Advances and challenges for the expanded programme on

Advances and challenges for the expandedprogramme on immunization

F T CuttsWHO Collaborating Centre for the Clinical Evaluation of Vaccines in Developing Countries,Infectious and Tropical Disease Department, London School of Hygiene and Tropical Medicine,London, UK

Over 3 million deaths from measles, neonatal tetanus and pertussis areprevented by vaccination each year. In the Americas, poliomyelitis has beeneliminated, and measles is close to elimination. Globally, reported poliomyelitisincidence has declined by over 80% since 1988.

Strategies have evolved from strengthening routine childhood immunizationservices, to establishing disease surveillance and defining specific activities fordisease control and elimination. Efforts to ensure the supply and quality ofvaccines are underway. New vaccines against major pathogens will be licensedsoon. Some of these will be used for groups other than mothers and infants,requiring re-definition of the 'EPI target groups'.

Despite global successes, in 1995, six of the world's most populous developingcountries reported coverage levels below 70% and coverage is below 50% inseveral African countries. Immunization programmes will need to be tailored tothe level of economic and health systems development of a country.Industrialized countries must offer sustained support to expand immunizationprogrammes in ways that strengthen health systems in developing countries.

Correspondence toDr FT Cutts, Infectious

and Tropical Disease

Department LondonSchool of Hygiene and

Tropical Medicine,Keppel Street,

London WC1E 7HT, UK

Over 3 million deaths from measles, pertussis and neonatal tetanus areestimated to be averted each year by vaccination1. In 1995, measlesvaccination was estimated to have reduced measles-associated mortalityworldwide by 88% from the pre-vaccination levels of 5.7 million deathsper year2. Poliomyelitis has been eradicated from the Americas and thegoal to eradicate wild polio virus from the world is well on its way.

Despite these successes, the recent resurgence of diphtheria3'4,increasing spread of yellow fever in Africa5, and continuing highmorbidity and mortality from hepatitis B, measles, pertussis andneonatal tetanus in low income countries6 emphasize the need forcontinued support for vaccination programmes. At the same time, newvaccines against major infectious diseases are becoming available,bringing new challenges for the Global Expanded Programme onImmunization (EPI).

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Tropical medicine: achievements and prospects

Current disease control goals of the global EPI are that by the year2000, poliomyelitis will be eradicated; neonatal tetanus will beeliminated (incidence rate less than 1 case per 1000 live births in alldistricts); measles mortality and morbidity will be reduced, respectively,by 95% and 90% from the pre-immunization era, and new hepatitis Bvirus carrier incidence will be reduced by at least 80% (adapted fromNinth General Programme of Work, 1996-2001, World HealthOrganization, Geneva). In this paper, the strategies used to pursue andmonitor these goals are reviewed, achievements are summarized, andchallenges facing the EPI are discussed.

Strategies for routine immunization

The World Health Organization (WHO)7 recommends that the primarychildhood vaccination series in developing countries include BacilleCalmette-Guerin (BCG) and oral polio vaccine (OPV) at birth; OPV anddiphtheria-tetanus-pertussis (DTP) vaccines at 6, 10 and 14 weeks ofage, and measles vaccine at 9 months of age.8 In countries whereperinatal transmission of hepatitis B (HBV) is important, HBVvaccination should commence at birth. In countries where HBVtransmission is predominantly in childhood, the vaccine is recommendedat the time of each DTP dose. In countries endemic for yellow fever, YFvaccine is recommended at the time of measles vaccination.

The number and frequency of booster doses depends on theepidemiological patterns of diseases in a particular country, the level ofhealth services infrastructure and resources7, and the relative priority ofboosters compared, e.g. to introduction of new vaccines into theprimary vaccination schedule. The importance attached to booster doseshas increased in recent years because of the resurgence of diphtheria4.Booster doses of DTP are recommended in the second year of life and,where disease is documented among school children, a further dose isrecommended at school entry.

To prevent neonatal tetanus, in countries where most women ofchildbearing age were not immunized as children, or lackdocumentation of such vaccination, a 5-dose TT programme for womenof childbearing age is recommended (Table 1). In future, increasingnumbers of women of childbearing age will have documentation of priorreceipt of TT-containing vaccines, and adult women will need fewerbooster doses of TT.

Delivery sites for vaccination range from fixed sites to mobile teams.Fixed sites include health centres and health posts that offer a range ofprimary health care (PHC) activities, and/or curative services. Utilization

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Challenges for immunization

Table 1 Tetanus toxoid immunization schedule for women of childbearing age7

Dose When to give Expected durationof protection

TT 1 At first contact or as early as possible in pregnancy None guaranteedTT 2 At least 4 weeks after TT 1 1-3 yearsTT 3 At least 6 months after TT 2 5 yearsTT 4 At least 1 year after TT 3 or during subsequent pregnancy 10 yearsTT 5 At least 1 year after TT 4 or during subsequent pregnancy All childbearing years

is higher when sites are easily accessible, have minimal administrativebarriers9, and also provide good quality curative care and an adequatesupply of essential drugs10. Wherever vaccinations are offered, it is vitalto use all opportunities to administer vaccines9. For this, theimmunization status of all children in the target age group should bescreened routinely and immunization provided to eligible children andmothers. Health workers should be taught which are true and which arefalse contra-indications, and supervisors should monitor compliancewith recommendations, for example using the EPI training module onmissed opportunities11.

In areas progressively further from a health facility, regular outreachservices from the nearest health facility or district centre, or mobileteams (which involve stay of at least one night in a distant village) areused. Outreach and mobile services may be scheduled throughout theyear, or in annual campaigns or 'pulses'12-13. Pulse campaigns areplanned at district level and conducted by local staff and village healthworkers or volunteers. Where possible, the pulses are timed for themonths preceding the seasonal peaks of diseases such as measles12.Advantages include easier management of vaccines, fuel and equipmentin a relatively concentrated period of activity, in areas where year-roundoutreach activities are hard to maintain.

The role of national mass campaigns in the EPI has been debated14.Experience with campaigns that were conducted with the sole purposeof raising immunization coverage rapidly was often poor15. Suchcampaigns were seen as being imposed on countries or districts bydonors, interrupting other health services and increasing donordependency16. Increases in coverage were short lived in countries such asGuinea17, Ghana and Senegal14, and the quality of vaccination was lowin some campaigns18. In contrast, in the region of the Americas, wherethey have been a major component of disease eradication programmes,they are implemented effectively with predominantly local funding19.Campaigns are now used in most countries as a strategy within a long-term plan of action to improve disease control or eradication rather thana short-term measure to increase coverage (see below).

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No single strategy is likely to be appropriate for all circumstances andall diseases. The choice of strategy should depend upon the epidemi-ology of the disease, the characteristics of the vaccine, the facilitiesavailable, the accessability of the population, their cultural attitudes andpractices and the socio-economic level and health systems context of thecountry. There is a need for continued capacity building for national anddistrict-level managers to select strategies that are appropriate for theirown context.

Disease elimination/eradication initiatives

In 1985, the region of the Americas adopted a goal of eradication ofpoliomyelitis from the Western Hemisphere by the year 199020. Threeyears later, the 41st World Health Assembly ratified the goal of globaleradication by the year 200021. The last case of poliomyelitis due to wildvirus in the Americas occurred on 23 August 1991, in Peru.

To achieve polio eradication, National Immunization Days (NIDs) arerecommended, in which all children in the target age, usually under 5years, receive OPV during a short period with the aim of displacing thewild virus from communities by the mass circulation of the vaccinevirus. Once transmission is reduced only to focal areas, 'mopping up'operations, consisting of door to door vaccination are conducted inareas at risk. Every case of acute flaccid paralysis (AFP) is investigated,and stool specimens are collected from cases and contacts for viralisolation20.

The region of the Americas has adopted a measles eradication goal,and a global goal is under consideration22. In the measles eradicationstrategy, initial mass 'catch-up' campaigns, targeting the age groupwhere most susceptibles have accumulated (1-15 years in the Americas),are used. To prevent resurgence of measles, programmes must sustainhigh routine vaccination coverage of infants, and conduct periodicsupplemental campaigns when susceptibles (comprising unvaccinatedpersons and vaccine failures) accumulate. Surveillance of suspectedmeasles cases with laboratory confirmation of cases is another keyelement of the strategy23.

Another disease, neonatal tetanus (NT) has been targeted forelimination (defined as a reduction in the incidence of NT to less than 1per 1000 live births in all districts of the world). The recommendedstrategies include routine immunization of pregnant women with TT,immunization of all women of childbearing age in high risk areas,improvement of clean delivery and hygienic cord care practices andeffective NT surveillance.

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Table 2 Selected indicators and methods to monitor the EPI

Indicator Commonly used methods

Immunization coverageMedian age at receipt of vaccinesDropout between DTP1/OPV1 and measles vaccines(indicator of effectiveness of tracking activities)

Missed opportunities for vaccination

Cold chain quality

Adverse events

Target disease incidence ± mortality

Age-specific levels of susceptibility

Costs per fully Immunized childCost per dose administered (e.g. in NID)

Routine reports on number of vaccine dosesadministered to 0-11 month olds, compared tobirth cohortCoverage surveys using the EPI clustersampling method

Comparing DTP and OPV coverageComparing measles and yellow fever coverageHealth-facility based surveys and supervision

Supervision; use of temperature records andcold chain monitors

Routine reports of abscesses, lymphadenitis,unusual or severe events, with lot numbers ofvaccines administeredOutbreak investigations (e.g. lymphadenitis)

Surveillance from routine notification systems± sentinel sitesLaboratory reports of confirmed casesOutbreak investigationsSpecial surveys

Serological surveillance or special surveys (usedat more advanced stages of immunizationprogrammes)

Monitoring administrative financial andbudgetary dataPeriodic costing studies

Monitoring and evaluation

The EPI has developed indicators and methods to monitor programmeperformance24, coupled with operational research to identify and solveproblems (Table 2).

Programme quality should be monitored through regular supervisionand periodic operational research24. Health facility-based studiescombining exit interviews with mothers, interviews with providers, andobservation using check-lists, are used to evaluate timeliness ofvaccination, drop-out rates, and missed opportunities among childrenand mothers who attend vaccination sites, and to assess providerknowledge and practices. Inexpensive surveys of households near tohealth facilities can be used to investigate reasons for failure to useaccessible vaccination services25.

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There is increasing recognition of the importance of adverse eventsthat occur because of programme failure26. In some cases vaccine causedside-effects because it was reconstituted with the wrong diluent.Elsewhere, contaminated needles or syringes were used, or dangerousdrugs were mistakenly administered instead of vaccines. Outbreaks oflymphadenitis have occurred after BCG vaccination, following a changein strain of vaccine and/or problems in intradermal injectiontechnique27. To detect such adverse events, every country should reportcases of abscesses, and unusual or severe events such as septicaemia ordeath, that are temporally related to vaccination26. Clinics and vaccinestores should note the manufacturer, lot number and expiry date of eachvaccine received.

In addition to monitoring the coverage and quality of vaccinationprogrammes, reasons for non-vaccination or incomplete vaccinationshould be investigated through a mixture of qualitative and quantitativemethods. Distance to vaccination sites28'29, waiting times29'30, availabilityof curative services10-31, and cost17-32 affect utilization. Characteristicssuch as low parental educational level29-33"35, recent migration33-34, andlarge family size36 can be used to identify families at risk of under-vaccination. Door-to-door canvassing37 can increase uptake among suchgroups. The involvement of communities and local leaders in promotingimmunization, planning immunization services and informing familiesabout the availability of vaccination services is important30-38.

Disease surveillance was a crucial component of the smallpoxeradication programme and poliomyelitis elimination in the Americas20,but it remains one of the weak links in the EPI. Methods of surveillancevary depending on the stage of the programme and the resourcesavailable39. Surveillance is complemented by outbreak investigations.Substantial effort is currently being invested in improving surveillance,through development of training materials, conduct of workshops, andprovision of laboratory and communications support, not just for EPIbut also for diseases of epidemic potential. Public health programmesand services are automating the management and analysis ofsurveillance data, using computers to enhance the timely and systematiccollection of data, its consolidation, analysis, evaluation and feed-back.

Laboratories play an essential role in the surveillance of most vaccine-preventable diseases, particularly once disease incidence decreases andclinical diagnosis may become less reliable. For the poliomyelitiseradication programme, WHO has set up a global polio laboratorynetwork capable of detecting wild poliovirus. A similar network is beingprepared for measles laboratory diagnosis worldwide and for yellowfever in the 33 countries of Africa endemic for yellow fever5. For newcandidates for inclusion in the programme such as Haemophilusinfluenzae type B (Hib) and conjugate pneumococcal vaccines, which




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protect against diseases with less specific clinical manifestations,laboratory support in surveillance will also be essential.

With the rapid growth of enzyme linked immunoassay (EIA) techniques,often in kit form, serological surveillance may be more widely used infuture. The detection of virus-specific antibody in saliva has beenreported40 and further development of this assay could greatly facilitatefield surveys. Randomised age-structured serosurveys can provide usefulbackground information by which to compare subsequent profiles of herdimmunity, for example, of measles, rubella41 and polio.

Data from clinical and laboratory-based surveillance systems can beused to develop and validate mathematical models of diseasetransmission. Models are used to describe the dynamics of infections inpopulations, to predict changes induced by a vaccination programme42"14,to explore the effects of different vaccination policies41'43'45, to comparedifferent delivery strategies44, and to explore thresholds for elimination oreradication of infections from populations42.

Last, but not least, it is important to assess the costs of immunizationprogrammes. The EPI developed costing guidelines in 197946 andsubsequently developed spreadsheet software (EPICOST) to supportcosting studies. The average cost of fully immunizing a child (cost perFIC) in low-income countries in studies from 1979-87 was US$ 13,excluding technical assistance (1987 US$ rate), and US$15 if technicalassistance was included47. For all strategies, personnel costs accountedfor the largest proportion, with supervision and management the secondlargest cost46. Vaccines represented approximately 10% of all costs. Ingeneral, costs per FIC decreased as the number of children immunizedincreased46, but the marginal costs are likely to increase when trying toreach the last 15-20% of infants.

Economic analyses have helped to show problems in the process ofdisbursing funds, including irregular and delayed receipt of donor funds;poor accountability; over-centralization of management of funds so thatthere is no access to funds for running costs at health centre level; non-standardization of payments for daily allowances between differentvaccination strategies and/or between agencies48. Monitoring the processof utilization of resources and establishing transparent and co-ordinatedsystems for accountability of donors as well as government healthservices could greatly improve efficiency.

Summary of achievements

For over 20 years, the EPI programme has helped to create a globalconsensus on disease prevention and immunization. The EPI quickly

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developed effective training programmes and modules for peripheralhealth workers, mid-level and senior-level managers. A series of clearguidelines on immunization practices were developed, and the strongfield-base of the EPI enabled WHO to update and clarify theseguidelines to resolve questions raised by health workers. Guidelineswere followed up by supervision and monitoring through programmereviews and ad hoc studies using simple protocols. Extensive innovativework was conducted to develop and standardize appropriate cold chainand injection technology and simple methods for monitoring its use inthe field.

The pragmatic and field-based approach of the EPI, with itscontinuous cycle of planning, conducting applied research on priorityproblems, disseminating guidelines, monitoring closely all aspects of theprogramme and feeding back on progress, have benefited industrializedcountries as well as developing countries49. Survey tools such as the EPIcluster sample, missed opportunity, and cold chain monitor surveys haveenabled peripheral health workers to evaluate their own programmes.They have been modified for use in richer countries50, and for a widerange of public health programmes51.

Challenges

The EPI has shown remarkable progress throughout the world, but thereare now several potentially competing demands for expansion52.Coverage of existing vaccines needs to be increased, particularly in sub-Saharan Africa. Additional activities are being promoted to eliminate oreradicate diseases. The quality and safety of vaccines and injections mustbe ensured, and countries are being encouraged to become self-sufficientin vaccine procurement and/or supply. A range of new vaccines is beingdeveloped and licensed. There may be tension between global priorities{e.g. disease eradication) and local priorities {e.g. introduction of newvaccines), and careful evidence-based decision-making will be necessary.

Coverage

Immunization coverage is a key indicator of access to and utilization ofimmunization services. In spite of continuous efforts to raiseimmunization coverage, since 1990 global figures for EPI vaccines havelevelled off at around 80% for infants (Fig. 1), and considerabledisparity remains both between and within countries (Fig. 2). Averagecoverage of DTP-3 in the African region has not yet reached 60%. To




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Percentage coverage for infants under one year

Fig. 1 ExpandedProgramme onImmunization

coverage 1980-1996.Data before 1984 areestimated: (a) up to 2

years of age; (b)tetanus toxoid

(mothers). Figureskindly provided by the

World HealthOrganization Global

Programme forVaccines and

Immunization.

/ BCGOPV Jnfdo»»

DPTJrddowMonk* (a)

T«tanu* (b) 2nd dose

80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96

Year

B Tetanus (b) 2nd dote • Measles (a) D DPT 3rd dose • OPV 3rd dose D BCG

Eradication

improve coverage in the lowest income countries, long-term, co-ordinated and reliable investment by national governments and donorsis required16.

Two vaccines have been recommended for inclusion in the EPI forseveral years, but are still not widely used. Hepatitis B results in morethan 1 million deaths every year, worldwide53. The high effectiveness ofthe vaccine has been demonstrated by dramatic reductions in the carrierrate in immunized cohorts of children54. In Taiwan, 10 years afterimplementation of a mass vaccination programme, a fall in the annualincidence of hepatocellular carcinoma in children aged 10-14 years hasalready been documented54. However, introduction of universal HBVvaccination globally has been determined more by the economic statusof the country than by its disease burden (Fig. 3). A minority of the 33African at-risk countries include yellow fever vaccine in their EPI, andThe Gambia is the only country to achieve high coverage and impact ondisease55. In 1994 and 1995, outbreaks of yellow fever were reported insix African countries55.

Substantial progress has been achieved towards the goal of globaleradication of poliomyelitis56. Reported OPV-3 coverage in 1996 wasover 80% in all regions except Africa, where it was 60%. By the end of1996, only 17 endemic countries in the world had not yet conductedNIDs (15 of these were in Africa). AFP surveillance is now conducted in126 (86%) of the 146 recently or currently endemic countries. However,




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such surveillance is still in its infancy in the southeast Asia and Africanregions, and requires substantial strengthening. A total of 3,997 cases ofpoliomyelitis were reported globally in 1996, with declines in all WHORegions. Activities will concentrate increasingly on countries affected bycivil conflict and those with the weakest health service infrastructure56.The total external funding support required for the period 1997-2005 isestimated at over US$ 1000 million.

Regions which have already eradicated poliomyelitis are adopting neweradication goals. Measles eradication is theoretically possible becausethere is no known animal reservoir and measles vaccine is highly effective.In practice, the high infectivity of measles makes it difficult to eradicate,because more than 90% (and possibly more than 95%) of the populationmust be immune in order for incidence to decline towards zero42. Despiteencouraging progress in the Americas23, questions remain about theselection of the most appropriate strategies for measles control/eradication in different countries, the ability to ensure safe injectionpractices, and the feasibility and cost of reaching high enough coveragefor eradication in the poorest countries. The marginal cost-benefit ofaiming for eradication rather than control needs to be assessed. Lastly,the effects of an eradication programme on social development need tobe considered.

Improving vaccine supply, quality and injection safety

The increasing demand for vaccines generated in part by additional massvaccination activities for disease eradication has highlighted the need toensure a sustainable supply of adequate quantities of vaccines. Strategiesinclude targeting donor assistance for vaccine purchase to the smaller,poorer countries, while the larger countries, particularly those withhigher income/capita, are encouraged to produce their own vaccines.Revolving funds, in which countries contribute funds in local currencyto funds supported by international agencies such as UNICEF to procurevaccines, are also promoted.

There is heightened awareness of the need to monitor vaccine quality.In a review of 43 vaccine-producing countries conducted by theChildren's Vaccine Initiative (CVI), only 21 had appropriate controlfunctions in place. Failure to meet WHO minimum standards of purityof diphtheria and tetanus toxoids was documented for 10% ofproducers assessed57 and tetanus toxoids from 8 manufacturers had lowpotency values58.

The most important areas of technology transfer for developingcountries are those relevant to achieving and maintaining GoodManufacturing Practice standards in vaccine production, establishing




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independent and credible national quality control laboratories, andinstituting national (or perhaps regional, if necessary) regulatorycapability59.

Another priority area is ensuring safe injection practices. In 1994, theWHO reported that up to one-third of immunization injections in 4 ofits 6 Regions were unsterile, carrying the risk of iatrogenic infectionsincluding fatal septicaemia, and transmission of bloodbornepathogens60. EPI has had a long-standing policy of 'a single sterile needleand a single sterile syringe should be used with each injection' and iscontinuing to develop and evaluate alternative injection technologies,such as autodestruct syringes and jet injectors, to minimize the risk ofunsafe injection practices.

Introduction of additional vaccines

A number of effective vaccines are available but not yet included in theEPI, while still more are near to licensure. H. influenzae type b (Hib)vaccine is a highly effective vaccine against a major pathogen. In TheGambia, it had an efficacy of over 90% against invasive Hib disease, andsignificantly reduced the incidence of radiologically-defined pneumoniaby 21% (95% CI, 4.6-34.9%)61. Since pneumonia is estimated to underlie18% of deaths in developing countries, the development of mechanismsto make Hib vaccine affordable to children in the poorest countries is amajor challenge for the international health community.

Rubella vaccine has been used for almost 30 years in industrializedcountries. A review completed for the WHO in 1995 showed that 7developing countries have documented rubella outbreaks withcongenital rubella syndrome (CRS) incidence rates as high as those inindustrialized countries pre-vaccination62. All 7 countries now havenational rubella vaccination policies. Although 28% of developingcountries already include rubella vaccine in their national immunizationprogrammes, many countries need further data urgently to determinethe relative priority to give to control of CRS62.

Lower respiratory infections and diarrhoeal diseases were among thetop four causes of death worldwide in 19906; therefore, vaccines that areunder development against these diseases have immense potential toimprove health status. Some new vaccines will be licensed for the existingEPI target groups, e.g. rota virus vaccine, conjugate pneumococcal andmeningococcal vaccines; some will be targeted at adolescents, e.g. herpesvirus vaccines, HIV vaccines, and others will be indicated for persons ofah1 ages, e.g. dengue, malaria63. This means that the 'EPI target groups'will need to extend beyond pregnant women and infants, giving furtherimpetus to the drive to strengthen PHC through the EPI.




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Conclusions

Immunization programmes have spearheaded the development of publichealth worldwide. Through immunization, over 3 million deaths areaverted each year. Health professionals around the world have beentrained to use a range of simple tools to plan, manage and monitor theirprogrammes. Nevertheless, the context in which immunizationprogrammes operate has changed markedly over the last decade, andprogrammes will need to respond innovatively to these changes.

Healthcare absorbs an increasingly large share of global resources. In1990, average per capita expenditure on health care was about US$ 1500in industrialized countries, yet official development assistance has declinedto US$ 0.3 per capita, its lowest level in real terms for 25 years64.Developing countries spent an average of only US$ 41 per capita, andmany of the poorest countries spent less than US$ 5. Sizable sums of publicmoney are spent on tertiary level hospitals, while access to basic healthservices remains low in many rural and dispersed communities.Implementation of health programmes is becoming increasinglydecentralized, thus the role of Ministries of Health and internationalagencies is changing to one of advice, policy-making and advocacy. Theincreasing involvement of the private sector in health care raises challengesfor co-ordination, standardisation and quality control of interventions.

To meet these challenges, the trend towards inequitable use of globalresources must be reversed. Measles continues to cause approximatelyhalf a million deaths per year in sub-Saharan Africa2, and 16 of the 26countries that account for 90% of globally estimated cases of NT are inAfrica. Coverage for routine childhood immunizations and TT is below50% in much of western and Central Africa, where the PHCinfrastructure is still weak. Campaigns can reach communities that lackaccess to routine services, but donors must be convinced to invest notonly in campaigns but also in strengthening the physical, human andmanagerial infrastructures in those countries19. Polio NIDs are beingimplemented even in low income countries, but AFP surveillance lagsbehind, and the implementation of national campaigns in countriesaffected by civil conflict is a major challenge. Hepatitis B vaccine, whichwas to have been introduced in all highly endemic countries by 1997, isavailable in only a minority. Immunization services, which are alreadyhighly cost-effective, will become increasingly so as new vaccines aredeveloped which can be delivered using the same contacts. Despitedecades of sustained progress through development and targeted healthinterventions, 5 of the 10 leading causes of death are still communicableor perinatal disorders6. Mobilizing governments in industrializedcountries to help developing countries profit fully from vaccines is amajor challenge for public health professionals throughout the world.

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Acknowledgements

I would like to thank Dr Jean-Marc Olive, World Health Organization,for helpful discussions on the topics reviewed in this paper and provisionof data from WHO.

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Documents

Advances and challenges for the expanded programme on