

mal

ia19

81–1

986

Com

mun

ity-b

ased

sur

vey

<10

0W

orld

Hea

lth O

rgan

izat

ion

1987

aSu

dan

1981

–198

6C

omm

unity

-bas

ed s

urve

y<

100

Wor

ld H

ealth

Org

aniz

atio

n 19

87a

Tha

iland

1980

Com

mun

ity-b

ased

sur

vey

14W

orld

Hea

lth O

rgan

izat

ion

1993

cTo

go19

81–8

6C

omm

unity

-bas

ed s

urve

ys10

–22

Wor

ld H

ealth

Org

aniz

atio

n 19

87a

Uga

nda

1981

–86

Com

mun

ity-b

ased

sur

veys

<10

0W

orld

Hea

lth O

rgan

izat

ion

1987

a cont

inue

d


Zai

re19

81–8

6C

omm

unity

-bas

ed s

urve

ys<

100

Wor

ld H

ealth

Org

aniz

atio

n 19

87a

Zim

babw

e19

81–8

6C

omm

unity

-bas

ed s

urve

ys10

–22

Wor

ld H

ealth

Org

aniz

atio

n 19

87a

Tota

l tet

anus

Den

mar

k19

82–1

987

Hos

pita

l-bas

ed d

ata

66Si

mon

sen,

Blo

ck &

Her

on 1

987a

Engl

and

and

Wal

es19

69–1

978

Surv

eilla

nce

data

25G

albr

aith

, For

bes

& T

illet

t 19

81Ja

mai

ca19

88H

ospi

tal-b

ased

dat

a32

Figu

eroa

& C

lark

e 19

88Sw

itzer

land

1980

–198

9Su

rvei

llanc

e da

ta81

–100

aZ

uber

et

al. 1

993

Switz

erla

nd19

80–1

989

Surv

eilla

nce

data

6–13

Zub

er e

t al

. 199

3U

.S19

79–1

984

Surv

eilla

nce

data

76Su

tter

et

al. 1

990

a.no

tifi c

atio

n ef

fi cie

ncy

is fo

r te

tanu

s de

aths

(no

t ca

ses)

Tab

le 6

.5

N

otifi

catio

n ef

fi cie

ncie

s of

tet

anus

cas

es, 1

969–

1992

(con

tinue

d)

Coun

try

Year

(s) t

o w

hich

da

ta p

erta

inSt

udy

type

Not

ifi ca

tion

effi c

ienc

y (%

)Re

fere

nce

169Tetanus

000 in 1980 to 39 000 in 1990. In contrast, the number of neonatal tetanus cases increased until 1988, probably refl ecting a combination of improved notifi cation effi ciency within countries, more use of health facilities to treat cases, and better reporting by national authorities to WHO. The surge in reported cases between 1987–1988 is an artifact; Bangladesh and India did not provide data on tetanus cases to WHO in 1987, but did so in 1988. In 1996, neonatal tetanus cases were reported for the fi rst time from China. Despite these artifacts, the reported data suggest that neonatal tetanus contributes an increasing proportion to the overall tetanus burden. In 1980 and 1990, reported neonatal tetanus cases accounted for 11 per cent and 39 per cent, respectively, of the total reported tetanus cases, compared to the 5–6 per cent contribution noted in the 1970s.

Reported morbidity by regions

Global fi gures hide variations among regions and countries. Some devel-oping countries have demonstrated a spectacular impact of immunization on tetanus incidence (Galazka & Gasse 1995). The reported numbers of non-neonatal and neonatal tetanus cases from 1974 to 1996 in six WHO regions are presented in Figure 4. A decreasing trend in non-neonatal tetanus cases has been seen in all WHO regions. The trend for neonatal tetanus cases varies by Region. In 1994, 58 per cent of all tetanus cases and 38 per cent of neonatal tetanus cases were reported from India and other Asian countries (data from China are unavailable).

Figure 6.3 Number of tetanus cases and immunization coverage reported to WHO by national authorities, 1975–1995

Non-neonatal tetanusNeonatal tetanus

0

10

20

30

40

50

60

70

80

90

100

0

20 000

40 000

60 000

80 000

100 000

120 000

140 000

TT2plusb

1975

1976

1977

1978

1979

1980

1981

1982

1938

1984

1985

1986

1987

1988

1989

1990

1991

1992

1993

1994

1995

Num

ber

of r

epor

ted

case

s

Rep

orte

d im

mun

izat

ion

cove

rage

(%

)

Year

a Third dose of diptheria, tetanus and pertussis vaccine in infants

b Two or more doses of tetanus toxoid in pregnant women in developing countries or in countries with economies in transition.

Source: WHO 2003


Figure 6.4 Reported number of neonatal and non-neonatal tetanus cases by WHO region, 1974–1992

Source: World Health Organization 1996 continued

Non-neonatal tetanus Neonatal tetanus

0

5 000

10 000

15 000

20 000

25 000

1975

1974

1976

1977

1978

1979

1980

1981

1982

1938

1984

1985

1986

1987

1988

1989

1990

1991

1992

Num

ber

of c

ases

Year

African region

0

2 000

4 000

6 000

8 000

1975

1974

1976

1977

1978

1979

1980

1981

1982

1938

1984

1985

1986

1987

1988

1989

1990

1991

1992

Num

ber

of c

ases

Year

Region of the Americas

0

5 000

10 000

15 000

20 000

25 000

1975

1974

1976

1977

1978

1979

1980

1981

1982

1938

1984

1985

1986

1987

1988

1989

1990

1991

1992

Num

ber

of c

ases

Year

Eastern Mediterranean region

171Tetanus

Figure 6.4 Reported number of neonatal and non-neonatal tetanus cases by WHO region, 1974–1992 (continued)

Source: World Health Organization 1996

Non-neonatal tetanus Neonatal tetanus

0

1 000

2 000

3 000

1975

1974

1976

1977

1978

1979

1980

1981

1982

1938

1984

1985

1986

1987

1988

1989

1990

1991

1992

Num

ber

of c

ases

Year

European region

0

20 000

40 000

60 000

100 000

80 000

1975

1974

1976

1977

1978

1979

1980

1981

1982

1938

1984

1985

1986

1987

1988

1989

1990

1991

1992

Num

ber

of c

ases

Year

South-east Asia region

0

2 000

4 000

6 000

8 000

1975

1974

1976

1977

1978

1979

1980

1981

1982

1938

1984

1985

1986

1987

1988

1989

1990

1991

1992

Num

ber

of c

ases

Year

Western Pacific region


Tab

le 6

.6

Es

timat

ed n

eona

tal m

orta

lity

rate

s an

d ne

onat

al t

etan

us m

orta

lity

rate

s, an

d pr

opor

tion

of a

ll ne

onat

al d

eath

s du

e to

te

tanu

s, 19

53–1

995

Cou

ntry

Are

a

Year

(s)

to

whi

ch d

ata

pert

ain

Mor

talit

y ra

tes

per

1000

liv

e bi

rths

Perc

enta

ge

of n

eona

-ta

l dea

ths

attr

ibut

-ab

le t

o te

tanu

sR

efer

ence

Neo

nata

lN

eona

tal

teta

nus

Com

mun

ity-b

ased

su

rvey

sA

fgha

nist

anK

abul

1989

1912

56W

orld

Hea

lth O

rgan

izat

ion

1995

Bang

lade

shM

atla

b19

75–1

977

37C

hen,

Rah

man

& S

arde

r 19

80Ba

ngla

desh

Mat

lab

1975

–197

737

Wor

ld H

ealth

Org

aniz

atio

n 19

95Ba

ngla

desh

Tekn

af19

76–1

977

2731

Wor

ld H

ealth

Org

aniz

atio

n 19

95Ba

ngla

desh

Tekn

af, C

hitt

agon

g 19

76–1

977

89

27.4

31Is

lam

198

2Ba

ngla

desh

1978

4827

56G

alaz

ka, G

asse

& H

ende

rson

1989

Bang

lade

shM

CH

are

a19

8645

3 7

Fauv

eau

et a

l. 19

90Ba

ngla

desh

non-

MC

H a

rea

1986

5411

21Fa

uvea

u et

al.

1990

Bang

lade

sh19

8682

4150

Gal

azka

, Gas

se &

Hen

ders

on19

89Ba

ngla

desh

1989

10W

orld

Hea

lth O

rgan

izat

ion

1995

Bang

lade

shC

hitt

agon

g19

9013

Wor

ld H

ealth

Org

aniz

atio

n 19

95Ba

ngla

desh

Raj

shah

i div

isio

n19

9018

Wor

ld H

ealth

Org

aniz

atio

n 19

95Ba

ngla

desh

1993

22 2

12W

orld

Hea

lth O

rgan

izat

ion

1995

Bang

lade

sh19

93–1

994

15Ba

qui e

t al

. 199

8Ba

ngla

desh

1994

25 6

23W

orld

Hea

lth O

rgan

izat

ion

1995

Bang

lade

shD

haka

1995

15Pe

rry

et a

l. 19

98Bh

utan

1978

–198

319

1367

Stan

fi eld

& G

alaz

ka 1

984

Bhut

an19

8219

1867

Wor

ld H

ealth

Org

aniz

atio

n 19

82a

Burk

ina

Faso

Bam

, San

mat

enga

, Nam

en-

teng

a di

stri

cts

1989

30 3

11Sc

hwoe

bel e

t al

. 199

2

Burm

aEP

I are

a19

8515

321

Stro

h et

al.1

987

173TetanusBu

rma

non-

EPI a

reas

1985

23 9

41St

roh

et a

l. 19

87Bu

rma

1985

18 5

30St

roh

et a

l. 19

87Bu

rund

i19

84 8

Gal

azka

& K

ardy

mow

icz

1989

Cam

eroo

n19

82 7

Gal

azka

& K

ardy

mow

ics

1989

Cam

eroo

n19

84 8

Gal

azka

& K

ardy

mow

ics

1989

Chi

na30

0 co

untie

s19

8945

613

Wor

ld H

ealth

Org

aniz

atio

n 19

93b

Chi

na9

Prov

ince

s19

8922

419

Wor

ld H

ealth

Org

aniz

atio

n 19

93b

Chi

naru

ral

1989

5W

orld

Hea

lth O

rgan

izat

ion

1993

bC

hina

urba

n19

89 2

Wor

ld H

ealth

Org

aniz

atio

n 19

93b

Col

ombi

a19

61–1

966

1100

New

ell e

t al

. 199

6C

ongo

1988

15 2

15St

eing

lass

, Bre

nzel

& P

ercy

199

3C

ôte

d’Iv

oire

Boun

dial

i, Ten

grel

a 19

81–1

982

3418

58So

kal e

t al

. 198

8D

Yem

en

1978

–198

319

420

Stan

fi eld

& G

alaz

ka 1

984

Egyp

tA

lexa

ndri

a19

80 8

463

Riy

ad &

El G

enei

dy 1

983

Egyp

tal

l Eg

ypt

1986

12 7

54W

orld

Hea

lth O

rgan

izat

ion

1987

bEg

ypt

urba

n19

86 5

253

Wor

ld H

ealth

Org

aniz

atio

n 19

87b

Egyp

tru

ral

1986

1810

54W

orld

Hea

lth O

rgan

izat

ion

1987

bEg

ypt

(urb

an)

1981

3G

alaz

ka 1

985

Ethi

opia

Nor

th &

Sou

th O

mo

1988

–198

916

740

Ale

mu

1993

Ethi

opia

Gon

dar

1983

8 5

63G

alaz

ka, G

asse

& H

ende

rson

1989

Ethi

opia

1988

5M

aru,

Get

ahun

& H

osan

a 19

88G

ambi

a19

8011

Gal

azka

, Gas

se &

Hen

ders

on19

89G

hana

1989

26 7

29W

orld

Hea

lth O

rgan

izat

ion

1995

Gha

na19

92 2

Wor

ld H

ealth

Org

aniz

atio

n 19

95In

dia

Raj

asth

an (

rura

l)19

9317

33G

upta

& K

eyl 1

998

Indi

aM

eeru

t di

stri

ct19

9119

521

Gar

g et

al.

1993

Indi

aU

ttar

Pra

desh

, rur

al

1981

6772

Basu

& S

okhe

y 19

84In

dia

Mad

hya

Prad

esh,

rur

al19

8120

36Ba

su &

Sok

hey

1984

Indi

aU

ttar

Pra

desh

, urb

an19

81–1

982

1559

Gal

azka

198

5

cont

inue

d


Indi

aM

adhy

a Pr

ades

h,ur

ban

1981

–198

2 1

30G

alaz

ka 1

985

Indi

aW

est

Beng

al, r

ural

1981

1240

Basu

& S

okhe

y 19

84In

dia

Biha

r, ru

ral

1981

–198

211

38G

alaz

ka 1

985

Indi

aO

riss

a, ru

ral

1981

–198

2 9

23G

alaz

ka 1

985

Indi

aH

arya

na, P

unja

b &

C

hand

igar

h, r

ural

1981

–198

2 8

30G

alaz

ka 1

985

Indi

aA

ndhr

a Pr

ades

h, r

ural

1981

–198

2 7

28G

alaz

ka 1

985

Indi

aG

ujar

at &

Dad

ra&

N

agar

Hav

eli,

rura

l

1981

–198

2 6

17G

alaz

ka 1

985

Indi

aBi

har,

rura

l19

8111

38Ba

su &

Sok

hey

1984

Indi

aBi

har,

urba

n19

81–1

982

565

Gal

azka

198

5In

dia

Kar

nata

ka &

Goa

, rur

al19

81–1

982

524

Gal

azka

198

5In

dia

Tam

il N

adu

&

P

ondi

cher

ry, r

ural

1981

–198

2 5

31G

alaz

ka 1

985

Indi

aM

ahar

asht

ra, u

rban

1981

–198

2 5

37G

alaz

ka 1

985

Indi

aM

ahar

asht

ra, r

ural

1981

–198

2 5

16G

alaz

ka 1

985

Indi

aR

ajas

than

, rur

al19

8114

42Ba

su &

Sok

hey

1984

Indi

aR

ajas

than

, urb

an19

81–1

982

322

Gal

azka

198

5In

dia

Har

yana

, Pun

jab

&

C

hand

igra

rh, u

rban

1981

–198

2 3

26G

alaz

ka 1

985

Indi

aA

ndhr

a Pr

ades

h, u

rban

1981

–198

2 3

18G

alaz

ka 1

985

Indi

aO

riss

a, ur

ban

1981

–198

2 2

13G

alaz

ka 1

985

Tab

le 6

.6

Es

timat

ed n

eona

tal m

orta

lity

rate

s an

d ne

onat

al t

etan

us m

orta

lity

rate

s, an

d pr

opor

tion

of a

ll ne

onat

al d

eath

s du

e to

te

tanu

s, 19

53–1

995

(con

tinue

d)

Cou

ntry

Are

a

Year

(s)

to

whi

ch d

ata

pert

ain

Mor

talit

y ra

tes

per

1000

liv

e bi

rths

Perc

enta

ge

of n

eona

-ta

l dea

ths

attr

ibut

-ab

le t

o te

tanu

sR

efer

ence

Neo

nata

lN

eona

tal

teta

nus

175TetanusIn

dia

Guj

erat

, Dad

ra, H

agar

H

avel

i, ur

ban

1981

–198

2 2

10G

alaz

ka 1

985

Indi

aK

eral

a, ru

ral

1981

–198

2 2

36G

alaz

ka 1

985

Indi

aK

eral

a, ur

ban

1981

–198

2 2

22G

alaz

ka 1

985

Indi

aK

arna

kaka

&

G

oa, u

rban

1981

–198

2 2

14G

alaz

ka 1

985

Indi

aD

elhi

, urb

an19

81–1

982

110

Gal

azka

198

5In

dia

Wes

t Be

ngal

, urb

an19

81–1

982

1 6

Gal

azka

198

5In

dia

Tam

ilnad

u &

Pon

dich

erry

, ur

ban

1981

–198

2 0

0G

alaz

ka 1

985

Indi

aru

ral

1978

–198

319

–93

5–67

16–7

2St

anfi e

ld &

Gal

azka

198

4In

dia

urba

n19

78–1

983

5–26

0–1

50

–59

Stan

fi eld

& G

alaz

ka 1

984

Indi

aBo

mba

y19

73–1

974

1320

30Bh

at, J

oshi

& K

ando

th 1

979

Indi

aru

ral H

arya

na19

86 4

Kum

ar e

t al

.198

8In

dia

Alig

arh

1989

–199

051

1229

Kha

lique

, Sin

ha &

Yun

us 1

993

Indi

aG

una

1986

37 5

14W

orld

Hea

lth O

rgan

izat

ion

1995

Indi

aJJ

colo

nies

1990

4W

orld

Hea

lth O

rgan

izat

ion

1995

Indi

aR

eset

tlem

ent

colo

nies

1990

0W

orld

Hea

lth O

rgan

izat

ion

1995

Indi

ato

tal

1982

8W

orld

Hea

lth O

rgan

izat

ion

1995

Indo

nesi

a19

7211

Wor

ld H

ealth

Org

aniz

atio

n 19

82a

Indo

nesi

a 19

7949

2346

Wor

ld H

ealth

Org

aniz

atio

n 19

82a

Indo

nesi

aru

ral

1980

12W

orld

Hea

lth O

rgan

izat

ion

1982

aIn

done

sia

Jaka

rta

1982

17 7

Arn

old,

Soe

war

so &

Kar

yadi

198

6In

done

sia

19 o

f 27

prov

ince

s 19

8221

1151

Arn

old,

Soe

war

so &

Kar

yadi

198

6In

done

sia

urba

n19

8317

1740

Gal

azka

, Gas

se &

Hen

ders

on19

89In

done

sia

1983

17W

orld

Hea

lth O

rgan

izat

ion

1995

Indo

nesi

aA

ceh

Prov

ince

1984

3921

54Yu

suf,

Solte

r &

Ber

tsch

199

1In

done

sia

Pidi

e D

istr

ict

1984

6032

54Yu

suf S

olte

r &

Ber

tsch

199

1In

done

sia

Jaw

a Ba

rat

1984

15A

rnol

d &

Soe

war

so 1

986

Indo

nesi

ace

ntra

l Jav

a19

86 3

Wor

ld H

ealth

Org

aniz

atio

n 19

95

cont

inue

d


Indo

nesi

aPi

die

Dis

tric

t19

8729

517

Yusu

f, So

lter

& B

erts

ch 1

991

Indo

nesi

aru

ral

1978

–198

321

1151

Stan

fi eld

& G

alaz

ka 1

984

In

done

sia

urba

n19

78–1

983

17 7

40St

anfi e

ld &

Gal

azka

198

4

Iran

(Is

lam

ic R

epub

lic o

f)to

tal

1985

21 5

24G

alaz

ka, G

asse

& H

ende

rson

1989

Iran

(Is

lam

ic R

epub

lic o

f)Fa

rs P

rovi

nce

1986

18 6

34H

asan

abad

i 198

7Ir

an (

Isla

mic

Rep

ublic

of)

Sepi

dan

dist

rict

1986

2413

54H

asan

abad

i 198

7Ir

an (

Isla

mic

Rep

ublic

of)

Eqlid

dis

tric

t19

86 6

0 0

Has

anab

adi 1

987

Iran

(Is

lam

ic R

epub

lic o

f)Fi

rouz

abad

dis

tric

t19

8614

643

Has

anab

adi 1

987

Iran

(Is

lam

ic R

epub

lic o

f)K

azer

oun

dist

rict

1986

29 6

19H

asan

abad

i 198

7Ir

an (

Isla

mic

Rep

ublic

of)

Nei

reez

dis

tric

t19

8616

638

Has

anab

adi 1

987

Iran

(Is

lam

ic R

epub

lic o

f)to

tal

1986

18 6

34H

asan

abad

i 198

7Jo

rdan

1983

7 2

13G

alaz

ka, G

asse

& H

ende

rson

1989

Ken

yaK

isii

1983

10 6

59W

orld

Hea

lth O

rgan

izat

ion

1995

Ken

yaM

eru

1984

1611

71W

orld

Hea

lth O

rgan

izat

ion

1995

Ken

ya19

84–1

985

1611

69M

elga

ard,

Mut

ie &

Kim

ani 1

988

Ken

yaM

eru

1986

14 4

25W

orld

Hea

lth O

rgan

izat

ion

1995

Ken

yaK

isii,

Mer

u, T

ana

Dis

tric

ts,

Rur

al19

8813

870

Mel

gaar

d, M

utie

& K

iman

i 198

8

Ken

yaK

ilifi

1989

21 3

20Bj

erre

gard

, Ste

ring

lass

& M

utie

199

3La

o PD

R19

8516

425

Gal

azka

& K

ardy

mow

iscz

198

9Le

soth

o19

86 4

Gal

azka

& K

ardy

mow

iscz

198

9Le

soth

o19

89 4

0 0

Wor

ld H

ealth

Org

aniz

atio

n 19

95Li

beri

a19

84–1

985

8015

19Be

cker

, Dio

p &

Tho

rnto

n 19

93

Tab

le 6

.6

Es

timat

ed n

eona

tal m

orta

lity

rate

s an

d ne

onat

al t

etan

us m

orta

lity

rate

s, an

d pr

opor

tion

of a

ll ne

onat

al d

eath

s du

e to

te

tanu

s, 19

53–1

995

(con

tinue

d)

Cou

ntry

Are

a

Year

(s)

to

whi

ch d

ata

pert

ain

Mor

talit

y ra

tes

per

1000

liv

e bi

rths

Perc

enta

ge

of n

eona

-ta

l dea

ths

attr

ibut

-ab

le t

o te

tanu

sR

efer

ence

Neo

nata

lN

eona

tal

teta

nus

177TetanusLi

beri

a19

86–1

988

88 6

7Be

cker

, Dio

p &

Tho

rnto

n 19

93M

adag

asca

rru

ral

1989

20 8

38W

HO

199

5M

adag

asca

rur

ban

1989

7 1

18W

HO

199

5M

alaw

i19

78–1

983

2912

41St

anfi e

ld a

nd G

alaz

ka 1

984

M

alaw

i19

90 5

Min

istr

y of

Hea

lth, M

alaw

i 199

1

Mal

awi

Lilo

ngw

e D

istr

ict,

rura

l19

9128

Chi

omba

199

1M

exic

oJa

lisco

, rur

al19

8819

420

Fidl

er e

t al

199

4M

exic

oVe

racr

uz, r

ural

1988

–198

9 8

450

Aya

la e

t al

199

5M

exic

oVe

racr

uz, u

rban

19

88–1

989

4 2

50A

yala

et

al 1

995

Mex

ico

Vera

cruz

1988

–198

9 7

343

Aya

la e

t al

199

5N

epal

Tera

i19

8037

1539

Gal

azka

, Gas

se &

Hen

ders

on19

89N

epal

1982

4424

55G

alaz

ka, G

asse

& H

ende

rson

1989

Nep

alM

oran

g D

istr

ict

1988

19 4

23W

orld

Hea

lth O

rgan

izat

ion

1995

Nep

alD

hanu

sa19

9033

1027

Wor

ld H

ealth

Org

aniz

atio

n 19

95N

epal

4

dist

rict

s (D

ang,

Kap

ilasp

u,

Panc

htha

r, Si

ndhu

li)19

8322

Wor

ld H

ealth

Org

aniz

atio

n 19

95

Nep

al

Dan

g di

stri

ct19

9122

939

Wor

ld H

ealth

Org

aniz

atio

n 19

95N

iger

19

8926

933

Wor

ld H

ealth

Org

aniz

atio

n 19

95N

iger

iaK

war

a St

ate

1988

12Ba

bani

yi &

Par

akoy

i 199

1 N

iger

iaK

ano

1989

–199

030

2168

Ereg

ie 1

993

Nig

eria

Kan

o19

9030

2168

Ereg

ie 1

993

Nig

eria

Ile If

e19

91–1

995

24D

avie

s-A

detu

gbo,

Tom

imir

o &

Nai

199

8Pa

kist

an19

78–1

983

5231

60St

anfi e

ld &

Gal

azka

198

4

Paki

stan

Punj

ab19

8152

3260

Wor

ld H

ealth

Org

aniz

atio

n 19

82b

Paki

stan

rura

l: ag

ricu

ltura

l19

8157

3460

Stan

fi eld

& G

alaz

ka 1

984

Pa

kist

anur

ban

slum

1981

4118

45St

anfi e

ld a

nd G

alaz

ka 1

984

Pa

kist

an19

8428

Gal

azka

198

5Pa

kist

anPu

njab

, Nor

th W

est

Fron

-tie

r Pr

ovin

ce19

86–1

987

11 4

36K

han

& H

ardj

otan

ajo

1989

Paki

stan

1987

14 4

29G

alaz

ka &

Kar

dym

owic

z 19

89

cont

inue

d


Paki

stan

Non

-Pun

jab

area

s19

90D

ietz

et

al. 1

996

Paki

stan

Punj

ab19

90D

ietz

et

al. 1

996

Paki

stan

ru

ral:

catt

le/h

orse

rai

sing

1981

5842

73St

anfi e

ld &

Gal

azka

198

4

Paki

stan

19

8821

1258

Wor

ld H

ealth

Org

aniz

atio

n 19

95Ph

ilipp

ines

1978

–198

313

648

Stan

fi eld

& G

alaz

ka 1

984

So

mal

ia19

78–1

983

9121

23St

anfi e

ld &

Gal

azka

198

4

Som

alia

Bala

d, M

ogad

ishu

1981

49A

den

& B

irk

1981

Som

alia

1981

9121

23G

alaz

ka &

Kar

dym

owic

z 19

89So

mal

ia2

villa

ges

1987

–198

948

3880

Ibra

him

199

6Sr

i Lan

kaK

alut

ara

1982

8<

1 6

Wor

ld H

ealth

Org

aniz

atio

n 19

95Sr

i Lan

kaA

nura

dhap

ura

1984

15 1

7G

alaz

ka &

Kar

dym

owic

z 19

89Sr

i Lan

ka19

84 1

De

Silv

a 19

84Su

dan

Nat

ionw

ide,

nor

th a

nd

sout

h19

8129

932

Oliv

e, G

adir

El S

id &

Abb

as 1

982

Suda

nN

atio

nwid

e, r

ural

1981

3110

31O

live,

Gad

ir E

l Sid

& A

bbas

198

2Su

dan

Nat

ionw

ide,

urb

an19

8114

535

Oliv

e, G

adir

El S

id &

Abb

as 1

982

Suda

nN

orth

, rur

al19

8121

528

Oliv

e, G

adir

El S

id &

Abb

as 1

982

Suda

nN

orth

, sem

i-urb

an19

8120

1050

Oliv

e, G

adir

El S

id &

Abb

as 1

982

Suda

nN

orth

, urb

an19

8114

538

Oliv

e, G

adir

El S

id &

Abb

as 1

982

Suda

nN

orth

, urb

an+

rura

l19

8119

531

Oliv

e, G

adir

El S

id &

Abb

as 1

982

Suda

nSo

uth,

rur

al19

8138

1333

Oliv

e, G

adir

El S

id &

Abb

as 1

982

Suda

nSo

uth,

urb

an19

8114

532

Oliv

e, G

adir

El S

id &

Abb

as 1

982

Suda

nSo

uth,

urb

an+

rura

l19

8135

1233

Oliv

e, G

adir

El S

id &

Abb

as 1

982

Tab

le 6

.6

Es

timat

ed n

eona

tal m

orta

lity

rate

s an

d ne

onat

al t

etan

us m

orta

lity

rate

s, an

d pr

opor

tion

of a

ll ne

onat

al d

eath

s du

e to

te

tanu

s, 19

53–1

995

(con

tinue

d)

Cou

ntry

Are

a

Year

(s)

to

whi

ch d

ata

pert

ain

Mor

talit

y ra

tes

per

1000

liv

e bi

rths

Perc

enta

ge

of n

eona

-ta

l dea

ths

attr

ibut

-ab

le t

o te

tanu

sR

efer

ence

Neo

nata

lN

eona

tal

teta

nus

179Tetanus

Suda

nC

entr

al S

udan

1989

–199

020

–36

629

Taha

, Gra

y &

Abd

elw

ahab

199

3Sy

rian

Ara

b R

epub

lic19

81 5

Kha

n &

Har

djot

anaj

o 19

89

Syri

an A

rab

Rep

ublic

1990

1W

orld

Hea

lth O

rgan

izat

ion

1995

Tanz

ania

Zan

ziba

r19

88 9

225

Wor

ld H

ealth

Org

aniz

atio

n 19

95Ta

nzan

ia19

8911

1 9

Wor

ld H

ealth

Org

aniz

atio

n 19

95T

haila

nd19

53–1

957

16 6

38St

ahlie

196

0T

haila

nd19

78–1

983

21 5

23St

anfi e

ld &

Gal

azka

198

4

Tha

iland

rura

l 19

93 6

Cho

ngsu

viva

twon

g, Im

pat

& T

ayak

kano

nta

1993

Tha

iland

ru

ral

1980

21 5

23W

orld

Hea

lth O

rgan

izat

ion

1982

aT

haila

nd

1991

11 1

22W

orld

Hea

lth O

rgan

izat

ion

1995

Togo

1984

11 6

52G

alaz

ka &

Kar

dym

owis

cz 1

989

Tuni

sia

rura

l19

8821

314

Wor

ld H

ealth

Org

aniz

atio

n 19

95Tu

nisi

aur

ban

1988

8 0

4W

orld

Hea

lth O

rgan

izat

ion

1995

Tuni

sia

1988

12 1

10W

orld

Hea

lth O

rgan

izat

ion

1995

Uga

nda

Mba

le D

istr

ict

1984

3815

40G

alaz

ka &

Kar

dym

owis

cz 1

989

Uga

nda

3 re

gion

s19

9016

642

Wor

ld H

ealth

Org

aniz

atio

n 19

95V

ietN

am19

8512

216

Gal

azka

& K

ardy

mow

iscz

198

9V

ietN

amBi

nh T

ri T

hien

1989

13 5

39T

hanh

et

al. 1

990

Vie

tNam

Han

Gia

ng19

89 3

150

Tha

nh e

t al

.199

0V

ietN

amV

inh

Phu

1989

7 3

38T

hanh

et

al. 1

990

Vie

tNam

1989

8 3

40T

hanh

et

al. 1

990

Yem

en19

8419

420

Gal

azka

& G

asse

199

5Ye

men

19

78–1

983

31 3

8St

anfi e

ld &

Gal

azka

198

4

Zai

re19

83 9

Wor

ld H

ealth

Org

aniz

atio

n 19

87a

Zai

rePa

i-Kon

gila

1984

12 1

7W

orld

Hea

lth O

rgan

izat

ion

1995

Zam

bia

1986

14 4

30W

orld

Hea

lth O

rgan

izat

ion

1995

Zim

babw

e19

8310

439

Gal

azka

& K

ardy

mow

iscz

198

9H

ospi

tal-b

ased

dat

aN

iger

iaC

alab

ar19

83–1

986

31A

ntia

-Obo

ng &

Ikpa

tt 1

991

Nig

eria

Cal

abar

1984

–198

749

Asi

ndi,

Ibia

& U

do 1

994

Sene

gal

Nia

khar

rur

al19

83–1

986

5116

31Le

roy

& G

aren

ne 1

991

Sing

apor

e19

6045

Che

n 19

73Si

ngap

ore

1970

74C

hen

1973

Sout

h A

fric

a19

53–1

955

14M

iller

197

2U

gand

a19

85–1

989

1540

Bwir

e &

Kaw

uma

1992


Estimated morbidity and mortality due to tetanus

Estimated morbidity and mortality attributable to neonatal tetanusThere are no valid reported data on neonatal tetanus morbidity and mor-tality because of the variable (and generally low) notifi cation effi ciency associated with tetanus cases (Table 6.5). Knowledge of the magnitude of neonatal tetanus mortality increased greatly with the conduct of community surveys in the 1980s. More than 40 developing countries, including 18 of the 25 most populous countries, undertook special community-based surveys to measure the neonatal tetanus mortality (Basu & Sokhey 1984, Galazka & Stroh 1986) (Table 6.6). Neonatal tetanus mortality rates ranged from 1–2 per 1000 live births in Jordan, Sri Lanka and Tunisia to 67 per 1000 live births in some areas in India. Based on these studies, it was estimated in 1987 that, globally, approximately 800 000 newborns die every year from tetanus (Galazka & Kardymowicz 1989). By exposing the magnitude of neonatal tetanus mortality, the community-based surveys were critically important in providing baseline information, in changing the perception of health policy makers and in generating political support for the control of neonatal tetanus. Surveys of mortality were repeated in some countries in the late 1980s or early 1990s, and the results generally suggest decreasing neonatal tetanus mortality rates and a lower proportion of neonatal tetanus deaths among total neonatal mortality (Table 6.6).

Using the results of these mortality surveys, a methodology was devel-oped by the WHO to estimate the number of neonatal tetanus deaths and cases still occurring in the presence of tetanus toxoid immunization and clean delivery practices. Each country is assigned a pre-immunzation era mortality rate for neonatal tetanus, using data from the fi rst community-based neonatal tetanus mortality survey in the country. In the absence of a survey, countries are assigned rates based on the surveys done in neigh-bouring countries at similar risk. This rate is multiplied by the country’s annual number of live births to calculate a baseline number of neonatal tetanus deaths that would occur without tetanus toxoid immunzation activities.

Using a country’s most recent and reliable coverage estimates for two or more doses of tetanus toxoid in pregnant women (TT2+) and assuming a vaccine effi cacy of 95 per cent, the annual number of neonatal tetanus deaths which would occur is estimated. Specifi cally, TT2+ coverage data and assumed vaccine effi cacy are used to estimate the number of births that would still be susceptible to neonatal tetanus NT in the presence of tetanus toxoid immunization activities. The number of susceptible births is then multiplied by the baseline neonatal tetanus mortality rate assigned to that country to obtain an estimate of the number of neonatal tetanus deaths. This result is subtracted from an estimate of neonatal tetanus deaths using the same method but assuming no tetanus toxoid immunization to determine the annual number of neonatal tetanus deaths prevented by immunization services.

The same method is not used for estimates in countries achieving at

181Tetanus

least 70 per cent coverage with clean delivery practices. It is assumed that a health system able to achieve such a high level of clean delivery cover-age would also have a surveillance system with data reliable enough to be adjusted and used to derive an estimate of neonatal tetanus cases. For most of the countries in this category, the notifi cation effi ciency of the surveillance system is assumed to be about 33 per cent and the number of neonatal tetanus cases reported is therefore multiplied by three.

Assumed case fatality ratios are applied to derive neonatal tetanus death estimates from the neonatal tetanus case estimates, or vice versa (depend-ing on which method was used). A CFR of 90 per cent is used for least developed countries, 80 per cent for developing countries, 60 per cent for countries with economies in transition, and 40 per cent for countries with developed market economies.

This method was used to produce an estimate of 446 000 neonatal tetanus deaths in 1990, excluding China. A rough estimate of 18 000 teta-nus deaths was made for China assuming a neonatal tetanus incidence rate of 1 per 1000 live births and a case fatality ratio of 80 per cent. Including China, an estimated total of 464 000 deaths occurred in 1990 that were attributable to neonatal tetanus.

Estimated morbidity and mortality attributable to non-neonatal tetanus

There are no reliable data showing the real magnitude of non-neonatal tetanus globally. It was estimated that in the 1980s, 120 000 to 300 000 deaths attributable to non-neonatal tetanus occurred each year in the world, excluding China (Rey & Tikhomirov 1989). Estimates of non-neonatal tetanus cases occurring in developing countries are derived from estimates of neonatal tetanus cases and a general assumption that in 1990 the latter accounted for approximately 80–85 per cent of all cases under fi ve years of age, although in reality this proportion varies according to the level of childhood immunization against tetanus. With this assumption, an estimate was derived of tetanus cases among children under fi ve years of age. Tetanus cases were then assigned to older age groups by extrapolation, according to an estimated age distribution based on reported age-specifi c distributions and age-specifi c population immunity (Rey & Tikhomirov 1989, Galazka & Gasse 1995).

For countries with developed market economies and economies in transi-tion (i.e. former Soviet Union countries), reported tetanus cases and a 75 per cent notifi cation effi ciency were used to derive the estimated numbers of tetanus cases. Once estimated cases were calculated, case fatality ratios were applied by age group and income level to estimate deaths (Table 6.7). Based on these methods, we estimated that 155 000 cases and 78 000 deaths occurred in 1990 as result of non-neonatal tetanus. The total estimated burden for tetanus (both neonatal and non-neonatal) in 1990 was 542 000 deaths.


Tab

le 6

.7

Es

timat

ed n

umbe

r of

non

-neo

nata

l tet

anus

cas

es a

nd d

eath

s by

age

in d

evel

opin

g an

d de

velo

ped

coun

trie

s, 19

90

Age

in y

ears

Dev

elop

ing

and

leas

t dev

elop

ed c

ount

ries

Coun

trie

s w

ith e

stab

lishe

d m

arke

t eco

nom

ies

and

econ

omie

s in

tran

sitio

nTo

tal e

stim

ated

nu

mbe

r of

cas

esTo

tal e

stim

ated

nu

mbe

r of

dea

ths

Est.

no. o

f cas

es

Est.

CFR

(%)

Est.

no. o

f dea

ths

Est.

no. o

f cas

es

Est.

CFR

(%)

Est.

no. o

f dea

ths

< 5

90 6

3150

45 3

1512

253

90 6

4245

318

5–14

24 2

1350

12 1

070

024

213

12 1

0715

–29

17 7

9650

8 89

835

259

17 8

318

907

30–

4414

435

507

218

5825

1514

494

7 23

245

–59

8 02

555

4 41

458

3018

8 08

34

431

60–

693

760

602

256

350

4014

04

110

2 39

670

–79

2 32

565

1 51

135

050

175

2 67

51

686

80+

2 21

765

1 44

130

350

152

2 52

11

593

Tota

l16

3 40

251

83 1

591

167

4451

016

4 56

883

670

CFR

= c

ase

fata

lity

rate

.

183Tetanus

Updated Estimates

Based on more complete data available since the early 1990s, the estimates for burden of tetanus in 1990 have since been updated. The estimate for China was updated based on a review of community surveys conducted in 1993 of tetanus incidence in 300 high risk counties (World Health Orga-nization 1993b). The review team concluded that, based on a neonatal tetanus mortality rate of 4.2 per 1000 live births, an estimated 90 000 neonatal tetanus deaths were occurring annually in China. We considered this estimate to be high, since it was based on surveys conducted in high risk counties only. Using the methods described in this chapter for estimating the burden of neonatal tetanus and assuming a pre-immunization neonatal tetanus mortality rate of 3 per 1000 live births, we revised the estimate for neonatal tetanus for China to 71 000 neonatal tetanus deaths.

With these and other minor updates to some pre-immunization neonatal tetanus mortality rates assigned to countries, we estimated that 427 000 neonatal tetanus deaths and 514 000 cases occurred in 1990. Neonatal tetanus was the second leading cause of deaths among childhood diseases prevented by routine immunization services. An estimated 533 000 infant deaths were prevented through tetanus toxoid immunization and clean delivery practices in 1990. The updated estimate would suggest a 6 per cent notifi cation effi ciency when compared to the neonatal tetanus cases reported to WHO for 1990. The Regions with the highest burden in terms of absolute numbers are Asia and sub-Saharan Africa with 67 per cent and 28 per cent, respectively, of the total estimated deaths (Figure 6.5). Several small countries of Africa have some of the highest estimated neonatal tetanus mortality rates (Figure 6.6).

The updates made to the neonatal tetanus model also caused changes

Figure 6.5 Estimated number of tetanus deaths occurring in the world by WHO region, 1990

Non-neonatal tetanus

AFR180 000

AMR3 000

EMR15 000

EUR300

SEAR28 000

WPR19 000

Neonatal tetanus

AFR113 000

AMR9 000

EMR78 000

EUR200

SEAR146 000

WPR82 000


Fig

ure

6.6

E

stim

ated

neo

nata

l tet

anus

mor

talit

y ra

te p

er 1

000

live

birt

hs, 1

990

<1

1–4

>4

Neo

nata

l tet

anus

m

orta

lity

rate

per

10

00 li

ve b

irth

s

185Tetanus

in the non-neonatal tetanus estimates (since the model for the latter is based on the former). The updated estimates for non-neonatal tetanus in 1990 are 165 000 cases and 84 000 deaths. For China, we assumed that only about one-third of all tetanus cases were non-neonatal because of the high infant immunization coverage levels already being achieved in 1990 relative to the low level of tetanus protection at birth. In all, 70 per cent of all non-neonatal deaths were estimated to occur in India and other Asian countries, and 24 per cent in sub-Saharan Africa.

In summary, based on updated estimates, an estimated 679 000 cases and 511 000 deaths occurred worldwide as a result of tetanus (both neo-natal and non-neonatal) in 1990.

Estimated morbidity and mortality by age

The age distribution of tetanus cases and age-specifi c case-fatality ratios are different for the developing and industrialized world. In industrialized countries, a neonatal tetanus case is a rare event and non-neonatal tetanus is limited to older persons. In developing countries, neonatal tetanus con-tinues to be an important cause of preventable morbidity and mortality. Non-neonatal tetanus also takes a terrible toll, especially in younger seg-ments of the population. It is estimated that in 1990 about 70 per cent of all non-neonatal tetanus cases and deaths occurred among persons under 15 years of age. The large majority of these cases and deaths occurred in developing countries (Table 6.7).

Conclusions

Tetanus is a preventable disease. Maternal and neonatal tetanus could be eliminated through the immunization of women to produce and maintain immunity against tetanus during their childbearing years and through clean delivery and umbilical stump care practices. A review of empirical studies and simulations concluded that tetanus immunization is highly cost-effective and an effective means of reducing infant mortality in the developing world (Steinglass, Brenzel & Percy 1993). Providing tetanus toxoid during pregnancy is the most cost-effective tetanus immunization strategy in developing countries, particularly when it is targeted at high-risk populations (Cvjetanovic et al. 1972). To protect the rest of the population from wound tetanus, the strategy of fi rst choice includes immunization in infancy and early childhood, reinforced by booster doses as part of a school health programme.

In 1989, recognizing the magnitude of neonatal tetanus incidence and the fact that the disease is preventable through simple interventions, the World Health Assembly resolved to eliminate neonatal tetanus from the globe by 1995. This goal was reaffi rmed at the World Summit for Children in 1991. The defi nition of neonatal tetanus elimination is the achievement of less than one case of neonatal tetanus per 1000 live births in every district of every country.


Immunisation with tetanus toxoid

For previously non-immunized women, the WHO recommends an immuni-zation schedule consisting of fi ve doses of adsorbed tetanus toxoid (TT) be given to women of childbearing age, and especially to pregnant women. In developing countries, TT coverage among pregnant women has progressed slowly (Figure 6.3). Between 1990 and 1995, coverage with at least two doses of TT rose from 43 per cent to 49 per cent in developing countries and of the former Soviet Union, a pace too gradual to eliminate neonatal tetanus by 1995. By 1995, China, the world’s most populous country, had only begun widespread TT immunization by targeting all women of child-bearing age in 320 counties considered at high risk.

High TT coverage levels are attainable. By 1995, a total of 23 (17 per cent) of the 135 developing countries which are WHO Member States reported TT2+ coverage of at least 80 per cent (Figure 6.7). Coverage with TT immunization in developing countries may rise substantially in the next few years as China introduces routine TT immunization for pregnant women. All countries are providing TT-containing-vaccines (Diphtheria-Pertussis-Tetanus and Diptheria-Tetanus) in their immunization services for children. Globally, according to WHO/UNICEF estimates, 72 per cent of infants received a primary series of three doses of DPT vaccine in 1995. There are, however, considerable differences in immunization coverage between regions, countries and areas within individual countries (Table 6.8).

Clean delivery practices

Over the past decade, many developing countries have concentrated on training traditional birth attendants, providing home delivery kits and

Table 6.8 Percentage of children immunized in the fi rst year of life with 3 doses of DTP vaccine and percentage of pregnant women immunized with at least 2 doses of tetanus toxoid, by WHO Region, 1993

WHO region3 doses of DTP

vaccineAt least 2 doses of

tetanus toxoid

African Region 51 35Eastern Mediterranean Region 65 50European Region 84 77Region of the Americas 81 43South East Asia Region 64 77Western Pacifi c Region 91 21Global 72 49No. of countries providing data 1730 107% of global population represented by reporting

countriesa 98 88

a. For tetanus toxoid, this fi gure represents the percentage of the population from developing countries and countries of the Former Soviet Union only.

b. Based on WHO/UNICEF estimates based on offi cial country reports.

187Tetanus

Fig

ure

6.7

R

epor

ted

cove

rage

with

at

leas

t tw

o do

ses

of t

etan

us t

oxoi

d am

ong

preg

nant

wom

en, 1

995

Sour

ce: W

orld

Hea

lth O

rgan

izat

ion

1996

<50

%N

o da

ta

50%

–79%

≥80%

TT

2+ c

over

age


educating pregnant women about the “three cleans” (clean hands, clean delivery surface and clean cord care). Operational research has shown that training traditional birth attendants alone can reduce both the total neonatal death rate and neonatal tetanus death rate (Mangay-Angara 1981, Rahman 1982). It was found that total neonatal mortality was reduced more by training traditional birth attendants than by immunizing against tetanus, although immunzation alone was more effective in reducing the incidence of neonatal tetanus (Rahman 1982).

The results of a small number of nationwide surveys are available to estimate global and regional coverage rates with clean delivery, defi ned as those with a trained attendant present (World Health Organization 1996). The latest regional and subregional estimates show that countries in Latin America have the highest rates of maternity care coverage in the developing world, 75 per cent of women having a skilled person attending at delivery, followed by 53 per cent in Asia, 52 per cent in Oceania, and 42 per cent in Africa (World Health Organization 1996).

Priority activities to eliminate neonatal tetanus

The fi rst priority for all countries where neonatal tetanus is endemic is to identify foci of high neonatal tetanus risk so that women of child-bearing age in these foci can be immunized with tetanus toxoid. Implementing intensifi ed immunization activities in such high risk areas will rapidly reduce the incidence of neonatal tetanus. Meanwhile, longer term strategies should be put in place to achieve and sustain high levels of routine tetanus immunization as well as clean delivery services and umbilical stump care, particularly among those most at risk.

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193Tetanus

Gek LH (1951) A review of tetanus neonatorum in Singapore during the years 1946–50. The Medical Journal of Malaya, 5(3):3:181–194.

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195Tetanus

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LeprosyD Daumerie

Chapter 7

Introduction

Leprosy is an infectious disease caused by Mycobacterium leprae. Humans are considered to be the main reservoir, and the main mode of transmis-sion is droplet dispersion from multibacillary cases. The clinical spectrum of leprosy varies from a single skin patch that may heal spontaneously to widespread damage to nerves, bones, eyes and vital organs. The disease may produce severe mutilation of the face and extremities, making the psychological trauma of leprosy patients as important as the physical suffering. The onset of leprosy is usually gradual, and the fi rst signs may appear 2 to 10 years after infection (Godal & Negassi 1973, Prasad & Mohamed Ali 1967).

According to the cellular immune response to the infectious agent, the number of bacilli that patients harbour may vary from less than 1 million (paucibacillary leprosy or PB) to more than 100 billion (multibacillary leprosy or MB). Before the days of chemotherapy, the duration of illness was almost lifelong. With the introduction of multidrug therapy (MDT), the duration of the disease has been drastically reduced to less than 1 year for PB patients and less than 3 years for MB patients (World Health Organization 1988). Although the fatality rate is negligible in leprosy (less than 1 per 1000, Noordeen 1972), the occurrence of severe disabilities has important consequences. The disability and economic loss, together with the social and psychological problems the patient suffers, are a burden for many communities and societies.

A fi rst attempt to estimate the global leprosy burden was made by the World Health Organization in 1966 (Bechelli & Martinez-Dominguez 1966): the estimated total number of cases in the world was 10 786 000. This fi gure was updated in 1972 and 1976 and again in 1983 and has varied from 10 to 12 million. Estimated prevalence was based on cross-sectional random sample surveys in the most endemic countries, complemented by questionnaires for less endemic countries. For each country, a correction


factor was applied. Correction factors were derived from reliable informa-tion available from a limited number of areas, information on prevalence among children, prevalence of deformities and rapid village surveys.

Definition and measurement

Leprosy is defi ned as a chronic human disease resulting from infection with Mycobacterium leprae, which affects mainly nerves and skin. This defi ni-tion has not changed over time but is of very little use for epidemiological studies (Pannikar 1992).

The defi nition of a case of leprosy is not universally accepted (Fine 1982, 1992). This is because there is no “gold standard” to identify lep-rosy infection in the large majority of patients (Sirumban et al. 1988). The diagnosis of leprosy is mainly based on clinical grounds and therefore lacks specifi city, notwithstanding intra-observer and inter-observer variations (Gupte et al. 1990, Ponnighaus & Fine 1988).

Newell (1966) said “there is no defi nite, fi nite or absolute test, sign or fi nding which can be said to divide a person with leprosy infection or leprosy illness from the rest of the population”. Clinical, bacteriological, histopathological and immunological tools are all unsatisfactory with regard to reaching a high positive predictive value for screening leprosy in the community.

In view of the above, the WHO has proposed an operational defi ni-tion of a case of leprosy as “a person showing clinical signs of leprosy, with or without bacteriological confi rmation of the diagnosis, and requir-ing chemotherapy”. (World Health Organization 1988). This defi nition excludes individuals cured of the infection but having residual disabilities attributable to leprosy.

The classifi cation of various forms of leprosy is also very controversial. For operational purposes, the WHO has proposed classifying patients

Box 7.1 Categories relating to leprosy in the International Classifi -cation of Diseases

ICD 9 ICD 10030.9 Leprosy A30 Leprosy030.0 Lepromatous leprosy A30.0 Indeterminate030.1 Tuberculoid leprosy A30.1 Tuberculoid

A30.2 Borderline tuberculoidA30.3 BorderlineA30.4 Borderline lepromatousA30.5 LepromatousA30.8 Other formsA30.9 Unspecifi edB92 Sequelae of leprosy

203Leprosy

as either paucibacillary or multibacillary leprosy cases (World Health Organization Study Group 1985). The paucibacillary group will include smear-negative, indeterminate, tuberculoid, and borderline tuberculoid cases. The multibacillary group will include all smear-positive cases.

Most of the endemic countries use the operational defi nitions proposed by WHO for the preparation of annual reports (Lechat, Mission & Walter, 1981). This has greatly contributed to standardizing information, but can make the comparison of time series diffi cult, particularly with information collected before the 1980s.

With regard to disabilities caused by leprosy, the situation is more complex and several grading systems have been developed. In 1969, the WHO proposed a simple classifi cation, which was modifi ed in 1988. The WHO’s 3-grade classifi cation (see Box 7.3) is a simple tool allowing rapid assessment of the problem in the fi eld.

Data sources

In many parts of the world, sample surveys and even total population sur-veys have been conducted to assess the magnitude of the leprosy problem at national level (Burkina Faso, India, Indonesia, Myanmar). These surveys were very useful in enabling a better understanding of the distribution of the disease, and in standardizing procedures. They were acceptably cost-effective (manageable sample size) when prevalence of the disease was about 1 per cent. Prevalence and incidence of leprosy are, however, decreas-ing in most endemic countries, and surveys have become too expensive, time-consuming and often inadequate (Jesudasan et al. 1984). Statistical methods to assess small rates, especially for very unevenly distributed events, are less robust. For these reasons, sample surveys are conducted only in special situations and in limited places, mainly for research pur-poses. But the results of such surveys do not help in estimating the leprosy problem at national or global levels (Fine 1981).

Since 1985, the leprosy situation has undergone major changes fol-lowing the widespread introduction of multidrug therapy (MDT) (World Health Organization Study Group 1982). With the implementation of the global strategy for elimination of leprosy as a public health problem, it was decided to use existing information and to improve existing information systems in order to update estimates annually (Noordeen, Lopez Bravo & Sundaresan, 1992).

Recent information on registered cases shows that 25 countries con-tribute nearly 95 per cent of all registered cases in the world (International Federation of Anti-Leprosy Associations 1993, Noordeen, Lopez Bravo & Daumerie 1991). Therefore, in order to make a reasonably reliable global estimate of the prevalence of the disease, greater attention has been given to making estimates for those 25 countries by a complete review of infor-mation on registered cases. In general, estimates are obtained by applying correction factors to registered cases, in addition to extrapolating from


other related information provided by the WHO and using results from the most recent total or random-sample population surveys.

Most of the information available on the leprosy burden in the world is based on registration. Annual reports from most endemic countries provide point prevalence, annual detection, treatment coverage and number of patients released from registers. Some countries provide more details, such as age-specifi c detection (under 15 years of age or adults), the proportion of multibacillary patients among new cases and the proportion of disabled patients (WHO classifi cation, grade 2, see Box 7.3) among new cases.

Information generated by national information systems is supplemented by:

surveys (total population surveys, selected population surveys, random sample surveys);

WHO questionnaires;

regular evaluations of national programmes;

reports from various consultants;

prospective studies for research purpose (such as the vaccine trials in India, Venezuela and Malawi).

It is clear that data collected by control programmes are mainly action-oriented and provide limited information on the epidemiological pattern of the disease (Fine 1992). More detailed information is collected through special studies. In addition, epidemiometric modelling, as developed by Lechat et al. (1986) is used for a better understanding of transmission of the disease and the impact of control measures. A new leprosy simulation model is being developed in India to enable the best use to be made of existing information, to validate estimates, and to predict future leprosy trends according to various control strategies.

Estimation Methods

Leprosy estimates at the global level are coordinated by the WHO. Although these estimates are crude, they have nevertheless been found to be useful for planning purposes and for setting priorities.

Estimates of prevalence are based on the operational case defi nition of leprosy, i.e. on the number of cases requiring chemotherapy. Greater attention is given to the most endemic countries, using the following methods:

systematic review of all available information, including re-examination of registered cases in Brazil, India, Madagascar, Nigeria, Sudan (Rao & Sirumban 1990);

review of latest epidemiological surveys;

discussion with national programme managers;

205Leprosy

making estimates based on registered fi gures at country level, follow-ing the guidelines outlined in Box 7.2 (World Health Organization 1994b).

Information on incidence of leprosy is very limited. Some prospective studies are carried out in highly endemic areas for research purposes; how-ever, the results cannot be used for extrapolation to country or regional levels.

Considering the major diffi culties in assessing the incidence of leprosy (case defi nition, incubation period, age at onset, delay between onset and detection), incidence is not estimated and it is assumed that reported detec-tion refl ects incidence.

Age-specifi c incidence and prevalence

Detailed information is not available on the age-specifi c incidence and prevalence of leprosy. Some programmes report the proportion of children (0–14 years) among newly detected cases. For the purpose of making the estimates given here, the following assumptions were made, based on a number of studies (Brubaker, Meyers & Bourland 1985, Irgens & Skjaerven, Becx-Bleumink 1992, Ponnighaus et al. 1994) and on other expert opinion.

In endemic countries (crude prevalence above 1 per 10 000 population) 1 per cent of incident and prevalent cases are found in the 0–4 year age group, 20 per cent in the 5–14 year age group, 60 per cent in the 15-44 year age group, 15 per cent in 45–59 year age group and 4 per cent in over-60 year age group, as reported by Noordeen during the dapsone era (before 1981). For the MDT era (after 1981), the distribution is as follows: 0 per cent, 18 per cent, 64 per cent, 20 per cent, 9 per cent (Ponnighaus et al. 1994).

In non-endemic countries, most of the incident and prevalent cases are from age groups over 45 years. This assumption is based on observa-tions in China, Norway and the United States of America.

Age at onset for each age group

Most of the available information refers to age at detection for two age groups: 0–14 years; and 15 years and above. In this report, age at onset is estimated by using the median age of the age group.

Sex-specifi c incidence and prevalence

In the past, in many parts of the world, males were reported to be more frequently affected by leprosy than females. Sex difference in leprosy is often attributed to ascertainment bias, and it seems reasonable to assume that the risk is equal for males and females. For this reason, tables for each region do not show sex distribution, and specifi c rates will vary only according to the size of population by sex.


Box 7.2 Method for estimating leprosy prevalence based on registered fi gures at country level

Step 1

List all areas of the country. An area is defi ned using administrative, geographical or operational criteria.

Step 2

For each area, indicate the registered prevalence, detection, the year of multidrug therapy (MDT) implementation, and the year of 100 per cent MDT coverage. Calculate the preva-lence-to-detection ratio.

Step 3

For each area, assess the situation and apply the appropriate score, as follows.

Score 1 No leprosy control and no information available in the area.

Score 2 MDT has not been implemented (MDT coverage below 20 per cent), and the prevalence-to-detection ratio is equal to or above 5.

Score 3 MDT has not been implemented (MDT coverage below 20 per cent), and the prevalence-to-detection ratio is below 5.

Score 4 MDT coverage has been 20 to 100 per cent for less than 5 years.

Score 5 MDT coverage has been about 100 per cent for 5 years or more.

Step 4

Calculate the correction factor. Extrapolation factors are based on experience in imple-menting MDT in various countries (Sundaresan 1990).

Score 1 Population of the area × prevalence rate of the whole country.

This situation is the most diffi cult to assess and may refl ect: the absence of leprosy endemicity; the absence of health services; a low leprosy control coverage; a combination of the above.

The easiest way to estimate the number of potential cases is to apply the exist-ing national prevalence rate to the population of the area. Of course, this is not very satisfactory and urgent action should be taken to implement leprosy control activities in such areas.

Score 2 Registered cases in the area × 1.

Very often in this situation the number of registered cases is cumulative. Review-ing registers and re-examining patients would lead to a 50 per cent reduction in the prevalence, but it could be estimated that an equal number of existing patients would not have been detected.

Score 3 Registered cases in the area × 2.

Registers have been updated, and the MDT is being implemented. In this situa-tion we generally observed a dramatic increase in detection.

Score 4 Registered cases in the area × 1.5.

MDT is being implemented and the backlog has been reduced.

Score 5 Registered cases in the area multiplication sign × 1.2.

The registered fi gures are very close to reality, and the correction factor refl ects mainly the delay in detection.

207Leprosy

Duration of the disease

The duration of the disease is computed using the following assump-tions:

the fatality rate is negligible;

the self-healing rate is 10 per cent a year for paucibacillary patients (Sirumban 1988);

monotherapy treatment cures paucibacillary patients (PB) in 5 years and multibacillary patients (MB) in 15 years; assuming that 75 per cent of the patients are PB, the average duration with monotherapy is 7.5 years;

multidrug therapy (MDT) cures PB patients in 1 year and MB patients in 3 years so the average duration with MDT is 1.5 years;

the relapse rate is negligible.

For each region, the duration was computed according to the MDT coverage (proportion of estimated cases treated with MDT).

Biases and Limitations of Estimates

Crude prevalence and detection rates derived from registered fi gures are reasonably accurate. Age-specifi c and sex-specifi c indicators are, however, based only on expert opinion and need to be refi ned through special stud-ies. Duration of the disease is based on assumptions made according to the most recent results of research projects on MDT treatment. Assump-tions on the natural history of the disease are based on research studies conducted before 1981 and on epidemiological analysis of information collected by special programmes.

Prevalence and incidence

Estimates of prevalence and incidence are derived mainly from registered fi gures and the primary data are subject to biases arising from various fac-tors: standardization; coverage of information systems; and sensitivity and specifi city of the diagnosis. Efforts were made to standardize defi nitions and reporting systems as far as possible, but there is no simple way to validate the quality of the information. Figures for age-specifi c prevalence and incidence were estimated using well-documented studies.

With the introduction of MDT, leprosy trends are changing rapidly and most likely the risk of infection is also changing. In the context of declining prevalence, it becomes more diffi cult to use stable assumptions (constant risk of infection and exposure).

Duration of the disease

During the past decade, the extensive use of MDT and the improvement of many leprosy control programmes have led to a drastic revision of the concepts of the disease. The duration of the disease is still controversial.


The main issue is that the defi nition of cure is not universally accepted. For operational purposes, the WHO recommends that a patient who has completed an adequate course of MDT should be considered cured. The question of considering as leprosy patients those who have completed treatment but who are disabled as a result of the disease, is very much debated.

Considering that a large majority of incident cases are cured without disability, it was considered practical to estimate an average duration of the disease taking into account self-healing rates, cure rates with mono-therapy, and cure rates with MDT. The main limitation of this method is that drop-out rates and survival statistics are not included.

Complications and disabilities after cure

While the estimates relate to cases requiring or receiving chemotherapy, there are a significant number of patients who have been cured and discharged from registers but still have residual deformities (WHO clas-sifi cation grade 2, see Box 7.3). This problem is discussed and tentatively estimated below.

Leprosy Estimates By World Bank Region

The global number of leprosy cases in 1993 was estimated to be about 2.5 million, of which 1.7 million were registered. The same year, about 600 000 new cases were detected.

Sub-Saharan Africa

Leprosy is endemic in most of the sub-Saharan African countries: Cote d’Ivoire, Chad, Ethiopia, Guinea, Madagascar, Mali, Mozambique, Nige-ria, Niger, Sudan, and Zaire. The national authorities in these countries have reviewed the registered fi gures and published estimates for 1993. A correction factor of 1.9 was applied to registered fi gures. Tables 7.1 and 7.2 summarize the results of the major studies in the region.

India

India contributes 60 per cent of the global leprosy burden. The correction factor applied to registered fi gures was 1.2. The disease is not equally

Table 7.1 Detection and prevalence of leprosy in fi ve African countries, 1986–1989

Country (year) Sample sizePrevalence

per 100 000Detection

per 100 000Cameroon (1986)

Central African Rep. (1986)

Gabon (1988)

Congo (1989)

Equatorial Guinea (1989)

12 683

6 468

6 227

6 542

6 428

720

1 370

940

940

580

360

840

360

150

110

Source: Louis et al. (1991).

209Leprosy

distributed in the country and wide variations in prevalence and incidence are observed. The fi rst epidemiometric model was based on data collected in Polambakkam, southern India, and gives an indication of age- and sex-specifi c incidence as well as mean age at onset. Table 7.3 summarizes the results of epidemiological studies conducted in southern India. Table 7.4gives specifi c incidence rates from Polambakkam in 1967–1971.

China

Leprosy in China is endemic in three south-western provinces. Epidemio-logical surveillance and specialized services provide accurate information, and the correction factor applied to registered fi gures was 1.25.


The most endemic countries in this region are Bangladesh, Indonesia, Myanmar, Nepal, Philippines, and Viet Nam.


Brazil is the most endemic country in this region. Motta & Zuniga (1990) predicted the trend of incidence in Brazil based on actual detection rates from 1950 to 1983. The results are summarized in Table 5.

Table 7.2 Detection rates per 1000 by age and sex in fi ve African countries

Age (Years)a 15–19 20–24 25–29 30–39 40–49 >50

Male 2.0 5.0 5.7 5.5 6.0 6.5Female 2.0 1.3 2.8 3.0 7.5 5.5

a. People 0–14 years of age not included in the sample.

Source: Louis et al. (1991).

Table 7.3 Detection by age group and type of leprosy in four districts, India, 1993

District

Under 15 years of age(number detected)

Age 15 years and over,(number detected) Detection rate per 1 000

PB MB PB MB PB MB Total

Chenglepet

Chittoor(total population)

North Arcot(total population)

Visakhapatnam(total population)

—

1 738

2 416

(0.8)a

—

381

10

(0.0)a

—

1 044

3 582

(0.8)a

—

27

651

(0.1)a

—

—

1.18

0.80

—

—

0.13

0.10

1.64

1.05

1.31

0.90

a. Detection rate per 1000.



Egypt, the Islamic Republic of Iran and Pakistan are the most endemic countries in this region. Based on a cluster sample survey conducted in Egypt in 1986, Sundaresan (1986) estimated the age-specifi c prevalence (using a case-defi nition differing from the World Health Organization defi nition); the results are shown in Table 7.6.

Estimation of Disabilities Attributable to Leprosy

While disability is an important measure in evaluating the leprosy burden and the impact of control programmes, data on disabilities are scarce and not easy to interpret. Most of the epidemiological studies on disabilities attributable leprosy are based on cross-sectional surveys and give an indication of the prevalence of visible disabilities. Since the implementa-tion of multidrug therapy, some experts have been collecting informa-tion on cohorts of patients, making it possible to estimate the incidence

Table 7.4 Incidence rates by age, sex and type of leprosy, Polambakkam, India, 1967–1971

Age group (years)

Male incidence per 10 000 Female incidence per 10 000

PB MB PB MB

0–45–910–1415–1920–2425–2930–3435–3940–4445–4950–5455–5960–6465+

539533635414239333230302121

03589

141618151110783

530321820283132303128281542

023333.554543.532.50

Source: Lechat et al. (1986).

PB = paucibacillary leprosy; MB = multibacillary leprosy.

Table 7.5 Detection rates of leprosy, Brazil: actual rates, 1950 to 1983; predicted rate, 2000

Year Detection per 100 000

19501973197819832000

5.55 7.40 9.8713.1735.03

Source: Molta & Zuniga (1990).

211Leprosy

of disability. Based on information provided by countries, Bechelli & Martinez-Dominguez (1966) estimated that globally 3.87 million leprosy patients had disabilities of all grades, and 2 million of these had severe disabilities. In 1975, it was estimated that 3.5 million individuals had been disabled by leprosy (World Health Organization 1976). In 1994, the World Health Organization (1994b) estimated this number at between 2 and 3 million.

Defi nition and measurement of disabilities related to leprosy

Recognizing that no single system of grading would meet all requirements, in 1988 the WHO proposed a simplifi ed 3-grade system of classifi cation for collecting general data on disabilities or impairments, as shown in Box 7.3 (World Health Organization 1988).

The International classifi cation of impairments, disabilities and handi-caps (World Health Organization 1980) is related more to rehabilitation

Table 7.6 Age-specifi c and type-specifi c prevalence of leprosy in four Governorates, Egypt, 1986

Prevalance per 1000

Age group (years) Sample size PB MB

0–45–910–1415–1920–2930–3940–4950–5960+

4 9554 4313 9803 2214 5023 5422 8511 8801 925

—1.352.011.243.551.973.50

10.6308.31

———

0.620.222.542.804.208.83

Total 31 2870 2.78 1.43

Source: Sundaresan (1986).

Box 7.3 Classifi cation of grades of disability attributable to leprosy

Grade Hands and feet Eyes

0 No anaesthesia, no visible deformity or damage

No eye problem attributable to lep-rosy, no evidence of visual loss

1 Anaesthesia present, but no visible deformity or damage

Eye problems attributable to leprosy but vision not severely affected as a result of these (vision 6/60 or better, can count fi ngers at 6 metres)

2 Visible deformity or damage present Severe visual impairment (vision worse than 6/60, inability to count fi ngers at 6 metres)


needs than to the collection of information for epidemiological purposes. It describes three stages:

impairment: loss or abnormality of psychological, physiological, or anatomical structure or function;

disability: restriction or lack of ability to perform an activity in the manner within the range considered as normal for a human being;

handicap: a disadvantage for a given individual, resulting from an impairment or disability, that limits or prevents fulfi llment of a role that is normal, depending on age, sex, and social and cultural factors for the individual.

Disability in Leprosy: Magnitude of the Problem

Before the implementation of multidrug therapy Before the widespread application of MDT, leprosy was generally con-sidered as a lifelong disease, and cross-sectional studies were carried out to estimate prevalence and risk factors for disabilities. The disability rate, defi ned as the proportion of patients disabled at a given point of time, ranged from 13 to 57 per cent. The most generally observed risk factors were age, duration of the disease, sex, type of leprosy, occupation, and treatment.

Results of the most important studies on prevalence of disabilities are summarized in Table 7.7. Almost all the studies show that the disability risk is higher for males and for multibacillary patients, and that this risk

Table 7.7 Prevalence of disability among leprosy patients before the implementation of multidrug therapy: results of various studies

Type of study Case defi nition Results Country Reference

Patient survey WHO 41.5%

37.6%

41.5%

Cameroon

Nigeria

Thailand

Martinez-Dominguez, Bechelli & Patwary (1966)

Patient survey Social & physical 165/465 (35.5%) India Noordeen & Srinivasan (1966)

Retrospective cohort

WHO 15 869 patients from 28% in 1956 to 13% in 1978

India Christian, Jesudasan & Pannikar (1980)

Patient survey Deformity 120/1334 (9%) India Srinivasan (1982)


WHO 48/145 (33.1%) Myanmar Htoon & Win (1994)


WHO 229/514 (44.6%) India Girdhar et al. (1989)


WHO 282/1264 (22.3%) India Saha & Das (1993)

Patient survey WHO 8122/14 257 (57%) China Zhang et al. (1993)

213Leprosy

increases with age and duration of the disease. Based on these studies, we estimate that, before the implementation of MDT, the number of indi-viduals suffering from severe disabilities because of leprosy varied from 1 million to 4 million at any given time.

There is no published literature on the incidence of disabilities attribut-able to leprosy before 1981. Most leprosy control programmes use the disability rate at detection as an indirect indicator of the effectiveness of case-fi nding activities. This indicator could be used to approximate annual incidence of disability without interventions. Considering the results of surveys and the proportion of patients who are already disabled at the time of diagnosis, we estimate that the crude disability attack rate ranges from 1 to 3 per 100 person-years.

For modelling purposes, Htoon, Bertolli & Kosasih (1993) estimated that 16 per cent of individuals affected by leprosy would be permanently disabled and that all patients will be temporarily disabled, for an average period of 30 days.

With multidrug therapy interventions

Many experts considered that chemotherapy might increase the incidence of disabilities, especially while using powerful bactericidal drugs. With the introduction of MDT and its relative short duration, the occurrence of reactions—and of subsequent disabilities during and after treatment—was expected to be high. Nevertheless, data accumulated in the fi eld do not confi rm this expectation. On the contrary, by reducing the duration of the disease, the incidence and seriousness of leprosy reaction, as well as the incidence of the disease, MDT has also reduced the overall incidence of disabilities. This reduction is not entirely attributable to the effi cacy of drugs. Other factors, such as regular monthly contacts with patients, and improved monitoring and treatment of leprosy reactions in the fi eld, have also played an important role in this process.

Ponnighaus et al. (1990) have reported a disability incidence of 5 per 1000 person-years in Karonga district (Malawi) and Rao (1994) has observed a disability incidence of 0.68 per 1000 person-years among patients treated with MDT. Table 7.8 summarizes the most recent infor-mation on the risk of disabilities for patients treated with MDT.

Available information shows clearly that MDT interventions have signifi cantly reduced the risk of disability. This risk ranges from 1 to 5 per 1000 person–years. It seems that application of MDT prevents the occurrence of 80–90 per cent of disability.

Situation in 1994

In collaboration with the WHO, the major endemic countries estimated the disability problem defi ned according to the WHO grading scheme as follows:

number of individuals already disabled at the time of case detection:


47 100 (8.4 per cent) of 558 066 cases diagnosed in 34 countries, accounting for 88 per cent of the leprosy detected globally;

number of individuals estimated to be disabled because of leprosy: 1 255 700 in 11 countries, representing 72 per cent of the global leprosy burden.

Based on this information, the WHO estimated that in 1994 the annual incidence of disability attributable to leprosy was about 100 000, and that the prevalence of individuals disabled because of leprosy was between 2 and 3 million (World Health Organization 1995).

Burden and intervention

Only severe and permanent physical disabilities have been considered here. Temporary physical disabilities before and during treatment, reactions and complications, and the inconvenience of sustaining long-duration treatment, should be considered in order to estimate the global burden. Moreover, among all infectious diseases, leprosy has a specifi c cultural connotation, and it is diffi cult to assess the individual social and psycho-logical impact it causes. With or without disabilities, any individual in any part of the world classifi ed as a leprosy patient will be exposed to social problems and stigma.

The benefi ts of leprosy control programmes are very often underes-timated. The elimination strategy based on MDT has contributed to an impressive reduction in the global prevalence. Estimated prevalence was reduced from 10 million in 1966 to 5 million in 1991, and to 2.5 million

Table 7.8 Impact of multidrug therapy on disability related to leprosy—prevalence of disability: results of various studies

Type of study Case defi nition Results Country Reference

Retrospective 5-year cohort

Modifi ed WHO 1654 patients: 2.9 to 8 per 1000 person years (average 5 per 1000)

Malawi Ponnighaus et al. (1990)

Retrospective 4-year cohort

WHO 12/482 (2.5%) Malawi Boerrigter et al. (1991)


Nerve damage 87/2161 (4%) India Smith (1992)


Deformity 5655 urban patients: 1.8%

6104 rural patients: 2%

India Thomas (1993)

Retrospective 7- year cohort

WHO 2285 patients: 0.68 per 1000 person years (MB 6.14, PB 0.19)

India Rao (1994)

MB = multibacillary leprosy; PB = paucibacillary leprosy.

215Leprosy

in 1993. Many factors have contributed to the reduced leprosy burden, but it is clear that MDT interventions have had a tremendous impact on prevalence and thus on the caseload and disabilities. The effi cacy and acceptability of MDT are now very well known to health workers and the patients themselves. This contributes to increased opportunities for diagnosis and to reduced stigma. The incidence of the disease is decreasing in many parts of the world.

Even if it is diffi cult to measure to what extent MDT contributes to this reduction, it is clear that secondary and primary resistance to the drugs used previously would have hampered leprosy control. It is estimated that MDT has averted 0.5 to 1 million relapses compared to previous interventions. In India, it is estimated that extensive implementation of MDT will avert 1.2 million cases. Since the implementation of MDT in 1982, about 6.5 million patients have been cured with MDT, including about 2.5 million old cases (backlog). About 4 million new cases have been detected during the past 10 years. Assuming that 30 per cent of those patients were already disabled before starting treatment, we estimate that MDT intervention has prevented 1 to 2 million people from becoming disabled.

The cost of implementing the elimination strategy varies from US$30 to US$400 per patient (global average US$100) according to prevalence, the PB/MB ratio and the existence of a health infrastructure (Htoon, Bestolliz & Kosasik 1993, World Health Organization 1994). A cost-effectiveness analysis indicates that the cost per year of healthy life gained (YHLG) from implementing MDT is very low, from US$10 to US$38 per YHLG (Htoon, Bertolliz & Kosasik 1993).

Conclusions

Leprosy is a public health problem in terms of widespread occurrence in the world, its potential to cause permanent progressive disability, and the social consequences unique to the disease. The signifi cant progress made in leprosy control enabled most of the endemic countries to reach the goal of eliminating leprosy as a public health problem (prevalence below one per 10 000 population) by the year 2000.

Update

The elimination of leprosy as a public health problem (prevalence below one per 10 000 population) was attained at the global level by the end of 2000. At the beginning of 2003, the number of leprosy patients in the world was around 530 000, as reported by 106 countries. About 615 000 new cases were detected during 2002. Among newly detected cases 17 per cent were children (below the age of 15 years), 39 per cent had MB based on the clinical classifi cation (more than 5 skin lesions), and 4 per cent presented grade 2 disability at the time of diagnosis. With a cumulative number of about 13 million patients cured with MDT, the numbers of relapses remain


remarkably low, at less than one case per 1000 patients per year. No drug resistance following MDT has been reported. The number of countries showing prevalence rates above 1 per 10 000 population has been reduced from 122 in 1985 to 12 at the end of 2002. Today, Brazil, India, Nepal, Madagascar, and Mozambique are the most endemic countries.

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Dengue and dengue haemorrhagic feverJames W LeDuc, Karin Esteves, Norman G. Gratz

Chapter 8

Introduction

Dengue, a mosquito-borne viral disease, is becoming an increasing public health problem in developing countries. This was recognized by the WHO, which confi rmed in a resolution at the forty-sixth World Health Assembly in 1993 that dengue prevention and control should be among the priorities of the Organization.

Dengue is caused by any of four antigenically and genetically distinct viruses of the family Flaviviridae, named dengue-1, -2, -3 and -4 (Craven 1991). Humans are the primary vertebrate hosts of these viruses, although there is evidence of a silent zoonotic cycle involving mosquitoes and monkeys in parts of Asia and Africa (Rudnick 1965, Fagbami, Monath & Fabiyi 1977, Rudnick 1984, Cordellier et al. 1983). The Aedes aegypti mosquito is the Aedes aegypti mosquito is the Aedes aegyptiprincipal urban vector (Clark & Casals 1965). Dengue fever is character-ized by an abrupt onset of fever, headache, myalgia, loss of appetite, and varying gastrointestinal symptoms, often accompanied by rash and bone or joint pains (Rush 1789, Hammon, Rudnick & Sather 1960, Ehrenkranz et al. 1971, San Juan Laboratories 1979, Kuberski et al. 1977, Lopez-Correa et al. 1979). Symptoms persist for 3–7 days, and while convalescence may be prolonged for several weeks, mortality is rare. Homologous immunity is lifelong, but cross-protection to other dengue viruses is not elicited and, indeed, there is evidence to suggest that heterologous antibodies may form infectious immune complexes which may increase the severity of subsequent infections (Halstead, Nimmannitya & Margiotta 1969, Halstead 1970, 1980, Kliks et al. 1989). Infected people are infective for feeding mosquitoes during the febrile phase of their illness, and mosquitoes may then transmit the virus to others at subsequent blood-meals after an incubation period of approximately one week, depending upon ambient temperatures (Watts et al. 1987). Infected female mosquitoes may also pass the virus on to prog-eny by transovarial transmission (Rosen et al. 1983, Khin & Than 1983, Hull et al. 1984, Freier & Rosen 1987, 1988, Rosen 1987, 1988, Fauran,


Laille & Moreau 1990, Shroyer 1990, Mitchel & Miller 1990, de Souza & Freier 1991, Bosio et al. 1992, Serufo et al. 1993). Mosquitoes infected transovarially may transmit dengue virus to susceptible humans at their fi rst blood-meal. Once infected, mosquitoes remain infected for life and may transmit dengue virus either during probing, interrupted blood feeding, or when feeding to repletion. Thus, a single infected mosquito may transmit the virus to several susceptible humans over its lifetime.

Dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS) are more severe manifestations of dengue infection, and are most often associated with infection of people with pre-existing antibodies to dengue, either actively or passively acquired (Quintos et al. 1954, Hammon et al. 1960, Halstead, Nimmannitya & Margiotta 1969, Ramirez-Ronda et al. 1979, Halstead 1970, 1980). The clinical course follows that of classic dengue fever initially; however, as the febrile phase subsides, the patient’s condition rapidly deteriorates with signs of circulatory failure, neurologi-cal manifestations, and hypovolemic shock with potential fatal outcome if prompt, proper, clinical management is not implemented. Haemorrhage may be evident by petechiae, easy bruising, bleeding at injection sites, and occasionally gastrointestinal bleeding, especially where gastric ulcers already exist (Tsai et al. 1991).

There is no specifi c treatment for dengue fever. Although convalescence may last several weeks following dengue infection, especially among adults, disabling sequelae are not thought to follow infection. Dengue haemor-rhagic fever and DSS require symptomatic treatment, coupled with careful assessment of fl uid and electrolyte balance for management of shock (World Health Organization 1986, Craven 1991). Areas where clinicians are not familiar with the proper treatment of DHF/DSS may have case fatality rates substantially higher than those where physicians are experienced in the proper treatment of the disease. Diagnosis is made on clinical grounds and confi rmed by laboratory demonstration of specifi c immune response, virus isolation, or identifi cation of dengue virus nucleic acid sequences in clinical material (Russell & McCown 1972, Russell, Brandt & Dalrymple 1980, Pan American Health Organization 1982, Repik et al. 1983, Henchal et al. 1986, Kerschner et al. 1986, World Health Organization 1986).

Dengue is the most widespread vector-borne virus disease in the world, and DHF/DSS are rapidly increasing in incidence in many tropical areas (Halstead 1992, 1993a, 1993b). This dramatic increase is a result of changes in human lifestyle, increased international travel, and urban crowding. Dengue has been known for at least 200 years, but DHF/DSS has only been routinely recognized since the 1950s, although there is evidence to suggest that DHF occurred as early as 1897 in north-eastern Australia (Hare 1898, Craven 1991, Halstead 1993a). Following the end of the Second World War, Asian cities experienced rapid growth and urban crowding, and with these came increased habitat for the vector mosquito of dengue, Aedes aegypti, which selectively breeds in water containers associ-ated with human habitations. These breeding sites can include water jugs,

221Dengue and dengue haemorrhagic fever

blocked drain spouts, decorative plant containers, discarded refuse that may retain water, and many other items associated with modern life (Gratz 1993a). A pattern of dengue transmission then became evident, especially in major cities of South East Asia, fi rst with increasingly frequent epidemics of classic dengue, then merging to continuous endemic transmission and appearance of DHS/DSS, initially sporadically but becoming more com-mon within the last 20 years, until these too are now endemic (Akiyama 1993, Gratz 1993b, Gubler 1993, Itoh 1993, Kojima 1993, Lam 1993). This pattern has been seen in varying degrees throughout much of tropical Asia, from the southern provinces of China to the west coast of India, and south to northern Australia and many Pacifi c island nations.

The same evolutionary pattern is now being repeated in the urban centres of Latin America (Gubler 1993, Halstead 1992, 1993a). In the 1960s, a hemisphere-wide Aedes aegypti eradication programme was in existence, and nearly succeeded in total eradication of the vector. How-ever, the decision was made to change the strategy from eradication to control. As a result, Aedes aegypti has now reinfested virtually all areas where it was once eliminated, and has even expanded to new habitats. As a result of this reinfestation, transmission of dengue has recently occurred in almost all parts of Latin America and the Caribbean (Pan American Health Organization 1993). It is currently limited to increasingly frequent epidemics of dengue fever, often coupled with sporadic cases or outbreaks of DHF/DSS. The pattern is, however, identical to that experienced in Asia during the 1950s and 1960s, and it is clear that DHF/DSS will become increasingly common in the years to come (Gubler 1993). Indeed, in 1994 a major outbreak of dengue and DHF occurred in north-eastern Brazil, and some experts have suggested that as many as 300 000 cases might have occurred.

In Africa, similar conditions exist, but reporting has been fragmentary, and there are no reliable estimates of the number of persons infected or the virus serotypes in circulation (Monath et al. 1974, Fagbami, Monath & Fabiyi 1977, Roche et al. 1983). As a typical example, however, in 1993 an outbreak of dengue occurred in Comoros, during which an estimated 60 000 cases occurred (Pan American Health Organization 1993).

Review of major studies and data available

Because of the variation in clinical presentation and lack of readily avail-able, inexpensive diagnostic tests, dengue fever is generally not formally reported. In some endemic countries, such as Thailand, DHF/DSS may be systematically recorded and reports of such surveillance are periodically published. Both WHO and the Rockefeller Foundation have monitored formal country reports of DHF/DSS, and these reports formed the basis of our estimates for incidence of disease (Halstead 1992, 1993b, Okabe 1993, Pan American Health Organization 1993). The published scientifi c literature is generally limited to reports of specifi c outbreaks and most


often does not offer a quantitative historical perspective of dengue or DHF/DSS. It is thus of limited usefulness in preparing burden of disease analyses. The problem is further complicated by the fact that dengue and DHF/DSS frequently occur as outbreaks or epidemics, often above a background of endemic transmission. Consequently, larger outbreaks may be recognized and reported; indeed, estimates of the number of cases may be infl ated, since many febrile diseases may be reported then as dengue. Between outbreaks, uncomplicated dengue may be merged with all other causes of febrile illness, and thus there may be general underreporting of the disease.

The most comprehensive cost-benefi t analysis of dengue and DHF/DSS was prepared by Shepard & Halstead (1993), and their estimates are incorporated into the present model whenever possible.

It is generally believed that millions of people suffer from dengue fever each year in Asia, Africa, the Pacifi c Islands, and the Americas (Pan American Health Organization 1993). It is virtually impossible, however, to document the global impact of dengue fever given the general absence of surveillance. For the purposes of this publication, we have focused on the more severe complications of dengue infection, DHF/DSS, and severe dengue fever cases. These conditions often require hospitalization and form the basis for the limited number of offi cially reported cases. Thus, our calculations are based on reported numbers of cases whenever possible. As these estimates refl ect only the most clinically severe cases, they almost certainly underestimate the true burden of disease. We also used average incidence rates whenever possible. These were usually determined based on the number of cases reported over the past decade. This is justifi ed since dengue and DHF are usually epidemic diseases, where the number of cases reported during an outbreak may well be 100 times greater than during inter-epidemic periods. Averaging over a 10-year period serves to compensate for these wide annual fl uctuations. The trend, however, in nearly all endemic areas, and especially in the Americas, is towards more frequent and larger outbreaks. Unfortunately, our estimates fail to refl ect this upward trend, and thus also lead to an underestimate of the true disease burden.

International Classification of Diseases

The specifi c categories related to dengue in the ninth and tenth revisions of the International Classifi cation of Diseases (ICD) are listed in Box 8.1.

Ninth revision

Uncomplicated dengue fever, also listed as breakbone fever, is coded as 061 in the ninth revision of the International Classifi cation of Diseases. Alternative codings could include 066: other arthropod-borne viral dis-eases, and 780.6: fever of unknown origin. Dengue haemorrhagic fever is coded as 065.4, with the following synonyms—Bangkok, Chikungunya,


mosquito-borne, Philippine, Singapore, South-East Asia and Thailand haemorrhagic fever—all sharing the same code, even though Chikungu-nya is both antigenically and taxonomically a completely different virus. Other classifi cations could result from coding based on clinical disease rather than viral etiology, and might include 785.5: shock, hypovolaemic without mention of trauma, and 448.9: haemorrhage, capillary, diseases of capillaries, other, and unspecifi ed.

Tenth revision

Classical dengue fever is coded as A90 in the tenth revision of the Inter-national Classifi cation of Diseases, and dengue haemorrhagic fever is classifi ed as A91. The codes for arthropod-borne viral fevers and viral haemorrhagic fevers are A90–A99. Related codes that might include dengue or dengue haemorrhagic fever include B33: other viral diseases, not elsewhere classifi ed, and B34: viral infection of unspecifi ed site. Codes based on clinical disease rather than specifi c etiology might include: D65: disseminated intravascular coagulation (defi brination syndrome); D69: purpura and other haemorrhagic conditions, especially D69.9: haemor-rhagic condition, unspecifi ed; R04: haemorrhage from respiratory passages, especially R04.8: haemorrhage from other sites in respiratory passages; R21: rash and other nonspecifi c skin eruption; R50: fever of unknown origin; R57: shock, not elsewhere classifi ed, especially R57.1: hypovolae-mic shock, and R57.9: shock, unspecifi ed; and H58: haemorrhage, not elsewhere classifi ed.

Estimated Burden of Dengue and Dengue Haemorrhagic Fever

The most comprehensive data available for dengue and DHF/DSS originate in South East Asia, in the Other Asia and Islands region. We have based our estimates on data from this region, then tried to estimate the situation in other areas by comparison with Other Asia and Islands.

Box 8.1 International Classifi cation of Diseases (ICD) codes related to dengue and dengue haemorrhagic fever

ICD 9 ICD 10

061 Uncomplicated dengue fever (also called breakbone fever)

A90 Classical dengue fever

A91 Dengue haemorrhagic fever

A90–99 Anthropod-borne viral haemorrhagic fevers and viral haemorrhagic fevers



Population at risk. Countries within the region were reviewed to exclude those nations not thought to be at risk of severe dengue/DHF. An estimate of 86.4 per cent of the regional population was considered at risk of this disease. Countries or areas considered not at risk included: Bhutan, Demo-cratic Peoples’ Republic of Korea, Mongolia, Nepal, Republic of Korea, and Hong Kong (total population 92 652 000). The age-specifi c and sex-specifi c population at risk was determined by multiplying the regional age-specifi c and sex-specifi c population estimates by 0.864.

Overall incidence rates. The average number of reported cases in the decade prior to 1992 was calculated based on statistics summarized in recent publications (Halstead 1993a, 1993b) or those obtained by Gratz (unpublished data). Those averages were used to determine country-specifi c annual incidence rates per 1000 population based upon population estimates for those countries.

These incidence rates were then used to estimate an overall incidence rate for the regional populations at risk of severe dengue/DHF. The over-all incidence rate among the population at risk was estimated to be 0.3 per 1000. Because of general underreporting and differences in reporting criteria, this estimate is likely to be low. Furthermore, it is based on a 10-year average, and in most parts of this region the incidence of dengue and DHF/DSS is increasing, another reason to suspect that the estimate is low. Nonetheless, there are no better estimates available for this or any other region, and we therefore have based our calculations on this estimate.

Sex-specifi c incidence rates. Published reports indicate that female cases of severe dengue/DHF exceed male cases by a ratio of 1.2:1.0 (Shepard & Halstead 1993). Thus, we estimated the contribution of male cases at an incidence rate of 0.27 per 1000, and females at 0.33 per 1000. These rates were used to determine the total estimated number of cases.

Age-specifi c incidence rates. Published reports indicate that approximately 95 per cent of severe dengue/DHF occurs in children under 15 years old (Shepard & Halstead 1993). Among these children, 75 per cent of cases are estimated to occur in the 5–14 year age group, and 25 per cent in the 0–4 year age group. We estimated the contribution from the remaining age groups as 3 per cent for 15–44 year, 1.5 per cent for 45–59 year, and 0.5 per cent for 60 years and over. We found no published reports to validate the estimates for adults.

Estimated number of cases. Age-specifi c incidence rates were used to estimate the age-specifi c number of cases by multiplying the fraction by the total sex-specifi c estimated number of cases.

Estimated number of deaths. Case fatality rates for dengue/DHF were


reviewed for countries within the region where information was avail-able. Case fatality rates clustered into two groups: those with rates that averaged 0.5 per cent, and those with rates that averaged 5.2 per cent. We included Malaysia, Singapore, Taiwan, Thailand and Viet Nam as “low threat areas”, and Bangladesh, Cambodia, Indonesia, Lao People’s Democratic Republic, Myanmar, Papua New Guinea, Philippines, and Sri Lanka, and all islands as “high threat areas”, even though reliable estimates of disease attributable to dengue/DHF do not exist for some of these countries. A total of 27.7 per cent of the at-risk population lived in “low-threat areas,” and 72.3 per cent in “high-threat areas.” We calculated the estimated number of age-specifi c and sex-specifi c cases in these areas by multiplying these factors by the total estimated number of cases. We did not have suffi cient information to divide populations into risk areas in the other regions examined. The number of deaths in “high-threat areas” is estimated by multiplying the estimated number of cases in that area by the average case fatality rate, 5.2 per cent. The number of deaths in “low threat areas” was estimated by multiplying the estimated number of cases in that area by the average case fatality rate, 0.5 per cent. These values were summed to estimate the total number of deaths for the region, and are shown in Table 8.1.

India

Population at risk. Based on very limited information presented at a meeting on dengue held in 1994 in Pune, India, and cosponsored by the National Institute of Virology, the Rockefeller Foundation and the World Health Organization, we estimated that roughly 80 per cent of the population of

Table 8.1 Estimates of the burden of dengue haemorrhagic fever, Other Asia and Islands

Sex and age (years)

Regional popula-tion (thousands)

Population at risk (thousands)

Estimated number of cases

Estimated number of deaths

Males0–4 43 763 37 811 19 002 7365–14 84 032 72 604 57 005 2 20815–44 160 825 138 953 2 400 9345–59 34 138 29 495 1 200 4660+ 20 208 17 460 400 15

Total 342 966 296 323 80 007 3 099

Females0–4 41 988 36 278 22 994 8915–14 80 217 69 307 68 983 2 67215–44 159 611 137 904 2 905 11245–59 35 090 30 318 1 452 5660+ 22 662 19 580 484 19

Total 339 568 293 387 96 818 3 750


India is at risk of infection with dengue/DHF (World Health Organiza-tion 1994c).

Overall incidence rates. We found no reliable estimates of dengue incidence in India; however, it was apparent from discussions during the meeting that the problem may approach or exceed the magnitude of that seen in the Other Asia and Islands Region. Consequently, we used the same estimate for overall incidence as applied for that region, 0.3 per 1000.

Sex-specifi c incidence rates. We used the same sex-specifi c incidence rates as used for the Other Asia and Islands Region.

Age-specifi c incidence rates. We used the same age-specifi c incidence rates as used for the Other Asia and Islands Region.


Estimated number of deaths. A presentation made at the meeting on den-gue indicated that there is a wide spread need for educational programmes for medical staff on the proper management of DHF/DSS patients (World Health Organization 1994c). Existing mortality rates attributable to DHF may be approximately the same as in areas considered as high threat in the Other Asia and Islands Region. We therefore used a case fatality rate of 5.2 per cent, realizing that additional information is clearly needed to form the basis for a more accurate estimate.

The number of deaths was estimated by multiplying the estimated num-ber of cases by the case fatality rate, 5.2 per cent. Estimates for the disease burden attributable to DHF in India are shown in Table 8.2.

China

Population at risk. Only the southern provinces of China are at risk for dengue/DHF; dengue does not occur in areas where hard freezes occur in winter. Consequently, we estimated that 10 per cent of the total population of China is at risk for dengue/DHF.

Overall incidence rates. The incidence of dengue/DHF in southern China is less than in India or the Other Asia and Islands Regions, but nonetheless thought to be substantial. We found no quantitative estimates of dengue/DHF incidence rates in China, so we estimated an incidence rate of 0.2 per 1000, somewhat less than that used for the Other Asia and Islands Region. One might suspect that the incidence in southern China would approximate that seen in adjacent areas of the Lao People’s Democratic Republic and Viet Nam.


Sex-specifi c incidence rates. We used the same ratio of sex-specifi c incidence rates as used for the Other Asia and Islands Region; thus the incidence rate for males was 0.18 per 1000 and for females 0.22 per 1000.

Age-specifi c incidence rates. We used the same age-specifi c incidence rates as for the Other Asia and Islands Region.


Estimated number of deaths. We used an intermediate case fatality rate of 3.7 per cent for the entire population at risk. The number of deaths was estimated by multiplying the estimated number of cases by this rate. These estimates are presented in Table 8.3.

Sub-Saharan Africa

Population at risk. There is very little quantitative information regarding the actual population at risk of severe dengue/DHF in Africa. Periodic reports have been published that clearly indicate that dengue viruses are present in many different parts of Africa, and recent outbreaks of dengue have occurred in Comoros and among United Nations personnel deployed to Somalia (Halstead 1992, World Health Organization 1993). Few sero-logical surveys have been attempted and interpretation of those done is hampered by the presence of other fl aviviruses, which cross-react with dengue in many serological tests. Dengue viruses are present, particularly around urban centres where Aedes aegypti may be abundant. Based on very Aedes aegypti may be abundant. Based on very Aedes aegypti

Table 8.2 Estimates of the burden of dengue haemorrhagic fever, India

Sex and age (years)





Males0–4 59 789 47 831 22 541 1 1725–14 101 752 81 402 67 624 3 51615–44 200 525 160 420 2 847 14845–59 47 567 38 054 1 424 7460+ 29 768 23 814 475 25

Total 439 401 351 521 94 911 4 935

Females0–4 56 679 45 343 25 714 1 3375–14 95 263 76 210 77 142 4 01115-44 183 242 146 594 3 248 16945–59 46 005 36 804 1 624 8460+ 28 924 23 139 541 28

Total 410 113 328 090 108 270 5 630


crude estimates, we considered that 20 per cent of the residents of Africa were at risk of dengue/DHF, even though we could locate no confi rmed record of DHF in sub-Saharan Africa.

Overall incidence rates. The limited information currently available indi-cates that dengue/DHF is less abundant than in India or the Other Asia and Islands Region. We estimated the incidence to be 0.1 per 1000, with little factual basis for this fi gure.

Sex-specifi c incidence rates. We used the same ratio of sex-specifi c incidence rates as for the Other Asia and Islands Region, thus we used an incidence rate of 0.09 per 1000 males and 0.11 per 1000 females.



Estimated number of deaths. We used a high case fatality rate of 5.2 per cent, based on the fact that the incidence rate is relatively low, thus giving clinicians little experience with the disease, and realizing that virtually no special training has been provided to clinicians in Africa for management of DHF/DSS. We used only a single case fatality rate for all of the Sub-Saharan Africa Region. The estimated number of deaths was calculated by

Table 8.3 Estimates of the burden of dengue haemorrhagic fever, China

Sex and age (years)





Males0–4 60 243 6 024 2 502 935–14 96 997 9 700 7 505 27815–44 306 305 30 631 316 1245–59 72 674 7 267 158 660+ 48 980 4 898 53 2

Total 585 199 58 520 10 534 390

Females0–4 57 946 5 795 2 866 1065–14 90 401 9 040 8 598 31815-44 284 078 28 408 362 1345–59 64 403 6 440 181 760+ 51 666 5 167 60 2

Total 548 494 54 849 12 067 446


multiplying the case fatality rate by the estimated number of cases. These estimates are presented in Table 8.4.


Population at risk. Dengue and DHF/DSS are rapidly expanding through-out Latin America and the Caribbean, closely following the reinfestation of most urban centres and many rural areas by the vector mosquito of dengue, Aedes aegypti. As a result, the general trend has been to increasing incidence of disease, especially over the past decade. Limited quantitative information is available to support specifi c country estimates, although the Pan American Health Organization has attempted to monitor dengue and DHF for more than a decade (Pan American Health Organization 1993). The most dramatic outbreak of dengue and DHF/DSS occurred in Cuba in 1981, primarily between the months of June and October, when 344 203 cases of dengue were reported, of which 116 151 were hospitalized (Kouri, Guzman & Bravo 1986). Of the hospitalized cases, 9203 were considered “serious,” and an additional 1109 were considered “very serious.” A total of 158 deaths were recorded (the case fatality rate was 1.5 per cent of serious and very serious cases, or 0.14 per cent of hospitalized cases). While Cuba has subsequently virtually eliminated Aedes aegypti mosquito populations, the dramatic potential impact of epidemic dengue or DHF on a nation’s health care system is nonetheless evident from these fi gures. Indeed, at the peak of the Cuban epidemic, approximately 10 000 cases were hospitalized per week, enough to swamp even the most sophisticated medical system. Considering the expanding dengue incidence throughout most of Latin America and the Caribbean in both urban and rural settings,

Table 8.4 Estimates of the burden of dengue haemorrhagic fever, Sub-Saharan Africa

Sex and age (years)





Males0–4 47 484 9 497 1 079 565–14 70 258 14 052 3 236 16815–44 103 764 20 753 136 745–59 20 308 4 062 68 460+ 10 508 2 102 23 1

Total 252 322 50 464 4 542 236

Females0–4 47 030 9 406 1 035 545–14 69 818 13 964 1 536 8015-44 106 257 21 251 2 338 12245–59 22 117 4 423 487 2560+ 12 730 2 546 280 15

Total 257 952 51 590 5 675 295


we have estimated that 60 per cent of the population of this region is at risk of severe dengue/DHF.

Overall incidence rates. While the incidence of dengue is less in Latin America and the Caribbean than in Asia, it is nonetheless signifi cant and increasing. From 1988 to 1992, an average of 102 162 cases of dengue fever were reported in the region. During that same period, an average of 2100 DHF cases were reported annually, with a mean of 31 deaths attributed to the disease (Pan American Health Organization 1993), as shown in Table 8.5.

Based on these reported rates, we have estimated the annual incidence of DHF to be 0.006 per 1000.

Sex-specifi c incidence rates. We used the same ratio of sex-specifi c incidence rates as for the Other Asia and Islands Region; thus the rate for males was 0.0056 per 1000 and for females 0.0063 per 1000.


Estimated number of cases. Although dengue fever is rapidly increasing in most countries of the region, DHF remains relatively uncommon, and thus we used the same annual incidence rate for all populations at risk.

Estimated number of deaths. We used a case fatality rate of 1.5 per cent based on the average number of deaths reported from 1988 to 1992. A summary of estimates for the population at risk, number of cases and deaths is found in Table 8.6.

Middle Eastern Crescent, Formerly Socialist Economies of Europe, and Established Market Economies

In these regions, dengue and DHF/DSS are generally limited to tourists travelling to and from endemic areas in other regions, although transmis-

Table 8.5 Reported cases of dengue fever, dengue haemorrhagic fever, and deaths attributable to dengue haemorrhagic fever in Latin America and the Caribbean, 1988 to 1992

Year Dengue fever Dengue haemorrhagic fever Deaths

1988 47 783 86 61989 89 138 2 682 331990 116 389 3 646 621991 155 543 1 760 311992 101 958 2 319 23

Average 102 162 2 099 31

Source: Pan American Health Organization (1993).


sion may exist in a few population centres. For example, in the Middle Eastern Crescent Region, there is growing evidence that active dengue transmission probably occurs in some locations. Nonetheless, the number of cases in these regions is relatively small, and no quantitative information exists upon which incidence estimates could be based.

Validity of incidence estimates

Clearly the estimate of incidence rates is the single most critical value in calculating the global burden of disease. Unfortunately, the data from which this estimate must be drawn, at least for dengue/DHF, are very weak. The incidence of dengue/DHF depends upon several factors, including the abun-dance of potential mosquito vectors, especially Aedes aegypti, the number of susceptible humans in the population at risk, and the presence of dengue viruses circulating in or introduced into those populations. Other factors, especially environmental and sociological, also infl uence estimates of the incidence of dengue/DHF. The fact that distinct viruses may cause dengue, the confusion among clinicians about what actually distinguishes dengue from DHF, and the limitations in availability of laboratory confi rmation, all contribute to the ambiguity of incidence estimates. Further, dengue and DHF tend to occur in epidemics, so that tremendous numbers of cases may occur during one period, followed by subsequent years when relatively few cases may be recorded. Finally, as with all diseases, the estimates are only as good as the surveillance and reporting systems from which the estimates are drawn. In general, for dengue and DHF, these are not well developed. Between outbreaks, there is likely to be underreporting, dengue

Table 8.6 Estimates of the burden of dengue haemorrhagic fever, Latin America and the Caribbean

Sex and age (years)





Males0–4 28 721 22 977 236 25–14 52 124 41 699 707 715–44 104 286 83 429 30 045–59 22 249 17 799 15 060+ 14 231 11 385 5 0

Total 221 611 177 289 993 10

Females0–4 27 676 22 141 267 45–14 50 744 40 595 800 1215-44 104 085 83 268 34 145–59 23 355 18 684 17 060+ 16 824 13 459 6 0

Total 222 684 178 147 1 122 17


being grouped with undifferentiated febrile illness or haemorrhagic diseases of undetermined origin. During outbreaks, there may be overreporting, since all febrile illnesses may be reported as dengue, and any febrile disease with bleeding manifestations as DHF.

To overcome these potential problems, we have concentrated our efforts at estimation on incidence in the Other Asia and Islands Region, where dengue and DHF are best known clinically and historically, and where we feel that the reporting systems are most reliable. To overcome the large annual variations in incidence of dengue and DHF, we have attempted to average the incidence rates for the most recent 10-year period for which complete information is available. The actual number of reported DHF cases by selected countries are presented in Table 8.7. We have attempted to calculate the overall regional incidence rates by taking into account the specifi c rates for those countries for which information is available, and estimating for other countries in the region where DHF is known to occur, but no published information on incidence rates is available. Whenever possible, we used these same techniques in the other areas considered; however, the data are generally much less reliable for the other regions. Consequently, we used the rate for the Other Asia and Islands Region as a reference point, then determined whether other regions had greater, equal, or lower incidence rates, based on informal reporting and published information from recent outbreaks. The gross estimates are summarized in Table 8.8.

We suspect that the fi nal product of this exercise grossly underestimates the true burden of DHF. The question that remains to be answered is the order of magnitude that this underestimation represents. Attempts are in progress to improve dengue diagnosis and surveillance in hopes of generating more accurate information on the true global burden of this increasingly important disease.

In reviewing the data available to estimate incidence, a striking trend is consistently seen. Dengue and DHF are increasing in virtually every location where they are found, and are rapidly appearing in new areas, following infestations by the vector mosquito, Aedes aegypti. This rapid increase is most notable in the Other Asia and Islands Region, where DHF has become endemic and a constant threat in many countries, and in Latin America and the Caribbean, where dengue epidemics are increasingly common and DHF is seen with increasing frequency. Given that the esti-mates for incidence were based on 10-year averages, they are most likely underestimates of the true incidence of disease. The global burden of this disease is likely to be much greater in the coming years.

Other considerations in estimating disease burden

The focus of this discussion has been on severe dengue and DHF, condi-tions likely to require hospitalization and thus be captured by a national surveillance system. Uncomplicated dengue fever has not been considered although it is acknowledged that there are many more dengue fever patients


Tab

le 8

.7

D

engu

e ha

emor

rhag

ic fe

ver

repo

rted

, sel

ecte

d co

untr

ies,

Oth

er A

sia

and

Isla

nds,

1982

–199

2

Year

Indo

nesia

Mal

aysia

Mya

nmar

Philip

pine

sSi

ngap

ore

Thai

land

Viet

Nam

Case

sD

eath

sCa

ses

Dea

ths

Case

sD

eath

sCa

ses

Dea

ths

Case

sD

eath

sCa

ses

Dea

ths

Case

sD

eath

s

1981

5 9

0923

148

614

1 52

490

123

813

30

25 6

4119

435

323

408

1982

4 6

6525

53

052

361

706

4930

5 3

121

60

22 2

5015

939

806

361

1983

13 8

7549

179

010

2 85

683

1 68

413

020

52

30 0

2223

114

9 51

91

798

1984

12 7

1038

270

25

2 32

339

2 54

5 8

986

069

597

451

30 4

9836

819

8513

875

460

384

112

666

134

2 09

621

012

62

80 0

7654

245

107

399

1986

12 7

1060

01

403

92

191

111

687

30

354

029

030

206

46 2

6651

119

8722

765

1 03

92

025

87

292

222

859

27

436

017

0 63

089

635

4 51

71

566

1988

47 5

731

527

1 44

82

1 18

165

2 92

2 6

824

50

26 9

2618

985

160

826

1989

10 3

6246

42

401

141

196

52 3

05 1

494

40

69 2

0428

040

205

289

1990

13 0

4345

82

071

386

318

182

588

271

733

411

3 85

542

237

569

255

1991

21 1

2057

874

139

8 05

530

51

865

202

179

643

782

119

94

630

403

1992

17 6

2050

964

925

1 51

440

n/a

n/a

2 87

84

n/a

n/a

51 0

4027

1

Tot

al19

6 22

706

994

16 1

5221

138

822

1 37

213

979

654

9 53

518

068

1 01

33

689

1 00

9 64

07

455


for each case of DHF. Consequently, the nearly half a million cases of DHF estimated here are likely to refl ect 5–50 million or more dengue infections annually. Certainly in epidemic years, this could well be an underesti-mation. The cost of uncomplicated dengue is perhaps most noticeable among the adult population, where the disease is more often clinically apparent, frequently leading to acute illness of about a week’s duration, and occasionally with prolonged convalescence. Those at greatest risk are residents of areas recently infested with vector mosquitoes and exposed for the fi rst time as adults to dengue, as is happening now in many parts of Latin America, and travellers (including deployed military personnel, business people, tourists and others). No attempt has been made to quantify either the economic or health impact of dengue on these groups, but it is undoubtedly substantial and growing.

Risk factors

Risk factors for dengue and DHF are primarily those associated with the potential to be fed upon by infected mosquitoes. Because the primary vector feeds mostly during daylight hours, and is well adapted to the urban environment, the socioeconomic conditions that favour the spread of other vector-borne disease, such as malaria, are not as important with dengue. Certainly lower-income neighbourhoods may be at increased risk of infection, especially if litter and refuse that may retain suffi cient water to support mosquito larval development are abundant; however, this mos-quito species breeds equally effi ciently in fl ower pots and other ornamental containers that hold water, and may be abundant in any area, including middle-income or upper-income neighbourhoods, or in public places such as schools and parks. This, coupled with its day-biting activity, means that people may easily be exposed to dengue-infected mosquitoes during their daily travels, even though their personal dwellings have screens and they live in a “nice” neighbourhood.

A second major risk factor is prior infection with a dengue virus, since heterologous anti-dengue antibodies may enhance dengue infection and predispose an individual to much greater risk of DHF on subsequent infec-tion. Similarly, maternally-acquired antibodies, as titres wane and are no longer able fully to inactivate dengue virus, place infants at increased risk

Table 8.8 Crude estimate for the global burden of disease attributable to dengue haemorrhagic fever, 1994

Region Cases Deaths

Other Asia and Islands 180 000 7 000India 205 000 11 000China 23 000 1 000Sub-Saharan Africa 11 000 600Latin America and Caribbean 3 000 100

Total 422 000 19 700


of antibody-enhanced dengue infection leading to increased risk of DHF. Other risk factors include the human population density, and thus the availability of susceptible individuals to sustain transmission, residence in tropical environments, where vector species survive best, and residence in an area where infected travellers may introduce the virus and precipitate epidemic transmission.

The risk of dying from dengue or DHF depends to a large extent on the skills of local attending physicians and nurses. Properly trained and experienced health care professionals can expertly manage critically ill patients and reduce mortality rates to below 1 per cent; however, those not familiar with the disease may fi nd mortality rates of 5 per cent or greater among their seriously ill patients.

Other diseases

Two other vector-borne diseases frequently occur under conditions similar to those which support dengue virus transmission: yellow fever and Chi-kungunya fever. Yellow fever is well known as a historical scourge of the tropics; thousand of individuals died, especially in the temperate and tropi-cal zones of the Americas, often seriously limiting national development projects, as was the case with the Panama Canal. What is often overlooked today is the fact that the same conditions that originally supported urban yellow fever transmission in the Americas are once again developing, with widespread and abundant populations of vector mosquitoes, Aedes aegypti, and large, susceptible human populations. All that is needed to initiate urban transmission is the introduction of infected humans into a situation where they may be fed upon by vector mosquitoes, and an outbreak could ensue. Currently, active yellow fever transmission is limited to endemic areas of sub-Saharan Africa and northern South America; however, with the frequency of air travel to and from virtually all parts of the world, it is not inconceivable that an individual could be infected in a remote endemic area, and shortly thereafter be fed upon by potential vector mosquitoes in a major urban centre far removed from the site of original infection.

Chikungunya is not as well known as yellow fever, but it too is transmit-ted by Aedes aegypti, and may cause massive outbreaks in urban settings. This virus is not known to cause fatal human infection, but it does cause a serious febrile illness similar to dengue fever, which may incapacitate infected individuals for about a week. Large epidemics have been reported in India, Indonesia and the Philippines, and the virus is known to be pres-ent in much of Africa.

Cost-effectiveness of interventions

At present, countries where dengue and DHF are endemic spend millions of dollars on vector control. This includes direct health care costs for treatment and indirect costs resulting from lost tourism and lost work.


The latter arises not solely in relation to infected individuals; since those infected are often children, parents may have to stop working while they care for their sick child. The average hospital stay for DHF patients is 5 to 10 days. Shepard & Halstead (1993) have summarized recent cost estimates for dengue epidemics and found the total for direct health care interventions, associated vector control activities, and indirect costs to be from several million to over US$100 million per outbreak. Unfortunately, the frequency of such outbreaks is increasing as new areas are infested with Aedes aegypti.

Future research priorities

Substantial research efforts are required to manage the problem of dengue/DHF. An immediate need exists for expanded medical training to teach physicians and nurses the proper management of DHF patients, especially in areas where the disease is just emerging and clinicians have little expe-rience in managing these seriously ill patients. Signifi cant reductions in the mortality rates in endemic areas can be realized with minimal costs through such efforts, and clearly this should be among the highest priority activities in dengue control efforts. Likewise, support is required in the clinical laboratory to ensure that dengue/DHF is properly and promptly diagnosed. Again, this can be accomplished with relatively little investment since common laboratory techniques are used, and all that may be required is provision of the appropriate diagnostic reagents. Accurate diagnosis should then feed into a well-organized surveillance and reporting system that could allow health managers to monitor disease trends and initiate outbreak control efforts at the fi rst indication of a pending epidemic.

Several organizations are attempting to develop a vaccine for dengue/DHF. A tetravalent vaccine would be especially benefi cial. Since humans represent the primary amplifying host of these viruses, a fully protective vaccine that was widely administered could interrupt transmission and signifi cantly reduce the risk of infection. This is an especially challenging task, however, since four distinct viruses may cause the disease, and the confounding factor of immune-enhancement where there is partial pro-tection, as would be elicited in a vaccine against only one, two or three of the four dengue viruses, may in fact place individuals at greater risk of DHF than unvaccinated persons. A live, attenuated, tetravalent vaccine for dengue viruses has entered into Phase 2 clinical trials, and appears to be safe and immunogenic.

At present, the only avenue for effective prevention of dengue/DHF is through vector control. Unfortunately, sustained vector control is costly, and as a consequence, frequently limited in success. Research is needed into better ways of controlling Aedes aegypti populations. These must not only be economically feasible, but also sustainable. Further, they need to take into account the movement of large segments of the populations from rural areas to urban centres in many affected countries. Current control efforts


are often directed towards routine pest management, and may include community involvement coupled with emergency insecticide applications when outbreaks are recognized. These efforts have met with marginal suc-cess, and it is clear that there is room for improvement. Historically, Aedes aegypti was controlled by highly regimented mosquito control programmes aegypti was controlled by highly regimented mosquito control programmes aegyptithat involved both source reduction and effective use of insecticides (Soper et al. 1943). Such programmes are, however, extremely expensive and dif-fi cult to maintain. Today, some countries have succeeded in controlling vector mosquito populations using these techniques (for example, Cuba after the 1981 outbreak), but in most cases countries have relied on insec-ticide applications after outbreaks are recognized, generally with much less success. It is clear that innovative measures are needed, which will be identifi ed only through multidisciplinary research efforts that consider both the sociological aspects of the local conditions leading to vector breeding, and of the biology of the vector mosquito itself.

Equally challenging are the characteristics of the viruses that cause dengue. Wide variations in the pathogenicity of dengue viruses have been observed. Some strains of the same serotype may cause outbreaks with little or no serious illness, while others may elicit signifi cant numbers of severe or fatal DHF cases. The molecular basis for this variation must be determined. Fortunately, the complete nucleotide sequence is now avail-able for strains of all four dengue serotypes, and infectious clones have been produced for some serotypes. These tools should help in the future defi nition of virulence factors of dengue viruses.

Conclusions

Dengue, and especially DHF/DSS, are signifi cant global diseases that are increasing in incidence and economic importance. Four distinct viruses may cause classic dengue fever, and while infections with one serotype leads to lifelong homologous protection, there is no lasting cross-protec-tion from other dengue serotypes; indeed, subsequent dengue infections are associated with increased risk of DHF/DSS. All four dengue viruses are transmitted primarily by the urban mosquito vector, Aedes aegypti, a species that is well adapted to life in close association with humans, and one whose distribution and abundance is rapidly expanding throughout tropical and subtropical cities, suburbs and villages of the world. Vector control is expensive and ineffi cient, and as a result, conditions are prime for epidemic dengue virus transmission in these areas. The result is that today much of the world’s population is at risk of dengue, either as an immediate threat in areas where the primary vector is abundant and dengue viruses are endemic, or to travellers to these areas.

We have attempted to estimate the global burden of disease attribut-able to severe dengue and DHF/DSS, based on reported numbers of cases. The greatest number of cases and deaths are thought to occur in India and the Other Asia and Islands Region; however, the fastest growing


region in terms of dengue fever is the Latin America and the Caribbean Region. Little information is available to document the burden of disease for the Sub-Saharan Africa Region. These analyses conclude that nearly half a million cases of dengue suffi ciently severe to reach formal report-ing occur annually. Of these, approximately 20 000, or about 4 per cent, end in death. These values clearly underestimate the true impact of severe dengue because:

they are based on reported cases only, and this information is fragmen-tary and incomplete;

they are based on annual estimates averaged over a decade and thus minimize the impact of the increasing incidence of DHF/DSS in some regions;

in some regions, little information is available on which to base any estimate.

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Intestinal nematode infectionsDAP Bundy, MS Chan, GF Medley, D Jamison, L Savioli

Chapter 9

Introduction

Effective control of the major intestinal nematode infections of humans involves relatively low-cost interventions (Savioli, Bundy & Tomkins 1992). Informed decisions about the need for investment in control pro-grammes, however, also require useable estimates of the scale of morbidity (Guyatt & Evans 1992).

Direct estimates of morbidity would be preferred, but the currently available techniques suffer from major limitations, examples of which follow. Active case detection can be useful at the local level (Pawlowski & Davis 1989), but demands a level of resources that makes its widespread use impractical. Passive case detection, which has more appropriate resource demands (Guyatt & Evans 1992), is unreliable for geohelmin-thiases because the symptoms are non-specifi c; in one prospective study of trichuris colitis, only 2 per cent of cases observed in the community had self-presented to the local health services (Cooper, Bundy & Henry et al. 1986). Furthermore, there is increasing evidence that the most com-mon and potentially important consequences of infection are insidious effects on nutritional status (Nesheim 1989, Tomkins & Watson 1989) and on physical and intellectual development (Stephenson 1987, Cooper et al. 1990, Nokes et al. 1992a, 1992b). Such effects are unlikely to result in self-presentation to passive case detection clinics, and will be grossly underestimated by survey procedures based on the active detection of clinical signs. This is especially so, as the infections are ubiquitous; both passive and active detection are usually based on deviations from local norms, which may be greatly infl uenced by the infections.

There are no direct estimates of the community morbidity caused by intestinal helminths. Instead, most studies have focused on estimating the prevalence of infections, only a fraction of which will be associated with disease. Perhaps the fi rst estimate of the global prevalence of intes-tinal nematode infections was presented by Stoll (1947). His technique


of extrapolation from survey data has proven robust and has been used to derive many of the more recent estimates which suggest that there are some billion infections with Ascaris lumbricoides and only slightly fewer infections with hookworm (both Necator americanus and Ancyclostoma duodenale) and Trichuris trichiura (World Health Organization 1987, Crompton 1988, 1989, Bundy & Cooper 1989). In the absence of reliable procedures for estimating disease directly, estimates of burden have been based on extrapolation from the infection prevalence data to provide an estimate of the proportion of infections that are likely to be associated with disease (Warren et al. 1993, Chan et al. 1994). This requires a careful and conservative approach because of the ubiquity of infection; extrapolat-ing from such large numbers has the consequence that even small errors in estimating the disability attributable to individual cases can result in considerable inaccuracy in estimating the total burden. Because of the inherent potential for error in the use of any extrapolation procedure, the major aims of this chapter are to encourage independent scrutiny of the methodology and to highlight areas that particularly warrant further empirical study.

This chapter builds on the studies of Chan et al. (1994) and Warren et al. (1993), and attempts to provide improved estimates of burden of disease based on extrapolation from observed estimates of prevalence of infection. The size of the population at risk of disability is estimated using epidemiological methods developed to describe the relationship between prevalence and mean intensity, and between intensity and potential morbid-ity (Guyatt et al. 1990, Lwambo, Bundy & Medley 1992), but modifi ed to incorporate the heterogeneity between communities and age classes (Chan et al. 1994). The disability per case at risk is estimated using pro-cedures described elsewhere in this series (Murray & Lopez 1996), and the regional and global burden of disease is obtained by extrapolation from these estimates.

Basic biological characteristics of intestinal nematodes

The analyses presented here focus on the four species of intestinal nema-tode that are of circumglobal distribution and occur at high prevalence: Ascaris lumbricoides, Trichuris trichiura, and the two major hookworm species, Necator americanus and Ancylostoma duodenale.

A. lumbricoides is the large roundworm (15 cm) and lies free in the human duodenum where it feeds on lumenal contents (see Crompton, Nesheim & Pawlowski (1989) for further details of the biology of this parasite). Like all the other nematodes considered here, the worms are dioecious, which is to say that they exist as male and female. The female produces some 100 000 eggs per day which pass out in the faeces of the host and embryonate externally at a rate determined by local environmental factors. The eggs hatch on ingestion, releasing a larva that undergoes a

245Intestinal nematode infections

tissue migration involving the cardiovascular and pulmonary systems. The larva moults as it migrates and ultimately is coughed up from the lungs, swallowed, and becomes established as the adult in the small intestine. The cycle from egg deposition to female patency, when the female is able to produce eggs, has a duration of some 50 days.

T. trichiura, the human whipworm, is a much smaller worm (25 mm) and inhabits the colon (Bundy & Cooper 1989). The anterior two-thirds of the worm is thin and thread-like and is laced through the mucosal epithelium, upon which the worm is believed to feed, leaving the blunt posterior projecting into the colonic lumen for excretion and oviposition. The female produces some 2000 eggs per day which pass out in the host faeces and embryonate externally. The infectious eggs hatch on ingestion and undergo a specifi cally local migration, via the crypts of Lieberkühn to the mucosal surface. The development cycle takes some 60 days.

The two major hookworm species, which are of similar magnitude to the whipworm, inhabit the small intestine, where they attach to villi with biting mouthparts (Schad & Warren 1990). The worms feed on host blood and move frequently to new sites, leaving multiple, bleeding petechial haemorrhages on the mucosal surface. A. duodenale is believed to be more voracious, consuming some 0.14–0.40 ml of blood per day compared with 0.01–0.10 ml by N. americanus. The eggs pass out in host faeces and embryonate. Unlike the roundworm and whipworm, the eggs hatch externally releasing a mobile infective larva that actively infects the human host by dermal penetration. A. duodenale is also able to infect by the oral route, and there is evidence for vertical transmission of this species either transplacentally or in maternal milk. Having entered the host, the larva undergoes a tissue migration to the lungs and is coughed up and swallowed to moult to the adult in the small intestine. The cycle takes approximately 60 days for both species. A. duodenale is apparently able to extend this period by arresting development to the adult stage; a mechanism which may allow avoidance of seasonally hostile external conditions.

Basic epidemiological characteristics of intestinal nematodes

Understanding the epidemiology of helminth infections requires a fun-damentally different approach from that required for all other infectious agents. Each worm’s establishment in a host is the result of a separate infection event, and the number of infective stages shed (the infectious-ness of the host) is a function of the number of worms present. In popu-lation dynamic terms this implies that the individual worm is the unit of transmission for helminths, while the individual host is the unit for microparasites (Anderson & May 1982). The size of the worm burden (the intensity of infection) is therefore a central determinant of helminth transmission dynamics, and is also the major determinant of morbidity since the pathology is related to the size of the worm burden, usually in


a non-linear fashion (Stephenson 1987, Cooper & Bundy 1987, 1988). Since the size of the worm burden varies considerably between individu-als, and infection implies only that worms are present, a population of “infected” people will exhibit considerable variation in the severity of disease manifestations. The intuitive assumption that all infections are equal may help to explain the historical confusion over the pathogenicity and public health signifi cance of helminth infection (Bundy 1988, Cooper and Bundy 1989). From these considerations it is apparent that an under-standing of helminth epidemiology centres around an understanding of the patterns of infection intensity.

Worm burden distributions

Worm burdens are neither uniformly nor randomly distributed amongst individuals, but are highly over-dispersed such that most individuals have few worms while a few hosts harbour disproportionately large worm bur-dens. This pattern has been described for Ascaris lumbricoides (Croll et al. 1982), both species of hookworm (Schad & Anderson 1985) and Trichuris trichiura (Bundy et al. 1985). Most studies suggest that approximately 70 per cent of the worm population is harboured by 15 per cent of the host population. These few heavily infected individuals—the “wormy persons” described by Croll & Ghadirian (1981)—are simultaneously at highest risk of disease and the major source of environmental contamination.

Studies of reinfection suggest that individuals are predisposed to a high or low intensity of infection; the size of the worm burden reacquired after successful treatment is positively associated with the intensity of infec-tion before treatment. This association has been shown for all the major geohelminths (Anderson 1986, Elkins, Haswell-Elkins & Anderson 1986, Bundy & Cooper 1988, Holland et al. 1989), and persists over at least two reinfection periods (Chan, Kan & Bundy 1992). Longitudinal studies of T. trichiura (Bundy et al. 1988) and A. lumbricoides (Forrester et al. 1990) confi rm that this positive association refl ects a direct relation between the rate of reinfection and initial infection status. Thus in an endemic community it appears that there is a consistent trend for an individual to have an above (or below) average intensity of infection. This trend is more apparent in children with A. lumbricoides (Haswell-Elkins, Elkins & Anderson 1987) and T. trichiura (Bundy & Cooper 1988) infection, and more apparent in adults with Necator americanus (Bradley & Chandiwana 1990) infection, perhaps refl ecting the different age-intensity patterns of these species. This pattern is also apparent at the family level (Chai et al. 1985, Forrester et al. 1988, 1990, Chan, Bundy & Kan 1994).

Worm burden and age of host

Over-dispersed distributions, where the highest intensity infections are aggregated in a few individuals of infection intensity, are observed in the community as a whole and also in individual age-classes. The degree of over-dispersion, however, shows some age-dependency. In hookworm


infection the distribution becomes more over-dispersed in adults (Bradley & Chandiwana 1990), while in A. lumbricoides and T. trichiura there is evidence that dispersion increases to a peak in the child age groups (Bundy et al. 1987b) and then declines in adults (Chan, Kan & Bundy 1992). These changes refl ect age-specifi c trends in the proportion infected (the size of the zero class in the frequency distribution) and in the mean intensity of infection (the mean of the distribution).

The age-dependent pattern of infection prevalence is generally rather similar amongst the major helminth species, exhibiting a rise in childhood to a relatively stable asymptote in adulthood. Maximum prevalence is usually attained before 5 years of age for A. lumbricoides and T. trichiura, and in young adults with hookworm infection. In A. lumbricoides there is often a slight decline in prevalence during adulthood, but this is less common with the other major nematode species.

Prevalence data indicate the proportion of individuals infected and do not provide a simple indication of the number of worms harboured. The marked non-linearity of this relationship is a direct statistical consequence of the over-dispersed pattern of intensity (Guyatt et al. 1990). If worm burdens were normally distributed, there would be a linear relationship between prevalence and intensity (Anderson & May 1985). This is an important relationship since it is central to the method of extrapolation from infection prevalence to infection intensity described in this chapter. It is worth emphasising, therefore, that the relationships are fi rmly based on empirical studies of the major species of intestinal helminths (Guyatt et al. 1990, Lwambo et al. 1992, Booth 1994).

The lack of simple correspondence between prevalence and intensity has the consequence that the observed age-prevalence profi les provide little indication of the underlying profi les of age-intensity. For most hel-minth species the initial rise in intensity with age closely mirrors that of prevalence but occurs at a slightly slower rate. Maximum intensity occurs at a host age which is parasite species-specifi c and dependent on parasite longevity, but independent of local transmission rates (Anderson 1986). For A. lumbricoides and T. trichiura maximum worm burdens occur in human populations at 5–10 years of age and for hookworms at 20–25 years.

The most important differences in the age-intensity profi les of these species become apparent after peak intensity has been attained. A. lumbri-coides and T. trichiura both exhibit a marked decline in intensity to a low level which then persists throughout adulthood. Age-profi les based on egg density in stool had suggested that there was considerable variation in the patterns seen in hookworm (Behnke 1987, Bundy 1990), but it now appears, from studies where burdens have been enumerated by anithel-minthic expulsion, that the intensity attains a stable asymptote, or rises marginally, in adulthood (Pritchard et al. 1990, Bradley et al. 1992).

Thus, for those species with convex age-intensity profi les, but asymp-totic age-prevalence profi les, a similar proportion of children and adults are infected but the adults have substantially smaller worm burdens. With


hookworm infection, where both prevalence and intensity are asymptotic, more adults are infected and they have larger worm burdens.


For most helminthiases, the relationship between infection and disease is likely to be non-linear and complex. If we accept, for the moment, the simple premise that only heavy worm burdens cause disability, then it is apparent that disability will have an age-dependent distribution, since intensity is age-dependent, and also that disability will have an over-dis-persed pattern even within the susceptible age-classes. The relationship is further complicated by the non-linear relationship between the severity of disease and the intensity of infection, and by the interaction between symptomatology and the chronicity of infection. Helminthic infection does not inevitably lead to disease: a failure to appreciate this has led to appar-ently contradictory results from morbidity studies and may be the major contributor to the under-recognition of the public health signifi cance of helminthiasis (Cooper & Bundy 1987, 1988).

An essential prerequisite, therefore, to assessing the global burden of disease is the estimation of the sub-population of the infected population that has a suffi ciently large worm burden to put them at risk of disability. This requires some method of relating prevalence of infection data, which are available from empirical studies in all geographical regions, to intensity of infection data, which are not. In this section we describe procedures for extrapolating intensity from prevalence survey data, and for partitioning the risk of disability.

Worm burdens and morbidity

There is a general acceptance of the simple view that very intense infection results in illness, a view that refl ects both clinical experience of overwhelm-ing infection and, perhaps equally importantly, an atavistic repugnance at the insidious invasion of the body by large numbers of worms. Such extremes of infection result in the severe anaemia of necatoriasis and the intestinal obstruction of ascariasis (Stephenson 1987), and the chronic colitis of classical trichuris dysentery syndrome (Cooper & Bundy 1988). That helminth morbidity is dependent on infection intensity is, from this perspective, uncontroversial. An understanding of the pattern of the rela-tionship between infection intensity and clinical signs has proven more elusive. This appears to be the result of two main factors.

First, intensity and pathogenesis are non-linearly related. Studies of the anaemia associated with hookworm infection indicate that there is a disproportionate reduction in plasma haemoglobin concentration after some threshold worm burden is exceeded. Although profound anaemia is associated with thousands of worms, clinically signifi cant anaemia can be induced by a few hundred worms, the precise threshold depending on the host’s iron status (Lwambo, Bundy & Hedley 1992). Note that this


occurs despite the constant per capita blood loss attributable to hookworm feeding (Martinez-Torres et al. 1967), which might intuitively be expected to give a linear relationship between burden and anaemia. Studies of pro-tein-losing enteropathy in trichuriasis also indicate a non-linear relation-ship with worm burden (Cooper et al. 1990). The rate of gut clearance of a-1-antitrypsin at fi rst rises rapidly with increasing worm burden to a threshold and rises more slowly thereafter. The relationship is markedly non-linear. This implies that signifi cant intra-lumenal leakage of protein can occur with T. trichiura burdens of a few hundred worms. The clinical consequences of this loss will be determined by the nutritional and dietary status of the host and by the chronicity of infection (Cooper, Bundy & Henry 1986). In one study, children with the classical Trichuris Dysentery Syndrome had all experienced mucoid dysentery and rectal prolapse for more than three years (Cooper & Bundy 1987, 1988).

The second reason for the lack of understanding of the relationship between intensity and disease is the diffi culty of measuring and attributing morbidity. This is in part the classical epidemiological problem of iden-tifying specifi c morbidity in an endemic population subjected to multiple insults (Walsh 1984). It is exacerbated for helminth infection, however, by the absence of pathognomonic signs in moderate, but clinically signifi cant, infection. This problem has been addressed by intervention trials using specifi c antihelminthic therapy. Such studies have shown, for example, significant improvements in linear growth after treatment of moder-ately infected and stunted children with hookworm, A. lumbricoides or T. trichiura infection (Stephenson 1987, Stephenson et al. 1990, Cooper et al. 1990). Even more subtle consequences of infection are suggested by recent double-blind placebo trials, which show signifi cant improvement after antihelminthic treatment in the cognitive ability of school-children moderately infected with T. trichiura (Nokes et al. 1991, 1992a). These results suggest that even moderate helminthic infection may have insidious consequences that are unlikely to be attributed to helminthiasis in public health statistics. In one study of a village population with hyperendemic geohelminthiasis (Cooper, Bundy & Henry 1986), only 2 per cent of actual morbidity had been reported to the health authorities.

Some insights into the relationship between infection and disability can be provided by data analysis (Guyatt et al. 1990, Lwambo, Bundy & Med-ley 1992). Empirical studies can provide estimates of the threshold number of worms associated with risk of disability (see above). Then, using models which describe the empirical relationship between infection intensity and prevalence, it is possible to estimate the proportion of individuals in whom the threshold worm burden is exceeded (and are thus are likely to suffer disability) at a given prevalence of infection. Non-linear relationships of this form have been shown in studies of schistosome infections, for which adequate country based morbidity data are available (Jordan & Webbe 1982). There is a need to obtain similar data for intestinal nematodes, but this is currently confounded by the diffi culties in estimating morbidity


directly for these infections. One important conclusion of this analysis, however, is that the threshold need not be precisely defi ned, since the form of the relationship between infection and disease is relatively insensitive to the threshold value, provided the value is relatively large (> 20 worms).

These analyses indicate that the proportion at risk of disability increases dramatically as infection prevalence rises. For example, if 25 A. lumbri-coides worms are associated with disease, then 20 per cent of the popula-tion will be at risk at an infection prevalence of 80 per cent, and less than 2 per cent at an infection prevalence of 70 per cent. It is worth noting that both these infection prevalences could reasonably be considered to be high, which may help explain why studies of helminth morbidity in “high” prevalence areas often reach very different conclusions about the public health signifi cance of helminthiasis (for example, Keusch 1982).

The relationships described here form the basis for the extrapolation procedure developed in this chapter. This procedure involves the use of infection prevalence survey data from individual countries to give an estimate of regional and global prevalence of infection. Empirical data are then used to estimate the fraction of this infected population which is at risk of disability. The following sections describe this procedure and discuss the validity of its assumptions.

Estimation of risk of disability from infection prevalence data

The risk of disability is estimated on the basis of the relationship between worm burden and prevalence of infection. The frequency distribution of worm burdens between individuals has been consistently shown to be highly over-dispersed. Within a community, the majority of people have few or no worms and a few people have very high worm burdens. Observed distributions can be represented empirically by a negative binomial distri-bution (Anderson & Medley 1985, Guyatt et al. 1990, Lwambo, Bundy & Medley 1992, Bundy & Medley 1992). This theoretical distribution has two parameters, the mean worm burden, m, and the aggregation parameter, k (see Anderson and Medley, 1985 for explanation of this parameter). General values used in this study are k = 0.54 for A. lumbricoides (Guyatt et al. 1990), k = 0.23 for T. trichiura (Booth 1994) and k = 0.34 for hook-worms (Lwambo, Bundy & Medley 1992). These values are estimated from empirical data from fi eld surveys that estimated the distribution of intensity in human populations.

The basis for estimating potential disability is that a) the risk of dis-ability is higher in individuals with higher worm burdens and b) there is some threshold worm burden above which disability is more likely to occur (Table 9.1). The proportion of the population with worm burdens higher than this threshold can then be estimated from the negative bino-mial distribution (Guyatt & Bundy 1995, Lwambo, Bundy & Medley


1992, Medley, Guyatt & Bundy 1993). This approach is necessarily an approximation, since the effects of a given worm burden on an individual will be modifi ed by that individual’s condition (e.g. nutritional status and concurrent infections) and the chronicity of the infection.

Studies indicate that developmental effects of infection (e.g. cognitive and growth defi cits) occur at lower worm burdens than the more serious clinical consequences. We therefore use two sets of thresholds for each species, where the lower threshold corresponds to a higher estimate of potential disability from cognitive and growth defi cits. These thresholds are shown in Table 9.1. The thresholds for A. lumbricoides and T. trichi-ura correspond to those given by Chan et al. 1994. The thresholds for hookworm have been adjusted downwards. This refl ects the analyses presented by Crompton & Whitehead (1993), and the observation that the thresholds reviewed by Lwambo, Bundy & Medley (1992) apply to adults rather than children, as had been assumed in the previous calcula-tions. Because children are smaller than adults, it is assumed that a similar worm burden is associated with more morbidity in children.

There is a lack of data on the relationship between disability threshold and age. However, since a given worm burden is more likely to cause disability in children than in adults, the use of a single, age-independent threshold would tend to considerably overestimate the potential disability.

Table 9.1 Worm burden thresholds for morbidity used in the model

Species Age (years)Higher estimate, lower threshold

Lower estimate, higher threshold

A. lumbricoides 0–4 10 205–9 15 3010–14 20 4015+ 20 40

T. trichiura 0–4 90 2505–9 130 37510–14 180 50015+ 180 500

Hookworms 0–4 20 805–9 30 12010–14 40 16015+ 40 160

Note: The lower thresholds are based on empirical observations of worm numbers associated with develop-mental defi cits. The higher thresholds are a more conservative value intended to provide a lower bound to the estimate of morbidity. The thresholds were estimated for children in the 5–10 year age group, and then adjusted for other age group using the procedure described in the text. The lower threshold estimate for Ascaris lumbricoides assumes that 30 000 eggs per gram (epg) is associated with defi cits in growth and fi tness (see Stephenson et al. 1989,1990) and that worm fecundity is equivalent to approximately 3000 epg for female worm. The higher threshold assumes that morbidity is associated with twice this burden. The Trichuris trichiuralower threshold is taken from studies of growth stunting in 5–10 year old children (Cooper et al. 1990), while the higher threshold is estimated from studies of clinical colitis (ES Cooper, personal communication). The hookworm thresholds are based on upper and lower bound estimates of the relationship between infection intensity and anaemia (Lwambo, Bundy & Medley 1992).


In order to approximate this age effect, in the absence of empirical data, the same proportional changes with age are used for all worm species. The threshold for children under 5 years of age was taken as 50 per cent of that for adults (i.e. adults require twice the worm burden of pre-school children before suffering ill effects), for 5–9 year old children it was taken as 75 per cent of that for adults, and the adult threshold was used for 10–14 year old children (Table 1). These estimates are, we believe, conservative; but they are not fi rmly based on empirical observation.

Other age-dependent differences are also incorporated into the model. A. lumbricoides and T. trichiura infections are usually more prevalent in children, whereas hookworm infections are more prevalent in adults. For simplicity, a single age-prevalence relationship (one for each species) was used, based on the typical age-prevalence relationship observed in fi eld studies (Table 9.2). The use of different prevalences for different age groups implies that a separate negative binomial distribution must be calculated for each age group. In order to ensure that the overall prevalence remains unchanged by this procedure, the observed demographic age distribution of the population must be taken into account. The effect of host age on the aggregation parameter (k) remains undefi ned, and the present framework uses a single (species-specifi c) aggregation parameter for all age groups.

Incorporating geographical heterogeneity

The prevalence of infection is non-linearly related to the mean intensity of infection in a community, such that the proportion of the population potentially suffering morbidity is disproportionately greater at higher levels of prevalence (Guyatt & Bundy 1991). If the average prevalence among communities is used as a basis for estimating intensity (and potential disability) for a geographical region, this will grossly underestimate the actual morbidity. It is therefore necessary to incorporate geographical

Table 9.2 Age weights for prevalences used in the model

Species Age (years) Age weight

A. lumbricoides 0–4 0.75 5–9 1.2 10–14 1.2 15+ 1

T. trichiura 0–4 0.75 5–9 1.2 10–14 1.2 15+ 1

Hookworms 0–4 0.25–9 0.5 10–14 0.9 15+ 1


heterogeneity in prevalence within the estimation procedure (Chan et al. 1994). Spatial heterogeneity in intestinal nematode infection is a relatively neglected area of study (Bundy et al. 1991, Booth & Bundy 1992) but its potential importance has been convincingly demonstrated for micropara-sitic infections (Anderson 1982, May & Anderson 1984).

Heterogeneity was considered at several geographical levels in the extrapolation procedure. The highest level is the regional level, as defi ned for the eight World Bank regions. Two regions (EME and FSE) were excluded from the analysis since the prevalences of intestinal nematode infections are very low. The remaining six regions were then divided into “population units” of 20 to 100 million people for which mean prevalence values, based on empirical data, were input into the model. Generally these population units coincide with politically defi ned countries (which is the unit for which prevalence data are most readily available) but some countries with exceptionally large populations, especially China and India, were subdivided into smaller units based on states or provinces for prevalence estimates.

The subdivision of a region into population units captures some geo-graphical heterogeneity, but this does not include the heterogeneity within the population unit (or country). Literature searches yielded suitable data for examining intra-country variation in the six geographical regions. The level of heterogeneity among communities within the same country was assessed using community-level estimates of prevalence from differ-ent studies. Variation in prevalence within countries was estimated for 9 countries for A. lumbricoides, 8 countries for T. trichiura, and 10 coun-tries for hookworm. The number of prevalence surveys available within each country ranged from 21 to 115. A total of 1600 prevalence surveys were examined in this analysis. The within-country distributions differed between worm species and between countries but were not markedly skewed or asymmetrical. Good correspondence was found between the data and the theoretical normal distribution which was therefore used.

Highly signifi cant positive correlations between mean and standard deviation were observed for A. lumbricoides and T. trichiura distributions. Therefore, an estimate of “typical” geographical heterogeneity within a population unit could be estimated for these species from the regression. Hookworm distributions show a wider range of standard deviations and there was no signifi cant correlation between these and the means. This may refl ect the fact that the hookworm data include undifferentiated estimates for two quite different parasite species (A. duodenale and N. americanus). This additional source of variation was captured by taking the mean of the standard deviations as an estimate of heterogeneity within the population unit.

These estimates of the geographical variation in prevalence within a population unit were assumed characteristic of each species and were incorporated in the model for all subsequent calculations.


Summary of estimation procedure assumptions

The framework for estimation of the population at risk of disability involves a set of assumptions about the patterns of infection observed at both the community and the regional level.

Community-level assumptions

Worm burden frequency distributions are adequately described by the negative binomial distribution. This probability distribution is the most widely accepted empirical description of observed worm burden distributions (Anderson & May 1991). However, it has been shown in some parasite species to underestimate the proportion of very low worm burdens and thus, potentially, overestimate the number of people in the higher worm burden classes. This could lead to an overestimation of the population at risk.

The frequency distribution of worm burdens is species-specifi c and largely independent of geographical region, infection prevalence or age group. Analyses of the available empirical data suggest that the degree of aggregation, as assessed by the negative binomial parameter, k, is remarkably consistent between studies and largely independent of geographical region for all the nematode species considered here (Guyatt et al. 1990, Lwambo, Bundy & Medley 1992, Booth 1994). There is some evidence that k increases slightly with prevalence of A. lumbricoides (Guyatt et al. 1990) and even more marginally with hookworm prevalence (Lwambo, Bundy & Meadley 1992). Exclusion of this effect would lead to overestimation of potential morbidity. There is confl icting and limited evidence for the relationship between worm burden distribution and age, with some studies showing an increase and others a decrease in aggregation with age (Bundy et al. 1987b). The current assumption of an age-independent distribution could lead to either overestimation or underestimation of potential morbidity.

Disability occurs above a worm burden threshold that is higher for adults than children. Thresholds were estimated from empirical data (Table 9.1). Two sets of thresholds were used for each species. An over-estimate of the threshold worm burden would lead to an underestimate of potential morbidity and vice versa. No information is available on the variation of the threshold with age.

The age prevalence profi le can be generalized between communities. A similar general pattern is seen when age prevalence profi les from differ-ent studies of the same species are compared (Anderson & May 1985). The effect on the estimates of changing the shape of the age-prevalence profi le are likely to be complex but, in general, the larger the differences in prevalence between different age groups, the higher the estimate of population at risk.


Regional-level assumptions

Infection prevalences between communities in the same country are normally distributed. Examination of the actual distributions suggested that a normal approximation would be appropriate (Chan et al. 1994). The use of a symmetrical distribution is the most conservative assump-tion since with a skewed distribution with the same mean (such as the negative binomial distribution), the frequency of very high prevalences will be increased. The current assumption may therefore tend to under-estimate the population at risk.

The standard deviations of these normal distributions increase linearly with the mean prevalence for A. lumbricoides and T. trichiura and are independent of mean prevalence for hookworms. These assumptions are the best available estimates of the effect of spatial heterogeneity on the prevalence distribution, and are based on data presented by Chan et al. (1994).

The mean standard deviation relationship is the same in different geo-graphical regions of the world. The data available suggest a consistent relationship but there are insuffi cient data to assess this relationship by region. It is not known if there are any regional differences nor whether these might increase or decrease the estimates.

A population unit of 20 to 100 million people is a suffi ciently fi ne-grained spatial stratifi cation to capture geographical variation in a population of 4.1 billion people. The size of this unit is constrained by the availability of empirical data. Larger units would reduce the preci-sion of the estimates of potential morbidity.

Estimation procedure

The method used for estimation is essentially an integration of all the pro-cesses described in the text. Fuller details are given by Chan et al. (1994). In summary, the procedure involved the following steps.

1. Country (or other population unit) prevalence data were obtained and divided into prevalence classes. Five prevalence classes were defi ned and an intermediate prevalence value (S) was used for calculation purposes. These classes are shown in Table 9.3. In this round of calculations the highest two prevalences classes were combined and the set prevalence of the lower class was used for estimation (67 per cent) of community morbidity. This was necessary because with very high prevalences, the negative binomial distribution greatly overestimates potential morbidity. This calculation is not exactly equivalent to merging the two highest prevalence classes since countries in class 5 have a different distribution of community prevalences with a greater proportion in the class 4+5. The estimated morbidity for these countries will therefore be higher.


2. The total populations in each prevalence class were multiplied by the transition matrix (M) to give an estimated community distribution of prevalences for the region (C). The matrix is derived using the follow-ing procedure. For each reference prevalence class in the estimation, a normal distribution for the individual community prevalence class distribution in the countries concerned was calculated. For A. lumbri-coides and T. trichiura a standard deviation that increased with mean was used, whereas with hookworms a constant standard deviation given by the average standard deviation of the data sets was used. The regional community distribution of prevalences can then be obtained by multiplying a vector of the country mean prevalence distribution with a species-specifi c transition matrix which consists of the calculated normal distributions: C = R.M.

The community prevalence distribution has one zero prevalence class and four non-zero-prevalence classes equivalent to the four lower prevalence classes of the country prevalence distribution (Table 9.3). Note that in the previous estimation (Chan et al. 1994) a fi fth prevalence class (> 75 per cent) was included. This is now considered to over-emphasize the top end of the prevalence range and thus to overestimate the population at risk, and was therefore not used in the present calculations.

The transition matrices used for each of the species are shown respec-tively, in Tables 4a, 4b and 4c.

3. Using regional demographic data, the population is divided into classes of community prevalence and age group and the age-weighted preva-lence is calculated for each of these classes. The age weights (A) are shown in Table 9.2. Given a community prevalence si for prevalence class i, the prevalence in adults (pi,15+) is given by:

i,i

jj j

p s15+ =

∑( )j j( )j ja d( )a dj ja dj j( )j ja dj j

Table 9.3 Prevalence classes and reference (set) prevalences used in the model

ClassPrevalence range

(percentage)Reference prevalence

(percentage)

1 < 25 10 2 25–45 35 3 45–60 52 4 60–75 67 5 75–100 804+5a 60–100 67

a. Combined classes 4 and 5 were used for community prevalence distribution.


where aj is the age weight for age group j and djdjd is the proportion of the population in age group

jthe population in age group

jj. The age specifi c prevalence in the other

jThe age specifi c prevalence in the other

j

age groups are then given by:

ij i, jp pijp pij ap p=p p +15 .

4. For each of the classes, using the species-specifi c aggregation parameter (k) and age specifi c morbidity threshold (tjtjt ), the potential morbidity estimate (eij) is calculated using the negative binomial distribution. This

j) is calculated using the negative binomial distribution. This

j

theoretical distribution has two parameters, the mean worm burden µ, ij

theoretical distribution has two parameters, the mean worm burden µ, ij

and the aggregation parameter k. These are related to the prevalence (P) in the following way:

P 1 1k

k= −P 1= −P 1 + −( )µ

Table 9.4c Transition matrix for hookworms

Community prevalence distribution

Reference class 0 1 2 3 4+5

1 0.309 0.464 0.187 0.04 02 0.040 0.269 0.382 0.203 0.1063 0 0.089 0.274 0.292 0.3454 0 0.018 0.118 0.227 0.6375 0 0 0.040 0.119 0.841

Note: A zero class community distribution denotes a prevalence of 0%.

Table 9.4b Transition matrix for Trichuris trichiura



1 0.288 0.509 0.177 0.026 02 0.097 0.259 0.288 0.180 0.1763 0.068 0.153 0.200 0.170 0.4094 0.028 0.087 0.149 0.157 0.5795 0.011 0.047 0.101 0.125 0.716


Table 9.4a Transition matrix for Ascaris lumbricoides



1 0.251 0.590 0.149 0.010 02 0.081 0.264 0.310 0.186 0.1593 0.057 0.149 0.214 0.175 0.4054 0.021 0.081 0.149 0.169 0.5805 0 0.048 0.097 0.133 0.722



The basis for the estimation of the population at risk of disability is that morbidity is mainly confi ned to the fraction of the population with high worm burdens. A threshold worm burden (T ) is defi ned over which morbidity effects are potentially observed (Table 9.1). The individual terms of the negative binomial, p(x),(the proportion of individuals with x worms) are given by:

π µ µµ

( )( )

( )x 1

kk+ x

x! k + k

k x

= +

−Γ

Γ

where Γ represents the gamma function. The proportion of the popula-tion with more than (T ) worms (the morbidity function Morb(P,T)) is therefore given by:

Morb P T = xx=0

x =T

( , ) ( )1−∑π

The potential morbidity estimate (eij) is obtained by multiplying the morbidity function by the population in each class (

ijmorbidity function by the population in each class (

ijnij):

ij ij ij je n Morb p t= ( , )

5. The above estimates are summed to give the age specifi c population at risk estimates for each region (fjfjf ):

f ejf ejf ei

ijf e=f e∑f e∑f e

These procedures were followed for each of the parasitic infections under consideration.

Estimates of population infected and at risk of disability

The estimates of population infected and at risk or disability are shown in Tables 9.5 to 9.7. For each nematode species, these estimates are given for different age classes and for different geographical regions. Two estimates of population at risk were used for each infection, based on different esti-mates of worm burden thresholds. Both thresholds are based on empirical data and were chosen to be relatively conservative. The lower estimate of worm burden refl ects probable developmental consequences of infection such as impaired growth or fi tness, while the higher estimate is intended to refl ect the likelihood of more serious consequences of infection.

The estimates of population infected are all slightly lower than those presented by Chan et al. (1994), because of the exclusion of the high-est reference prevalence class from the present extrapolation procedure. This has had an even greater effect on reducing the estimated size of the


population at risk of disability from ascariasis and trichuriasis, and on the estimated population above the high threshold for hookworm infection. The estimated population above the lower threshold of hookworm burdens has, however, increased as a result of the change in threshold.

The estimates for A. lumbricoides are shown in Table 9.5. The esti-mated total number of A. lumbricoides infections is 1382 million, slightly higher than estimates from other sources (World Health Organization 1987, Crompton 1988, Bundy 1990). The number at risk of morbidity is estimated in the range 15–63 million. The overall infection prevalence is 34 per cent in the exposed population while the prevalence of those at risk

Table 9.5a Estimates of numbers infected and at risk of disability for Ascaris lumbricoides, by World Bank region

RegionPopulation (millions)

Infections (millions)

Infections (as a percentage)

Population at risk (millions)

Population at risk (percentage)

SSA 512 104 20.25 3.04 0.590.78 0.15

LAC 441 171 38.76 8.04 1.821.92 0.44

MEC 503 96 19.15 2.94 0.580.74 0.15

IND 850 188 22.13 6.60 0.781.62 0.19

CHN 1 160 532 45.85 25.320 2.185.72 0.49

OAI 654 291 44.53 16.380 2.503.99 0.61

Total 4 120 1 382 62.32014.760

Table 9.5b Estimates of numbers infected and at risk of disability for Ascaris lumbricoides, by age group

Age group (years)

Population (millions)


Infections (percentage)


Population at risk percentage)

0–4 553 130 24 1.84 0.330.05 0.01

5–9 482 182 38 27.810 5.779.45 1.96

10–14 437 169 39 17.990 4.124.65 1.06

15+ 2 647 901 34 14.680 0.550.61 0.02

Total 4 120 1 382 34 62.320 1.5114.760 0.36


in the exposed population is between 0.4 per cent and 1.5 per cent. The highest prevalences are found in China and the Other Asia and Islands region.

The model assumes that prevalence of A. lumbricoides infection is slightly higher in children of 5 to 15 years old than in adults and younger children (Anderson & May 1985). The results show that this difference is greatly magnifi ed in the estimates of population at risk, such that potential morbidity is signifi cantly higher in school age children than in any other

Table 9.6b Estimates of numbers infected and at risk of disability for Trichuris trichiura, by age group

Age group (years)






0–4 553 96 17.38 0.04 0.010.00 0.00

5–9 482 135 28.04 19.920 4.1310.400 2.16

10–14 437 125 28.60 15.930 3.657.69 1.76

15+ 2 647 650 24.57 9.63 0.360.30 0.01

Total 4 120 1 007 24.43 45.530 1.1118.390 0.45

Table 9.6a Estimates of numbers infected and at risk of disability for Trichuris trichiura, by World Bank region






SSA 512 85 16.57 2.21 0.430.97 0.19

LAC 441 146 33.16 7.27 1.652.97 0.67

MEC 503 64 12.64 0.04 0.010.00 0.00

IND 850 134 15.78 3.02 0.361.25 0.15

CHN 1 160 340 29.29 17.290 1.496.65 0.57

OAI 654 238 36.41 15.700 2.406.54 1.00

Total 4 120 1 007 24.43 45.530 1.1118.390 0.45


age group. This is a result of the non-linear relationship between prevalence of infection and potential morbidity (Guyatt et al. 1990).

The estimates for T. trichiura are shown in Table 9.6. The totals show a lower number of infections than for A. lumbricoides, there being 1007 million infections resulting in a global prevalence of 24 per cent. The total population at risk is also lower for T. trichiura, in the range 18–45 million. As with A. lumbricoides, the highest prevalences of disability risk are found in Other Asia and Islands, in China and in children of school age.

The estimates for hookworm infections are shown in Table 9.7. There

Table 9.7a Estimates of numbers infected and at risk of disabililty for hookworm, by World Bank region






SSA 512 138 26.93 18 2.468 1.06

LAC 441 130 29.40 15 3.443 0.70

MEC 503 95 18.81 8 1.542 0.47

IND 850 306 36.00 47 5.4811 1.32

CHN 1 160 340 29.29 29 2.473 0.24

OAI 654 242 37.04 35 5.298 1.29

Total 4 120 1 250 30.34 151 3.6636 0.87

Table 9.7b Estimates of numbers infected and at risk of disability for hookworm, by age

Age group (years)






0–4 553 41 7.35 0 0.000 0.00

5–9 482 89 18.54 0 0.000 0.00

10–14 437 145 33.31 10 2.291 0.16

15+ 2 647 975 36.81 141 5.3335 1.32

Total 4 120 1 250 30.34 151 3.6736 0.87


are an estimated 1250 million hookworm infections and between 36 million and 151 million people at risk of disability. The distributions of infection and morbidity, both by age and region, are different from those for A. lumbricoides and T. trichiura. The disability risk attributable to hookworm infections is much higher in adults. The regional distribution is also differ-ent, with the highest prevalence of estimated disability in India.

Review of empirical databases by region

Direct estimates of the community morbidity attributable to intestinal helminthiases are unavailable. Hence the disability-adjusted life year (DALY) estimates are based on extrapolating the population at risk (intensely infected) from empirical observations of the proportion of the population infected.

The data on prevalence of infection used in the current estimation are from a database held at Oxford University, derived from fi eld survey data compiled for a UNESCO report on global prevalence of helminth infection (Bundy & Guyatt 1990). They are based on an extensive search of the original literature and, as far as possible, represent data collected within the last 20 years; older data were used only if no other data were avail-able for a particular country. Additional criteria for data selection include large sample size and community-based studies (i.e. not hospital records or institutional data). The number of studies available for each country varied, hence the reliability of the estimate for mean prevalence also varies. For the majority of countries, the sample size was at least several thousand individuals. Note that the data presented in Table 9.8 exclude a substantial number of unpublished surveys used in the actual analysis.

The survey estimates are based on the microscopic detection of parasite eggs in faecal specimens. While A. lumbricoides and T. trichiura eggs can be readily identifi ed, the eggs of the two hookworm species, Ancyclostoma duodenale and Necator americanus, cannot be distinguished by normal diagnostic methods and are recorded here as the combined prevalence of both species. The stool examination procedure also fails to detect light infections, particularly when single examinations are made as in the case of fi eld surveys (Hall 1982). Furthermore, the procedure will not detect non-fecund infections (e.g. single worm or single sex) which may repre-sent a signifi cant minority of infections (Guyatt 1992, Guyatt & Bundy 1995). Thus the survey data are conservative and underestimate the true prevalence of infection.

Estimation of DALYs

The analyses to this point have produced estimates of the size of the popula-tions with worm burdens that are likely to result in some form of disability. This section focuses on the estimation of the proportion of the population at risk who are likely to be disabled and the degree of disability, and how


Tab

le 9

.8

S

umm

ary

of p

reva

lenc

e st

udie

s of

hel

min

th in

fect

ions

, by

Wor

ld B

ank

regi

on a

nd c

ount

ry o

r ar

ea

Coun

try

or a

rea

Sam

ple

size

Num

ber

of s

ites

Prev

alen

ce e

stim

ate

(per

cent

age)

Hoo

kwor

ma

Sour

ceAs

caris

Tric

huris

Sub-

Saha

ran

Afric

aBe

nin

423

160

135

135

N.a

= 1

9Pa

mpl

iglio

ne &

Ric

ciar

di 1

971

Burk

ina

Faso

913

20.

5Fa

uche

r et

al.

1984

C

amer

oon

27 0

4053

045

Rat

ard

et a

l. 19

915

040

1853

N.a

= 4

9C

arri

e 19

82, R

iper

t et

al.

1978

, Rip

ert,

Leug

ueun

-Ngo

ugbe

ou &

Sa

me-

Ekob

o 19

82C

ape

Verd

e1

572

72de

Mei

ra, N

ogue

ira

& S

imoe

s 19

47 B

arbo

sa 1

956,

Nog

ueir

a &

C

oito

1950

Cen

tral

Afr

ican

R

epub

lic21

45

1917

Ric

ciar

di 1

972

126

3N

.a =

34

Brum

pt e

t al

.,197

288

2A

.d =

83

Ethi

opia

32 2

7629

040

Tedl

a &

Aye

l 198

61

059

4140

Tatic

heff,

Abd

ulah

i & H

aile

-Mes

kal 1

981

5 50

695

N.a

= 2

0A

.d =

1G

abon

2

684

2139

6843

Gar

in 1

978,

Ric

hard

-Len

oble

198

2G

ambi

a68

43

29M

cGre

gor

& S

mith

195

2; M

arsd

en 1

963

Gha

na42

24

5230

17A

nnan

et

al. 1

986

Libe

ria

690

817

1960

Stur

chle

r et

al.

1980

M

adag

asca

r21

71

6120

A.d

= 3

0C

erf,

Burg

ess

& W

heel

er 1

981

Mad

eira

3 31

32

70.

5A

.d =

18

Sant

os 1

952

N.a

= 0

.1

cont

inue

d


Mal

awi

289

104

15Bu

rges

s, Bu

rges

s &

Whe

eler

197

3M

ali

2 17

44

0.5

Rou

gem

ent

et a

l. 19

742

974

50.

5R

anqu

e 19

82

1 79

73

N.a

. = 5

8N

iger

ia1

266

667

46.5

31O

dunt

an 1

974

Réu

nion

2 80

310

4985

24Bo

nnef

oy &

Lsa

utie

r 19

78Se

nega

l35

94

3615

N.a

= 9

Jum

iner

, Dia

llo &

Lau

rens

197

1 So

mal

ia55

65

1334

Bian

chin

i et

al. 1

981

Suda

n31

93

A.d

. = 8

Ilard

i et

al. 1

980,

198

1, 1

987

Kun

tz, L

awle

ss &

Man

sour

195

5To

go93

504

6+7

1A

.d. =

7La

pier

re, T

ourt

e-Sc

haef

fer

1982

U

gand

a15

73

00

38So

rvill

o 19

82U

nite

d R

epub

lic o

f Ta

nzan

ia27

61

243

N.a

. = 6

2St

urro

ck 1

964

Zam

bia

4 92

017

0W

enlo

ck &

Ash

197

7Z

imba

bwe

38 4

840.

5G

olds

mid

et

al. 1

976

595

0.5

10Bl

acki

e 19

32; G

olds

mid

197

6

Indi

a23

949

598

13Sa

xena

& P

rasa

d 19

711

270

4816

Bidi

nger

, Cro

mpt

on &

Arn

old

1981

; Aro

ra 1

975;

Cho

wdu

ry 1

968;

C

hatt

erje

e &

Muk

hopa

dhya

y 19

85; M

uker

ji &

Mat

hen

1950

; Lan

e et

al.

1917

; Bag

chi,

Pras

ad &

Mat

hur

1964

; San

yal e

t al

. 197

2

Chin

a1

477

742

2 84

347

1917

Yu 1

994

Tab

le 9

.8

S

umm

ary

of p

reva

lenc

e st

udie

s of

hel

min

th in

fect

ions

, by

Wor

ld B

ank

regi

on a

nd c

ount

ry o

r ar

ea (c

ontin

ued)

Coun

try

or a

rea

Sam

ple

size

Num

ber

of s

ites

Prev

alen

ce e

stim

ate

(per

cent

age)

Hoo

kwor

ma

Sour

ceAs

caris

Tric

huris


Oth

er A

sia &

Isla

nds

Indo

nesi

a51

364

7771

4829

Cro

ss e

t al

. 197

0, 1

975,

197

6, 1

977a

& b

; Cla

rke

et a

l. 19

73; C

arne

y et

al.

1974

, 197

7; S

taffo

rd e

t al

. 198

0; Jo

seph

et

al. 1

978

Rep

ublic

of K

orea

39

81

1442

0.5

Seo

et a

l. 19

83

Lao

Peop

le’s

Dem

o-cr

atic

Rep

ublic

2 49

311

4950

A.d

= 4

1So

rnm

ani e

t al

. 197

4

Mal

aysi

a96

075

3048

5549

Kan

198

2, 1

985;

Rus

sell

1928

, 193

4; D

unn

1972

Sin

niah

et

al. 1

978

Papu

a N

ew G

uine

a1

304

3324

Ash

ford

et

al. 1

981

1 02

332

272

Shie

ld e

t al

. 198

6 Ph

ilipp

ines

1 30

04

54.8

22C

ross

et

al. 1

977c

286

369

Tate

ngco

, Mar

xan

& C

astr

o 19

72

Sing

apor

e61

47

4572

37D

esow

itz 1

963

Taiw

an, C

hina

622

791

447

Berg

ner

1964

; Cha

ng, S

un &

Chi

n 19

73T

haila

nd67

300

856

5.8

Jone

s 19

76

68 1

5310

135

Preu

ksar

aj e

t al

. 198

1; P

apas

arat

horn

et

al. 1

975

Sadu

n 19

55V

iet

Nam

40

98

3314

57C

olw

ell e

t al

. 197

1

Latin

Am

erica

& C

arib

bean

Braz

il2

511

1060

3627

Vin

ha 1

971

Chi

le

34 7

9938

19N

eghm

e &

Silv

a 19

52, 1

963,

198

3; S

chen

one

et a

l. 19

81; R

amir

ez e

t al

. 197

2; P

uga

et a

l. 19

8090

277

8126

Cos

ta R

ica

33 1

613

1228

4Z

amor

a et

al.1

978;

Roj

as &

Zum

bado

198

0D

omin

ica

1 00

02

3892

N.a

. = 1

1G

rell

& Z

umba

do 1

981

Ecua

dor

3 97

014

5060

Pepl

ow 1

982

1 56

812

33O

rtiz

196

9 G

uate

mal

a15

383

173

1819

Agu

ilar

1981

M

exic

o60

41

6267

Stoo

pen

& B

eltr

an 1

964

Suri

nam

854

1062

45A

sin

& v

an T

hiel

196

3

cont

inue

d


Tab

le 9

.8

S

umm

ary

of p

reva

lenc

e st

udie

s of

hel

min

th in

fect

ions

, by

Wor

ld B

ank

regi

on a

nd c

ount

ry o

r ar

ea (c

ontin

ued)

Coun

try

or a

rea

Sam

ple

size

Num

ber

of s

ites

Prev

alen

ce e

stim

ate

(per

cent

age)

Hoo

kwor

ma

Sour

ceAs

caris

Tric

huris

Mid

dle

East

ern

Cres

cent

Alg

eria

565

641

2913

Pam

pigl

ione

& H

adje

res

1965

Eg

ypt

41 4

768

16M

oham

ed e

t al

. 198

539

574

517

A.d

. = 1

Fara

g 19

85; T

adro

s 19

73; W

ells

& B

lagg

195

6; M

oham

ed e

t al

. 198

8;

Law

less

, Kun

tz &

Str

ome

1956

; Ir

an1

137

722

0.5

A.d

= 2

9C

olet

t 19

66; N

azar

i & M

asso

ud 1

980

Iraq

4 00

016

1.3

Nia

zi e

t al

. 197

5 M

oroc

co61

995

31

Cad

i-Sou

ssi e

t al

. 198

2 62

004

32

Paki

stan

295

361

5549

Kun

tz 1

960

Saud

i Ara

bia

835

10.

10.

10

El-R

ahim

y et

al.

1986

Tu

nisi

a24

047

11T

hier

s, La

ssou

ed &

Abi

d 19

76

a.N

.a =

Nec

ator

am

eric

anus

; A.d

. = A

neas

lost

oma

duod

enal

e.

b.Fo

r ho

okw

orm

, Anc

ylost

oma

duod

enal

e ac

coun

ts fo

r 50

% a

nd N

ecat

or a

mer

icanu

s m

akes

up

2%.

c. H

ookw

orm

onl

y am

ong

Jasm

in w

orke

rs.


this varies with such factors as age and sex. It also attempts to determine the relatively rare mortality attributed to intestinal nematode infection.

The calculation of disability-adjusted life years (DALYs) is based on the population at risk of disability. It is assumed that there are three sources of DALY loss: contemporaneous disability, which occurs in individuals with worm burdens above the higher threshold in Table 9.1 and which persists as long as the individual remains infected; chronic disability, which occurs in a small proportion of children with worm burdens above the lower threshold and which is life-long; and life years lost from mortality. The sum of these three effects gives the overall DALY estimate.

Population at risk of disability

Estimates of the populations at risk of disability are shown in Tables 9.9 to 9.11. Note that these populations are not the populations infected but some fraction of these which are at risk of disability because their worm burdens exceed a threshold that has been shown to be associated with some disability. For each species there are two populations considered to be at risk, based on two estimates of threshold burden: a larger population with worm burdens exceeding the lower threshold (associated with chronic or developmental disability); and a smaller population with burdens exceeding the higher threshold (associated with acute or contemporaneous disability). The proportion of the population at risk (not the prevalence of infection) not the prevalence of infection) notis given in Tables 9.9 to 9.11.

These estimates have been recalculated and differ from the original estimates (World Bank 1993, Chan et al. 1994). For A. lumbricoides and T. trichiura they are substantially lower than the earlier estimates as a result of removing the highest prevalence reference class from the extrapola-tion analysis. This change avoids overemphasis on the highest prevalence classes, which contribute disproportionately to the at risk population, and so gives a more conservative estimate. For the hookworm estimates, there was the same change in procedure but also a change in the worm burden thresholds. The change in thresholds was necessary to correctly assign the thresholds to the appropriate age classes in the light of new information. The effects of these changes for hookworm infection are to substantially reduce the estimated size of the population above the higher threshold and to slightly increase the population above the lower threshold.

Contemporaneous effects of infection

Given that people in endemic areas are continuously infected and reinfected throughout life it can be assumed, for present purposes, that incidence is numerically equivalent to prevalence and that infection duration is one year. The contemporaneous effects are assumed to occur in 100 per cent of the population with worm burdens above the higher threshold, and persist as long as an individual remains infected.

With A. lumbricoides, the most common consequences of infection are insidious effects, which are often manifested as effects on development


(reviewed by Crompton, Nesheim & Pawlowski 1989). They are, however, contemporaneous effects in that they can be partially reversed on treatment; that is, they occur only while infection persists. Such effects include reduc-tion in growth rate (height-for-age and weight-for-age), physical fi tness and appetite, for school-age and younger children (Stephenson et al. 1989, 1990, 1993). There is also evidence that this infection has consequences for congnitive ability in school-age children.

Cognitive consequences have yet to be sought in adults, but it would be surprising if adults responded differently from children since the effect is on ability rather than development. We assume here that adults with above-threshold worm burdens are affected, although the proportion of adults in this category is very small (0.02 per cent).

Table 9.9 Data for DALY calculation, Ascariasis, both sexes, 1990

Region Age Group

Proportion at riskAverage age

at onsetDuration of risk

Duration of disability

Acute Permanent Acute Permanent

Sub-Saharan Africa

0–4 0 120 2 1 1 81.35–14 525 1 720 10 1 1 71.715–44 10 170 30 1 1 51.945–59 10 170 50 1 1 32.560+ 10 170 70 1 1 14.9

Latin America & Caribbean

0–4 10 410 2 1 1 81.35–14 1 790 5 950 10 1 1 71.715–44 20 580 30 1 1 51.945–59 20 580 50 1 1 32.560+ 20 580 70 1 1 14.9


0–4 0 120 2 1 1 81.35–14 555 1 815 10 1 1 71.715–44 10 180 30 1 1 51.945–59 10 180 50 1 1 32.560+ 10 180 70 1 1 14.9

India 0–4 0 170 2 1 1 81.35–14 770 2 530 10 1 1 71.715–44 10 250 30 1 1 51.945–59 10 250 50 1 1 32.560+ 10 250 70 1 1 14.9

China 0–4 20 600 2 1 1 81.35–14 2 810 8 870 10 1 1 71.715–44 40 890 30 1 1 51.945–59 40 890 50 1 1 32.560+ 40 890 70 1 1 14.9

Other Asia & Islands

0–4 10 540 2 1 1 81.35–14 2 345 7 850 10 1 1 71.715–44 30 770 30 1 1 51.945–59 30 770 50 1 1 32.560+ 30 770 70 1 1 14.9


The disabling consequences of reduced physical fi tness and cognitive ability have yet to be empirically quantifi ed, as is the case for many of the morbid effects for which DALY estimation is attempted. We assume here, by default, that the contemporaneous effects of moderate ascariasis result in disability at the lowest disability weight (Class 1) (Murray & Lopez 1996).

There are also more serious consequences of infection, largely associ-ated with obstruction of ducts and intestinal lumen by these large worms. Systematic data on these acute complications are lacking, but the numerous reports based on inpatient records suggest that ascariasis is an important cause of hospitalization in endemic areas (reviewed by Pawlowski & Davies 1989). Ascariasis was the cause of 2.6 per cent of all hospital admissions in Kenya in 1976, and 3 per cent in a children’s hospital in Myanmar between 1981 and 1983 (Stephenson, Lathan & Oduori 1980, Thein-Hla-ing 1987). Complications resulting from ascariasis accounted for 0.6 per cent of all admissions to a paediatric surgery department in South Africa in 1987, 5.8 per cent of emergency admissions to a hospital in Mexico in 1975, 10.6 per cent of admissions for acute abdominal emergency to a children’s hospital in Myanmar, and between 0.8 and 2.5 per cent of admissions in a survey of hospitals in China (Flores & Reynaga 1978, World Health Organization 1987, Thein-Hlaing et al. 1990). The most common abdominal emergencies presenting are intestinal obstruction and biliary ascariasis, the proportions varying geographically, perhaps because of differences in diagnostic procedures (Maki 1972). The classical surgi-cal presentation is in patients between 3 and 10 years of age, although adults also may be affected (Davies and Rode 1982, Chai et al. 1991). Laparotomy attributable to ascariasis was the second most common cause of all laparotomies in 2–4 year old children in Durban, Lishiu and Sao Paulo, and the fi fth or sixth cause in adults in Myanmar, China and Nigeria (World Health Organization 1987). Reports using unstandard-ized indicators indicate that between 0.02 and 0.9 per cent of infections may require hospitalization (Pawlowski & Davies 1989), the proportion presumably varying with the local intensity of infection. Thus of the 4.5 per cent of infected children under 10 years of age who are here estimated to exceed the higher threshold of infection, between 0.4 and 20 per cent are likely to require hospitalization. These children will suffer a severely disabling condition, which may be life-threatening (see below), but which can be alleviated by appropriate clinical management. If it is assumed that such cases are managed appropriately, then the duration of disability is likely to be a few weeks. Complicated ascariasis has a reported history of over 10 days followed by 5 days of management, while the management of biliary ascariasis involves 4–6 weeks of observation before opting for surgical intervention (Davies & Rode 1982). The disability therefore is considered, for the present analyses, to be contemporaneous with infec-tion, to have a duration of 4 weeks, to have a severity of Class III (Mur-ray & Lopez 1996), and to affect 5 per cent of children under 15 years


of age with burdens exceeding the higher threshold. Note that this is a conservative assumption since it excludes the documented, though rare, occurrence of complications in adults. Furthermore, the case rates for children are based on records from tertiary facilities to which a substantial proportion of the most disadvantaged and heavily infected children may have limited access.

With T. trichiura there is evidence that moderate intensity infections result in growth defi cits that can be reversed by the antihelminthic removal of the worms (Cooper et al. 1990), and that these infections result in a protein losing enteropathy and anaemia (Cooper et al. 1991, 1992, Mac-Donald et al. 1991, Ramdath et al. 1995). In young children there are also

Table 9.10 Data for DALY calculation, Trichuriasis, both sexes, 1990

Region Age Group





Sub-Saharan Africa

0–4 0 0 2 1 1 81.35–14 680 1 340 10 1 1 71.715–44 0 110 30 1 1 51.945–59 0 110 50 1 1 32.560+ 0 110 70 1 1 14.9


0–4 0 10 2 1 1 81.35–14 2 855 5 795 10 1 1 71.715–44 10 470 30 1 1 51.945–59 10 470 50 1 1 32.560+ 10 470 70 1 1 14.9


0–4 0 0 2 1 1 81.35–14 0 30 10 1 1 71.715–44 0 0 30 1 1 51.945–59 0 0 50 1 1 32.560+ 0 0 70 1 1 14.9

India 0–4 0 0 2 1 1 81.35–14 620 1 240 10 1 1 71.715–44 0 100 30 1 1 51.945–59 0 100 50 1 1 32.560+ 0 100 70 1 1 14.9

China 0–4 0 10 2 1 1 81.35–14 3 380 6 475 10 1 1 71.715–44 20 570 30 1 1 51.945–59 20 570 50 1 1 32.560+ 20 570 70 1 1 14.9


0–4 0 20 2 1 1 81.35–14 3 980 8 050 10 1 1 71.715–44 20 650 30 1 1 51.945–59 20 650 50 1 1 32.560+ 20 650 70 1 1 14.9


effects on development quotient (Griffi ths locomotor subscale), anaemia and growth that are at least partially reversible by antihelmintic therapy (Callender et al. 1994). There is also an increasing body of evidence that both cognitive function (Tables 9.12a and 9.12b) and educational achieve-ment are impaired by moderate intensity infections, and that at least some of these effects can be reversed by antihelmintic treatment (Nokes et al. 1992a, 1992b, Simeon, Grantham-McGregor & Wong 1995, Simeon et al. 1995). As for ascariasis, it is assumed that these are contemporaneous effects of trichuriasis and result in the lowest disability weight (Class 1).

Particularly large burdens of T. trichiura may result in the “classical” dysenteric form of trichuriasis, synonymous with Trichuris Dysentery Syn-

Table 9.11a Data for DALY calculation, Hookworm disease, males, 1990

Region Age Group





Sub Saharan Africa

0–4 0 0 2 1 1 80.05–14 180 1 260 10 1 1 70.415–44 2 650 5 760 30 1 1 50.545–59 2 650 5 760 50 1 1 31.060+ 2 650 5 60 70 1 1 13.6


0–4 0 0 2 1 1 80.05–14 30 945 10 1 1 70.415–44 1 090 5 030 30 1 1 50.545–59 1 090 5 030 50 1 1 31.060+ 1 090 5 030 70 1 1 13.6


0–4 0 0 2 1 1 80.05–14 30 480 10 1 1 70.415–44 770 2 400 30 1 1 50.545–59 770 2 400 50 1 1 31.060+ 770 2 400 70 1 1 13.6

India 0–4 0 0 2 1 1 80.05–14 70 1575 10 1 1 70.415–44 2 070 8150 30 1 1 50.545–59 2 070 8 150 50 1 1 31.060+ 2 070 8 150 70 1 1 13.6

China 0–4 0 0 2 1 1 80.05–14 10 540 10 1 1 70.415–44 330 3 260 30 1 1 50.545–59 330 3 260 50 1 1 31.060+ 330 3 260 70 1 1 13.6


0–4 0 0 2 1 1 80.05–14 70 1545 10 1 1 70.415–44 2 060 7 980 30 1 1 50.545–59 2 060 7 980 50 1 1 31.060+ 2 060 7 980 70 1 1 13.6


drome (Ramsey 1962) and Massive Infantile Trichuriasis (Kouri & Valdes Diaz 1952). This typically occurs in children between 3 and 10 years of age and is associated with burdens involving at least several hundreds of worms carpeting the colonic mucosa from ileum to rectum. The colon is infl amed, oedematous and friable, and often bleeds freely (Venugopal et al. 1987). Reviews of case histories suggest that the mean duration of disease at the time of presentation is typically in excess of 12 months and that relapse after treatment frequently occurs (Gilman et al. 1983, Cooper et al. 1990, Callender et al. 1994). The probability of relapse, and of a child experiencing multiple episodes, is greatly enhanced because a proportion of heavily infected children are predisposed to reacquire heavy infection

Table 9.11b Data for DALY calculation, Hookworm disease, females, 1990

Region Age Group





Sub Saharan Africa

0–4 0 0 2 1 1 82.55–14 180 1 260 10 1 1 73.015–44 2 650 5 760 30 1 1 53.345–59 2 650 5 760 50 1 1 34.060+ 2 650 5 760 70 1 1 16.2


0–4 0 0 2 1 1 82.55–14 30 945 10 1 1 73.015–44 1 090 5 030 30 1 1 53.345–59 1 090 5 030 50 1 1 34.060+ 1 090 5 030 70 1 1 16.2


0–4 0 0 2 1 1 82.55–14 30 480 10 1 1 73.015–44 770 2 400 30 1 1 53.345–59 770 2 400 50 1 1 34.060+ 770 2 400 70 1 1 16.2

India 0–4 0 0 2 1 1 82.55–14 70 1 575 10 1 1 73.015–44 2 070 8 150 30 1 1 53.345–59 2 070 8 150 50 1 1 34.060+ 2 070 8 150 70 1 1 16.2

China 0–4 0 0 2 1 1 82.55–14 10 540 10 1 1 73.015–44 330 3 260 30 1 1 53.345–59 330 3 260 50 1 1 34.060+ 330 3 260 70 1 1 16.2


0–4 0 0 2 1 1 82.55–14 70 1 545 10 1 1 73.015–44 2 060 7 980 30 1 1 53.345–59 2 060 7 980 50 1 1 34.060+ 2 060 7 980 70 1 1 16.2


even after successful treatment (Bundy et al. 1987a, 1987b). The typical signs of the syndrome (see Bundy & Cooper 1989a for a review of 13 stud-ies involving 697 patients) are rectal prolapse, tenesmus, bloody mucoid stools (over months or years), growth stunting, and a profound anaemia, which may lead to a secondary anaemia. The complete spectrum of clini-cal features associated with the syndrome occurs in some 30 per cent of children with intense trichuriasis. Many of the major clinical effects are reversible by appropriate therapy (Cooper, Bundy & Henry 1986, Gilman et al. 1983), hence the disability is considered here to be a contemporane-ous consequence of infection. For the present analyses it is assumed that the disability is contemporaneous with infection, has a duration of over 12 months, has a severity of Class II (Murray & Lopez, 1996), and affects 20 per cent of children under 15 years of age experiencing the higher threshold of intensity.

With hookworm the major consequence of infection is anaemia (see Schad & Banwell 1984 and Crompton & Stephenson 1990 for reviews of the extensive literature in this area). Anaemia is associated with: reduced worker productivity; reduced adult and child fi tness; reduced fertility in women; reduced intrauterine growth rate, prematurity and low birth weight; and cognitive defi cits (Fleming 1982, Stephenson et al.1993, Pol-litt et al. 1986, Boivin et al. 1993) (Tables 9.12a and 9.12b). Since the higher threshold for the intensity of hookworm infection was selected on the basis of the development of anaemia, it is here assumed that 100 per cent of those exceeding this threshold suffer at least Class I disability. As discussed elsewhere (World Bank 1993), the consequences of anaemia will be more serious for a subset of the affected population, resulting in Class II and Class III disability. The disability weight distribution for anaemia was used for the present analyses, 70 per cent in Class II, 24 per cent in Class III and 6 per cent in Class IV.

For all species it is assumed here that the effects are independent of host sex. It is also assumed that the disability weight is age-independent since the method of extrapolating the population at risk incorporates age-weights in both the prevalence of infection and the threshold associated with disability by age.

Chronic effects of infection

In addition to the contemporaneous effects of infection, there is evidence that some consequences of infection are irreversible. This is the case for some cognitive defi cits (Table 9.12a), some elements of development quo-tient (Callendar et al. 1994), and some growth effects during childhood (Stephenson et al. 1993). In all studies, some forms of disability in a propor-tion of children do not respond to therapy. We estimate that in any annual cohort of heavily infected children some 5 per cent suffer these permanent consequences. Studies of reinfection show that children are predisposed to a particular intensity of infection (Keymer & Pagel 1990, Hall, Anwar & Tomkins 1992), such that some 30 per cent of heavily infected children


Tab

le 9

.12

aSe

lect

ed s

tudi

es in

vest

igat

ing

the

effe

cts

of p

aras

itic

helm

inth

infe

ctio

ns o

n m

enta

l pro

cess

ing

Para

site

Coun

try

Stud

y de

sign

Sam

ple

size

Tim

e be

twee

n ba

selin

e an

d fo

llow

-up

(if

appr

opria

te)

Age

of

subj

ects

(y

ears

)

Sign

ifi ca

nt e

ffect

s of

hel

min

th in

fect

ion

on m

enta

l pro

cess

ing

Inve

stig

ator

s

Base

line

diffe

renc

es

betw

een

infe

cted

and

un

infe

cted

gro

upIn

terv

entio

n di

ffere

nces

Tric

huris

tric

hiur

a

Mod

erat

e in

tens

ity

Jam

aica

Inte

rven

tion

Plac

ebo

con-

trol

led

Alb

enda

zole

T =

206

P =

201

C =

206

26 w

eeks

7–11

* R

eadi

ng

x Sp

ellin

g

* A

rith

met

ic

x Sc

hool

Att

enda

nce

Test

s in

bat

tery

= 4

Trea

tmen

t in

tera

ctio

n ef

fect

s:

•he

avily

infe

cted

and

re-

ceiv

ed t

reat

men

t im

prov

ed

in s

pelli

ng;

•st

unte

d an

d re

ceiv

ed t

reat

-m

ent

impr

oved

in s

choo

l at

tend

ance

.

Sim

eon

et a

l. 19

94

Inte

rven

tion

Plac

ebo

con-

trol

led

Alb

enda

zole

T =

96

P =

93

C =

100

14 w

eeks

8–10

x Fl

uenc

y

x Fr

ench

lear

ning

(in

itial

)

* Le

tter

sea

rch

Test

s in

bat

tery

= 6

Trea

tmen

t in

tera

ctio

n ef

fect

s:

Und

erw

eigh

t ch

ildre

n im

-pr

oved

in fl

uenc

y.

Sim

eon

et a

l. 19

94

Inte

rven

tion

Plac

ebo

con-

trol

led

Alb

enda

zole

T =

49

P =

48

C =

48

14 w

eeks

10–1

1*

Silly

sen

tenc

es

x Le

tter

sea

rch

Test

s in

bat

tery

= 8

Non

e si

gnifi

cant

Badd

eley

, M

eeks

-Gar

dner

&

Gra

ntha

m-

McG

rego

r 19

95

Inte

rven

tion

Plac

ebo

con-

trol

led

Alb

enda

zole

T =

66

P =

67

C =

63

10 w

eeks

9–11

x D

igit-

span

forw

ards

x D

igit-

span

bac

kwar

ds

x A

nalo

gica

l rea

soni

ng

x Pe

gboa

rd n

on-d

omi-

nant

han

d

Test

s in

bat

tery

= 9

Non

e si

gnifi

cant

Ster

nber

g, Po

wel

l &

McG

rane

, 199

5

275Intestinal nematode infectionsTr

ichu

ris tr

ichi

ura

Mod

erat

e–he

avy

inte

nsity

Jam

aica

Inte

rven

tion

Plac

ebo

con-

trol

led

Alb

enda

zole

T =

62

P =

41

C =

56

63 ±

8 d

ays

9–12

Flue

ncy

Dig

it-sp

an fo

rwar

ds

Dig

it-sp

an b

ackw

ards

Ari

thm

etic

Cod

ing

Com

preh

ensi

on

Mat

chin

g fa

mili

ar fi

gure

s: ea

sy

Mat

chin

g fa

mili

ar fi

gure

s: ha

rd

Test

s in

bat

tery

= 8

Flue

ncy

Dig

it-sp

an fo

rwar

ds

Dig

it-sp

an b

ackw

ards

Nok

es e

t al

.199

2a,

1992

b

Hoo

kwor

m

pres

ence

Zai

reIn

terv

entio

n,

Cas

e co

ntro

l

Leva

miz

ole

+ m

alar

ia

trea

tmen

t if

infe

cted

onl

y

T =

47

C =

50

4 w

eeks

8.75

±

1.6

Sequ

entia

l pro

cess

ing,

incl

udin

g nu

mbe

r re

call

Wor

d or

der

* M

enta

l pro

cess

ing

tota

l

Test

s in

bat

tery

= 1

0

Spat

ial m

emor

yBo

ivin

et

al. 1

993

Hoo

kwor

m

+ Ir

on s

tatu

s

pres

ence

Zai

reIn

terv

entio

n,

plac

ebo

con-

trol

led

Leva

miz

ole

iron

sup

ple-

men

ts

T +

Iron

=

17

P +

Iron

; T

only

; P o

nly;

= 3

0

4 w

eeks

Mal

e =

7.

7

Fem

=

8.0

Not

rep

orte

d

Test

s in

bat

tery

= 1

0

Effe

ct =

iron

+ h

ookw

orm

tr

nt

Spat

ial m

emor

y

Num

ber

reca

ll

Wor

d or

der

Face

rec

ogni

tion

Ges

talt

Mat

rix

anal

ogie

s

Men

tal p

roce

ssin

g to

tal

Sequ

entia

l tot

al

Sim

ulta

neou

s to

tal

Boiv

in &

Gio

rdan

i

1993

cont

inue

d


Tric

huri

s tr

ichi

ura

TD

S –

very

he

avy

inte

nsity

Jam

aica

Cas

e co

ntro

l, in

terv

entio

ns

pair-

mat

ched

Alb

enda

-zo

le g

iven

to

infe

cted

ch

ildre

n ev

ery

4 m

onth

s

T =

19

C =

19

12 m

onth

s 3–

6G

riffi

ths

DQ

sub

scal

es

Loco

mot

or

Eye

hand

coo

rdin

atio

n

Hea

ring

and

spe

ech

Perf

orm

ance

Loco

mot

orC

alle

nder

et

al.

1991

Asc

aris

lu

mbr

icoi

des

Pres

ence

(Stu

dy a

ctua

lly

desi

gned

to

inve

stig

ate

T.

tric

hiur

a)

Jam

aica

Cro

ss-s

ectio

n,

mat

ched

for

clas

s

Infd

= 1

96

Uni

nfd

=

207

(Infd

with

T.

tric

hiur

a =

40

9)

—7–

11*

Rea

ding

* Sp

ellin

g

* A

rith

met

ic

* Sc

hool

att

enda

nce

Test

s in

bat

tery

= 4

Sim

eon

et a

l. 19

94

Asca

ris

lum

brico

ides

pres

ence

Ecua

dor

Cro

ss-s

ectio

nIn

fd =

103

Uni

nfd

C

= 2

7

—9–

13*

Stro

op w

ords

* Pe

abod

y ra

w s

core

* D

igit

Sym

bol

* W

isco

nsin

Car

d So

rt-

ing

Test

Inte

ract

ion

with

nut

ri-

tion

in

Not

don

eLe

vav

et a

l. 19

95

Tab

le 9

.12

aSe

lect

ed s

tudi

es in

vest

igat

ing

the

effe

cts

of p

aras

itic

helm

inth

infe

ctio

ns o

n m

enta

l pro

cess

ing

(con

tinue

d)

Para

site

Coun

try

Stud

y de

sign

Sam

ple

size

Tim

e be

twee

n ba

selin

e an

d fo

llow

-up

(if

appr

opria

te)

Age

of

subj

ects

(y

ears

)

Sign

ifi ca

nt e

ffect

s of

hel

min

th in

fect

ion

on m

enta

l pro

cess

ing

Inve

stig

ator

s

Base

line

diffe

renc

es

betw

een

infe

cted

and

un

infe

cted

gro

upIn

terv

entio

n di

ffere

nces


Peab

ody

Test

* =

con

trol

led

for

nutr

i-tio

n st

atus

All

sam

ple

had

high

EEG

Test

s in

bat

tery

= 1

3

Poly

para

sitis

m

A. lu

mbr

icoid

es,

T. tr

ichi

ura,

H

ookw

orm

inte

nsity

Jam

aica

Cro

ss-s

ectio

nIn

fd =

473

Uni

nfd

=

170

—9–

11A

cade

mic

str

eam

(c

hild

ren

stre

amed

by

teac

hers

acc

ordi

ng t

o ac

adem

ic a

bilit

y; ch

ildre

n w

ith le

ast

abili

ty m

ore

likel

y to

be

infe

cted

and

he

avily

infe

cted

)

Onl

y te

st in

bat

tery

Not

don

eN

okes

et

al. 1

991

Poly

para

sitis

m

A. lu

mbr

icoid

es,

T. tr

ichi

ura,

ho

okw

orm

, Sc

hist

osom

e sp

p. P

roto

zoa

Inte

nsity

Sout

h A

fric

aC

ross

-sec

tion

all i

nfec

ted

with

diff

eren

t sp

p.

Subj

ects

=

110

—10

* Su

stai

ned

atte

ntio

n

(pat

hoge

nici

ty o

f par

a-si

tic s

peci

es m

ore

im-

port

ant

than

pre

vale

nce/

inte

nsity

at

pred

ictin

g pe

rfor

man

ce)

Oth

er t

est

= M

emor

y

Not

don

e

(Inte

rven

tion

disr

upte

d by

fl o

odin

g)

Kva

lsvi

g C

oopp

an

& C

onno

lly 1

991

Tric

huris

tric

hiur

a

Low

-Mod

erat

e an

d he

avy

inte

nsity

Ital

yC

ross

-sec

tion

Uni

nf =

232

Infd

= 1

24

—6–

10x

Low

er s

choo

l gra

de

corr

elat

ed w

ith in

ten-

sity

. No

rela

tions

hip

whe

n co

ntro

lled

for

soci

al a

nd h

ygie

nic

cond

ition

s.

Oth

er o

utco

me

= p

ro-

mot

ion.

Not

don

ede

Car

neri

196

8

cont

inue

d


Tric

huris

tric

hiur

a

Low

–Mod

erat

e &

hea

vy

Inte

nsity

Ital

yC

ross

-sec

tion

Uni

nf =

125

Infd

= 2

33

—6–

11x

Slow

er p

rom

otio

n,

poor

gra

des

corr

e-la

ted

with

inte

nsity

.

No

rela

tions

hip

whe

n co

ntro

lled

for

soci

al a

nd

hygi

enic

con

ditio

ns.

Oth

er o

utco

me

= a

bsen

-te

eism

Not

don

ede

Car

neri

G

arof

ano

&

Gra

ssi 1

967

Hoo

kwor

m

Inte

nsity

Aus

tral

iaC

ross

-sec

tion

Uni

nfd

=

116

Infe

cted

: lo

w in

ten-

sity

= 6

5

Infe

cted

: hi

gh in

ten-

sity

= 1

59

—6.

5–15

.5Bi

net-

Sim

on t

est

and

Port

eus

Maz

es c

or-

rela

ted

with

inte

nsity

of

infe

ctio

n.

Not

don

eW

aite

& N

eils

on

1919

Hoo

kwor

m

pres

ence

Uni

ted

Stat

es o

f A

mer

ica

Cro

ss-s

ectio

n78

—6–

17*

Gra

de a

dvan

cem

ent

(defi

cit

of 0

.23

grad

es/

year

)

Not

don

eSt

iles

1915

Tab

le 9

.12

aSe

lect

ed s

tudi

es in

vest

igat

ing

the

effe

cts

of p

aras

itic

helm

inth

infe

ctio

ns o

n m

enta

l pro

cess

ing

(con

tinue

d)

Para

site

Coun

try

Stud

y de

sign

Sam

ple

size

Tim

e be

twee

n ba

selin

e an

d fo

llow

-up

(if

appr

opria

te)

Age

of

subj

ects

(y

ears

)

Sign

ifi ca

nt e

ffect

s of

hel

min

th in

fect

ion

on m

enta

l pro

cess

ing

Inve

stig

ator

s

Base

line

diffe

renc

es

betw

een

infe

cted

and

un

infe

cted

gro

upIn

terv

entio

n di

ffere

nces


Tab

le 9

.12

bSe

lect

ed s

tudi

es in

vest

igat

ing

the

effe

cts

of p

aras

itic

helm

inth

infe

ctio

ns o

n ph

ysic

al fi

tnes

s

Para

site

Coun

try

Stud

y de

sign

and

Mea

sure

of a

ctivi

tySa

mpl

e siz

e

Tim

e be

twee

n ba

selin

e an

d fo

llow

-up

(if a

ppro

pria

te)

Age

of

subj

ects

(y

ears

)

Base

line

diffe

renc

es

betw

een

infe

cted

and

un

infe

cted

gro

upIn

terv

entio

n di

ffere

nces

Inve

stig

ator

s

Poly

para

sitis

m

T. tr

ichi

ura

A. lu

mbr

icoid

es

Hoo

kwor

m

Pres

ence

Ken

yaIn

terv

entio

n pl

aceb

o co

ntro

lled

Alb

enda

zole

Har

vard

Ste

p Te

st

T=

18

P=15

7 w

eeks

6–12

Fitn

ess

nega

tivel

y co

rrel

-at

ed w

ith h

aem

oglo

bin/

ir

on s

tatu

s.

No

chan

ge in

fi tn

ess

scor

e an

d pu

lse

rate

in p

lace

bo g

roup

. Si

gnifi

cant

impr

ovem

ent

in fi

tnes

s in

tre

atm

ent

grou

p. Im

prov

emen

t si

gnifi

cant

ly r

elat

ed t

o re

duct

ion

in

hook

wor

m a

nd A

. lum

brico

ides

egg

co

unts

.

Step

hens

on

et a

l.199

0

Poly

para

sitis

m

T. tr

ichi

ura

A. lu

mbr

icoid

es

Hoo

kwor

m

pres

ence

Ken

yaIn

terv

entio

n pl

aceb

o co

ntro

lled

Alb

enda

zole

Har

vard

Ste

p Te

st

T=

27

P=26

4 m

onth

s7–

13N

o di

ffere

nce

betw

een

infe

cted

gro

ups.

No

chan

ge in

fi tn

ess

scor

e an

d pu

lse

rate

in p

lace

bo g

roup

. Si

gnifi

cant

impr

ovem

ent

in fi

tnes

s in

tre

atm

ent

grou

p. Im

prov

emen

t si

gnifi

cant

ly r

elat

ed t

o re

duct

ion

in h

ookw

orm

, wei

ght

gain

and

in

crea

se in

ene

rgy

inta

ke d

urin

g th

e 4

mon

th s

tudy

per

iod.

Step

hens

on

et a

l.199

3

Defi

niti

ons

Inte

rven

tion

One

gro

up r

ecei

ves

trea

tmen

t. G

roup

s te

sted

pre

-inte

rven

tion

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nsity

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tens

ity

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i.e.

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with

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asite

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ith p

aras

ite s

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r co

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and

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d no

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undi

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aria

bles

.

Tab

le 9

.12

bSe

lect

ed s

tudi

es in

vest

igat

ing

the

effe

cts

of p

aras

itic

helm

inth

infe

ctio

ns o

n ph

ysic

al fi

tnes

s (c

ontin

ued)


in an annual cohort would be expected to reacquire heavy infection. Thus each year the proportion of children exceeding the threshold worm burden will consist of some 70 per cent of individuals who have not previously experienced heavy infection, which implies a cumulative increase in the proportion suffering permanent disability. We therefore assume that each year 3 per cent of newly heavily infected children, and children only, suffer life-long consequences of infection.

The disability attributable to these effects has yet to be empirically determined. Stunted children may be disadvantaged in education (Moock & Leslie 1986, Jamison 1986, Glewwe & Jacoby 1995), as are children with low development quotients or cognitive impairment (Pollitt 1990). On the other hand, physical and mental maturation may eventually com-pensate, to some degree, for initial retardation (Pollitt et al. 1986). In a recent study of two years nutritional supplementation of stunted children, locomotor development improved in the fi rst year, as seen with antihelmin-thic treatment of trichuriasis (Callender et al. 1994), while other areas of development did not improve until the second year (Grantham-McGregor et al. 1991). Given this uncertainty we assume that the permanent conse-quences of infection result in disability at the lowest weight (Class 1). Thus in calculating the DALYs for all the helminth infections it is assumed here that 3 per cent of children experiencing worm burdens above the lower threshold suffer permanent disability of Class 1.

Mortality

This is the weakest area of DALY estimation because of the lack of empirical data. Ascariasis is the best documented helminthiasis in terms of mortality. There are numerous studies of case fatality rates in hospitals (reviewed by Pawlowski & Davies 1989). These indicate that the outcome of acute complications of ascariasis is modifi ed by the general health status of the patient, the intensity of infection and the medical procedure (see Pawlowski & Davies 1989). In one hospital in Sao Paulo, for example, the case fatality rate was 1.35 per cent for conditions which could be managed conservatively, and 26.1 per cent in patients undergoing surgery (Okumura et al. 1974). These studies confi rm that death is a not infrequent outcome of complications of ascariasis, but provide little insight into mortality rates in the community. An extrapolation from central hospital data in Myanmar suggests there are 0.008 deaths per 1000 infections per year (Thein-Hliang 1987), but this is considered to be a considerable underestimate since only a small proportion of children with severe complications are likely to have access to the hospital (Pawlowski & Davies 1989). Only two population based estimates are available: one for the Darmstadt epidemic (0.1 deaths per 1000 infected per year) (Krey 1949) and one for Japan prior to national control efforts (0.061 deaths per 1000 infected per year) (Yokogawa 1976). Based on the present estimate of global infection, these rates suggest that between 8 000 and 14 000 children die each year.

The fi nal estimate of global mortality due to ascariasis in the Global


Burden of Disease project was 11 000 concentrated in the age group 5–14 years (Murray and Lopez 1996). Mortality was distributed by region in proportion to the region-specifi c population at risk (above higher thresh-old) and to the region-specifi c probability of dying between birth and 4 years (World Bank 1993). This last quantity was added to take account of regional variations in access to acute medical services.

No population-based mortality estimates have been published for T. trichiura infection. Prior to the advent of safe and effective therapy for T. trichiura infection in the late 1970s a number of reports described paedi-atric inpatients with Trichuris Dysentery Syndrome who, despite clinical efforts, died as a result of profuse haemorrhage and secondary anaemia (Wong and Tan 1961, Fisher and Cremin 1970) or of intussusception (Reeder, Astacio & Theros 1968). Although there continue to be reports of the syndrome, a fatal outcome in a clinical setting today would suggest inappropriate management. The picture in the community, however, may be rather different since, in the absence of specifi c diagnosis, the aetiology of chronic bloody dysentery may be unrecognized. Nevertheless, mortality is undoubtedly a rare consequence of trichuriasis.

The profound anaemia of hookworm infection is life-threatening and has been estimated, although the means of estimation are not described, to result in 65 000 deaths per year (World Health Organization 1992). Again there is a lack of empirical data, presumably in this case because of the diffi culty in identifying the etiology of anaemia-related deaths. A fi gure of 4 300 deaths was used by Murray and Lopez (1996) and was distributed to ascribe the highest proportion of mortality to women of childbearing age (15–44 years) and to older age groups. The distribution of deaths between regions was divided in the same way as for the other infections.

In including these estimates of mortality we recognize that they are unsupported by vital registration statistics. But it should also be recognized that intense infection is most prevalent in the poorest regions of the poorest countries. In such areas mortality may be most likely because of limited access to appropriate management, while both the diagnosis of cause of death and its registration may be least reliable. There is clear evidence that deaths do occur. What is unclear is the extent of this mortality.

Disability

Much of the disability associated with helminth infection is insidious and would be unlikely to be brought to clinical attention. As such it is diffi cult to compare with the more classical clinical signs. On the other hand, cognitive defi cits may have profound consequences for educational outcomes and growth stunting is one of the best characterized correlates with underachievement, so these insidious effects may have far reaching societal consequences. Achieving some realistic balance between the clini-cal consequences for the individual and developmental consequences for


society goes beyond the scope of the present exercise, and would require a more sophisticated weighting system, if indeed the effects could be quanti-fi ed. For present purposes, the very low proportional weighting selected for the chronic effects of infection is infl uenced by the view that the Class 1 disability weight may be an overestimate of the effects of infection from a clinical perspective.

Other considerations in calculating burden

There are three main reasons why the burden of intestinal helminths may not be adequately captured by the present calculations. First, there are no direct measures of morbidity against which the extrapolation procedure could be conclusively validated. Although each step in the extrapolation was independently assessed against empirical data as far as possible, there must remain uncertainty until observed data become available. Second, the mortality data are largely unsubstantiated. Mortality has the potential to signifi cantly alter the overall burden estimates. It is therefore unsatisfac-tory that mortality data have received so little research attention. Third, there is a particular lack of information on the morbid consequences of infection in young children. It is possible that even very low worm burdens may have disproportionately severe effects on developing physiologies and organ systems. Anecdotal evidence suggests that the current estimates of threshold and disability weights may signifi cantly underestimate the burden in children under 10 years of age, and particularly those under 5 years.

The societal consequences of growth stunting and educational under-achievement may be of substantially greater relevance than the disability in the individual.

Intestinal nematode infections as risk factors for other diseases

Intestinal nematode infection is associated with malabsorption and is a potentially important predisposing factor for malnutrition in communi-ties on marginal diets. These effects may relate broadly to protein-energy malnutrition, or to specifi c defi ciencies. For example, A. lumbricoides infection has been associated with malabsorption of vitamin A.

Hookworm infection and to a lesser extent trichuriasis are associated with iron loss predisposing to anaemia. It is self evident that the risk of anaemia is dependent on iron balance and thus that infection may be an important contributing factor.

The attributable contribution to global malnutrition is potentially con-siderable given the ubiquity of infection and its specifi cally high prevalence in the poorest societies with the least adequate diets.



The major intestinal helminth infections can be effectively treated simul-taneously with single dose oral therapy. The treatment is widely available, safe, simple and inexpensive. Prevention of reinfection requires reduction in transmission, which can be achieved by synchronized treatment pro-grammes and by improvements in sanitation.

In the absence of currently fi nanced health interventions there would be some increase in the current burden. For example, there would be a greater number of deaths from intestinal obstruction in the absence of operative procedures, and from severe anaemia or malnutrition in the absence of rehabilitation therapy. However, with some important exceptions such as Japan and the Republic of Korea, control of intestinal helminth infections is only rarely a component of national public health programmes.

It could be argued that the entire burden could eventually be avoided by appropriate application of currently available interventions. For example, evidence from the Republic of Korea and Japan indicates that reduction in the prevalence of A. lumbricoides infection at the national level results in a signifi cant decline in acute complications of ascariasis requiring hospi-talization (Chai et al. 1991) and in ascariasis related mortality (Yokogawa 1976). Curative treatment would mitigate the contemporaneous or acute effects of infection, while measures to control transmission would avoid chronic developmental disability, although neither could reverse the defi cits that are already present in the population.

Economic analyses suggest that carefully targeted community treatment programmes are exceptionally cost-effective (Warren et al 1993, Guyatt & Evans 1992, World Bank 1993). This arises because the therapy is inexpensive (US$0.20 or less per dose), is required at infrequent inter-vals (of the order of one year), can have community-wide effects even if targeted at some fraction of the population which makes the greatest contribution to transmission (such as school-age children), and can be delivered through existing infrastructures (such as schools or the primary health care system).

Conclusions

The global morbidity attributable to intestinal nematode infections, although generally accepted to be large, has proven diffi cult to quantify. The method presented here provides a framework whereby the potential global burden may be estimated in the absence of any direct measures of morbidity. The estimates are intended to give some indication of the potential burden of intestinal helminthiases rather than to provide abso-lute values. It would of course be possible to seek further refi nement of the approach, but our view is that the most pressing need is to obtain reliable community data on the observed levels of morbidity and on the consequences of disability. The present analyses indicate that even low


levels of individual disability can sum to a considerable burden with such ubiquitous infections; the important question is what this implies for com-munities in practice. The analysis has revealed important lacunae in our knowledge of these infections and it is hoped that this might guide future applied research.

The present estimates suggest that the potential morbidity attribut-able to geohelminthiases is much greater than previously supposed. This refl ects the inclusion of both the traditionally recognized clinical effects of helminthiases (see World Health Organization 1992) and more recently recognized developmental effects, which rarely result in clinical presenta-tion but which may have major consequences for the individual and the community.

Another general implication of the results arises from the similarity of the age and regional distributions for A. lumbricoides and T. trichi-ura infection and morbidity. This observation has been made before for prevalence data (Booth & Bundy 1992), and strong positive correlations between A. lumbricoides and T. trichiura prevalences in communities have been demonstrated. This suggests that these two infections could be controlled within a single programme. The age distribution of the burden also supports the conclusion that there are particular benefi ts in targeting control of A. lumbricoides and T. trichiura infection at school age children (Bundy et al. 1985, Savioli, Bundy & Tomkins 1992).

The results suggest that the vast majority of the morbidity attributable to intestinal nematodes is readily avoidable or reversible using existing and cost-effective approaches, and that the mortality is also a largely avoidable consequence of acute infection. These observations, and the scale of the burden of current disease, argue for greater public health emphasis on the control of intestinal helminthiases.

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Zamora AVC et al. (1978) Estado actual de parasitismo intestinal en la zona de Puriscal [Current situation of intestinal parasitosis in the Puriscal area]. Acta Medica Costarricense, 21:271–273.

Trachoma-Related Visual LossB Thylefors, K Ranson, A-D Négrel, R Pararajasegaram

Chapter 10

Introduction

Trachoma as a cause of blindness has been known to mankind for many centuries; it was documented in ancient China, Egypt and India. The disease probably came to Europe with the Napoleonic troops returning from Egypt and was endemic in most European countries well into the 20th century (Jitta & Luharis 1930).

Trachoma, a communicable eye disease most commonly found amongst poor populations living in crowded conditions with insuffi cient personal and environmental hygiene, is the most important cause of preventable blindness in the world. The disease is still commonly found in many developing countries, usually in the poorest population groups in rural areas. Trachoma is a typical socioeconomically determined disease, with poverty, low living standards, and lack of hygiene as main risk factors. The disease is typically “clustered” in relation to community development and social class (Dawson, Jones & Tarizzo 1981). The trachomatous infection starts early in life, but the blinding outcome usually does not occur until adulthood, with a predominance of visual loss in women. The disease can constitute a signifi cant cause of visual disability, adding to the already high burden of disease commonly found in poor rural populations.

Trachoma is caused by Chlamydia trachomatis, a microorganism that is intracellular (like viruses) but susceptible to some antibiotics (like bacteria). Chlamydial infection may give systemic manifestations, including respira-tory tract infections in infants and genital tract infections in adults. The relationship between ocular and genital chlamydial infections is complex and not the subject of this review.

The epidemiology of trachoma is characterized by the early infl amma-tory phase, often during childhood, involving the tarsal conjunctive (the mucous membrane lining inside the eyelids). The upper eyelid is the main site of infl ammation and the infection is invariably bilateral. The invasion of chlamydiae into the conjuctival cells leads to the formation of small


follicles, which represent the infl ammatory reaction to the presence of the infectious agent. The follicles gradually increase in size, up to 1–2 mm; as they “mature,” reaching their optimal size, they rupture and are eventu-ally replaced by scar tissue. The scars can be seen as discrete white lines or stars on the tarsal conjuctival surface. With an increasing number of scars, there is traction inside the eyelid, leading eventually to an inturned lid (entropion), with eyelashes rubbing against the cornea (trichiasis). This causes superfi cial lesions in the corneal epithelium, which over time result in a gradual infi ltrate and opacifi cation of the cornea, often following severe secondary infections.

The classical profi le of trachoma is a severe blinding disease, usually hyperendemic amongst poor and underserved rural populations. The disease can, however, also exist in a non-blinding form with less intense infection, although still prevalent in the communities concerned. Under such circumstances, there is still typically a substantial burden of active infl ammatory disease amongst children, whereas there are very few cases of trichiasis or corneal opacifi cation in the adults.

Trichiasis and corneal opacifi cation usually do not occur until the third or fourth decade of life, but this varies in relation to the intensity of infec-tion. Women tend to have more active infl ammatory disease because of their close contact with children, who constitute a reservoir of infection. Accordingly, trichiasis is particularly common in middle-aged and elderly women (Dawson, Jones & Tarizzo 1981).

The prevention of blindness from trachoma can be effectively achieved by: prevention of trachoma infection through health education and improved standards of living; antibiotic treatment of infl ammatory dis-ease; or surgery against trichiasis to prevent corneal opacifi cation. Specifi c guidelines have been developed for the antibiotic treatment of trachoma, as well as for standard surgical procedures (Reacher et al. 1992).

There have been few attempts in the past to measure the global disease burden of trachoma and the resulting visual loss.

A WHO Scientifi c Group on Trachoma Research in 1959 referred to an estimated 400 million cases of trachoma (World Health Organization 1959). In the 1960s, the results of a number of surveys on trachoma and experience gained in several national campaigns led to a global estimate of 500 million cases of trachoma worldwide, with at least 2 million blind as a result of the disease (Bietti, Freyche & Vozza 1962). Subsequently, in the light of better epidemiological data on blindness, the fi gure for the estimated number of blind was adjusted to 6–9 million (World Health Organization 1984).

In 1985, Dawson & Schachter (1985) estimated by means of a simple model that there could be some 360 million people with trachoma. A more comprehensive model was developed a few years later by the WHO, partially based on the results of a global questionnaire on trachoma (Thy-lefors, Négrel & Pararajasegaram 1992). Thus, it was estimated in 1992 that approximately 146 million people had active infl ammatory disease.

303Trachoma-Related Visual Loss

That estimate took into account only cases of active disease in need of treatment, in accordance with a new and simplifi ed grading system for trachoma (Thylefors et al. 1987). A separate estimate was subsequently put forward, taking into account the number of blind attributable to trachoma and cases with disabling, or potentially disabling, lesions, i.e. corneal opacifi cation and trichiasis (Thylefors et al. 1995). The overall fi gure for this category of blind and those at immediate risk of blindness was 5.9 million.

Definition

A multitude of defi nitions of blindness were in use up to 1972, when a WHO study group on the prevention of blindness recommended a uni-form defi nition for use in surveys and reporting systems. The defi nition is expressed as vision less than 3/60 (0.05) in the better eye with best pos-sible optical correction. This corresponds to the inability to distinguish the fi ngers of a normal hand at a distance of 3 metres (10 feet), and it implies loss of “walk-about” vision. The 1972 recommendation has become uni-versally accepted and is included in the ninth and tenth revisions of the International Classifi cation of Diseases (ICD) (World Health Organization 1977, 1992). The WHO study group also defi ned other categories of visual loss, notably the concept of “low vision,” i.e. signifi cant or severe visual impairment, but not quite blindness, in the individual. Low vision is thus defi ned as vision less than 6/18 (0.3) but equal to or better than 3/60 (0.05). It should be noted that the above recommended defi nitions are mainly for uniform reporting of data; each country may still have its own criteria for social and rehabilitative care for people with visual loss.

The defi nition of trachoma, as given by the WHO Expert Committee on Trachoma in 1962, reads: “Trachoma is a specifi c, communicable kerato-conjunctivitis, usually of chronic evolution, …characterized by follicles, papillary hyperplasia, pannus, and it its later stages, cicatriza-tion” (World Health Organization 1962). The defi nition for a case of trachomatous blindness commonly applied is the central opacifi cation of the cornea (leucoma) in the presence of typical conjunctival scars and entropion/trichiasis.

The classifi cation of trachoma and its complications has evolved over a period of several decades, from the classifi cation proposed by MacCallan in the early part of this century, up to the most recent simplifi ed grading system proposed by the WHO (Thylefors et al. 1987).

Differential diagnostic problems refer mainly to other forms of fol-licular conjunctivitis; criteria for the fi eld diagnosis of trachoma were laid down by the WHO Expert Committee on Trachoma (World Health Organization 1962), e.g. the presence of typical follicles or infi ltrate in the tarsal conjunctiva. Trachoma tends to be underestimated as a cause of blindness, especially in situations where complications of trachoma,


such as suppurative keratitis and phthisis bulbi, are mistakenly recorded as the primary cause.

Review of empirical data bases

Data sources on trachoma are unfortunately very limited. The epidemiol-ogy of the disease is such that only population-based assessments are of value. Surveys of schoolchildren were carried out in many countries in the 1960s, but they are limited by the low rate of school attendance in some settings and the lack of data on trichiasis to confi rm the blinding poten-tial of trachoma in the particular population. Community-based surveys have not been undertaken in many countries in recent years, although the assessment of trachoma is part of the WHO-suggested procedure for an overall blindness survey (Thylefors 1987). The sampling poses a problem in such a situation, when in fact the epidemiological mapping of trachoma is the priority for the planning of intervention. Data for eye clinics are notoriously unreliable for trachoma, in view of the patchy distribution of the disease and its social profi le, being most common in impoverished rural populations.

Overall, trachoma studies tend to be biased to focus on areas where trachoma is strongly suspected or known to exist. Very few nationwide surveys have attempted to give a mapping of trachoma, which is obviously diffi cult, given the focal distribution of the disease in relation to socioeco-nomic, cultural and environmental circumstances.

Available data on trachoma and related visual loss are reviewed in Table 10.1. Studies are included in this compilation only if they are population-

Box 10.1 International Classifi cation of diseases (ICD) codes related to trachoma

ICD-9 ICD-10

076 Trachoma A.71 Trachoma

076.0 Initial stageTrachoma dubium

A.71.0 Initial stage of trachomaTrachoma dubium

076.1 Active stageGranula conjunctivities

(trachomatous)Trachomatous– follicular conjunctivitis– pannus

A.71.1 Active stage of trachomaGranular conjunctivitis

(trachomatous)Trachomatous– follicular conjunctivitis– pannus

076.9 Unspecifi edTrachoma NOS

A.71.9 Trachoma, unspecifi ed

374.0 Entropion and trichiasis of eyelid B.94.0 Sequelae of trachoma

139.1 Late effects of trachoma H.02.0 Entropion and trichiasis of eyelid


Tab

le 1

0.1

R

evie

w o

f ava

ilabl

e da

ta o

n tr

acho

mat

ous

blin

dnes

s: po

pula

tion-

base

d su

rvey

s af

ter

1974

Wor

ld B

ank

Regi

on

Coun

try

or a

rea

Dat

e of

st

udy

Popu

latio

n ex

amin

edBl

indn

ess

(low

vis

ion)

defi

niti

onCo

mm

ents

Prev

alen

ce p

er 1

00 0

00

Refe

renc

eBl

indn

ess

(< 3

/60)

Trac

hom

atou

s Bl

indn

ess

(< 3

/60)

CHI

Chi

na19

82–1

985

433

083

< 3

/60

Sam

ple

surv

ey in

sub

urba

n an

d ru

ral a

reas

. No

info

rmat

ion

on s

ampl

ing

met

hod

is p

rovi

ded.

W

HO

end

orse

d ex

amin

atio

n m

etho

d w

as u

sed.

335

32W

orld

Hea

lth O

rgan

i-za

tion

1985

Chi

na19

871

579

316

< 3

/60

Nat

iona

l ran

dom

sur

vey.

Litt

le in

form

atio

n is

pr

ovid

ed o

n th

e sa

mpl

ing

met

hod.

No

defi n

ition

of

“ru

ral”

and

“ur

ban”

is p

rovi

ded.

432

47Z

hang

et

al. 1

992

Chi

na19

8510

279

—Tr

acho

ma

surv

ey in

one

cou

nty.

Doe

s no

t pr

es-

ent

prev

alen

ce o

f tra

chom

atou

s bl

indn

ess

NR

NR

Hu

et a

l. 19

89

EME

Aus

tral

ia19

76–1

977

5 13

4≤

6/60

Surv

ey o

f Abo

rigi

nes

in w

est

and

cent

ral A

ustr

a-lia

. Met

hod

of s

ampl

e se

lect

ion

is n

ot c

lear

.71

110

7Ta

ylor

198

7

Aus

tral

ia19

901

514

< 3

/60

Surv

ey o

f Abo

rigi

nes

in o

ne a

rea

of s

outh

ern

Aus

tral

ia. S

tudy

pop

ulat

ion

cons

iste

d of

peo

ple

who

vol

unta

rily

pre

sent

ed fo

r ex

amin

atio

n.

1 32

159

4St

ocks

, New

land

&

Hill

er 1

994

IND

Indi

a19

731

060

≤ 6/

60C

omm

unity

sur

vey

in r

ural

Utt

ar P

rade

sh. T

he

villa

ge s

urve

yed

is in

the

are

a of

a r

ural

hea

lth

cent

re. R

epor

ts o

n bl

indn

ess

attr

ibut

able

to

both

tra

chom

a an

d as

soci

ated

con

junc

tiviti

s.

1 03

837

7C

hakr

abar

ti, G

ary

&

Sidd

hu 1

974

Indi

a19

7620

134

≤ 3/

60C

omm

unity

sur

veys

in r

ural

Utt

ar P

rade

sh. V

il-la

ges

clos

est

to t

he h

ealth

cen

tre

wer

e ch

osen

fo

r th

e st

udy.

Onl

y th

ose

repo

rtin

g vi

sual

dif-

fi cul

ty w

ere

exam

ined

.

353

30Sr

ivas

tava

& V

erm

a 19

78

cont

inue

d


Indi

a19

8168

5 20

0 00

0<

3/6

0N

atio

nal c

ensu

s. R

epor

t in

clud

es n

o in

form

atio

n on

exa

min

atio

n m

etho

ds. R

epor

ts o

n bl

indn

ess

attr

ibut

able

to

both

tra

chom

a an

d as

soci

ated

in

fect

ion.

250

50N

SSO

sur

vey

1981

Indi

a19

86–1

989

254

758

< 6

/60

Nat

iona

l ran

dom

clu

ster

sur

vey.

Sam

ple

size

s w

ere

dete

rmin

ed b

ased

on

the

fi ndi

ngs

of t

he

1981

NSS

O s

tudy

. Clin

ical

sta

ging

of t

rach

oma

not

cons

iste

nt w

ith W

HO

cla

ssifi

catio

n. R

esul

ts

are

inco

nsis

tent

from

one

rep

ort

to a

noth

er.

Onl

y 11

cas

es o

f tra

chom

a bl

indn

ess

(< 3

/60)

fo

und.

697

4M

ohan

198

9

LAC

Braz

il19

862

908

< 3

/60

Ran

dom

clu

ster

sam

ple

in o

ne m

unic

ipal

ity in

so

uthe

aste

rn B

razi

l. WH

O S

impl

ifi ed

Gra

d-in

g Sc

hem

e is

use

d fo

r as

sess

ing

prev

alen

ce o

f tr

acho

ma

infe

ctio

n.

NR

0Lu

na e

t al

. 199

2

MEC

Wes

t Ba

nk &

Gaz

a St

rip

1982

–198

36

038

< 3

/60

Ran

dom

clu

ster

sam

ple

in t

wo

geog

raph

ical

ly

sepa

rate

are

as m

ainl

y po

pula

ted

by P

ales

tinia

n A

rabs

. Mos

t ch

ildre

n un

der

the

age

of 5

and

a

smal

l num

ber

of o

lder

chi

ldre

n an

d ad

ults

wer

e un

able

to

unde

rsta

nd o

r co

oper

ate

in v

isua

l ac

uity

tes

ting.

Aut

hors

sta

te t

hat

the

prev

alen

ce

of t

rach

omat

ous

blin

dnes

s in

Wes

t Ba

nk w

as

twic

e th

at in

Gaz

a st

rip.

2 73

336

4T

hom

son

& C

hum

bley

19

84

Tab

le 1

0.1

R

evie

w o

f ava

ilabl

e da

ta o

n tr

acho

mat

ous

blin

dnes

s: po

pula

tion-

base

d su

rvey

s af

ter

1974

(con

tinue

d)

Wor

ld B

ank

Regi

on

Coun

try

or a

rea

Dat

e of

st

udy

Popu

latio

n ex

amin

edBl

indn

ess

(low

vis

ion)

defi

niti

onCo

mm

ents

Prev

alen

ce p

er 1

00 0

00

Refe

renc

eBl

indn

ess

(< 3

/60)

Trac

hom

atou

s Bl

indn

ess

(< 3

/60)


Mor

occo

1992

8 87

8<

3/6

0N

atio

nal,

rand

omiz

ed, s

trat

ifi ed

, com

mun

ity-

base

d su

rvey

.76

030

Mor

occo

Min

istr

y of

Pu

blic

Hea

lth 1

992

Mor

occo

1993

4 79

7—

Ran

dom

ized

clu

ster

sur

vey

of a

tra

chom

a en

dem

ic a

rea.

Obv

ious

bia

s.N

RN

RC

ham

i-Kha

zraj

i, N

égre

l &

Ott

man

i 199

4

Paki

stan

1989

6 69

0<

3/6

0Po

pula

tion-

base

d su

rvey

in t

he N

orth

Wes

t Fr

ontie

r Pr

ovin

ce. O

bvio

us b

ias.

1 00

090

Paki

stan

Min

istr

y of

H

ealth

198

9

Saud

i Ara

bia

1984

14 7

6<

3/6

0N

atio

nal r

ando

m c

lust

er s

ampl

e re

pres

entin

g th

e se

ttle

d po

pula

tion

of S

audi

Ara

bia.

1 50

916

0Ta

bbar

a &

Ros

s-D

eg-

nam

198

6

Saud

i Ara

bia

1981

–199

04

268

< 3

/60

Ran

dom

clu

ster

sam

ple

in a

sin

gle

prov

ince

. T

his

prov

ince

was

foun

d to

hav

e hi

gher

leve

ls o

f bl

indn

ess

than

oth

er r

egio

ns o

f Sau

di A

rabi

a in

th

e 19

84 s

tudy

.

1 50

014

1Ba

dr e

t al

. 199

2

Saud

i Ara

bia

1991

2 88

2<

3/6

0R

ando

m c

lust

er s

ampl

e in

a s

ingl

e pr

ovin

ce.

Defi

niti

on o

f low

vis

ion

used

is u

ncle

ar.

659

0A

l Far

an e

t al

. 199

3

Tuni

sia

1993

3 54

7<

3/6

0N

atio

nal,

rand

omiz

ed c

lust

er s

urve

y. O

bvio

us

bias

(un

der

repr

esen

tatio

n of

mal

es 1

5–54

ye

ars

of a

ge).

800

34Tu

nisi

a 19

93

OAI

Mon

golia

1991

–92

4 34

5<

3/6

0R

ando

m c

lust

er s

ampl

e in

3 o

f the

18

regi

ons

in

Mon

golia

. Onl

y pe

ople

age

d 40

yea

rs a

nd o

lder

w

ere

exam

ined

.

1,58

80

Baas

anhu

et

al. 1

994

Mya

nmar

1990

21 1

03<

3/6

0Ex

amin

atio

n of

non

rand

omly

sel

ecte

d vi

llage

s be

long

ing

to 4

Reg

ions

of t

he P

reve

ntio

n of

Bl

indn

ess

Prog

ram

me.

1,24

062

Tha

n 19

90

Nep

al19

80–8

139

887

< 3

/60

Nat

iona

l ran

dom

clu

ster

sur

vey.

Mos

t tr

acho

ma

is lo

cate

d in

the

Far

Wes

tern

ter

ai (

wes

tern

N

epal

).

840

23Br

illia

nt e

t al

. 198

5

cont

inue

d


Tong

a19

914

056

< 3

/60

Nat

iona

l ran

dom

clu

ster

sur

vey.

Stud

y w

as

rest

rict

ed t

o pe

rson

s ag

ed 2

0 ye

ars

and

over

.46

825

New

land

et

al. 1

994

Vanu

atu

1989

3 52

0<

3/6

0N

atio

nal r

ando

m c

lust

er s

ampl

e. O

nly

incl

uded

pe

rson

s ag

ed 6

yea

rs o

r ol

der.

369

0N

ewla

nd e

t al

. 199

2

Vie

t N

am19

9015

071

< 3

/60

Surv

ey c

arri

ed o

ut in

4 n

orth

ern

and

4 so

uth-

ern

prov

ince

s. N

o in

form

atio

n in

rep

ort

as t

o m

etho

ds u

sed

for

sam

plin

g or

exa

min

atio

n.

860

27N

guye

n et

al.

1992

SSA

Beni

n19

907

047

< 3

/60

Nat

iona

l ran

dom

clu

ster

sam

ple.

Aut

hors

sta

te

that

tra

chom

a is

onl

y pr

eval

ent

in t

he n

orth

ern

part

of t

he c

ount

ry.

600

0W

orld

Hea

lth O

rgan

i-za

tion

1991

Burk

ina

Faso

1991

1

841

—R

ando

miz

ed c

lust

er s

urve

y of

one

reg

ion.

NR

NR

Hut

in e

t al

. 199

2

Cha

d19

84–1

985

5 00

2<

3/6

0N

atio

nal r

ando

m c

lust

er s

ampl

e. L

ittle

info

rma-

tion

rega

rdin

g th

e sa

mpl

ing

and

exam

inat

ion

met

hods

is p

rovi

ded.

2 31

052

6W

orld

Hea

lth O

rgan

i-za

tion

1987

Con

go19

886

185

< 3

/60

Nat

iona

l ran

dom

clu

ster

sam

ple.

Litt

le in

form

a-tio

n re

gard

ing

the

sam

plin

g an

d ex

amin

atio

n m

etho

ds is

pro

vide

d.

307

0W

orld

Hea

lth O

rgan

i-za

tion

1990

Ethi

opia

1981

1 38

3<

3/6

0R

ando

m c

lust

er s

ampl

e in

one

pro

vinc

e. C

on-

duct

ed in

a h

ot, d

ry, d

usty

pro

vinc

e. T

he t

erm

s “u

rban

” an

d “r

ural

” ar

e po

orly

defi

ned

.

940

434

Cer

ruti

et a

l. 19

81

The

Gam

bia

1986

874

< 3

/60

Nat

iona

l ran

dom

clu

ster

sam

ple.

Wel

l-con

duct

-ed

stu

dy w

ith n

o ob

viou

s so

urce

of b

ias.

700

119

Faal

et

al. 1

989

Gha

na19

9196

2<

3/6

0R

ando

m c

lust

er s

ampl

e in

one

dis

tric

t. C

on-

duct

ed in

a s

avan

nah

area

in c

entr

al G

hana

. St

udy

did

not

incl

ude

indi

vidu

als

youn

ger

than

30

yea

rs o

ld. O

nly

67%

of t

he s

ampl

e po

pula

-tio

n w

ere

exam

ined

.

2 49

50

Mol

l et

al. 1

994

Tab

le 1

0.1

R

evie

w o

f ava

ilabl

e da

ta o

n tr

acho

mat

ous

blin

dnes

s: po

pula

tion-

base

d su

rvey

s af

ter

1974

(con

tinue

d)

Wor

ld B

ank

Regi

on

Coun

try

or a

rea

Dat

e of

st

udy

Popu

latio

n ex

amin

edBl

indn

ess

(low

vis

ion)

defi

niti

onCo

mm

ents

Prev

alen

ce p

er 1

00 0

00

Refe

renc

eBl

indn

ess

(< 3

/60)

Trac

hom

atou

s Bl

indn

ess

(< 3

/60)

309Trachoma-Related Visual LossK

enya

1990

895

< 3

/60

Surv

eys

cond

ucte

d at

non

rand

omly

sel

ecte

d si

tes

in o

ne r

egio

n. C

ondu

cted

in a

sem

i-des

ert

area

in n

orth

-wes

t K

enya

. Stu

dy is

too

sm

all

to r

elia

bly

asse

ss p

reva

lenc

e of

tra

chom

atou

s bl

idne

ss.

1 11

722

3Lo

ewen

thal

& P

eer

1990

Ken

ya19

7684

4<

3/6

0Si

mpl

e ra

ndom

sam

ple

at t

wo

nonr

ando

mly

se

lect

ed s

ites.

In c

entr

al K

enya

. Met

hods

use

d fo

r de

term

inin

g ca

use

of b

lindn

ess

are

not

prov

ided

. Defi

niti

ons

of “

activ

e” a

nd “

inac

tive”

di

seas

e ar

e no

t pr

ovid

ed. S

tudy

is t

oo s

mal

l to

rel

iabl

y as

sess

pre

vale

nce

of t

rach

omat

ous

blin

dnes

s.

1 65

911

8W

hitfi

eld

et

al. 1

983

Ken

ya19

7613

803

< 3

/60

Ran

dom

clu

ster

sam

ple

in 8

rur

al a

reas

.70

013

0W

hitfi

eld

et

al. 1

990

Mal

awi

1983

1 57

4<

3/6

0Su

rvey

s of

ran

dom

ly s

elec

ted

villa

ges

in o

ne

regi

on. C

ondu

cted

in a

reg

ion

of c

entr

al M

alaw

i w

here

blin

dnes

sis

par

ticul

arly

com

mon

. Peo

ple

youn

ger

than

6 y

ears

wer

e no

t ex

amin

ed.

1 27

10

Chi

ram

bo e

t al

. 198

6

Mal

i19

853

538

< 3

/60

Ran

dom

ized

, com

mun

ity b

ased

sur

vey

of a

rur

al

regi

on. T

his

thes

is s

tudy

was

con

duct

ed in

the

K

ayes

Reg

ion.

1 30

036

9Ya

ttas

saye

198

5

Mal

i19

853

299

< 3

/60

Ran

dom

ized

, com

mun

ity b

ased

sur

vey

of a

rur

al

regi

on. T

his

thes

is s

tudy

was

con

duct

ed in

the

M

opti

Reg

ion.

1 00

034

0Bo

ré 1

985

Nig

er19

902

958

<3/

60C

omm

unity

-bas

ed, r

ando

miz

ed c

lust

er s

urve

y. O

bvio

us b

ias.

1 30

040

0K

abo

1990

Nig

eria

1988

–198

96

831

< 3

/60

Surv

eys

of n

onra

ndom

ly s

elec

ted

rura

l com

-m

uniti

es. S

tudy

con

duct

ed in

an

onch

ocer

cias

is

mes

oend

emic

are

a in

nor

ther

n N

iger

ia. S

tudy

di

d no

t in

clud

e ch

ildre

n yo

unge

r th

an 5

yea

rs.

Wou

ld b

e a

good

stu

dy fo

r lo

okin

g at

sex

rat

io,

but

does

not

rep

ort

tota

l num

bers

of m

ales

and

fe

mal

es e

xam

ined

.

3 32

327

8A

bios

e 19

94

cont

inue

d


Tab

le 1

0.1

R

evie

w o

f ava

ilabl

e da

ta o

n tr

acho

mat

ous

blin

dnes

s: po

pula

tion-

base

d su

rvey

s af

ter

1974

(con

tinue

d)

Wor

ld B

ank

Regi

on

Coun

try

or a

rea

Dat

e of

st

udy

Popu

latio

n ex

amin

edBl

indn

ess

(low

vis

ion)

defi

niti

onCo

mm

ents

Prev

alen

ce p

er 1

00 0

00

Refe

renc

eBl

indn

ess

(< 3

/60)

Trac

hom

atou

s Bl

indn

ess

(< 3

/60)

Sout

h A

fric

a19

761

207

< 6

/60

Ran

dom

clu

ster

sam

ple

in a

rur

al c

omm

unity

. C

ondu

cted

in a

n ar

ea k

now

n to

be

trac

hom

a en

dem

ic. S

ampl

e no

t re

pres

enta

tive;

wor

king

ag

e m

ales

und

erep

rese

nted

.

NR

331

Balla

rd, S

utte

r &

Fot

h-er

ingh

an 1

978

Sout

h A

fric

a19

791

749

< 6

/60

Ran

dom

clu

ster

sam

ple

in a

rur

al c

omm

unity

. C

ondu

cted

in a

n ar

ea k

now

n to

be

trac

hom

a en

dem

ic. S

ampl

e no

t re

pres

enta

tive;

wor

king

ag

e m

ales

und

erep

rese

nted

.

NR

610

Balla

rd e

t al

. 198

3

Sout

h A

fric

a19

8518

962

< 3

/60

Exam

inat

ion

of a

ll re

side

nts

in r

ando

mly

se

lect

ed v

illag

es in

one

dis

tric

t. D

istr

ict

has

an

opht

halm

ic h

ospi

tal.

Far

few

er m

ales

exa

min

ed

than

fem

ales

.

575

58Bu

cher

& Ij

sslm

uide

r 19

88

Tanz

ania

1986

1 82

7<

3/6

0R

ando

m c

lust

er s

ampl

e in

an

area

kno

wn

to b

e hy

pere

ndem

ic fo

r tr

acho

ma.

Vis

ual a

cuity

was

on

ly m

easu

red

in in

divi

dual

s ol

der

than

7 y

ears

1 25

932

8R

apoz

a et

al.

1991

Togo

1981

–198

611

081

< 3

/60

Ran

dom

clu

ster

sur

veys

of 4

rur

al a

reas

. WH

O

sam

plin

g pr

oced

ures

. Pre

vale

nce

of t

rach

oma-

tous

blin

dnes

s is

onl

y av

aila

ble

for

1 of

4 a

reas

.

NR

NR

Wor

ld H

ealth

Org

ani-

zatio

n 19

89

NR

= n

ot r

epor

ted


based surveys in which the criteria for blindness are clearly defi ned. Only studies conducted after 1974 are included.

In Table 10.1, blindness and trachomatous blindness refer to best corrected visual acuity less than 3/60. Values from studies that used dif-ferent defi nitions of blindness have been adjusted based on the following assumptions:

the prevalence of best corrected visual acuity less than 6/60 is 1.5 times the prevalence of best corrected visual acuity less than 3/60;

the prevalence of best corrected visual acuity less than or equal to 6/60 is 2 times the prevalence of best corrected visual acuity less than 3/60 (Thylefors et al. 1995).

Only 11 country-wide, population-based surveys (13 studies) were found to have looked at the prevalence of trachomatous blindness.

Estimation of the burden of trachoma

The calculation of disability adjusted life years (DALYs) lost as a result of trachomatous blindness and low vision requires the following informa-tion: age-specifi c and sex-specifi c values of the prevalence of trachomatous blindness and low vision for each of the eight GBD regions; the increased risk of mortality incurred by trachomatous blindness or visual loss; and disability weights for both blindness and low vision, which express the fraction of a year of life lost because of having to live for that year with disability (disability weights are discussed in the next section.

In order to develop regional prevalence values for trachomatous blind-ness, countries were grouped by the authors according to the following scale:

0 = no known trachoma;

1 = trachoma infection, but no trachomatous blindness;

2 = trachoma infection, low prevalence of trachomatous blindness (≤ 100 per 100 000);

3 = trachoma infection, high prevalence of trachomatous blindness (> 100 per 100 000).

For each region with endemic blinding trachoma, estimates based on the 11 available country studies and the country populations concerned were then applied for categories 2 and 3 above. Box 10.2 sets out these estimates.

To consider both blindness and low vision caused by trachoma, the above-mentioned comprehensive review of available population-based surveys was used to determine the ratio of visual loss to blindness. It was found, based on 13 studies, that for each case of trachomatous blindness


there are 1.16 individuals with trachomatous visual loss (Table 10.2). This proportion has subsequently been applied in the assessment of low vision attributable to trachoma in each region and globally. Data analysis based on seven studies gave a sex ratio of 1.00:2.86 for male-to-female prevalence of trachomatous blindness. This ratio was applied uniformly to all countries with trachoma-related blindness and low vision (Table 10.3). Furthermore, the age distribution of the prevalence of blindness and low vision was calculated based on four studies, and the fi nal result was applied to all endemic countries or areas (Table 10.4).

Regional prevalence values for trachomatous blindness and low vision are shown in Table 10.5. Tables 10.6 to 10.11 provide age-specifi c and sex-specifi c values for the prevalence of trachomatous blindness in each of the regions and globally.

Box 10.2 Regional prevalence per 100 000 for trachomatous blindness according to prevalence level

World Bank Region Low prevalence (category 2) High prevalence (category 3)

SSA 75 203

MEC 31 160

OAI 26 —

CHI 47 —

IND 4 —

Table 10.2 Ratio of people with low vision (< 6/18 – 3/60) to people with blindness (< 3/60)

ReferencePopulation examined

Number of Blind (< 3/60)

Number with low vision

(</6/18–3/60)

Ratio of low visioned to

blind

Zgang et al. 1992 1 579 316 742 869 1.17:1.00Thomson & Chumbley 1984 6 038 22 11 0.50:1.00Chami-Khazraji et al. 1992 8 878 3 3 1.30:1.00Pakistan Ministry of Health x1989

6 690 6 1 0.17:1.00

Badr et al. 1992 4 268 6 8 1.33:1.00Tunisia 1993 3 547 1 1 0.99:1.00Whitfi eld et al. 1983 844 1 3 3.00:1.00Whitfi eld et al. 1990 13 803 18 46 2.54:1.00Yattassaye 1985 3 538 13 10 0.78:1.00Boré 1985 3 299 11 11 1.00:1.00Abiose 1994 6 831 19 12 0.63:1.00Rapoza et al. 1991 1 927 6 3 0.50:1.00

Totals 1 645 926 848 981 1.16:1.00


Table 10.3 Ratio of female prevalence of trachomatous blindness to male prevalence

Reference

Prevalence of trachomatous blindness per 100 000

Ratio of female prevalence to male prevalenceMales Females

Taylor 1987 62 147 2.37 :1.00Tabbasa & Ross-Degnan 1986 146 173 1.19 :1.00Bucher & Ijsselmuiden 1958 13 89 6.81:1.00

Total 37 104 2.86 :1.00

Table 10.4 Age distribution of the prevalence of trachomatous blindness

Age (years)

Total population surveyed for visual

impairmenta

Trachomatous blindness

Number blindaPrevalence per

100 000Distribution of prevalence (%)

0–4 4 280 0 8 05–14 6 459 1 11 015–44 9 697 6 67 245–59 1 500 8 544 1860+ 1 240 30 2 419 80

Total 23 176 46 3 049 100

a. Numbers derived from Ballard et al. (1983), Tabbara & Ross-Degnan (1986), Rapoza et al. (1991), and Badr et al. (1992).

Table 10.5 Prevalence of trachomatous blindness and low vision by region

World Bank Region

1990 Population (thousands)

Trachomatous blindness Trachomatous low vision

Prevalence per

100 000 Number

Prevalence per

100 000 Number

China 1 134 693 47 533 096 54 616 386

Established Market xEconomiesa

797 790 0 0 0 0

Formerly Socialist xEconomies of Europeb

346 237 0 0 0 0

India 849 514 4 37 813 5 43 721

Latin America & the xCaribbeanc

444 295 0 0 0 0

Middle Eastern xCrescent

503 075 73 364 928 844 21 944

Other Asia & Islands 682 534 10 67 497 11 78 042

Sub-Saharan Africa 510 274 93 472 663 107 546 511

Total 5 268 412 28 1 475 997 32 1 706 604

a. Blinding trachoma is known to exist only among Australian Aborigines, who are not considered representa-tive of the region.

b. Pockets of trachoma may exist but no information on trachomatous blindness could be identifi ed.

c. Trachoma is known to be endemic in parts of Brazil, Guatemala, Mexico and Peru but its blinding propen-sity is considered insignifi cant.


Tab

le 1

0.6

A

ge a

nd s

ex d

istr

ibut

ion

of t

he p

eopl

e w

ith b

lindn

ess

or lo

w v

isio

n at

trib

utab

le t

o tr

acho

ma,

Chi

na, 1

990

Age

(yea

rs)

Popu

latio

n (th

ousa

nds)

Num

ber

Blin

ded

by Tr

acho

ma

Num

ber

with

low

visi

on a

ttrib

utab

le to

trac

hom

a

Mal

esFe

mal

esTo

tal

Mal

esFe

mal

esTo

tal

Mal

esFe

mal

esTo

tal

0–

460

243

57 9

4611

8 18

90

00

00

05–

1496

997

90 4

0118

7 39

80

00

00

015

–44

307

305

284

078

591

383

15 2

6537

616

53 8

8317

650

43 4

936

301

45–5

972

674

64 4

0313

7 07

732

489

76 7

5211

2 40

637

565

88 7

4312

9 96

860

+48

980

51 6

6610

0 64

697

318

273

656

366

807

112

523

316

411

424

116

Tota

l58

6 19

954

8 49

41

134

693

145

072

388

024

533

096

167

738

448

648

616

386

Tab

le 1

0.7

A

ge a

nd s

ex d

istr

ibut

ion

of t

he p

eopl

e w

ith b

lindn

ess

or lo

w v

isio

n at

trib

utab

le t

o tr

acho

ma,

Indi

a, 19

90

Age

(yea

rs)

Popu

latio

n (th

ousa

nds)

Num

ber

blin

ded

by tr

acho

ma

Num

ber

with

low

visi

on a

ttrib

utab

le to

trac

hom

a

Mal

esFe

mal

esTo

tal

Mal

esFe

mal

esTo

tal

Mal

esFe

mal

esTo

tal

0–

459

789

56 6

7911

6 46

80

00

00

05–

1410

1 75

295

263

197

015

00

00

00

15–

4420

0 52

518

3 24

238

3 76

71

136

2 87

34

061

1 31

43

322

4 69

545

–59

47 5

6746

005

93 5

722

426

6 49

28

911

2 80

57

506

10 3

0360

+29

768

28 9

2458

692

6 74

718

140

24 8

417

801

20 7

428

723

Tota

l43

9 40

141

0 11

384

9 51

410

309

27 5

0437

813

11 9

2031

802

43 7

21


Tab

le 1

0.8

A

ge a

nd s

ex d

istri

butio

n of

the

peop

le w

ith b

lindn

ess

or lo

w v

ision

att

ribu

tabl

e to

trac

hom

a, M

iddl

e Ea

ster

n C

resc

ent,

1990

Age

(yea

rs)

Popu

latio

n (th

ousa

nds)

Num

ber

blin

ded

by tr

acho

ma

Num

ber

with

low

visi

on a

ttrib

utab

le to

trac

hom

a

Mal

esFe

mal

esTo

tal

Mal

esFe

mal

esTo

tal

Mal

esFe

mal

esTo

tal

0–

441

161

39 7

3480

895

00

00

00

5–14

65 3

4561

999

127

344

00

00

00

15–

4411

3 89

510

7 21

122

1 10

612

872

30 9

9145

158

14 8

8335

832

52 2

1345

–59

22 3

3722

292

44 6

2922

720

57 9

9482

033

26 2

7067

055

94 8

5060

+13

651

15 4

5029

101

61 7

1217

8 40

237

738

71 3

5420

6 55

027

4 88

1

Tota

l25

6 38

924

6 68

650

3 07

597

304

267

624

364

928

112

507

309

437

421

944

Tab

le 1

0.9

A

ge a

nd s

ex d

istri

butio

n of

the

peop

le w

ith b

lindn

ess

or lo

w v

ision

att

ribu

tabl

e to

trac

hom

a, O

ther

Asia

and

Isla

nds,

1990

Age

(yea

rs)

Popu

latio

n (th

ousa

nds)

Num

ber

blin

ded

by tr

acho

ma

Num

ber

with

low

visi

on a

ttrib

utab

le to

trac

hom

a

Mal

esFe

mal

esTo

tal

Mal

esFe

mal

esTo

tal

Mal

esFe

mal

esTo

tal

0–

443

763

41 9

8885

751

00

00

00

5–14

84 0

3280

217

164

249

00

00

00

15–

4416

0 82

515

9 61

132

0 43

62

220

5 76

18

136

2 56

76

661

9 40

745

–59

34 1

3835

090

69 2

284

242

11 3

9815

820

4 90

513

179

18 2

9260

+20

208

22 6

6242

870

11 1

6032

716

43 5

4012

903

37 8

2850

343

Tota

l34

2 96

633

9 56

868

2 53

417

622

49 8

7567

497

20 3

7557

667

78 0

42


Tab

le 1

0.1

1A

ge a

nd s

ex d

istri

butio

n of

the

peop

le w

ith b

lindn

ess

or lo

w v

ision

att

ribu

tabl

e du

e to

trac

hom

a th

roug

hout

the

wor

ld, 1

990

Age

(yea

rs)

Popu

latio

n (th

ousa

nds)

Num

ber

blin

ded

by tr

acho

ma

Num

ber

with

low

visi

on a

ttrib

utab

le to

trac

hom

a

Mal

esFe

mal

esTo

tal

Mal

esFe

mal

esTo

tal

Mal

esFe

mal

esTo

tal

0–

432

1 30

430

9 25

363

0 55

70

00

00

05–

1455

1 20

552

5 54

31

076

748

00

00

00

15–

441

250

941

1 19

8 64

22

449

583

49 1

8312

3 18

117

6 48

756

867

142

427

204

061

45–5

931

2 38

531

1 06

762

3 45

293

036

239

697

337

796

107

572

275

990

390

573

60+

218

857

269

215

488

072

248

594

723

306

961

713

287

433

836

141

111

969

Tota

l2

654

692

2 61

3 72

05

268

412

390

813

1 08

5 18

41

475

997

451

872

1 25

4 73

11

706

604

Tab

le 1

0.1

0A

ge a

nd s

ex d

istr

ibut

ion

of t

he p

eopl

e w

ith b

lindn

ess

or lo

w v

isio

n at

trib

utab

le t

o tr

acho

ma,

Sub-

Saha

ran

Afr

ica,

1990

Age

(yea

rs)

Popu

latio

n (th

ousa

nds)

Num

ber

blin

ded

by tr

acho

ma

Num

ber

with

low

visi

on a

ttrib

utab

le to

trac

hom

a

Mal

esFe

mal

esTo

tal

Mal

esFe

mal

esTo

tal

Mal

esFe

mal

esTo

tal

0–

447

484

47 0

3094

514

00

00

00

5–14

70 2

5869

818

140

076

00

00

00

15–

4410

3 76

410

6 25

721

0 02

117

690

45 9

4165

250

20 4

5453

118

75 4

4545

–59

20 3

0822

117

42 4

2531

159

86 0

6211

8 62

736

027

99 5

0813

7 16

160

+10

508

12 7

3023

238

71 6

5622

0 15

528

8 78

682

852

254

552

333

906

Tota

l25

2 32

225

7 95

251

0 27

412

0 50

535

2 15

847

2 66

313

9 33

340

7 17

854

6 51

1


The increased risk of mortality associated with blindness and low vision is derived from a study conducted in Africa (Kirkwood et al. 1983), in the absence of data from other regions. This study found the standardized mortality rate to be 3.8 times higher among females blind as a result of all causes and 2.5 times higher among blind males than among normal sighted. The standardized mortality rate was found to be 1.5 times higher among females with low vision and 1.4 times higher among males with low vision than among normal sighted controls.

Disability

The rating of blindness in the grading of severity of disability needs to be adjusted. Blindness implies severe repercussions for daily living activities, as defi ned in category 6; all blind people should therefore be classifi ed in category 6, and people with low vision in category 5.

Other considerations

The pathway to blindness from trachoma is not specifi c, in the sense that the corneal opacifi cation induced by trachomatous trichiasis may be the result of secondary infections. Therefore, if there is not enough aware-ness of the endemicity of trachoma in an area, it is likely that there will be an underestimate as to the role of trachoma as a cause of blindness. Furthermore, in certain rural settings, particularly in north Africa, there are regular seasonal epidemics of conjunctivitis (Kupta, Nicetic & Reinhards 1968, Reinhards et al. 1968), which is transmitted by fl ies in great num-bers. There is a known interaction between conjunctivitis epidemics and the increased prevalence and intensity of trachoma in such populations, but this fact may easily be overlooked by local health staff.

A majority of victims of trachomatous blindness are women because of their prolonged and close contact with affected children, who act as a reservoir of Chlamydia. The impact of severe trachoma can therefore be considerable in making women of working age unable to fulfi l their family and socioeconomic role.

Disease as risk factor for other diseases

Trachoma in its advanced stage, with corneal complications, increases considerably the risk of secondary corneal infections, which often lead to ulcers and severe loss of vision. Long-standing cases of trachoma are likely to develop the “dry eye” syndrome because of tear gland involvement; this, again, acts as a further risk factor for blindness from infections as a result of increased susceptibility of the eye. Furthermore, it should be noted that cases of advanced trachoma with corneal complications are diffi cult and high risk cases for eye surgery such as corneal transplants or cataract or glaucoma surgery.


It has been demonstrated in Africa and North America that blindness is associated with increased mortality (Hirsh & Schwartz 1983, Kirkwood et al. 1983). This may be a result of increased vulnerability, as a consequence of neglect, absence of social care and increased risk of accidents; it may also be that blindness attributable to certain causes, such as cataract, is a marker of ageing and thus an increased mortality.

Burden of trachoma and intervention

Treatment of trachoma should be carried out on a priority basis in com-munities with blinding trachoma. The objective of treatment is normally limited to elimination of blindness from trachoma, as it is neither feasible to eradicate the disease nor to eliminate the chlamydiae in the populations concerned.

Treatment of trachoma is based on antibiotic topical or systemic treat-ment or both, surgery for inturned eyelids, and health education pertaining to improved personal and environmental hygiene. Given that trachoma is often highly endemic in affected rural communities, the antibiotic treat-ment is mainly a suppressive scheme (Dawson, Jones & Tarizzo 1981) to reduce disease intensity; reinfections rapidly occur in the communities or families concerned unless other measures to improve living standards and behaviour occur (West et al. 1991). Thus, the effectiveness of trachoma antibiotic treatment is limited to disease suppression, not to elimination. Trichiasis surgery has recently been systematically evaluated (Reacher et al. 1992) and a uniform method proposed.

Access to trachoma treatment for affected populations must be provided regularly and in a long-term (several years) perspective.

The annual cost of preventing blindness from trachoma can schemati-cally be calculated as the cost of one tube (5 gram) of tetracycline eye ointment per person per year; at present, this amounts to approximately 15 US cents in a bulk purchase. The preventive treatment should be provided throughout childhood if the level of intense infl ammatory disease remains high in the community concerned. Distribution costs will depend on how community-based the control programme is in terms of primary health care, or volunteer or self-treatment options. A more comprehensive model for the cost of preventive topical or systemic treatment of trachoma has been put forward (Dawson & Schachter 1985).

Trichiasis surgery can commonly be made available for a cost of approxi-mately US$5–10 (consumables and partial cost of instruments).

Cessation of the current trachoma control activities could potentially result in a doubling of the incidence of blindness from trachoma over a period of 10–20 years. In contrast, if currently available interventions were systematically applied in all endemic areas, it might be possible to eliminate trachoma as a cause of blindness over the next 10 years. This would necessitate strong governmental commitment with allocation of needed resources, as well as environmental improvements (water and sani-


tation) where needed, and behavioural changes for improved hygiene. A new and more effective antibiotic treatment could substantially improve the perspective of global trachoma control such as may be possible with azithromycin, a new and long-acting macrolide.

Discussion

Trachoma has been subject to numerous attempts of control in the past. Various medical and surgical treatment schemes have been used over the centuries to get rid of the characteristic follicles on the inside of the eye-lids, from copper-sulphate etching in pharaonic Egypt, to surgical com-pression of follicles with special forceps well into the 20th century. On a public health level, trachoma was recognized as an important infectious eye disease and cause of blindness; it was a matter of concern in relation to population movements in Europe, and in the past immigration to the United States of America in the 19th and early 20th centuries.

Effective public health measures specifi cally against trachoma were not taken until after the Second World War. By then antibiotics were becom-ing available, and when the WHO started its work in the late 1940s, trachoma was one of the fi rst diseases subject to fi eld research on more effective large-scale control measures. After a number of fi eld studies during the 1950s, particularly in North Africa, a control strategy was designed consisting of:

antibiotic treatment with 1 per cent tetracycline eye ointment, which could be applied on an intermittent basis;

access to simplifi ed and standardized trichiasis surgery;

health education.

This strategy was consistently implemented over the following two decades by the WHO, often in partnership with UNICEF , in most of the endemic countries. The results were often quite positive, particularly in areas of socioeconomic development, where there were improved living standards and opportunities for changes in lifestyle. This is not surprising; trachoma disappeared spontaneously in several European countries as a result of better hygiene and living standards well before the antibiotic era. Suppressive treatment of trachoma with antibiotics allows for rapid control of the blinding intensity of infection. That element of the strategy is very important in terms of preventing blindness, particularly in areas where there are no immediate prospects of improving living standards.

The global picture of trachoma has changed considerably over the past few decades as a result of the above-mentioned disease control efforts and socio-economic developments. As the disease is so closely linked to the social and public health situation, with poverty, crowding, and lack of hygiene as major propagating factors, the epidemiological pattern varies accordingly. This leads in many settings to diffi culties in properly


assessing trachoma and its blinding propensity. The distribution of the disease is often quite focal, with variations in its intensity. Furthermore, signifi cant differences in disease patterns can occur rapidly, as a result of sudden behavioural or environmental changes, for example urbanization or access to tap water.

Today trachoma is largely confi ned to the poorest population groups in some 40 developing countries that are still endemic. The disease has been pushed back in many countries, and is now found mainly in underserved rural areas where there is little hope of socioeconomic development. This makes it imperative to mount interventions for the prevention of blindness from trachoma in these particularly vulnerable populations, as it may take many years before the benefi ts of improved living conditions wipe out the disease as a cause of visual loss.

For the reasons given above, the present global estimate of trachoma given in this report can only be indicative. It is based on patchy epidemio-logical data, indicating only the likely magnitude of trachoma-related visual loss in known endemic countries. Still, in the absence of the large-scale population-based surveys that would be needed to derive a more reliable estimate, the present estimate is probably the most reasonable, recognizing the limitation of not having more accurate and updated information from several major populations where recent disease changes are likely to have occurred (e.g. China and India). It should also be noted that the present estimate is very conservative, as it is based on a strict defi nition of visual loss only in conjunction with trichiasis. This defi nition, although specifi c, does not take into account other pathways to blindness from trachoma, e.g. invasive pannus or corneal ulceration, often leading to a condition of phthisis bulbi, which can have multiple origins.

It is important to recognize the association of blinding trachoma with low standards of living; this allows for the focusing of interventions on the poorest population groups, where trachoma is likely to be a very signifi cant cause of blindness and an obstacle to community development. The SAFE strategy (surgery; antibiotics; facial cleanliness; environmental hygiene) includes all the essential elements for successful trachoma control. The surgery for trichiasis can prevent new cases of blindness; the antibiotics can control the infection; and the personal and environmental hygiene provide the answer to sustainability of achievements in the future. The recent avail-ability of much-improved antibiotic treatment with azithromycin opens up new perspectives for rapid and effective control of trachomatous infection in the target populations, thus allowing for an accelerated implementation of the SAFE strategy where needed.

Conclusions

Trachoma is the most important cause of easily preventable visual loss in the world. It adds signifi cantly to the disability burden amongst vulner-able poor population groups, where the disease is commonly found today.


Trachoma control efforts, together with socioeconomic progress, have pushed back the disease in many countries, but in remaining endemic areas there is still a great need for the prevention of blindness from trachoma. A comprehensive intervention strategy, including improved antibiotics, holds out the promise of eliminating trachoma as a public health problem.

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Chagas DiseaseA Moncayo

Chapter 11

Introduction

Chagas disease, named after the Brazilian physician Carlos Chagas who fi rst described it in 1909, exists only on the American continent (Chagas 1909). It is caused by a fl agellate protozoan parasite Trypanosoma cruzitransmitted to humans by blood-sucking triatomine bugs and by blood transfusion.

Chagas disease has two successive phases: acute and chronic. The acute phase lasts six to eight weeks. Once the acute phase subsides, most infected patients recover an apparently healthy status, in which no organ damage can be demonstrated by the current standard methods of clinical diagnosis. The infection can be verifi ed only by serological or parasitological tests. This form of the chronic phase of Chagas disease is called the indeterminate form. Most patients remain forever in this form of the disease. However, several years after of starting the chronic phase, and depending on the geographical area, 10–40 per cent of the infected individuals will develop lesions of different organs, mainly the heart and the digestive system. These conditions are called the cardiac or digestive forms of chronic Chagas disease. The chronic phase lasts the rest of the life of the infected individual.

Chagas disease is the primary cause of cardiac lesions in young, eco-nomically productive adults in the endemic countries in Latin America. It has been targeted for elimination by the World Health Assembly in Resolution WHA51.14, approved in May 1998 (World Health Organiza-tion 1998b).

Transmission by vectors

Chagas disease is a zoonosis transmitted in natural foci or ecological units within a well-defi ned geographical environment. The ecological unit is composed of sylvan or domestic mammals and of sylvan triatoma bugs,


both infected with T. cruzi. Continuous transmission is assured with or without the involvement of human beings.

These conditions of transmission are present from latitude 42°N to latitude 40°S. T. cruzi infection extends from the south of the United States T. cruzi infection extends from the south of the United States T. cruzito the south of Argentina.

There are two phases of the human disease: the acute phase, which appears shortly after the infection; and the chronic phase, which may last several years and irreversibly affect the autonomic nervous system and internal organs, in particular the heart, the oesophagus and the colon, and the peripheral nervous system.

After an asymptomatic period of several years, 27 per cent of those infected develop cardiac symptoms that may lead to chronic heart failure and sudden death, 6 per cent develop digestive damage, mainly mega colon and mega oesophagous, and 3 per cent suffer peripheral nervous involvement (Pereira, Willcox & Coura 1985, Coura, Anunziato & Willcox 1983, Coura et al.1985).

Transmission via blood transfusion

The rural-to-urban migration movements that occurred in Latin America in the 1970s and 1980s changed the traditional epidemiological pattern of Chagas disease as a rural condition and transformed it into an urban infection that can be transmitted by blood transfusion.

In most countries in Latin America it is now compulsory to screen for infected blood in blood banks, and systems have been established to do so.

Defi nition

Chagas disease and its clinical forms are classifi ed in the tenth revision of the International Classifi cation of Diseases (ICD-10) under code B57. There have been no changes in the classifi cation of the disease in the last three revisions of the ICD.

Methods and Measurement

Transmission by vectors

Data on the prevalence and distribution of Chagas disease improved in quality during the 1980s as a result of the demographically representative cross-sectional studies carried out in countries where accurate information was not available.

A group of experts meeting in Brasilia in 1979 devised standard pro-tocols to carry out countrywide prevalence studies on human T. cruziinfection and triatomine house infestation. These studies were carried out during the 1980s in collaboration with the Ministries of Health of Chile, Colombia, Ecuador, Honduras, Panama, Paraguay, and Uruguay. The accurate information obtained has made it easier for individual countries to plan and evaluate the effectiveness of national control programmes

327Chagas Disease

(Pan American Health Organization 1974, Cedillos 1975, Marinkelle 1976, Zeledon 1976, Cordova et al. 1980, Camargo et al. 1984, Ponce 1984, Reyes Lituma 1984, Lopez 1985, Matta 1985, Schenone et al. 1985, Sousa 1985, Salvatella et al. 1989, Acquatella 1987, Valencia 1990) (see Table 11.1).

On the basis of these individual countrywide surveys it is estimated that the overall prevalence of human T. cruzi infection in the 18 endemic countries is 17 million cases. Some 100 million people (25 per cent of all the inhabitants of Latin America) are at risk of contracting T. cruzi infec-tion (see Table 11.2).

The incidence was estimated in 1991 at 700 000–800 000 new cases per year and the annual deaths attributable to the cardiac form of Chagas disease at 45 000 (UNDP/World Bank/WHO 1991).

The endemic countries can be divided into three groups according to such indicators as: number of confi rmed human cases; prevalence of sero-positive tests in blood donors and population samples; and the presence of infected vectors and reservoirs. The main factors on which these criteria are based are the following: magnitude of the transmission; quantity and qual-ity of the available epidemiological information; and existence or absence of coordinated actions towards the control of this disease (UNDP/World Bank/WHO 1987). The groups are identifi ed as described below.

Table 11.1 Prevalence studies of human T. cruzi infection in Latin America

Sample size

Percentage infected Year Reference Remarks

Argentina nd 10.0 1976 Pan American Health Organization 1974

Estimation

Bolivia 56 000.a 24.0 1980 Valencia 1990 CountrywideBrazil 1 352 917.a 4.2 1980 Camargo et al. 1984 CountrywideChile 13 514.a 16.9 1985 Schenone et al. 1985 CountrywideColombia 20 000 30.0 1975 Marinkelle 1976 Endemic areasCosta Rica 1 420 11.7 1976 Zeledon 1976 Endemic areasEcuador 532 10.7 1984 Reyes Lituma 1984 Endemic areasEl Salvador 524 20.0 1975 Cedillos 1975 Rural areasGuatemala 3 952.a 16.6 1982 Matta 1985 CountrywideHonduras 3 802.a 15.2 1984 Ponce 1984 CountrywideMexico nd nd ndNicaragua nd nd ndPanama 1 770 17.7 1984 Sousa 1985 Endemic areasParaguay 4 037.a 21.4 1983 Lopez 1985 CountrywidePeru 92 9.8 1980 Cordova et al. 1980 Age group 0–6

yearsUruguaya 5 924 3.4 1985 Salvatella et al. 1989 CountrywideVenezuela 5 696 3.0 1983 Acquatella 1987 Age group < 24

years

a Demographic sample statistically representative of the country‘s population.

nd = no data


Group 1

The countries of this group present high prevalence of human T. cruziinfection and high triatomine house infestation rates. These conditions have induced the national health authorities to establish control activities through vertical programmes or, more recently, within the context of pri-mary health care strategies. Argentina, Bolivia, Brazil, Chile, Colombia, Honduras, Paraguay, Peru, Uruguay and Venezuela are included in this group.

Group 2

All the countries included in this group show evidence of intra-domicili-ary transmission, with a clear association between T. cruzi infection and electrocardiographic alterations as well as other pathologies attributable to Chagas’ disease. No formal control programmes have yet been estab-lished in these countries. Costa Rica, Ecuador, and Mexico belong to this group.

Group 3

These countries show evidence of domiciliary transmission, but more accurate epidemiological data are needed to support a clear correlation between T. cruzi infections and clinical records. In all these countries, the acute phase of Chagas disease is frequently observed, and recent serologi-

Table 11.2 Prevalence of human T. cruzi infection in Latin America, T. cruzi infection in Latin America, T. cruzi1975–1985


Percentage of total population

Number of infected people (thousands)

Argentina 6 900 23 2 640Bolivia 1 800 32 1 300Brazil 41 054 32 6 180Chile 11 600 63 1 460Colombia 3 000 11 900Costa Rica 1 112 45 130Ecuador 3 823 41 30El Salvador 2 146 45 900Guatemala 4 022 54 1 100Honduras 1 824 47 300Mexico nd nd ndNicaragua nd nd ndPanama 898 47 200Paraguay 1 475 31 397Peru 6 766 39 621Uruguay 975 33 37Venezuela 12 500 72 1 200

Total 99 895 25 17 395

nd = no data.

329Chagas Disease

cal data indicate that the prevalence of seropositive reactions to T. cruzi antigens is high. El Salvador, Guatemala, Nicaragua, and Panama are included in this group.

Transmission via blood transfusion

Table 11.3 shows the extent of the problem of transmission via blood transfusion in some selected Latin American cities between 1980 and 1989 (Schmunis 1991). The prevalence of T. cruzi infection in blood varies between 1.3 and 51.0 per cent, and is generally much higher than that of hepatitis or HIV infection.

The transmission of Chagas disease via blood transfusion is a real threat even in countries where the disease is not transmitted by vector, such as the United States of America and Canada, where cases of acute Chagas disease have been recently documented (Kirchoff et al. 1987, Grant, Gold & Wittener1989, Nickerson et al.1989).

Course of human infection

Morbidity

Controlled prospective studies that describe the clinical evolution of the cardiac form in T. cruzi-infected persons have been carried out in different geographical areas of the continent. They provide accurate data on the evolution of infection and clinical pathology of Chagas disease.

Overall, 58 per cent of the cases of myocardiopathy are observed in young, economically productive adults, aged 20–40 years. Signs and symptoms of congestive heart failure are observed in 65 per cent of these cardiac patients. Furthermore, 52 per cent of digestive system lesions, such as mega colon and mega oesophagus, are observed in this same age group. There are no differences in clinical manifestations by sex (Coura et al. 1983).

Sudden death is registered in 64 per cent of myocardiopathy patients with a median age of 47 years, whereas congestive heart failure is observed in 36 per cent of cardiac patients with a median age of 78 years (Pereira, Willcox & Coura 1985)

After 7 years of study of a Brazilian community in a prospective elec-trocardiographic survey, it was observed that cardiac lesions developed soon after infection and their incidence was highest in younger age groups. Most of those affected had become infected before 20 years of age.

As shown in Table 11.4, the incidence rates per 1000 person-years of right bundle branch block (RBBB)—a characteristic conduction alteration of chronic Chagasic myocardiopathy which leads to severe arrhythmia and heart failure—were 19.2 in the age group 10–14 years, 3.5 in the age group 20–39 years and 2.8 in the age group 40–59 years among seropositive people who had had a previously normal electrocardiogram. In contrast,


in the seronegative control groups there was no development of this char-acteristic circulatory lesion (Maguire, Hoff & Sherlock 1987).

In another 9-year prospective study the incidence of ventricular circula-tory defects (VCDs) including RBBB was 23.8 per 1000 person-years in the

Table 11.3 Prevalence of Trypanasoma cruzi infected blood in blood Trypanasoma cruzi infected blood in blood Trypanasoma cruzibanks of selected countries

Number of samples tested

Percentage positive Reference

ArgentinaBuenos Aires (1987)Santiago del Estero(1987)Cordoba (1982)

58 2842 0032 441

4.917.68.4

Perez & Segura 1989Perez & Segura 1989Perez & Segura 1989

Bolivia Santa Cruz (1990) 205 51.0 Carrasco 1990

BrazilBrasilia (1984)Parana (1987)Sao Paulo (1982)

2 4133 00056 902

14.64.82.9

Pereira 1984Marzochi 1981Dias & Brener 1984

Chile Santiago (1983)Vicuna (1983)

21462

3.714.5

Liendo et al.1985Liendo et al. 1985

Colombia Bogotá (1990)Cucuta (1987)

1 128 491

2.57.5

Guhl et al. 1987Guhl et al. 1987

Costa Rica San Jose (1985) 602 1.6 Urbina et al. 1991

Ecuador Guayaquil (1961) 1 054 3.2 Ecuador Ministry of Health 1961

Honduras

Tegucigalpa (1987) 1 225 11.6 Ponce & Ponce 1987

Mexico

Puebla (1986) 200 17.5 Velasco Castrejon & Guzman Bracho 1986

Paraguay

Asunción (1972) 562 11.3 Paraguay Ministry of Health 1972

Peru

Tacna (1972) 329 12.9 Peru Ministry of Health 1972

Uruguay Paysandu (1983–84)Salto (1983–84)Tacuarembo (1983–84)

44571699

4.74.27.7

Franca 1986Franca 1986Franca 1986

Venezuela

Various cities 195 476 1.3 Schmunis 1991

331Chagas Disease

seropositive patients aged 10–19 years and 88.2 per 1000 person-years in the seropositive patients aged 20–39 years, whereas the incidence of these defects was 3.3. and 6.8, respectively in the seronegative groups of the same ages (Mota et al. 1990).

Finally, in Chile after a 4-year follow-up study it was also found that RBBB was three times more frequent among people who were seroposi-tive for T. cruzi (25.8 per cent) than among those who were seronegative (8.6 per cent) and the difference was statistically signifi cant (p < 0.01) (Arribada, Apt & Ugarte 1986).

It is assumed that the evolution of the human infection towards the development of chronic cardiac lesions is similar in all endemic areas throughout the continent.

Mortality

In a recent study in Minas Gerais, Brazil, it was found that among all causes of death in a group young individuals aged 20–50 years old infected with T. cruzi, 21 per cent was attributable to chronic Chagasic cardiomy-opathy; in contrast, only 9 per cent of deaths in patients infected with T. cruzi and who were older than 60 years were attributable to this condition (Menezes 1989).

Mortality attributable to cardiac lesions in infected people is twice as high in males 20–40 years old (25 per cent) as in females of the same age group (11 per cent) (p < 0.01) (Coura et al. 1985). In another study, excess mortality rates in seropositive patients aged 30 years or younger were 71.4 per 1000 person-years, whereas no deaths were registered in the seronegative group of the same age (Mota et al. 1990).

As indicated in Table 11.5, the mortality rate per 1000 person-years for seropositive patients with RBBB was 33.5 and with ventricular extra systoles (VEs) was 39.2, whereas with the two conditions combined (RBBB and VEs) the mortality rate rose to 116.3 per 1000 person-years.

Table 11.4 Incidence of cardiac lesions and T. cruzi infection, rates per T. cruzi infection, rates per T. cruzi1000 person-years

Age group (years) ECG lesion

Rates per 1000 person-years

ReferenceSeropositive Seronegative

10–14 RBBB 19.2 0.0 Maguire, Hoff & Sherlock 198720–39 RBBB 3.5 0.0 Maguire, Hoff & Sherlock 198740–59 RBBB 2.8 0.0 Maguire, Hoff & Sherlock 198710–19 VCDs 23.8 3.3a Mota et al. 199020–39 VCDs 88.2 6.8a Mota et al. 199030–59 RBBB 4.6 0.0 Mota et al. 1990> 30 RBBB 25.8% 8.6% Arribada, Apt & Ugarte 1986

RBBB = right bundle branch block

ECG = electrocardiogram

VCDs = ventricular conduction defects

a. p < 0.01


In the seronegative group with normal ECG the mortality was 3.9 per 1000 person-years (Maguire, Hoff & Sherlock 1987). The data refl ected in Table 11.5 clearly indicate the much higher relative risk of developing myocardial lesions and dying as a consequence of these lesions in young individuals who are seropositive with regard to T. cruzi as compared with seronegative individuals of the same age group.

It is assumed that the mortality due to cardiac lesions follows a similar pattern in all endemic areas throughout the continent.


Economic impact

The economic impact of the disease during the chronic stage is very high, as shown by data from Brazil (Brazil Ministry of Health 1987).

If we consider that about 30 per cent of infected people will develop severe cardiac and digestive lesions such as cardiac arrhythmia (75 000 cases), mega oesophagus (45 000 cases), and mega colon (30 000 cases) per year, the estimated costs for pacemaker implants and corrective sur-gery (average US$5000) would amount to approximately US$750 million per year, which would be enough for the improvement or construction of more than 700 000 rural dwellings at a minimum estimated cost of US$1000 each in Brazil.

Between 1979 and 1981, 14 022 deaths were resulted from Chagas disease in Brazil, representing approximately 259 152 years of potential life lost (YPLL) before the age of retirement. Assuming that all the patients were unqualifi ed rural workers only and that the minimum daily wage at the time was US$2.50, the total economic loss attributable to premature deaths would amount to US$237 million.

Current control programmes

The traditional vertical control programmes in the Latin American coun-tries have focused on the spraying of insecticides on houses, household annexes and buildings. National control programmes aimed at the inter-

Table 11.5 Excess mortality rates with cardiac lesions, rates per 1000 person-years

ECG lesion Seropositive Seronegative Reference

RBBB 33.5 0.0 Maguire, Hoff & Sherlock 1987VEs 39.2 0.0 Maguire, Hoff & Sherlock 1987RBBB and VEs 116.30 0.0 Maguire, Hoff & Sherlock 1987VEs (< 30 years) 71.4 0.0 Mota et al. 1990VEs (> 30 years) 67.6 0.0 Mota et al. 1990

RBBB = right bundle branch block.

VEs = ventricular extra systoles.

333Chagas Disease

ruption of the domestic and peridomestic cycles of transmission involving vectors, animal reservoirs and humans are feasible and have proven to be very effective. Reaching the goal of eliminating vector borne transmission is more feasible in areas where the vector is domiciliated like Triatoma infestans.

Eight countries of the Americas have active control programmes that combine insecticide spraying with health education. The common pattern of the vertical, centralized control programmes comprises three operational phases:

preparatory phase for mapping and general programming of activities and estimation of resources;

attack phase during which a fi rst massive insecticide spraying of houses takes place and is followed by a second spraying 3 to 6 months later, with further evaluations for selective re-spraying of re-infested houses;

surveillance phase for the detection of residual foci of triatomines after the objective of the attack phase has been reached. Involvement of the community and the decentralization of residual control activities are essential elements of this last phase.

A prime example of an active control programme is the programme that has been operating in Brazil since 1975 when 711 Brazilian municipali-ties had triatomine-infested dwellings. Ten years later, in 1986, only 186 municipalities remained infested. This represents a successful accomplish-ment of the programme objectives in 74 per cent of the originally infested municipalities (Dias 1987).

In large parts of the Southern Cone countries, programmes have entered the surveillance phase characterized by monitoring of house infestation and, where necessary focal spraying.

New tools for vector control

Two new tools for triatomine control have been developed with the sup-port of the WHO: fumigant canisters and insecticidal paints (UNDP/World Bank/WHO 1998b).

After four years of implementation of a control programme in 600 scattered houses in Santiago del Estero, Argentina (covering some 3000 individuals), using fumigant canisters and a triatomine detection box for entomological surveillance, seropositivity in infants under 1 year of age dropped from 5.5 per cent to 0 per cent, while seropositivity in children under 4 years of age dropped from 12.4 to 0 per cent. In other words, the transmission of the disease through vectors was interrupted. The pro-gramme was implemented within a primary health care (PHC) context, and had a strong component of health education. The cost of the whole intervention, including canisters and triatomine detection boxes, PHC personnel, serological evaluation, and so on was US$4.70 per house per year, i.e. fi ve times lower than the cost of the traditional vertical approach


and insecticide application used in the government control programme (Chuit et al. 1992)

In another fi eld project in 4800 houses in central Brazil ( covering some 30 000 people), the insecticidal paints still had a high level of effi cacy 24 months after application, keeping more than 85 per cent of the treated dwellings free of triatomines. This compares very favourably with the 60 per cent effi cacy of traditional insecticide spraying. These insecticidal paints are manufactured in Sao Paulo, Brazil. The cost per treated house over the 24-month period was US$29 for the paints, compared to US$66.34 for Deltamethrin and US$73.40 for Benzene hexachloride. It was necessary to apply the insecticides twice during the 24-month period, while only one application of the paint was enough to attain the above-mentioned levels of effi cacy (Oliveira Filho 1988, 1989).

In an extended operation being carried out in selected areas of Argen-tina, Bolivia, Chile, Honduras, Paraguay, and Uruguay, these new control tools are being applied following a common protocol that will permit comparability of epidemiological and entomological effi cacy, social accept-ability and assessment of costs. A health education component will also be included in the common protocol.

Results from Argentina, Chile, Honduras, and Paraguay are very encouraging, based on the entomological evaluations at 12 to 24 months post-intervention. The rates of house re-infestation when using the insec-ticide paints are two to three times lower than for houses sprayed with traditional insecticides (see Table 11.6).

These innovations in triatomine control are being incorporated into the regular activities of the control programme by the Ministry of Health of Brazil in the State of Ceara, resulting in decreased operational costs and increased effi cacy of vector control.

Feasibility of interruption of transmission

The tools for interrupting the domestic cycle of T. cruzi transmission, such as chemical control, housing improvement and health education, are avail-able. In fact, the prevalence of the infection has decreased in countries that have consistently applied control measures. For example, after 20 years of control programmes in Argentina, positive serology in 18-year-old males has signifi cantly decreased since 1980, and the number of reported new acute cases has decreased since the 1970s (Segura et al. 1985).

In Brazil, transmission by vector has been interrupted throughout the State of Sao Paulo since the mid-1970s. Decreasing seropositivity in school children has paralleled the above control efficacy: in 1976, the incidence rate was 60 per cent, and in 1983 it dropped to 0 per cent (Souza et al. 1984).

Transmission through transfusion could be prevented if blood was screened serologically and positive units were discarded. In some coun-tries of the region, serological screening for T. cruzi is mandatory for blood donors.

335Chagas Disease

Available knowledge therefore indicates that the most common ways of transmitting human T. cruzi infection could be interrupted by:

implementing of vector control activities in houses in order fi rst to reduce and then to eliminate the vector borne transmission of T. cruzi;

strengthening the ability of blood banks to prevent transmission of Chagas disease and other diseases transmitted by blood transfusion, through the development and implementation of a policy for the use of human blood.

Update

Initiative of the Southern Cone Countries

In Brasilia in June 1991, the Ministers of Health of Argentina, Brazil, Bolivia, Chile, Paraguay and Uruguay launched an Initiative for the elimi-nation of Chagas disease during the 1990s (MERCOSUR 1991). Since Triatoma infestans, the vector of T.cruzi, is intra-domiciliary in these countries, sustained implementation of control measures has successfully

Table 11.6 Effi cacy of triatomine control tools: percentage of re-infested houses after different interventions, Argentina, Chile, Honduras and Paraguay, April 1994

Experimental groupNumber of

houses

Percentage of houses re-infested

Chilea Hondurasb Argentinac ParaguaycParaguaycParaguay

IPeri-domicile: traditional

insecticideIntra-domicile: paints

150 5.6d 1.6d 2.5d 5.6

IIPeri-domicile: traditional

insecticideIntra-domicile: canisters

150 nd 3.0 0.66d 8.0

IIIPeri-domicile: paintsIntra-domicile: paints

150 2.1d 0.8d 2.3d 2.6d

IV (control)Peri-domicile: traditional

insecticideIntra-domicile: traditional

insecticide

300 8.9 2.7 3.6 4.3

Source: Progress reports of fi eld research projects, Geneva, World Health Organization, June 1994 (unpub-lished data).

a. 24 months after interventions.

b. 18 months after interventions.

c. 12 months after interventions.

d. Statistically signifi cant difference compared with control group.


interrupted transmission of Chagas, disease as indicated in Table 11.7and Figure 11.1.

In these countries there are 11 million infected people and 50 million are at risk. This represents 60 per cent of the prevalence of infected indi-viduals for the whole continent.

Chagas disease is recognized as an important public health problem and is being given increased priority for control, as demonstrated by the initiative taken by the governments of the Southern Cone countries. That initiative has been very successful. By cutting transmission in the Southern Cone countries, the incidence of Chagas disease will be reduced by over 65 per cent in the whole of Latin America. A total of US$450 million has

Table 11.7 Human infection by Trypanosoma cruzi and reduction of inci-Trypanosoma cruzi and reduction of inci-Trypanosoma cruzidence, Southern Cone initiative for the elimination of Chagas disease: 1983–2000

Country

Age group (years)

Prevalence of infection (percentage) in 1980–1985

Prevalence of infection (percentage)

in 2001a

Reduction of incidence in the age group (percentage)

Argentina 18 5.8 (Segura et al.1985) 1.2b 80.0Brazil 0–4 5.0 (Camargo et al.1984) 0.12 98.0Chile 0–10 5.4 (Schenone et al. 1985) 0.38 94.0Paraguay 18 9.3c (Cerisola 1972) 3.9 60.0Uruguay 6–12 2.5 (Salvatella et al. 1989) 0.06 99.0

a. Reports to the 10th Meeting of the Intergovernment Commission of the Southern Cone Initiative, Monte-video, 2001.

b. Data for 1993.

c. Data for 1972.

Figure 11.1 Southern Cone Initiative for the elimination of transmission of Chagas disease: incidence of infection 1980–2000

Source: Reports by national Chagas disease control programmes, 1993–2000.

Year

Inci

denc

e (%

)

1980 1985 19951990 20000

0.1

1

10Argentina (18 years)

Paraguay (18 years)

Chile (<4 years)

Brazil (0–7 years)

Uruguay (<12 years)

337Chagas Disease

been allotted by the six countries for control operations since the start of the initiative.

Technical representatives of each ministry of the Southern Cone coun-tries have been designated to form an Intergovernmental Commission in charge of implementation and evaluation of the control programmes. The Pan American Health Organization (PAHO) has been appointed to act as the Secretariat of this Commission. A programme guide, designed by the Commission and incorporating revisions submitted by the professional staff of the control programmes, has been used for the development of the country programmes. The proposed plans for Argentina, Bolivia, Brazil, Chile, Paraguay, and Uruguay are approved on a yearly basis by their respective governments.

There have been 10 meetings of the Intergovernmental Commission, held in Buenos Aires, Argentina (1992), Santa Cruz, Bolivia (1993), Mon-tevideo, Uruguay (1994), Asuncion, Paraguay (1995), Porto Alegre, Brazil (1996), Santiago, Chile (1997), Buenos Aires, Argentina (1998), Tarija, Bolivia (1999), Rio de Janeiro, Brazil (2000), and Montevideo, Uruguay (2001). At these meetings, the fi eld activities of the country programmes were reviewed annually, using common indicators to assess the impact and cost-effectiveness of the national programmes.

Current data (World Health Organization 1994, 1995, 1996, 1997, 1998a, 1999a, 2000a, 2000b) on ridding of houses of insects, screening blood banks, and the incidence of infection in the under-5 years age group indicate that the vector-borne and tranfusional transmission of Chagas disease were interrupted in Uruguay in 1997, Chile in 1999, and Brazil in 2000. Argentina, Bolivia, and Paraguay were expected to follow soon after.

Argentina: The whole endemic area of the country has been placed under entomological surveillance, the most advanced phase of the elimi-nation process. In 1980 the average house infestation rate for the country as a whole was 30 per cent; in 1998 it was 1.2 per cent. That change is equivalent to a 96 per cent reduction in house infestation by the vector. The seroprevalence rates for the whole country for the age group 0–4 years is 0.9 per cent which confi rms the very low number of acute cases among children in this age group. In the age group 0–14 years, the rate is 1.9 per cent. These data show that the goal of interruption of vectorial transmission is being achieved.

Regarding blood safety, the coverage of the blood donations screened against Chagas disease is 100 per cent in the blood banks of the public sector and 80 per cent in the blood banks of the private sector (World Health Organization 1996).

Bolivia: Data on serological prevalence in the general population indi-cates a rate of 28.8 per cent while the serological prevalence rate in the age group of 0–4 years is 22.0 per cent in Cochabamba, it is 0.0 per cent in Potosi where there is an active vector control programme. In Tupiza, another department where there is an active control programme, the


house infestation rate is 0.8 per cent (Pan American Health Organization 1998b).

Brazil: The prevalence of human T. cruzi infection in the 7–14 year age group in 1999 was 0.04 per cent as compared with 18.5 per cent in 1980. This represents a 99.8 per cent reduction of incidence of infection in that age group.

Results of serological tests in a limited number of samples in the popula-tion of the 0–4 year age group in 1999 indicate that the seroprevalence in that age group is 0.0 per cent which can be interpreted as a proof of the interruption of vectorial transmission of Chagas disease in Brazil.

The number of domiciliated T. infestans insects captured by the control programme in the whole country in 1998 was only 485. This represents an average of 1 insect per 10 000 houses surveyed, i.e. an infestation rate far below the minimum required for effective transmission of the parasite to new patients. This information confi rms the interruption of vectorial transmission of Chagas disease in Brazil.

Chile: The overall infestation rate for the country was reduced from 3.2 per cent in 1994 to 0.14 per cent in 1999, a reduction of 99.8 per cent over three years. In 1999, just 26 T. infestans insects were captured in the interior of dwellings in the endemic areas of the whole country, represent-ing 2.5 insects per 1000 houses, an infestation rate far below the threshold required for effective transmission of the parasite to new individuals.

The infection rate in the age group 0–4 years in 1999 was 0.016 per cent which represents a reduction of 98.5 per cent as compared to the rate of 1.12 per cent that was found in the same age group in 1995.

An independent commission visited the endemic areas of Chile in November 1999 and based on the above data certifi ed the interruption of vectorial transmission (World Health Organization 1999a, 2000a).

Paraguay: In a serological survey carried out in 1997 in a representative sample (940 individuals) of children less than 13 years old in marginal areas of the capital city of Asunción a signifi cant decrease of prevalence rates was observed in all age groups when compared with data for 1982.

Rural-urban migration to these marginal areas of Asunción comes mainly from Paraguari, Cordillera, and Central, which have the highest domiciliary infestation rates by triatomines. The zero prevalence rate in the age group of less than 4 years old indicates interruption of transmis-sion by triatomines in the urban areas of the capital (Pan American Health Organization 1998a, 1998b).

Uruguay: The interruption of vectorial and transfusional transmission was certifi ed in 1997 and the whole country is under surveillance.

The incidence of infections in the age group 0–12 years was 0 per cent which confi rms the interruption of vectorial and transfusional transmis-sion of Chagas disease in Uruguay since 1997 (World Health Organization 1998b).

339Chagas Disease

Initiative of the Andean Countries

There are 5 million infected individuals in the Andean countries, and 25 million people those countries are at risk of contracting the infection. This represents 27 per cent of the prevalence of infected individuals for the whole continent.

As the vectors of Chagas disease in these countries are not strictly domiciliated, it is necessary to adapt and test the vector control strategies with respect to the local entomological conditions.

An initiative for the elimination of vectorial transmission in the Andean countries of Colombia, Ecuador, Peru, and Venezuela, was launched at an Intergovernmental meeting held in Bogotá, Colombia, in February 1997. At that meeting detailed country-by-country plans of action, including annual goals, budgetary needs, evaluation mechanisms and research needs, were prepared (OPS/OMS 1997).

A second Intergovernmental meeting Commission was held in Maracay, Venezuela, in March 1999. Progress in control activities was reported as indicated below.

Colombia: The preparatory phase of the national Chagas disease control programme has advanced. The prevalence survey has been completed and a map of the country featuring the risk areas has been prepared. There is a 100 per cent coverage of blood screening against T. cruzi infection in blood.

Ecuador: The preparatory phase of the national Chagas disease control programme has advanced. A law reorganizing the control programme was issued on 8 December 1998, placing the programme under the Secretary of Tropical Medicine, with specifi c functions and budget. A law for com-pulsory blood screening against T. cruzi was issued in August 1998. The seroprevalence of infected blood in blood banks for the whole country is 0.2 per cent.

Venezuela: The control programme was offi cially established in 1966. The objective of the programme was to interrupt intradomestic transmis-sion through vector control by insecticide spraying. The programme for improvement of rural housing, originally initiated in the 1960s, assists rural inhabitants to substitute palm roofs, to plaster adobe walls and to cement earthen fl oors. In addition, routine screening for T. cruzi in blood banks began in 1988.

In children under 10 years of age, the fi gures for seroprevalence rates of T. cruzi infection have decreased steadily in the past four decades: from 20.5 per cent in, 1958–1968 to 3.9 per cent in 1969–1979, and further down to 1.1 per cent in 1980-1989, to 0.8 per cent in 1990–1999. Between 1990 and 1999, incidence of infection in the age group 0–4 years old was reduced by 90 per cent to less than 1.0 per cent. The geographical distri-bution of T. cruzi transmission is restricted to the States of Portuguesa, Barinas and Lara. The prevalence of infected blood in blood banks was been reduced from 1.16 per cent in 1993 to 0.78 per cent in 1998 (World Health Organization 1999b).


Initiative of the Central American Countries

In Central American countries, there are 2 million infected individuals and 26 million are at risk of contracting the infection. This represents 11 per cent of the prevalence of infected individuals for the whole continent.

As the vectors of Chagas disease in these countries are not strictly domiciliated, it is necessary to adapt and test the vector control strategies with respect to the local entomological conditions.

In the Central American countries—Belize, Costa Rica, El Salvador, Guatemala, Honduras, Mexico, Nicaragua, and Panama—progress in control of blood banks is proceeding well. All of these countries except one have issued legislation for compulsory blood screening against blood infected by T. cruzi. An initiative for elimination of vectorial transmission was launched at an intergovernmental meeting held in Tegucigalpa, Hon-duras in October 1997. At the meeting, detailed country-by-country plans of action, including annual goals, budgetary needs, evaluation mechanisms and research needs, were prepared (OPS/OMS 1997).

Further follow-up intergovernmental meetings have been held in Gua-temala City, Guatemala, in 1998, in Managua, Nicaragua, in 1999, and in San Salvador, El Salvador, in 2000. A summary of progress regarding the updating of epidemiological and entomological data, vector control activities and control of blood banks is given in Table 11.8.

Conclusions

Cost-effectiveness of Control Interventions

The Ministry of Health of Brazil carried out a study to analyse the cost-effectiveness and cost-benefi t of the Chagas disease control programme in Brazil. Because of the chronic nature of the disease and the protracted period of evolution, a period of 21 years was chosen for the analysis: from 1975 to 1995. Data from different sources were used to carry out the evaluation (Akhavan 1997).

Effectiveness was defi ned using various parameters; the main one was the burden of disease prevented, measured in DALYs (disability-adjusted life-years). From 1975 to 1995, the programme (excluding blood banks) prevented an estimated 89 per cent of potential disease transmission, pre-venting 2 339 000 new infections and 337 000 deaths. This translated into the prevented loss of 11 486 000 DALYs, 31 per cent from averted deaths and 69 per cent from averted disability. These results illustrate the large role of disability in the overall burden of disease caused by Chagas disease.

The estimated benefi ts (expenditures prevented) of the programme (excluding blood banks) were US$7500 million, 63 percent of the savings being health care expenditures and 37 per cent social security expenditures (disability insurance and retirement benefi ts).

The cost-effectiveness analysis demonstrated that for each US$39 spent on the programme, 1 DALY was gained. This places the programme and its

341Chagas Disease

Tab

le 1

1.8

Su

mm

ary

of c

ontr

ol a

ctiv

ities

in C

entr

al A

mer

ica,

1999

Coun

try

Epid

emio

logi

cal i

nfor

mat

ion

Ento

mol

ogica

l inf

orm

atio

nM

ain

vect

orVe

ctor

con

trol a

ctivi

ties

Scre

enin

g of

blo

od

bank

s (c

over

age)

Beliz

eN

ot s

tart

edN

ot s

tart

edU

nkno

wn

Not

sta

rted

Unk

now

n

Cos

ta R

ica

Ong

oing

sur

vey

in a

ge

grou

p 0

–14

year

s O

ngoi

ngTr

iato

ma

dim

idia

taO

rgan

izat

ion

of c

ontr

ol p

rogr

amm

e at

the

M

inis

try

of H

ealth

Unk

now

n

El S

alva

dor

Star

ting

in 1

999

Ong

oing

Tria

tom

a di

mid

iata

Org

aniz

atio

n of

con

trol

pro

gram

me

at t

he

Min

istr

y of

Hea

lth10

0%

Gua

tem

ala

Ong

oing

sur

vey

in a

ge

grou

p 0

–14

year

sO

ngoi

ng s

urve

y to

map

vec

-to

rs a

t m

unic

ipal

ity le

vel.

Ong

oing

sur

vey

on m

obili

ty

of T

. dim

idia

ta

Rho

dniu

s pr

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us,

Tria

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mid

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Sp

rayi

ng a

ctiv

ities

will

sta

rt in

200

0 in

th

e D

epar

tmen

ts o

f Qui

ché,

Chi

quim

ula,

Jala

pa a

nd Z

acap

a, w

hich

are

end

emic

for

R. p

rolix

us

80%

Hon

dura

sO

ngoi

ng s

urve

y in

age

gr

oup

0–1

4 ye

ars

Ong

oing

sur

vey

on u

rban

in

fest

atio

n.

Ong

oing

sur

vey

on m

obili

ty

of T

. dim

idia

ta

Rho

dniu

s pr

olix

us,

Tria

tom

a di

mid

iata

Spra

ying

act

iviti

es s

tart

ed in

199

8 in

the

ce

ntra

l Dep

artm

ents

, whi

ch a

re e

ndem

ic

for

R. p

rolix

us

100%

Nic

arag

uaO

ngoi

ng s

urve

y in

age

gr

oup

0–1

4 ye

ars

Ong

oing

Rho

dniu

s pr

olix

us,

Tria

tom

a di

mid

iata

Star

ting

in 1

999

65%

Pana

ma

Star

ting

in 1

999

Ong

oing

Rho

dniu

s pa

llesc

ens,

Tria

tom

a di

mid

iate

Surv

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nce

activ

ities

as

the

vect

ors

are

sylv

atic

Unk

now

n


activities in the category of interventions with a very high cost-effectiveness. The results of the cost-benefi t analysis indicated savings of US$17 for each US dollar spent on prevention, also indicating that the programme is a health investment with a good rate of return. An analysis of other diseases with socio economic causes demonstrated that the decline in Chagas disease infection rates is attributable to the preventive activities, rather than to a general improvement in living conditions.

Research

Current and future research priorities will focus on operational field research for better planning of control activities, cost-effectiveness of inter-ventions and assessment of the impact of control interventions. Regarding blood banks, research is centred on standardization and improvement of screening tests, evaluation of sensitivity and specifi city of new screening tests, and cost analysis of multiple blood bank screening.

A task force will focus its activities on the study of population dynamics of non-domiciliated triatomine vectors of Chagas disease present in the northern part of South America and in Central America. It is expected that the entomological information generated will assist national control programmes to adapt the vector control strategies that have proven very successful in interrupting the vectorial transmission of Chagas disease in the countries of the Southern Cone.

Studies will be carried out on:

triatomine distribution and house/peridomicile infestation by non-domiciliated species;

genetic structure of populations of non-domiciliated triatomines;

sylvatic/domestic mobility of vector populations;

cost-effectiveness of different methods to ascertain house re-infestation;

sensitivity of methods to detect re-infestation by non-domiciliated species;

monitoring of insecticide effi cacy;

effect of bio-climatic changes on domiciliated and non-domiciliated vector populations.

References

Acquatella H (1987) Encuesta epidemiológica en sujetos con serología positiva para Enfermedad de Chagas [Epidemiological survey in individuals with positive serology for Chagas disease]. Ciencia y Tecnologia de Venezuela, 4:185–200.

Akhavan D (1997) Analysis of cost-effectiveness of the Chagas disease control programme, Brasilia, Ministry of Health, National Health Foundation.

343Chagas Disease

Arribada AC, Apt W Ugarte JM (1986) A four-year follow up survey of Chagasic cardiopathy in Chile. Bulletin of the Pan American Health Organization, 20:245–266.

Arturo AC, Werner AB, Ugarte JM (1986) A four-year follow up survey of Cha-gasic cardiopathy in Chile. Bulletin of the Pan American Health Association, 20:245–266.

Brazil Ministry of Health (1987) Alguns aspectos economicos e de custo-benefi cio em Doenca de Chagas no Brasil [Economic and cost-benefi t aspects of Chagas disease in Brazil], Informacoes Epidemiologicas SUCAM, V.54.

Table 11.9 The time table towards the interruption of transmission of Chagas disease

1980–1985 Prevalence cross-sectional studies on human infection and house infesta-tion in nine countries are carried out (Acquatella 1987, Camargo et al. 1984, Cedillos 1975, Cordova et al. 1980, Lopez 1985, Marinkelle 1976, Matta 1985, Pan American Health Organization 1974, Ponce 1984, Reyes Lituma 1984, Salvatella et al. 1989, Schenone et al. 1985, Sousa 1985, Valen-cia 1990, Zeledon 1976)

Standardization of serological techniques and creation of a continental network of reference laboratories (Camargo, Sequra & Kagan 1986)

1985–1990 Follow-up prospective studies on the course of human infection (Arribada, Apt & Ugarte 1986, Coura, Anunziako & Willcox 1983, Maguire, Hoff & Sherlock 1987, Mota et al. 1990, Pereira, Willcox & Cava 1985)

Cloning of parasite genome and production of defi ned antigens for improvement of diagnostic techniques (Peterson, Wrightsman & Manning 1986, Moncayo & Luquetti 1990)

Industrial production of kits for control of blood banks in Argentina

Development of new tools for vector control (Oliveira Filho 1988)

1990–1995 Multi-country fi eld studies for evaluation of new vector control tools (Oliveira Filho 1997)

Industrial production of paints, canisters and sensor boxes in Argentina and Brazil (Zerba 1988)

Initiative of the Southern Cone countries is launched (Schmunis, Zicker & Moncayo 1996, Moncayo 1997)

1997 Initiatives of the Andean countries and the Central American countries are launched (OPS/OMS 1997)

Uruguay declared free of vectorial and transfusional transmission of Cha-gas disease (World Health Organization 1998a, UNDP/World Bank/WHO 1998a)

1998 The 51st World Health Assembly endorses the goal for elimination of transmission of Chagas disease on the American continent in 2005 (World Health Organization 1998b)

1999 Treatment of the early chronic phase in children aged 7–11 years old, adopted as public health policy (PAHO/WHO 1999)

Chile declared free of vectorial and transfusional transmission of Chagas disease (World Health Organization 200a)

2000 Brazil declared free of vectorial transmission of Chagas disease


Camargo M et al. (1984) Inquerito sorológico da prevalencia de infeccao Chagásica no Brasil 1975/80 [Serological survey on prevalence of Chagasic infection in Brazil 1975/1980]. Revista do Instituto de Medicina Tropical de Sao Paulo, 26:192–204.

Camargo M, Segura EL, Kagan IG (1986) Three years of collaboration on the standardization of Chagas disease serodiagnosis: an appraisal. PAHO Bulletin, 20:233–244.

Carrasco R (1990) Prevalence of Trypanosoma cruzi infection in blood banks of seven departments of Bolivia. Memorias do Instituto Oswaldo Cruz, 85:69–73.

Cedillos RA (1975) Chagas disease in El Salvador. Bulletin of the Pan American Health Organization, 9:135–141.

Cerisola A (1972) Muestreo serológico para la Enfermedad de Chagas en conscriptos de la clase 1951 [Serological sampling for Chagas disease in conscripts of the year 1951]. Revista Paraguaya de Microbiología, 7:90.

Chagas C (1909) Nova tripanozomiase humana. Estudos sobre a morfolojia e o ciclo evolutivo do Schizotrypanum cruzi n.gen.,n,sp., ajente etiolojico de nova entidade morbida do homen [New human tripanosomiasis. Study of the morphology and evolutionary cycle of Schizotrypanum cruzi n.gen.,n,sp., etio-logical agent of the new human morbidity]. Memorias do Instituto Oswaldo Cruz, 1:159–218.

Chuit R, et al. (1992) Result of a fi rst step toward community-based surveillance of transmission of Chagas disease with appropriate technology in rural areas. American Journal of Tropical Medicine and Hygiene, 46:444–450.

Cordova E et al. (1980) Enfermedad de Chagas en el Sur del Peru [Chagas disease in southern Peru]. Boletin Peruano de Parasitologia, 2:46–50.

Coura JR et al. (1985) Morbidade da doenca de Chagas’: IV Estudo Longitudinal de dez anos em Pains e Iguatama, Minas Gerais, Brasil [Morbidity of Chagas’ disease: IV- Ten-year Longitudinal Study in Pains and Iguatama, Minas Gerais, Brasil]. Memorias do Instituto Oswaldo Cruz, 80:73–80.

Coura JR, Anunziato N, Willcox HPF (1983) Morbidade da doenca de Chagas’: I- Estado de casos procendentes de varios estados de Brasil, observados no Rio de Janeiro [Morbidity of Chagas’ disease. I. Study of cases originating in various states of Brazil, observed in Rio de Janeiro]. Memorias do Instituto Oswaldo Cruz, 78:363–372.

Dias JCP (1987) Control of Chagas disease in Brazil. Parasitology Today, 3:11, 336–341.

Dias JCP, Brener Z (1984) Chagas disease and blood transfusion. Memorias do Instituto Oswaldo Cruz, 79(Suppl.):139–147.

Ecuador Ministry of Health (1961). Report.

Franca ME (1986) Chagas disease in Uruguay in the last twenty years. Revista Medica del Uruguay, 2:125–131.

Grant IH, Gold JW, Wittner M (1989) Transfusion-associated acute Chagas disease acquired in the United States. Annals of Internal Medicine, 111:849–851.

345Chagas Disease

Guhl F et al. (1987) Rastreo seroepidemiológico de donantes de sangre chagásicos en una zona endemica (Norte de Santander, Colombia) [Seroepidemiologic tracing of chagasic blood donors in an endemic zone (Norte de Santander, Colombia)]. Revista Latinoamericana de Microbiologia, 29:63–66.

Kirchoff L, Gam A, Gillian F (1987) American trypanosomiasis (Chagas disease) in Central American immigrants. American Journal of Medicine, 82:915.

Liendo F et al. (1985) Enfermedad de Chagas en Chile, sectores urbanos: XIII-Prevalencia de infección por Trypanosoma cruzi en donantes de sangre del sector sur del area metropolitana de Santiago, 1985 [Chagas’ disease in Chile, urban sectors: XIII- Prevalence of infection by Trypanosoma cruzi in blood donors of the Southern sector of the metropolitan area of Santiago, 1985]. Boletin Chileno de Parasitologia, 40:82–84.

Lopez L (1985) Encuesta serológica de prevalencia de la Enfermedad de Chagas en Paraguay [Serological survey on the prevalence of Chagas disease in Paraguay]. SENEPA project Report. Asuncion, Paraguay, Ministry of Health.

Maguire JH, Hoff R, Sherlock I (1987) Cardiac morbidity and mortality due to Chagas disease: prospective electrocardiographic study of a Brazilian community. Circulation, 75:1140–1145.

Marinkelle C (1976) Aspects of Chagas disease in Colombia. In: American Try-panosomiases Research, PAHO Scientifi c Publication, No. 318, Washington DC, 340–346.

Marzochi MCA (1981) Chagas disease as an urban problem. Cadernos de Saude Publica, 2:7–12.

Matta V (1985) Seroepidemiología de la Enfermedad de Chagas en Guatemala [Seroepidemiology of Chagas disease in Guatemala] Memorias VII Congreso Centroamericano de Microbiologia, San Jose, Costa Rica, p. 17.

Menezes M (1989) Causas básicas de morte en Chagasicos Idosos [Basic causes of death in aged Chagas patients]. Arquivos Brasileiros de Cardiologia, 52:75–78.

MERCOSUR (1991) Reunión de Ministros de Salud del MERCOSUR, Brasilia, Junio 1991[Meeting of the Ministers of Health of MERCOSUR, Brasilia, June 1991], Resolución No. 04-3-CS.

Mota EA et al. (1990) A nine year prospective study of Chagas disease in a defi ned rural population in northeast Brazil. American Journal of Tropical Medicine and Hygiene, 42:29–440.

Moncayo A, Luquetti A (1990) Multicentre double blind study for evaluation of Trypanosoma cruzi defi ned antigens as diagnostic reagents. Memorias do Instituto Oswaldo Cruz, 85:489–95.

Moncayo A (1997) Progress towards elimination of transmission of Chagas disease in Latin America. WHO World Health Statistics Quarterly, 50:195–198.

Nickerson P et al. (1989) Transfusion-associated Trypanosoma cruzi infection in a non-endemic area. Annals of Internal Medicine, 111:851–853.

Oliveira Filho AM (1988) Development of insecticide formulations and determi-nation of dosages and application schedules to fi t specifi c situations. Revista Argentina de Microbiologia, 20(Suppl):39–48.


Oliveira Filho AM (1989) Cost-effectiveness analysis in Chagas disease vectors control interventions. Memorias do Instituto Oswaldo Cruz, 84(Suppl.4): 109–418.

Oliveira Filho AM (1997) Uso de nuevas herramientas para el control de triatominos en diferentes situaciones entomológicas en el Continente Americano. Revista da Sociedade Brasileira de Medicina Tropical, 30 :41–46.

Organización Panamericana de la Salud/Organización Mundial de la Salud (1997) Informes de las Iniciativas de los Países Andinos, Bogotá Febrero 1997 y Teguci-galpa, Octubre 1997 [Report of the initiatives of the Andean countries, Bogotá February 1997 and Tegucigalpa October 1997].

Pan American Health Organization/World Health Organization (1999) Treatment of the early chronic phase of Chagas disease in children and adults. Report of an Expert Group. Washington, DC, October 1999.

Pan American Health Organization (1974) Clinical aspects of Chagas disease. Bulletin of the Pan American Health Organization, 76:141–155.

Pan American Health Organization (1998a) Report of the VI Meeting of the Intergovernment Commission of the Southern Cone Initiative, Santiago, Chile, March 1997. Washington, DC, (OPS/HPC/HCT/98.102).

Pan American Health Organization (1998b) Report of the VII Meeting of the Intergovernment Commission of the Southern Cone Initiative, Buenos Aires, Argentina, 24–26 March 1998. Washington DC, (OPS/HPC/HCT/98.114).

Paraguay Ministry of Health (1972) Report.

Pereira JB, Willcox HP, Coura JR (1985) Morbidade da doenca de Chagas: III- estudo longitudinal de seis anos, em Virgen da Lapa, MG, Brasil [Morbidity of Chagas disease: III- six-year longitudinal study in Vigem da Lapa, MG, Brazil]. Memorias do Instituto Oswaldo Cruz, 80:163–71.

Pereira MG (1984) Characteristics of urban mortality from Chagas’ disease in Brazil’s Federal District. Bulletin of the Pan American Health Organization,96:213–221.

Perez A, Segura EL (1989) Blood transfusion and transmission of Chagas infection in Argentina. Revista Argentina de Transfusion, 15:127–132.

Peru Ministry of Health (1972). Report.

Peterson DS, Wrightsman RA, Manning JE (1986) Cloning of a major surface-antigen gene of Trypanosoma cruzi and identifi cation of a nonapeptide repeat. Nature, 322:566–568.

Ponce C (1984) Prevalencia de la enfermedad de Chagas en Honduras [Prevalence of Chagas disease in Honduras]. Tegucigalpa, Honduras, Ministry of Health.

Ponce C, Ponce E (1987) Infección por Trypanosma cruzi en donantes de sangre de diferentes hospitales de Honduras [Infection with Tripanosoma cruzi in blood donors in various hospitals in Honduras]. Presented at the 8th Latin American Congress of Parasitology, Guatemala, November 1987.

Reyes Lituma V (1984) Estudio de prevalencia de enfermedad de Chagas en Ecuador [Prevalence study of Chagas disease in Ecuador]. Guayaquil, Ecuador, Ministry of Health, Vector Control Programme.

347Chagas Disease

Salvatella R et al. (1989) Seroprevalence of antibodies against Trypanososma cruzi in 13 Departments of Uruguay. Bulletin of the Pan American Health Organization, 107:108–117.

Schenone H et al. (1985) Enfermedad de Chagas en Chile: sectores rurales y peri-urbanos del area de endemo-enzootia relaciones entre condiciones de la vivienda, infestación triatomidea domiciliaria e infección por Trypanosoma cruzi del vector, del humano y de mamíferos domésticos, 1982–1985 [Chagas disease in Chile: rural and periurban sectors of the endemo-enzootic area-relationship between housing conditions, domicilliary triatomid infestation and infection by Trypanosoma cruzi of the vector, humans and domestic mammals, 1982–1985]. Boletin Chileno de Parasitologia, 40:58–67.

Schmunis GA (1991) Trypanosoma cruzi, the etiologic agent of Chagas’ disease: status in the blood supply in endemic and non-endemic countries. Transfusion, 31:547–557.

Schmunis GA, Zicker F, Moncayo A (1996) Interruption of Chagas’ disease trans-mission through vector elimination. Lancet, 9035:171.

Segura EL, et al. (1985) Decrease in the prevalence of infection by Trypanosoma cruzi (Chagas disease) in young men of Argentina. Bulletin of the Pan American Health Organization, 19:252–264.

Sousa O (1985) Encuesta serológica de prevalencia de la enfermedad de Chagas en Pánama [Serological survey on prevalence of Chagas disease in Panama]. Project reportLaboratory of Biology, University of Panama, Informe de Proyecto (Project report), Ciudad de Panama.

Souza AG et al. (1984) Consolidation of the control of Chagas disease vectors in the State of Sao Paulo. Memorias do Instituto Oswaldo Cruz, 79(Suppl.):125–131.

UNDP/World Bank/WHO (1987) Special Programme for Research and Training in Tropical Diseases. Eighth programme report. Geneva, p. 92.

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SchistosomiasisKE Mott

Chapter 12

Introduction

Schistosomiasis, sometimes called bilharziasis (after the German physician Theodor Bilharz), ranks high among parasitic diseases in terms of socioeco-nomic and public health importance in tropical and subtropical areas. One measure of that importance within the development strategies of endemic countries is refl ected in executive level planning and inclusion of schisto-somiasis control activities in national budgets in Brazil, China, Egypt, the Philippines, and Morocco (World Health Organization 1993).

At least one form of schistosomiasis is now endemic in 74 tropical developing countries. It is estimated that over 200 million people resid-ing in rural agricultural and periurban areas are infected, while 500–600 million more run the risk of becoming infected as a result of poverty, sub-standard hygiene in poor housing, and inadequate public infrastructure. Schistosomiasis is a major health risk in the rural areas of central China and Egypt and ranks high in other developing countries.

Schistosomiasis is mainly a rural occupational disease that affects people engaged in agriculture or fi shing. In many areas, a large proportion of children are infected by the age of 14 years; in other areas, women face the highest risk because of domestic and occupational contact with fresh water. Increased population movements help to propagate schistosomiasis, as evidenced by its introduction into an increasing number of periurban areas of north-eastern Brazil and Africa and among refugees in Somalia, Zimbabwe and Cambodia. Controlling the disease is of strategic relevance for development of tourism in endemic countries; it is recognized that tourists now increasingly acquire schistosomiasis as “off-track” tourism increases, sometimes with severe acute infection and unusual sequelae, including paralysis of the legs.


Schistosome parasitic worms

The major forms of human schistosomiasis are caused by 5 species of fl at-worm, or blood fl ukes, called schistosomes. Urinary schistosomiasis, caused by Schistosoma haematobium, is endemic in 54 countries in Africa and the Eastern Mediterranean. Intestinal schistosomiasis, caused by the mansoniworm, occurs in 53 countries in Africa, the Eastern Mediterranean, the Caribbean and South America. In 41 countries, both parasites are endemic. Another form of intestinal schistosomiasis caused by S. intercalatum has been reported in 7 central African countries. Oriental or Asiatic intestinal schistosomiasis, caused by the S. japonicum group of parasites (including S. mekongi in the Mekong river basin), is endemic in 7 countries in the South-East Asia and the Western Pacifi c region.

Simple and inexpensive diagnosis

Diagnostic methods for schistosomiasis have recently been reviewed (Feldmeier & Poggensee 1993) (Table 12.1). For diagnosis of urinary schistosomiasis, a simple sedimentation can be used effi ciently. A syringe fi ltration technique using fi lter paper, or polycarbonate or nylon fi lters, makes it possible for a team of 5 to examine up to 200 children in an hour and a half. Children infected with S. haematobium nearly always have microscopic or visual blood in their urine (haematuria). Children needing treatment can be identifi ed by merely looking at the urine specimen or checking for microscopic blood using chemical reagent strips. The eggs of intestinal schistosomiasis can be detected in faecal specimens by a technique using cellophane soaked in glycerine, the Kato or Kato-Katz technique, or

Table 12.1 Diagnostic methods for schistosomiasis

Technique Parasite Sensitivity of single examination Reference

Kato-Katz S. mansoni 100% - infections > 100 epg

45% - infection 1–50 epg

Sleigh et al. (1982)

Glass slide S. mansoni 100% - infections > 50 epg Teesdale, Fahringer & Chitsulo (1985)

Questionnaire S. haematobium 77–92% - infections > 64 eggs/10 ml of urine over age 15 years

Specifi city = 62–82%

Mott et al. (1985a)

Reagent strips S. haematobium(haematuria)

Sensitivity = 97 per cent > 64 eggs/10ml of urine

Specifi city = 85%

Mott et al. (1985b)


Sensitivity = 88%

Specifi city = 97%

Stephenson et al. (1984)


Sensitivity = 67% overall = 83% = >50 eggs/10ml of urine

Specifi city = 80%

Savioli et al. (1990)

Filtration S. haematobium 100% - infections > 20 eggs/10ml Warren et al. (1978)

epg = eggs per gram

351Schistosomiasis

between glass slides. The cost of the tests requiring a microscope is now US$0.01 or less. The chemical reagent strips cost about US$0.05.

Safe and effective treatment

Three safe, effective drugs are now available for schistosomiasis and all can be taken by mouth. Praziquantel, oxamniquine and metrifonate are all included in the WHO’s model list of essential drugs (World Health Organization 1990). Their discovery has revolutionized treatment of this disease.

Praziquantel, effective against all forms of schistosomiasis, has proven to have few and only transient side-effects and millions of people have ben-efi ted from treatment. Oxamniquine is used exclusively to treat intestinal schistosomiasis in Africa and South America. Metrifonate has now proved to be safe and effective for the treatment of urinary schistosomiasis.

Box 12.1 Schistosomiasis: life history of a worm

People contaminate the environment by their unsanitary habits. They acquire schistoso-miasis infection through repeated daily contact with fresh water during fi shing, farming, swimming, bathing, washing and recreational activities.

Eggs, excreted in urine or faeces from an infected person, break open on reaching water, releasing a tiny parasite (a miracidium) which swims frantically through the water by means of the fi ne hairs (cilia) covering its body, in search of a freshwater snail in which it can develop further. The parasite must fi nd a snail host within 8–12 hours before it perishes.

Once it has penetrated the snail, the parasite divides many times until thousands of new forms (cercariae) break out of the snail into the water. This phase of development takes 4–7 weeks or longer, depending on the type of parasite.

Outside the snail, the cercariae, which have long forked tails, can live for 48 hours at the longest. They can penetrate a person’s skin within a few seconds in order to continue their growth cycle.

As the cercaria penetrates the skin using secretions from its special glands, its tail falls off. Within 48 hours it has passed completely through the skin into the blood vessels. Some-times this process causes itching (swimmer’s itch or cercerial dermatitis), but otherwise most people never notice it.

Within weeks, the young parasite transforms itself into a long worm—either a male or a female. The female can produce eggs only when a male worm is present. Male and female adult worms remain joined together for life (less than 5 years on average, though they can live for up to 40 years); the more slender female is held permanently in a groove in the front of the male’s body. Once eggs are produced—over 200 per day depending on the species—the cycle starts again.

In intestinal schistosomiasis, the worms attach themselves to the walls of the blood ves-sels lining the intestines. In urinary schistosomiasis, they live in blood vessels of the blad-der. Only about half of the eggs leave the body in the faeces (intestinal schistosomiasis) or in the urine (urinary schistosomiasis); the rest remain embedded in the body, damaging organs, including liver, spleen, heart and esophagus.

Heavy infections with schistosome parasites, occurring mainly in children, cause the actual disease. The eggs laid by the female worm—not the worms themselves—damage the bladder, intestines or other organs.


Even though re-infection may occur after treatment, the risk of devel-oping severely diseased organs is diminished and even reversed in young children in the short term for all forms of schistosomiasis (Jordan, Webbe & Sturrock 1993). In most areas, a reduction in the overall number of cases has been obtained by mass treatment and maintained for 1.5–2 years and in other areas up to 5 years without further intervention.

No long-term follow-up studies after treatment of S. haematobium or S. japonicum are available.


Historically, the term “bilharziasis” was commonly used for schistosomia-sis. Following an expert group report on the epidemiology and control of schistosomiasis (World Health Organization 1967), “schistosomiasis” became the offi cial terminology. Schistosomiasis is a group of diseases, rather than a single entity. The standard criteria on diagnosis of each type of schistosomiasis is the presence of eggs in excreta. The use of the term “schistosomiasis,” however, reduces the possibility of discriminating between the different diseases associated with each type of infection.

Efforts were undertaken to refi ne the reporting of morbidity attributable to schistosomiasis in the development of the Ninth Revision of the Interna-tional Classifi cation of Diseases (ICD-9), whose preparation began in 1969 and concluded in 1975. The ICD-9 categories are as follows:

120.0 Schistosoma haematobium

120.1 Schistosoma mansoni

120.2 Schistosoma japonicum

120.3 Cutaneous

120.8 OtherInfection by Schistosoma: Bovis Intercalatum Mattheei Spindale cherstermani

120.9 Schistosomiasis, unspecifi ed

In ICD-9, the adaptation of ICD-O for oncology permitted the desig-nation of the cell type of carcinoma. This was relevant to bladder cancer associated with schistosomiasis (S. haematobium only) in which squamous cell types predominate (M805–M808) as compared to transitional cell types (M812–M813).

Defi ciencies in the description of morbidity attributable to schistosomiasis (in contrast to the detail of morbidity regarding amoebiasis and Chagas

353Schistosomiasis

disease) were addressed in preparations for the tenth revision of the Inter-national Classifi cation of Diseases (ICD-10). The First Expert Committee on Control of Schistosomiasis proposed eight new defi nitions to be inte-grated into ICD-10 either under B65 or as a qualifi er under the disease state (World Health Organization 1985). These were provided to the secretariat of ICD-10 as part of the background preparatory documents. The suggestions were partially accepted. In ICD-10, schistosomiasis is classifi ed as B65 and each of the three main species infecting humans are classifi ed separately. S. intercalatum and S. mekongi come under B65.8—other schistosomiases. S. mekongi come under B65.8—other schistosomiases. S. mekongiThe ICD-10 categories are as follows:

B65.0 Schistosomiasis due to Schistosoma haematobium [urinary schisto-somiasis]

B65.1 Schistosomiasis due to Schistosoma mansoni [intestinal schisto-somiasis]

B65.2 Schistosomiasis due to Schistosoma japonicum [Asiatic schistoso-miasis]

B65.3 Cercarial dermatitis

B65.8 Other schistosomiasesInfections due to Schistosoma: Intercalatum Mattheei Mekongi

B65.9 Schistosomiasis, unspecifi ed

The category for infection attributable to S. chestermani (the same as S. chestermani (the same as S. chestermani S. intercalatum) in ICD-9 was removed in ICD-10. A number of codes were introduced to classify clinical sequelae of schistosomiasis infection in ICD-10 (see Box 12.2). In ICD-10, haematuria attributable to schistosomiasis is classifi ed under R31 rather than N02 since the origin is the bladder rather than the glomeruli.

Unlike most other infectious diseases, infection with Schistosoma is epidemiologically and clinically different from disease attributable to Schis-tosoma. Schistosomiasis is a chronic infection whose onset is diffi cult to detect. Thus, incidence is generally not measured; if it is, it refl ects only the specifi c geographical area studied and cannot be extrapolated. Prevalence of schistosomiasis is the usual epidemiological variable measured.

Morbidity (disease or impairment of the normal state that affects per-formance of vital functions) is a result of prior or concurrent infection with Schistosoma. With currently available techniques it is, however, dif-fi cult to measure clinical impairment in the early stages of disease or in light infections.

Schistosomiasis infection is thought to be associated with increased risk of other parasitic infections. Aside from the theoretical assumptions on


the frequency of the association of schistosomiasis with other diseases at the population level (Bundy et al 1991), published reports on community studies in Brazil (Lehman et al. 1976), Chad (Buck et al. 1970), Egypt (El Malatawy et al. 1992), Kenya (Thiongo and Ouma 1987), Sierra Leone (White et al. 1982), and Zambia (Wenlock 1979), have shown that Schis-tosoma infection is not consistently associated with other parasitic infec-tions. When present, the consequences of multiple infections on morbidity, disability and mortality have not been adequately studied.

In summary, a “gold standard” for the measurement of schistosomiasis morbidity has not been developed. This chapter will attempt to clarify this matter so that, within national development priorities, the impact of schistosomiasis can be accurately identifi ed and the ensuing changes induced by control and development can be reliably assessed.

Potential confounding diseases

Of all the types of schistosomiasis, disease attributable to Schistosoma haematobium is the most likely to be confounded with other diseases. When haematuria is present, the disease may be misdiagnosed as glo-merulonephritis (ICD-10 code N02.9) or haematuria of unknown etiology (ICD-10 code R31).

In a known endemic area, the direct correlation between gross and microscopic haematuria and infection attributable to S. haematobiumpermits the valid use of haematuria as a proxy for infection even after large scale treatment. The picture may be further complicated if renal biopsy is performed, since both S. mansoni and S. haematobium infection have been associated with morphological changes with clinical manifestations

Box 12.2 Tenth revision of the International Classifi cation of dis-eases (ICD 10) codes for schistosomiasis sequelae

ICD 10 code Sequela

K77.0 Liver disorders in infectious and parasitic diseases classifi ed elsewhere

Hepatosplenic schistosomiasis

Portal hypertension in schistosomiasis

J70.8 Cor pulmonale attributable to schistosomiasis would probably be designated under J70.8

N29.1 Disorders of the kidney and ureter in schisto-somiasis (bilharziasis)

N33.8 Bladder disorder in schistosomia-sis (bilharziasis)

R31 Haematuria due to schistosomiasis is to be classifi ed under R31 rather than N02 since the origin is the bladder rather than the glomeruli

Source: World Health Organization (1987)

355Schistosomiasis

ranging from nephrotic syndrome (ICD-10 code subdivisions .5 and .6, i.e. membranoproliferative glomerulonephritis types 1–3).

In most endemic areas of schistosomiasis attributable to S. haemato-bium, the incidence of squamous cell bladder cancer is high. Epidemio-logical data do not usually cite the association with schistosomiasis as an etiological agent. Such detail is subject to the thoroughness of the surgical pathological studies (incomplete in endemic areas) or the training and personal interest of the surgeon (as in Egypt).

Although most people in the endemic areas have light infections with no symptoms, the economic and health effects of schistosomiasis should not be underestimated. In the north-east of Brazil, in Egypt, and in Sudan, the work capacity of rural inhabitants is severely reduced because of the weakness and lethargy caused by the disease. The school performance and growth patterns of infected children are also retarded; after treatment, remarkable improvement occurs.

A major constraint in the determination of the burden of disease of schistosomiasis is that it does not occur in isolation. It is one of the dis-eases of poverty and is linked to all other infectious and parasitic diseases of poverty. Within any community, it most affects the poorest segment of the population.

Data sources available and their biases

The standard references for the current distribution and prevalence of schistosomiasis are two WHO documents. In the CEGET/WHO Atlas of the global distribution of schistosomiasis (Doumenge et al. 1987), the geographical distribution of all forms of schistosomiasis is identifi ed on the basis on an exhaustive compilation of published epidemiological studies as well as surveys carried out by ministries of health. The prevalence was estimated (extrapolated) using this geographical representation of data and the actual surveys or epidemiological data (Utroska et al. 1989).

The heterogeneity of the spatial distribution of the prevalence of parasitic diseases is widely recognized (Ashford, Craig & Oppenheimer 1992, 1993). The clustering of heavy infections attributable to S. mansoni and S. mansoni and S. mansoni S. japoni-cum is also heterogeneous (Mott 1982). With the exceptions of Algeria, Brazil, Botswana, China, Egypt, Mali, Malawi, Morocco, and Zimbabwe, however, the data available to Ministries of Health are not disaggregated to the village level; thus most national statistics are intrinsically inadequate.

Review of the empirical databases by world bank regions

There is no single standard database for schistosomiasis. Schistosomiasis is not usually reported as an infection nor are any of its disease manifes-tations reported separately (Iarotski & Davis 1981). The CEGET/WHOAtlas of the global distribution of schistosomiasis (Doumenge et al. 1987)


comprises the most complete database to the village level of endemic coun-tries. Systematic extrapolation of these data to obtain accurate national estimates of the prevalence or morbidity is not possible because of the heterogeneity of the data and the distribution of the infection and disease within any particular country. Despite these limitations, an attempt has been made to estimate prevalence in order to assess the potential need for antischistosomal drugs (Utroska et al. 1989).

Unlike the analysis of information on acute infectious diseases, the inter-pretation of incidence data has many limitations in schistosomiasis (Jordan, Webbe & Sturrock 1993). To calculate incidence accurately requires greater sensitivity of the diagnostic techniques than those currently available or in use by health services (Sleigh & Mott 1986).

Any age-specifi c data on prevalence of schistosomiasis attributable to S. mansoni and S. haematobium should be interpreted with caution and compared with the age distributions shown in Tables 12.2–12.8. There seems to be no standard age distribution for S. japonicum. This is prob-ably because no endemic area has not been exposed to intervention since 1950 and in some areas, transmission has been eliminated.

Extensive analytical reviews of the published literature on the morbidity of schistosomiasis have been conducted by Gryseels (1989) and Sleigh & Mott (1986). There is general agreement that heavy infections, as mea-sured by faecal or urinary egg counts, are associated with disease. Most of the relevant studies are referred to in Tables 12.2–12.8 or discussed in the text of this review. The major information gap is the lack of statistics on schistosomiasis as a cause of outpatient visits, hospitalization and even as a cause of death.


Only Japan is endemic in this region. No new cases have been reported since 1978. Thus no mortality could be attributed below age 15 years.

Formerly Socialist Economies

Schistosomiasis is not endemic in these countries.

India

S. haematobium has been confi rmed near Hyderabad. The extent of the problem requires further investigation and any estimates cannot be con-fi rmed.

China

The current prevalence estimate of 1.5 million people infected, proposed by the Ministry of Public Health of the People’s Republic of China, is based on a national sample survey in 1989 (China Ministry of Public Health 1992). The sex ratio in the sample survey was 14.2:8.3 (male:female). Prevalence studies for China are summarized in Table 12.2.

357Schistosomiasis

Tab

le 1

2.2

S.

Japo

nicu

m e

mpi

rica

l dat

abas

es, C

hina

Dat

eLo

catio

nPr

eval

ence

(%)

Mor

bidi

tySo

urce

Resu

ltsRe

fere

nce

Com

men

ts

1990

Chi

na

65 c

ount

ies

Not

sta

ted

Not

sta

ted

Surv

eys

on

nutr

ition

and

he

alth

in 4

9 co

untie

sAg

e gr

oup

(yea

rs)

Mor

talit

y Ra

te

per

milli

on

MF

1–4

00

5–9

01

10–1

41

015

–19

21

20–2

45

125

–29

82

30–3

417

635

–39

3011

40-4

442

1645

–49

7034

50–5

495

5855

–59

122

8460

–64

197

108

65–6

918

113

570

–74

247

183

75-7

920

917

780

+23

122

1A

ll29

21

Juns

hi e

t al

. (19

90)

Dat

a fr

om 4

9 co

untie

s us

ed in

ca

lcul

atio

ns. O

nly

20 a

re e

ndem

ic.

Mor

talit

y es

timat

es a

re p

roba

bly

low

.

Not

e: r

ecta

l can

cer

and

colo

n ca

ncer

(re

gist

ered

sep

arat

ely)

had

lo

wer

cum

ulat

ive

mor

talit

y ra

tes

for

0–

64 y

ears

tha

n sc

hist

oso-

mia

sis.

All

thes

e w

ere

sign

ifi ca

ntly

as

soci

ated

with

sch

isto

som

iasi

s ja

poni

ca.

cont

inue

d


1992

Chi

na11

.857

600

ad

vanc

ed c

ases

in

the

ent

ire

coun

try

Stra

tifi e

d gr

oup

rand

om s

ampl

e =

1 p

er c

ent

of

the

popu

latio

n of

the

end

emic

ar

ea: H

ubei

, H

unna

n, A

nhui

, Jia

ngxi

Age

grou

p (y

ears

)Pr

eval

ence

(%)

0–

4 2

.85–

9 6

.910

–14

10.0

15–1

913

.620

–29

12.3

30–3

9 8

.440

–49

13.4

50–5

913

.560

+12

.8M

14.2

F 8

.3

Chi

na M

inis

try

of

Publ

ic H

ealth

M =

mal

es, F

= fe

mal

es

Tab

le 1

2.2

S.

Japo

nicu

m e

mpi

rica

l dat

abas

es, C

hina

(con

tinue

d)

Dat

eLo

catio

nPr

eval

ence

(%)

Mor

bidi

tySo

urce

Resu

ltsRe

fere

nce

Com

men

ts

359Schistosomiasis


Schistosomiasis attributable to S. japonicum and S. mekongi are present in fi ve countries of this region. Available prevalence data are summarized in Table 12.3. The prevalence of infection resulting from S. japonicum in Indonesia is less than 1 per cent among a population at risk of 10 000 persons. S. malayensis has only been reported in 10 persons of a single ethnic group in Malaysia. In Thailand, less than 5 cases have been reported. Thus schistosomiasis is prevalent only in Cambodia and the Lao People’s Democratic Republic (S. mekongi) and the Philippines (S. japonicum). There are no studies on comparative morbidity between S. japonicumand S. mekongi. The distribution in the Lao People’s Democratic Republic overlaps with a higher prevalence of opisthorchiasis, and increased mor-bidity may be present in these areas.

In the Philippines, Tanaka et al. have attempted to measure incidence among schoolchildren (Tanaka et al. 1984) and to assess the impact of treatment on incidence (Tanaka et al 1985). Incidence at age 7 years was 18.6 per cent and at age 12 years was 33.9 per cent; no difference between sexes was observed.

Sub-Saharan Africa

Schistosomiasis attributable to S. mansoni or S. haematobium is endemic in 41 countries of this region. It is not endemic in Cape Verde, Comoros, Djibouti, and Lesotho. Representative population-based studies of the prevalence and morbidity of schistosomiasis are shown in Table 12.4. Brink-mann et al. (1988) have published data on age and sex distribution in 13 village clusters in Mali of infection with S. mansoni or S. mansoni or S. mansoni S. haematobium.

Schistosomiasis resulting from S. intercalatum has received more atten-tion recently and is now reported from eight West and Central African states. The geographical extent of risk is unknown, but the morbidity seems low (see Table 12.5).

One example of the limitations of estimating national prevalence of infection has been published by Ratard et al. (1992) concerning Cameroon. The data derived from a national school survey of 5th grade primary school students (average age 13 years: range 10–19 years) were extrapolated to show a maximum number of 719 000 cases (range 392 900–1 027 800) in contrast to an estimate of 2 239 591 cases (range 1 261 355–3 267 963), which was based on an assessment of published literature (Utroska et al. 1989). In general, national surveys have not been done in sub-Saharan African; where available, as in Zimbabwe (Taylor & Makura 1985), the limitations of these data are recognized and no attempt is made to estimate national prevalence.


Only schistosomiasis attributable to S. mansoni is present in this region. Several prevalence distributions are presented in Table 12.6. Mortality due to schistosomiasis in Brazil and Surinam is discussed below.


Tab

le 1

2.3

S

. japo

nicu

m e

mpi

rica

l dat

abas

es b

y re

gion

, Oth

er A

sia

and

Isla

nds

Dat

eLo

catio

nPr

eval

ence

(%)

Mor

bidi

tySo

urce

Resu

ltsRe

fere

nces

1979

Phili

ppin

es40

.125

% o

f tho

se in

fect

ed h

ad h

epa-

tom

egal

y or

spl

enom

egal

yV

illag

e

N =

851

(45

% o

f th

e re

side

nts)

Age

grou

p (y

ears

)

Prev

alen

ce (%

)

MF

1–4

0 2

5–9

1410

10–1

457

3715

–19

6347

20–2

973

4430

–39

6265

40–

4971

6050

+57

50

Lew

ert, Y

ogor

e &

Bla

s (1

979)

1980

Phili

ppin

es43

Hep

atom

egal

y an

d sp

leno

meg

aly

asso

icat

ion

with

infe

ctio

nV

illag

e

N =

755

(90

% o

f th

e re

side

nts)

Age

grou

p (y

ears

)

Prev

alen

ce (%

)

MF

<1

0 0

1–4

12 0

5–9

4021

10–1

468

4815

–19

8152

20–2

481

2525

–34

7446

35–

4477

5945

–54

6558

55–6

463

2365

+63

17

WH

O w

orks

hop

(198

0)

361Schistosomiasis

1980

Phili

ppin

es35

Hep

atom

egal

y as

soci

ated

with

in

fect

ion

Vill

age

N =

101

0Ag

e gr

oup

(yea

rs)

Prev

alen

ce (

%)

MF

1–4

4 8

5–9

1710

10–1

449

1815

–19

6846

20–2

444

1825

–29

5725

30–3

950

3840

–49

5153

50–5

947

3760

+42

11

Dom

ingo

et

al. (

1980

)

1983

Phili

ppin

esV

illag

e A

: 26

Vill

age

B: 3

9

Vill

age

C:

44

Hep

atom

egal

y an

d sp

leno

meg

aly

asso

ciat

ed w

ith in

fect

ion

Vill

age

AN

= 2

89

Vill

age

BN

= 8

24

Vill

age

CN

= 1

113

Age

grou

p (y

ears

)

Prev

alen

ce (%

)

Villa

ge

AB

C

MF

MF

MF

1–4

10 5

943

8 6

5–9

1327

3144

3324

10–1

437

1852

3570

4615

–19

1944

4640

6952

20–2

439

4030

5883

2925

–29

033

2335

3950

30–3

947

5341

3545

4740

–49

3330

4848

5555

50–5

925

031

3453

4960

+20

039

3962

49

M =

mal

es F

= fe

mal

es


Tab

le 1

2.4

S.

man

soni

em

piri

cal d

atab

ases

, sub

-Sah

aran

Afr

ica

Dat

eLo

catio

nPr

eval

ence

Mor

bidi

tySo

urce

Resu

ltsRe

fere

nce

Com

men

ts

1972

Uga

nda

89%

Age

grou

p (y

ears

)

Hae

ma-

tem

esis

(eve

r) (%

)

0–

40

5–9

610

–19

320

–39

940

+9

Vill

age

N =

231

Age

grou

p (y

ears

)

Prev

alen

ce (%

)(e

stim

ated

from

gr

aph)

< 1

30

1–4

60

5–9

80

10–1

4 9

515

–19

100

20–2

910

030

–39

100

40–

4910

050

–59

100

60+

100

Ong

om &

Bra

d-le

y (1

972)

Raw

dat

a no

t pr

e-se

nted

1976

Ken

ya82

%Sp

leno

meg

aly

3% v

s 0

in u

ninf

ecte

dV

illag

eN

=41

6Ag

e gr

oup

(yea

rs)

Prev

alen

ce (%

)

MF

1–4

7147

5–9

9195

10–1

910

0097

20–2

997

8030

–39

8067

40–

4973

7050

–59

6758

60–6

910

0067

70+

2086

Sion

gok

et a

l. (1

976)

Kat

o te

chni

que

used

363Schistosomiasis

1976

Ethi

opia

Vill

age

A =

43

.3%

Vill

age

B =

10

.7%

Low

50%

ho

useh

old

sam

ple:

Vill

age

AN

= 3

52

Vill

age

BN

= 1

55

Age

grou

p (y

ears

)

Prev

alen

ce (%

)

Villa

ge A

Villa

ge B

MF

MF

1–4

12 8

0 0

5–9

5249

6 7

10–1

493

6018

15–1

985

25 5

2020

–29

8127

829

30–3

948

25 0

040

–49

36 9

0 0

50+

2236

0 0

Hia

tt (

1976

)K

ato

tech

niqu

e us

ed

1979

Ken

ya47

%A

bdom

inal

pai

n30

%

hous

ehol

d sa

mpl

eAg

e gr

oup

(yea

rs)

Prev

alen

ce (%

)

MF

0–

415

175–

923

3210

–14

5755

15–1

973

5020

–24

8538

25–2

978

6730

–39

5857

40–

4910

0047

50–5

971

6760

+90

50

Smith

, War

ren

& M

ahm

oud

(197

9)

Kat

o te

chni

que

used

cont

inue

d


1988

Buru

ndi

33%

Hep

atom

egal

y an

d sp

leno

meg

aly

asso

ci-

ated

with

infe

ctio

n

5%

popu

latio

n sa

mpl

e

n =

6 2

03

Age

grou

p (y

ears

)

Prev

alen

ce (%

)

MF

0–

411

5–9

2710

–14

4315

–19

4620

–29

4430

–39

3740

–49

3450

–59

3560

+36

Gry

seel

s (1

988)

Kat

o te

chni

que

used

1992

Uga

nda

M =

82%

F =

81%

Hig

h in

tens

ity o

f in

fect

ion

20%

po

pula

tion

sam

ple

Age

grou

p (y

ears

)

Prev

alen

ce (%

) (e

stim

ated

from

gra

ph)

MF

0–

451

735–

983

7710

–14

9394

15–1

990

9120

–29

9081

30–3

991

7640

+75

84

Kab

ater

ine

et a

l. (1

992)

M =

mal

esF

= fe

mal

es

Tab

le 1

2.4

S.

man

soni

em

piri

cal d

atab

ases

, sub

-Sah

aran

Afr

ica

(con

tinue

d)

Dat

eLo

catio

nPr

eval

ence

Mor

bidi

tySo

urce

Resu

ltsRe

fere

nce

Com

men

ts

365Schistosomiasis

Tab

le 1

2.5

S

. inte

rcal

atum

em

piri

cal d

atab

ases

by

regi

on, s

ub-S

ahar

an A

fric

a

Dat

eLo

catio

nPr

eval

ence

(%)

Mor

bidi

tySo

urce

Resu

ltsRe

fere

nce

Com

men

ts

1990

Equa

tori

al

Gui

nea

21D

iarr

hoea

and

blo

od in

th

e st

ool a

ssoc

iate

d w

ith

infe

ctio

n

Peri

urba

nN

= 1

221

Age

grou

p (y

ears

)

Prev

alen

ce (%

)

MF

0–

412

105–

938

3510

–14

3248

15–2

418

2625

–44

7 9

45+

3 9

Sim

arro

, Sim

a &

M

ir (

1990

)N

ote

infe

ctio

n al

mos

t ab

sent

af

ter

age

45 y

ears

.

Kat

o te

chni

que

used

.

1992

Gab

on29

Sple

nom

egal

y ca

used

by

infe

ctio

nV

illag

eN

= 3

54Ag

e gr

oup

(yea

rs)

Prev

alen

ce (%

)

MF

0–

414

85–

948

4610

–14

5265

15–1

960

5320

–29

5035

30–3

925

2240

–49

018

50–5

9 0

060

+ 7

4

Mar

tin-P

reve

l et

al. (

1992

)Se

dim

enta

tion

used

fi rs

t, K

ato

for

quan

tifi c

atio

n.

M =

mal

es, F

= fe

mal

es


Tab

le 1

2.6

S.

man

soni

em

piri

cal d

atab

ases

by

regi

on, L

atin

Am

eric

a an

d th

e C

arib

bean

S. m

anso

ni e

mpi

rica

l dat

abas

es b

y re

gion

, Lat

in A

mer

ica

and

the

Car

ibbe

anS.

man

soni

Dat

eLo

catio

nPr

eval

ence

(%)

Mor

bidi

tySo

urce

Resu

ltsRe

fere

nce

Com

men

ts

1962

Braz

il83

52%

spl

een

Tow

nA

ge 1

0–1

4 ye

ars

= 5

0% o

f spl

een

and

heav

iest

infe

ctio

nsK

loet

zel (

1962

)Fi

rst

stud

y of

its

kind

Lim

ited

to

child

ren

1976

Braz

il80

Gro

ups

N =

363

Age

grou

p (y

ears

)

Prev

alen

ce (%

)

MF

< 1

1050

1–4

3933

5–9

6577

10–1

469

8615

–19

8986

20–2

410

0010

0025

–34

8596

35–6

480

9065

+73

79

Lehm

an e

t al

. (19

76)

Kat

o te

chni

que

used

M =

mal

es, F

= fe

mal

es

367Schistosomiasis


S. haematobium is endemic in 15 countries in this region and S. mansoniis present in 7 of these countries. Some distributions of prevalence by age and sex are shown in Tables 12.7 and 12.8.

Mortality from schistosomiasis

Mortality from schistosomiasis has been poorly documented in most endemic countries. Death certifi cates and patients’ records rarely identify schistosomiasis as the underlying cause of death. Well-designed prospective autopsy studies have nevertheless been published (Cheever et al. 1978). In that study, schistosomiasis was the direct cause of death in 9.2 per cent of the infected individuals and was the attributable cause of death in 6.2 per cent of all deaths. The breakdown of these causes among those infected is shown in Table 12.9. Table 12.10 summarizes the results of available mor-tality studies by World Bank region; these results are discussed below.

Sub-Saharan Africa

Annual mortality attributable to S. haematobium infection in East Africa has been estimated at 1–2 per 1000 infected adults (Forsyth 1969). In Chad, in 1966, the mortality rate of schistosomiasis attributable to S. haemato-bium infection was 1 per 1000 infected persons (Buck et al. 1970).

Latin American and the Caribbean

In 1984, the annual mortality attributable to schistosomiasis caused by S. mansoni in Brazil was estimated at 0.5 per 100 000 total population; at the same time in Suriname the figure was estimated to be 2.4 per 100 000 inhabitants. The control of schistosomiasis through large-scale chemotherapy in Brazil was associated with a decline in annual mortality between 1977 and 1988, from 0.67 to 0.44 deaths per 100 000 inhabit-ants. S. intercalatum infection has never been reported as a cause of death in the region.

China

Before the introduction of praziquantel in China, severe acute schistoso-miasis attributable to S. japonicum had a 2.5–20.7 per cent mortality rate, and in Leyte, the Philippines, the annual mortality among 135 untreated patients with severe schistosomiasis was 1.8 per cent (Blas et al. 1986). It is expected that the more widespread use of current antischistosomal drugs for morbidity control in highly endemic areas will also reduce mortality.

The national survey by the Ministry of Health of China appears to confi rm the total annual mortality rate. A total of 982 severe cases were detected among 165 384 people examined; (16 953 people in the sample cohort were infected). If it is assumed that only infected people had severe disease, the rate of severe cases was 5.79 per cent. This is probably not reasonable since many advanced cases do not excrete eggs. The peak mor-


Tab

le 1

2.7

S

. hae

mat

obiu

m e

mpi

rica

l dat

abas

es b

y re

gion

, Mid

dle

East

ern

Cre

scen

t

Dat

eLo

catio

nPr

eval

ence

(%)

Mor

bidi

tySo

urce

Resu

ltsRe

fere

nce

Com

men

ts

1981

Egyp

t29

2 vi

llage

sN

= 2

403

Age

grou

p (y

ears

)

Prev

alen

ce (%

) (e

stim

ated

)

MF

<1

1820

1–4

1918

5–9

5536

10–1

475

4315

–19

5418

20–2

430

1525

–29

35 9

30–3

927

540

–49

30 7

50–5

926

560

+24

12

Man

sour

et

al. (

1981

)

1982

Egyp

t37

6 vi

llage

sN

= 5

998

Age

grou

p (y

ears

)

Prev

alen

ce (%

)

MF

1–4

2021

5–9

5741

10–1

475

4915

–19

6635

20–2

441

2125

–29

4217

30–3

943

1140

–49

4212

50–5

940

1360

+32

13

Kin

g et

al.

(198

2)

M =

mal

es, F

= fe

mal

es

369Schistosomiasis

Tab

le 1

2.8

S

.man

soni

em

piri

cal d

atab

ases

by

regi

on, M

iddl

e Ea

ster

n C

resc

ent

S.m

anso

ni e

mpi

rica

l dat

abas

es b

y re

gion

, Mid

dle

East

ern

Cre

scen

tS.

man

soni

Dat

eLo

catio

nPr

eval

ence

Mor

bidi

tySo

urce

Resu

ltsRe

fere

nce

Com

men

ts

1976

Suda

n48

Sple

en

Age

grou

p (y

ears

)In

fect

ed

(%)

Not

in

fect

ed

(%)

1–4

9 4

5–9

2210

10–1

429

2315

–19

206

20–3

917

1740

+ 8

6

Vill

age

N =

174

7Ag

e gr

oup

(yea

rs)

Prev

alen

ce (%

)

MF

5–9

2424

10–1

980

8020

–29

6050

30–3

955

4540

–49

4022

50+

5015

Om

er e

t al

. (19

76)

1977

Egyp

tS.

man

soni

: 40

.525

% s

ampl

e in

8 v

illag

es

N =

871

2Ag

e gr

oup

(yea

rs)

Prev

alen

ce (%

)(e

stim

ated

from

gr

aph)

2–5

156–

1033

11–1

550

16–2

040

21–3

025

31+

18

El-A

lam

y &

Clin

e (1

977)

cont

inue

d


1980

Egyp

t74

Inte

nsity

(ge

omet

ric

mea

n no

. egg

s/gr

am)

Age

grou

p (y

ears

)M

F

1–4

134

95

5–9

204

67

10–1

933

121

320

–29

165

199

30–3

923

315

140

–49

194

109

50–5

919

411

260

+ 8

310

0

Vill

age

N =

537

Age

grou

p (y

ears

)

Prev

alen

ce (%

)

MF

1–4

2533

5–9

7157

10–1

989

8120

–29

8071

30–3

986

7840

–49

8056

50–5

975

5560

+50

50

Abd

el-W

ahab

et

al.

(198

0)

M =

mal

es, F

= fe

mal

es

Tab

le 1

2.8

S

.man

soni

em

piri

cal d

atab

ases

by

regi

on, M

iddl

e Ea

ster

n C

resc

ent

S.m

anso

ni e

mpi

rica

l dat

abas

es b

y re

gion

, Mid

dle

East

ern

Cre

scen

t S.

man

soni

(con

tinue

d)

Dat

eLo

catio

nPr

eval

ence

Mor

bidi

tySo

urce

Resu

ltsRe

fere

nce

Com

men

ts

371Schistosomiasis

tality was in the 45–59 year age group. Overall mortality rates were 29 per million population for males and 21 per million population for females.

The most recent data on mortality from to schistosomiasis have been produced by a study of 65 Chinese counties (Junshi et al. 1990). Schis-tosomiasis ranked as the most signifi cant cause of death resulting from colorectal, rectal and colon cancer. Only 20 of these counties were currently endemic for schistosomiasis. The cumulative mortality rate attributable to schistosomiasis for both sexes was as high as 38.99 per 1000 deaths.

S. japonicum is possibly carcinogenic in humans, causing colorectal carcinoma. The cumulative data from China support this conclusion; see also the comprehensive review by the International Agency for Research on Cancer (1994).


One in 20 deaths in the Khong district of the Lao People’s Democratic Republic were attributable to schistosomiasis (S. mekongi) according to survey data obtained in preparation for the national control programme on opisthorchiasis and schistosomiasis (A. Sleigh, personal communica-tion 1992).

The case fatality rate of schistosomiasis attributable to Schistosoma japonicum infection in the Philippines is estimated to be 1.78 per cent per year (Blas. et al 1986). The recognized number of cases in Thailand and Malaysia is so low that neither the populations nor the populations at risk should be included in the totals.


Mortality from schistosomiasis is the cause of 6 per cent of all deaths in Egypt. The annual crude mortality rate is 1 per 1000 infected individu-als, and is higher in men than in women. The male-to-female sex ratio is 47.2:23.0, based on the combined raw data of King et al. (1982) and Mansour et al. (1981).

Table 12.9 Causes of death related to schistosomiasis

Attributed cause of death Percentage of deaths Mean age (years)

Obstructive uropathy 2.5 42Bladder cancer 2.4 38Symmer’s fi brosis 3.1 30Colonic polyposis 0.8 35Salmonellosis 0.4 —

Total deaths in infected persons 9.2

Source: Cheever et al. (1978).

372 Global Epidemiology of Infectious DiseasesT

ab

le 1

2.1

0St

udie

s of

mor

talit

y ra

tes

asso

ciat

ed w

ith s

chis

toso

mia

sis,

Wor

ld B

ank

regi

ons

Regi

on a

nd ty

peRe

fere

nce

Sex

Age

grou

p (y

ears

)Po

pula

tion

(num

ber)

Num

ber

of p

eopl

e in

fect

edN

umbe

r of

dea

ths

per

year

Chi

na —

S. ja

poni

cum

onl

yC

hina

Min

istr

y of

Pub

lic

Hea

lth (

1992

)M

ales

0–1

415

7 24

0 00

020

5 42

7 5

015

–65+

427

959

000

741

240

530

Fem

ales

0–1

414

8 34

7 00

012

0 07

3 4

015

–65+

400

147

000

433

260

380

Mid

dle

East

Cre

scen

t —

S.

man

soni

El M

alat

awy

et a

l. (1

992)

Mal

es0

–14

106

506

000

1 55

0 68

71.

515

–65+

149

883

000

3 41

9 46

334

Fem

ales

0–1

410

1 73

3 00

01

347

793

315

–65+

144

953

000

2 97

2 05

730

Mid

dle

East

Cre

scen

t —

S.

haem

atob

ium

Utr

oska

et

al. 1

989.

Mal

es0

–14

106

506

000

2 12

7 15

221

15–6

5+14

9 88

3 00

01

719

416

1 71

9Fe

mal

es0

–14

101

733

000

1 03

6 54

410

15–6

5+14

4 95

3 00

0 8

37 8

5860

0

Latin

Am

eric

a &

Car

ibbe

an

— S

. man

soni

onl

yS.

man

soni

onl

yS.

man

soni

Lope

s (1

984)

Mal

es0

–14

80

845

000

1 75

5 72

5 3

15–6

5+14

0 76

6 00

03

244

275

64Fe

mal

es0

–14

78

420

000

1 98

6 48

6 3

15–6

5+14

4 26

4 00

02

913

514

62

Sub-

Saha

ran

Afr

ica

—

S. h

aem

atob

ium

Buck

et

al. (

1970

)M

ales

0–1

411

7 74

2 00

027

318

640

2715

–65+

134

580

000

22 0

82 1

602

208

Fem

ales

0–1

411

6 84

8 00

021

607

502

2115

–65+

141

104

000

13 8

72 7

971

000

Oth

er A

sian

Cou

ntri

es

& Is

land

s —

S. ja

poni

cum

(Phi

lippi

nes

& In

done

sia)

Blas

et

al. 1

986

Mal

es0

–14

151

252

315

–65+

208

748

55Fe

mal

es0

–14

99

248

215

–65+

140

752

39

S. m

ekon

gi (

Lao

PDR

&

S. m

ekon

gi (

Lao

PDR

&

S. m

ekon

giC

ambo

dia)

A. S

leig

h (p

erso

nal c

omm

uni-

catio

n 19

92)

Mal

es0-

1450

000

515

–65+

75 0

0025

Fem

ales

0–1

450

000

515

–65+

75 0

0025

373Schistosomiasis

Disability

In a critical review, Prescott (1979) pointed out that, at that time, no clear empirical basis had been found for the assumption that schistosomia-sis seriously impairs labour productivity. He attributed this to possible sampling bias resulting in the exclusion of workers with severe disease. Subsequent studies have lent more support to the thesis that not only does severe infection cause disability but infection alone limits productivity and well-being.

In the workplace, decreased productivity has infrequently been shown to be the result of to schistosomiasis. In contrast, increased absenteeism has consistently been shown to be related to schistosomiasis. In irrigation workers, who are at greatest risk, schistosomiasis infection was associ-ated with a 3.67 per cent greater absenteeism rate than among those not infected; in cane-cutters, schistosomiasis infection was associated with 1.64 per cent greater absenteeism (Foster 1967). These fi gures are based on observation of over 28 000 consecutive work shifts and the difference related to the irrigation workers was considered statistically signifi cant. As Prescott points out, the determinants of absenteeism were not analysed.

Since Prescott’s review, a substantial amount of data has been published supporting the hypothesis that infection without clinical manifestations causes work days lost: 26.2 to 41.6 work days lost per year as a result of S. japonicum (Blas 1989); 4.4 work days per year as a result of S. hae-matobium (Ghana Health Assessment Project Team 1981, Morrow et al. 1984). Absenteeism was noted to be twice as high among labourers infected with S. mansoni as among those uninfected (Ndamba et al. 1991); 6 work-ing days per year were estimated to be lost due to S. mansoni infection (Chowdhry & Levy 1988); in Madagascar 50 per cent of people reported unable to work had evidence of urinary schistosomiasis and remained out of work for at least 10 days (Breuil, Moyroud & Coulanges 1983). There is a latency period of 5–15 years between infection and development of severe disease due to S. mansoni, thus hepatosplenomegaly with portal hyperten-sion attributable to S. mansoni occurs after age 20 years. Approximately 10 per cent of those infected will develop severe disease.

Since 1980 a number of studies have shown that schistosomiasis result-ing from S. mansoni has a negative effect on productivity. A reduction of 18 per cent in the work output of those individuals with heavy infection or hepatosplenomegaly can be expected (Awad El Karim et al. 1980). According to a recent study, physical performance increased 4.3 per cent after treatment, and work output (as measured by the amount of sugar cane cut in a given time) increased 16.6 per cent (Ndamba et al. 1993). Infected individuals without organomegaly were observed to have no reduction of work output (Van Ee & Polderman 1984).

A minimum of 12 per cent lower exercise capacity was found in children with S. haematobium infection in Zimbabwe (Ndamba 1986). This defi cit was recovered within one month after treatment. Similarly, in Kenya, a


7–10 per cent improvement in exercise capacity was found one month after treatment in children with S. haematobium infection (Latham et al. 1990).

Of those with hepatosplenomegaly attributable to S. mansoni, 33 to 67 per cent have oesophageal varices (De Cock et al. 1982, Saad et al. 1991). Of those with oesophageal varices, 3 to 4 per cent have recurrent upper gastrointestinal bleeding. After oesophageal varices have bled once, there is a tendency for the bleeding to recur, and 3–4 months per year will be lost either in or out of hospital.

Disease of the central nervous system, affecting the spinal cord, is more frequent and causes more disability than is currently recognized, especially among migrants into endemic areas of S. mansoni transmission (World Health Organization 1989, Joubert et al. 1990). In the Philippines, the minimum contribution of schistosomiasis attributable to S. japonicumto the etiology of epilepsy is 6 per 1000 of the total rate of 11 per 1000 (Hayashi 1979). Spinal cord involvement attributable to schistosomiasis (S. mansoni mostly) is the cause of 1 in 4 of all hospital admissions to the S. mansoni mostly) is the cause of 1 in 4 of all hospital admissions to the S. mansonineurological nervice of a general hospital in Durban, South Africa (Haribhai et al. 1991).

Average disability weights for cases of schistosomiasis infection were estimated using expert panels, person-trade off methods for 22 indicator conditions, and rankings of other conditions (including schistosomiasis) against the indicator conditions as described by Murray & Lopez (1996a). The resulting average disability weights were 0.005 for children aged 0–14 years and 0.006 for adults aged 15 years and over.

Estimation of disability-adjusted life years

General methods used for the calculation of disability-adjusted life years (DALYs) lost due to a disease are given by Murray & Lopez (1996a). DALYs are the sum of years of life lost due to mortality (YLLs) and years lived with disability (YLDs). The prevalence of schistosomiasis and deaths attributable to schistosomiasis were calculated for the eight World Bank regions, based on the data reviewed above. The resulting estimates are shown in Tables 12.11 and 12.12 and have also been published by Mur-ray & Lopez (1996b).

YLLs are calculated directly from the deaths shown in Tables 12.11 and 12.12 Total global deaths in 1990 resulting from schistosomiasis were estimated to be around 8000. It must be emphasised that these are direct schistosomiasis deaths and do not include the cancer and other disease deaths attributable to schistosomiasis (as discussed below).

YLDs are usually calculated from regional estimates of incident cases and average durations. However, because of the very limited information available to estimate incidence rates for schistosomiasis from prevalence and case fatality data, YLDs for schistosomiasis were calculated directly from the prevalence estimates (in effect assuming a one year duration and prevalence equal to incidence).

375Schistosomiasis

Tables 12.11 and 12.12 also show the estimated DALYs for the eight World Bank regions and the regional variation in DALYs per 100 000 population resulting from schistosomiasis.

Schistosomiasis as a risk factor for other diseases

Cancer

Squamous cell bladder carcinoma is the leading cause of cancer among 20–44 year old men in Egypt and is a leading cause of death in this age group (Koroltchouk et al. 1987). El-Bolkainy & Chu (1981) estimated that the rate of squamous cell carcinoma among people with S. haematobiuminfection in Egypt is 2 per 1000 and 4 per 1000 among rural residents. In an older study, squamous cell bladder cancer was estimated to occur in 10 of every 1000 people infected with S. haematobium (Halawani & Tamami 1955); 26 per cent of deaths attributable to schistosomiasis were associated with bladder cancer in Egypt. The latency between initial infec-tion and onset was estimated to be 20–30 years, and the male-to-female ratio was 9.5:1.

In Angola the peak age of incidence of squamous cell carcinoma of the bladder is 44 years of age. An incidence rate of 8 per 10 000 rural inhabitants is suggested on the basis of epidemiological and clinical data (Lopes 1984). In Malawi, Mozambique and Zambia, the incidence rates of squamous cell bladder cancer are eight times as high as in the United States of America or the United Kingdom (Lucas 1982).

It has been estimated that primary prevention to control urinary schis-tosomiasis would reduce the global rate of carcinoma of the bladder by 5000–10 000 cases per year (Koroltchouk et al. 1987).

Other diseases

Intestinal schistosomiasis caused by S. mansoni and S. japonicum may complicate a variety of other diseases that increase disability.

Typhoid fever. If a person with schistosomiasis acquires typhoid fever, the duration of the typhoid fever will increase 2–3 times the average dura-tion and may lead to total incapacity or death in 30 per cent of untreated persons (Salih et al. 1977).

Hepatitis B. The effect of schistosomiasis infection on concurrent hepatitis B has been recently reviewed, and the limitations of the interpretation of clinical and epidemiological data have been analysed (Chen et al. 1993). There is a consensus among clinicians in the highly endemic areas of China and Egypt that in patients with schistosomiasis the duration of hepatitis increases up to 5 times the average, and the risk of chronic liver disease is greater and may result in total incapacity (Ghaffar et al. 1990).


Tab

le 1

2.1

1Ep

idem

iolo

gica

l est

imat

es fo

r sc

hist

osom

iasi

s,19

90, m

ales

Age

grou

p (y

ears

)

Prev

alen

ceD

eath

sYL

LsYL

Ds

DAL

Ys

Num

ber

(thou

sand

s)Ra

te p

er

100

000

Num

ber

(thou

-sa

nds)

Rate

per

10

0 00

0N

umbe

r (th

ou-

sand

s)Ra

te p

er

100

000

Num

ber

(thou

-sa

nds)

Rate

per

10

0 00

0N

umbe

r (th

ou-

sand

s)Ra

te p

er

100

000

Esta

blish

ed M

arke

t Eco

nom

ies

(EM

E)0–

40

—0

——

0 —

0 0

0 5–

140

—0

——

0 —

0 0

0 15

–44

0—

0 —

—0

—0

0 0

45–5

90

—0

——

0 —

0 0

0 60

+0

—0

——

0 —

0 0

0 A

ll A

ges

0—

0 —

—0

—0

0 0

Form

erly

Socia

list E

cono

mie

s (F

SE)

0–4

0—

0 —

—0

—0

0 0

5–14

0—

0 —

—0

—0

0 0

15–4

40

—0

——

0 —

0 0

0 45

–59

0—

0 —

—0

—0

0 0

60+

0—

0 —

—0

—0

0 0

All

Age

s0

—0

——

0 —

0 0

0

Indi

a 0–

40

—0

——

0 —

0 0

0 5–

140

—0

——

0 —

0 0

0 15

–44

0—

0 —

—0

—0

0 0

45–5

90

—0

——

0 —

0 0

0 60

+0

—0

——

0 —

0 0

0 A

ll A

ges

0—

0 —

—0

—0

0 0

377Schistosomiasis

cont

inue

d

Chin

a 0–

435

590

——

0 —

0 0

0 5–

1417

017

50

——

0 1

1 1

1 15

–44

501

164

0 0

4 1

4 1

9 3

45–5

914

519

90

04

61

1 5

7 60

+96

196

0 1

2 4

—0

3 6

All

Age

s94

716

21

011

2

7 1

17

3

Oth

er A

sia a

nd Is

land

s 0–

435

790

——

0 —

0 0

0 5–

1416

719

80

——

0 1

1 1

1 15

–44

192

119

0 —

1 1

2 1

3 2

45–5

955

162

0 0

2 6

—0

2 6

60+

3718

20

11

5—

0 1

5 Al

l Age

s48

514

10

04

13

1 7

2

Sub–

Saha

ran

Afric

a 0–

4 1

1 14

8 2

3 47

80

—1

2 24

51

25

53

5–

14 4

5 01

3 6

4 06

80

012

17

261

371

273

389

15–4

4 3

9 99

1 3

8 54

01

122

21

348

335

371

358

45–5

976

52 3

7 68

21

38

3947

23

1 56

27

6 60

+34

42 3

2 75

80

53

2914

13

3 18

17

1 Al

l Age

s 1

07 2

46 4

2 50

42

147

19

695

275

742

294

Latin

Am

erica

and

the

Carr

ibea

n 0–

4 3

01 1

047

— 1

3 1

35–

14 1

455

2 7

91—

8 1

5 9

17

15–4

4 2

549

2 4

44 3

3 2

2 2

1 2

5 2

445

–59

496

2 2

30 1

4 3

13

4 1

860

+ 1

99 1

398

— 1

7 1

7Al

l Age

s 5

000

2 2

56 5

2 3

5 1

6 4

0 1

8


Mid

dle

East

ern

Cres

cent

0–

4 6

30 1

531

— 1

2 2

55–

14 3

048

4 6

64 7

11

18

28

25

38

15–4

4 4

038

3 5

45 1

1 1

5 1

3 3

5 3

1 5

0 4

445

–59

786

3 5

192

6 2

7 5

22

10

45

60+

315

2 3

082

2 1

5 1

7 4

29

All A

ges

8 8

17 3

439

11

30

12

60

23

91

35

Wor

ld0–

4 1

2 14

9 3

781

1 2

6 8

28

95–

14 4

9 85

2 9

044

1 1

9 3

289

52

308

56

15–4

4 4

7 27

1 3

782

2 4

6 4

412

33

458

37

45–5

9 9

135

2 9

24 1

21

7 5

6 1

8 7

7 2

560

+ 4

089

1 8

68 1

10

5 1

7 8

27

12

All A

ges

122

495

4 6

16 5

97

4 8

00 3

0 8

98 3

4

YLL

s, ye

ars

of li

fe lo

st; Y

LDs,

year

s liv

ed w

ith d

isab

ility

; DA

LYs,

disa

bilit

y-ad

just

ed li

fe y

ears

.

Tab

le 1

2.1

1Ep

idem

iolo

gica

l est

imat

es fo

r sc

hist

osom

iasi

s,19

90, m

ales

(con

tinue

d)

Age

grou

p (y

ears

)

Prev

alen

ceD

eath

sYL

LsYL

Ds

DAL

Ys

Num

ber

(thou

sand

s)Ra

te p

er

100

000

Num

ber

(thou

-sa

nds)

Rate

per

10

0 00

0N

umbe

r (th

ou-

sand

s)Ra

te p

er

100

000

Num

ber

(thou

-sa

nds)

Rate

per

10

0 00

0N

umbe

r (th

ou-

sand

s)Ra

te p

er

100

000

379Schistosomiasis

Furthermore, there is a decreased response to hepatitis B vaccine (Bassily et al. 1987, Ghaffar et al. 1990).

Rift Valley Fever. During epidemics of Rift Valley Fever in Egypt and East Africa, it has been hypothesized that persons with intestinal schistosomiasis had a high mortality rate due to liver failure (WHO Regional Offi ce for the Eastern Mediterranean 1983). The haemorrhagic form may occur in up to 6 per cent of patients and the mortality rate of this form of RVF is about 30 per cent.

Economic Burden and intervention

The economic constraints in developing countries where schistosomiasis is endemic require careful analysis and review to assess the feasibility of control with limited resources. The cost of disease and the price of health have been a focus of attention of the World Health Organization since its inception (Winslow 1951).

Economic costs

The economic costs of schistosomiasis are substantial. In 1953 schisto-somiasis was estimated to cost Egypt about U$57 million dollars and to decrease productivity by 33 per cent (Wright & Dobrovolny 1953). The projected savings to be made by eradicating schistosomiasis from Japan was estimated in 1952 to be US$3 million per year (Hunter et al. 1952). In Fukuoka and Saga prefectures alone there were 28 617 infected people representing 24 213 520 man-hours lost per year and wages lost per year equivalent to US$2 522 200, while the estimated cost of treatment of infected invividuals per year was U$177 938 (U$6.22 per person).

Audibert (1986) estimated that, in the rice irrigation projects of north Cameroon, a 10 per cent increase in the prevalence of schistosomiasis resulted in a 4.9 per cent decrease in rice output.

Estimation of costs of interventions

An estimation of the cost of different interventions is the fi rst step in a cost-effectiveness analysis of control strategy options. In a strategy aimed primarily at morbidity control, the main elements are chemotherapy and health education. The simplest item to estimate is the actual cost of the antischistosomal drugs, but the cost of central and peripheral storage, transport to distribution centres, and administra tive support must also be considered.

After choosing the most appropriate drug and establishing a dosage schedule, the next cost is that of delivery. This will refl ect the choice of drug and the dosage schedule. Cost calculations must also include the requirements for diagnosis. Selective diagnosis of S. haematobium infec-tion using questionnaires or chemical-reagent strips costs relatively little compared with the high cost of stool examination to detect S. mansoni


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383Schistosomiasis

infection. The cost of large-scale chemotherapy will be affected by the method of identifying communities for treatment.

Cost calculations frequently omit the cost of employing the necessary personnel. The cost of equipment, particularly vehicles, usually appears in the accounting, but the cost of offi ces and laboratories is rarely considered, nor is the depreciation of these capital assets. In a strategy that aims at morbidity control and the reduction of transmission, the additional costs of, for example, mollusciciding and environmental management must be considered.

The cost of mollusciciding includes the purchase of molluscicides and the cost of their application (e.g. transportation, storage, administration, equipment and personnel). The cost of environmental management includes capital investments in engineering and equipment and recurrent operational costs (e.g. personnel and materials). Since the cost estimates above are intended to allow comparison, a uniform method of cost calculation must be used so that costs can be adjusted to refl ect local variation.

The costs of control

Studies on the costs of control programmes based on chemotherapy were evaluated by the World Health Organization Expert Committee (WHO 1993), which noted the inadequacy of the available data. Costs estimated in studies ranged from US$0.70 to US$3.10 per person, but development costs, salaries, and the cost of failure were often excluded.

The government health allocations for schistosomiasis control were last reviewed in 1976 (Iarotski & Davis 1981). Nineteen endemic countries responded to a World Health Organization questionnaire regarding: (1) the total health budget in US dollars and its proportion of the total national budget and (2) the allocation for schistosomiasis control in US dollars and as a proportion of the health budget. In those countries responding, between 2 per cent (Saudi Arabia) and 18 per cent (Dominican Republic) of the national budget was allocated to health and between 0.002 per cent (Indonesia) to 2.8 per cent (Saint Lucia) of the health budget was directly allocated to schistosomiasis control. Current expenditures for schistosomiasis control are not available.

Some hypothetical projections have been made based on pilot projects. The cheapest regimen using praziquantel involved existing health services in areas of low endemicity. When specialized programmes were required, costs varied from US$1.50 to US$6.53 per person per year. Costs per infected person treated were inevitably higher, with a minimum cost of US$3.00 for the specialized programmes.

When the annual per capita expenditure on all forms of primary health care is only between US$1 and US$4 in many endemic countries, most cannot afford vertical programmes, except perhaps in small areas. Drugs account for a relatively low proportion of total delivery costs in vertical programmes. On the other hand, their cost is more prominent and may be the major expenditure in programmes integrated into primary health


care. A reduction in the price of praziquantel could signifi cantly reduce the cost of such programmes.

The cost of identifying communities with a high prevalence of S. haema-tobium infection can be substantially reduced by using question naires and reagent strips. Chemotherapy targeted at schoolchildren will also reduce the costs of control, and in most communities will reach the groups with the highest prevalence and severity of infection. Increasing the interval between treatments will also reduce costs, but this has to be balanced against a reduced impact on morbidity. Further studies are needed on ways of reducing the cost of identifying commu nities for treatment (especially for S. mansoni infection) and the cost of drug delivery.

Estimation of effectiveness

Effectiveness has been estimated in terms of coverage (number of people receiving treatment per number of people infected or at risk) or cure (cov-erage per drug effi cacy). This allows estimation of the cheapest approach to delivering treatment, which is not necessarily the same as the most cost-effective approach to reducing disease.

For a better assessment of effectiveness, more information is required on the morbidity attributable to schistosomiasis at the community level, the relationship between this morbidity and the prevalence and intensity of infection, and the relationship between morbidity and disease predisposi-tion. This approach may require modelling the dynamics of transmission and morbidity, and the impact of control, in similar ways to methods developed for other helminthic infections.

Indirect costs

In assessing indirect costs of the disease, a distinction is traditionally made between the cost of health care for infected people and the cost of reduced economic productivity as a result of the disease. Little is known about the health-seeking behaviour of people suffering from schistosomiasis and the direct cost incurred by the health system; more research is needed in this area.

Given levels of prevalence and intensity of infection can be associated with very different levels of clinical disease both between and within coun-tries. Economic estimates show similar variations in the indirect cost of the disease. These inconsistencies do not imply that schistosomiasis has no demonstrable economic impact, but rather that the indirect costs might be considerable in certain circumstances, as in areas where the prevalence of clinical disease is high or in communities that have recognized schis-tosomiasis as a signifi cant health problem. In the assessment of indirect costs, rural household income should be the focus of analysis rather than the wages of individual workers.

The long-term economic consequences of the disease should also be explored. S. haematobium infection can be associated with malnutrition and stunting of growth in children. There is a positive correlation between

385Schistosomiasis

education and productivity, and if schistosomiasis inhibits educational achievement it could also eventually affect production.

Discussion and conclusions

This chapter has documented the data and methods used to estimate the global burden of schistosomiasis in 1990. The paucity of epidemiological data, particularly on the sequelae and consequences of schistosomiasis infection, have inevitably required that a very simplifi ed disease model be used for the estimations. Ideally, a number of other factors should be considered in the calculation of the burden of disease attributable to schistosomiasis.

Multiple schistosoma infections

In 35 sub-Saharan countries and in 6 countries of the Middle Eastern Crescent, both S. mansoni and S. haematobium are present and overlap in some areas. The age and sex distribution is similar to that of each infec-tion alone (Saladin et al. 1983, Granier et al. 1985, Kazura et al. 1985, El Malatawy et al. 1992). The only study to analyse the interaction between the two infections in the same individuals nevertheless showed that the intensity of S. haematobium infection is greater in those with concomitant S. mansoni infection than in those with S. mansoni infection than in those with S. mansoni S. haematobium alone; the converse was not observed (Robert, Bouvier & Rougemont 1989).

Multiple parasitic infections

Schistosomiasis may be only one of multiple parasitic infections in the same individual. Various intestinal helminthic infections have been associated with S. mansoni infection (Lehman et al. 1976)

Polyparasitism is the rule rather than the exception in most developing countries. Its occurrence is, however, focal and wide variations are pres-ent within any country (Bundy et al. 1991). Estimating the proportional contribution of each of multiple infections to the burden of disease has not been attempted.

Reinfection

In endemic areas re-exposure to infection is constant or seasonal and is proportional to the overall prevalence, i.e. high prevalence is associated with high rates of reinfection. In assessing the burden of schistosomiasis, the risk of reinfection should be considered.

It is hoped that future revised estimates of the global burden of disease for schistosomiasis will be able to take into account improved epidemio-logical information on the incidence, prevalence, sequelae and case fatality of the various types of schistosomiasis infection, and that control efforts will have resulted in reductions in the prevalence of this disease in most regions.


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THE GLOBAL EPIDEMIOLOGY OF INFECTIOUS DISEASES...The global epidemiology of infectious diseases [electronic resource] / edited by Christopher J. L. Murray, Alan D. Lopez, Colin D