8th Expert Comm 2012

8/21/2019 8th Expert Comm 2012

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WHO Expert Committeeon Leprosy

Eighth report

W H O T e c h n i c a l R e p o r t S e r i e s

This report contains the collective views of an international group of experts and

does not necessarily represent the decisions or the stated policy of the World Health Organization


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World Health Organization 2012

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Printed in Italy

WHO Library Cataloguing-in-Publication Data

WHO Expert Committee on leprosy: eighth report.

(WHO technical report series ; no. 968)

1. Leprosy - epidemiology. 2. Leprosy - prevention and control. 3. Leprosy - therapy.

I.World Health Organization. II.WHO Expert Committee on Leprosy (2010: Geneva, Switzerland).

III.Series.

ISBN 978 92 4 120968 7 (NLM classification: WC 335)

ISSN 0512-3054


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iii

ContentsWHO Expert Committee on Leprosy v

Declarations of interest vii

1. Introduction 1

2. Leprosy in the world 3

2.1 Assessment of global data 42.2 Global leprosy situation in 2010 42.3 New case detection 42.4 Trends in case detection 42.5 Profiles of new cases 8

3. Epidemiology 11

3.1 Definition of a leprosy case 113.2 Classification 123.3 Transmission, infection and incubation period 123.4 Infectiousness of leprosy 133.5 Risk factors 133.6 Interaction between HIV infection and leprosy 133.7 Geographical variations 14

4. Chemotherapy and management 174.1 Chemotherapy 17

4.1.1 Standard MDT regimens 174.1.2 Existing second-line antileprosy drugs 184.1.3 Promising new antileprosy drugs 194.1.4 Study on the uniform multidrug therapy regimen 214.1.5 Combined therapy with four weeks of daily ofloxacin and rifampicin 214.1.6 Treatment regimens for special situations 224.1.7 Relapses after multidrug therapy 22

4.2 Management of leprosy reactions and neuritis 234.2.1 Neuritis and nerve function impairment 234.2.2 Leprosy reactions 234.2.3 Treatment of leprosy reactions 24

4.3 Disability and rehabilitation 264.3.1 Magnitude of the problem 264.3.2 Disability grading for leprosy 264.3.3 Prevention, limitation and management of disabilities 264.3.4 Self-care 274.3.5 Community-based rehabilitation 27

5. Social issues 29

5.1 Equity, social justice and human rights 295.2 Gender 29

5.3 Enhancing the involvement of affected persons 305.4 Stigma and stigmatization 30


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iv

5.5 Counselling 31

5.6 Residential care 31

6. Leprosy control and prevention 33

6.1 Improving the quality of leprosy services 336.2 Integrating leprosy control into general health services 346.3 Referral system 346.4 Building and maintaining national capacity 366.5 Community awareness and education 36

6.5.1 Community awareness 366.5.2 Information, education and communication 37

6.6 Improving case detection 38

6.6.1 Case-finding and case-holding 386.6.2 Delay in diagnosis 386.7 Special areas and populations 38

6.7.1 Areas with a high disease burden 386.7.2 Areas with a low disease burden 396.7.3 Underserved population groups 396.7.4 Urban areas 40

6.8 Contact surveillance 416.9 Treatment adherence 42

6.9.1 Flexible treatment 426.10 Supply management for multidrug therapy 42

6.11 Disease prevention 436.11.1 Primary BCG immunization 436.11.2 Immunoprophylaxis of contacts 446.11.3 Chemoprophylaxis of contacts 446.11.4 Next steps prophylaxis strategy 45

6.12 Surveillance for drug resistance 456.13 Monitoring and evaluation 46

6.13.1 Indicators for monitoring 466.13.2 Independent evaluation of leprosy programmes 48

7. Strategy for further reducing the disease burden due

to leprosy setting targets 49

7.1 Elimination of leprosy as a public health problem 497.2 New targets based on case detection and disability prevention 49

8. Research priorities 51

9. Conclusions and recommendations 53

Acknowledgements 55

References 57


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v

WHO Expert Committee on LeprosyGeneva, 1219 October 2010

Members

Dr Y.A. Al-Qubati, Taiz University School of Medicine, Taiz, Yemen (Rapporteur)

Dr M.L.W. de Oliveira, Medical Professor, Rio de Janeiro Federal University, Rio de Janeiro,

Brazil

Dr M. De Palma Caldas, Director, National Program for Control of Tuberculosis and

Leprosy, Ministry of Health, Luanda, Angola

Professor P.E.M. Fine, Communicable Disease Epidemiology, Infectious and TropicalDisease Department, London School of Hygiene and Tropical Medicine, London,

England

Dr M.D. Gupte, Retired Director, National Institute of Epidemiology, Indian Council of

Medical Research, Chennai, India1

Dr H.J.S. Kawuma, Medical Advisor, German Leprosy Relief Association, Kampala,

Uganda

Dr T. Mori, Director Emeritus, Research Institute of Tuberculosis, Japan Anti-Tuberculosis

Association, Kiyose, Tokyo, JapanDr H. Sansarricq, Former Head, Leprosy Programme, WHO, Geneva, Switzerland

Professor W.C.S. Smith, Head, Department of Public Health, Medical School, University

of Aberdeen, Aberdeen, Scotland (Chairman)

Professor G. Zhang, Deputy Director, Institute of Dermatology and National Center for

Leprosy Control, Nanjing, China

Temporary advisers

Professor P.J. Brennan, Department of Microbiology, Immunology and Pathology,

Colorado State University, Fort Collins, CO, USA

Professor S. Cole, Global Health Institute, Department of Immunology, Ecole

Polytechnique Fdrale de Lausanne, Lausanne, Switzerland

Professor J.H. Grosset, Center for Tuberculosis Research, Johns Hopkins University School

of Medicine, Baltimore, MD, USA

Dr S.K. Noordeen, Former Director, Action Programme for Elimination of Leprosy, WHO,

Geneva, Switzerland

1 Unable to attend.


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WHOTechnicalReportSeries,No.96

8,2

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WHO Expert Committee on Leprosy Eighth report

Mr J. Ramirez Jr., USA Coordinator and Board Member of International Association for

Integration, Dignity and Economic Advancement (IDEA) and American Leprosy

Missions, Houston, TX, USA

Representatives of other organizations

International Federation of Anti-Leprosy Associations (ILEP)

Mr D. Soutar, General Secretary, International Federation of Anti-Leprosy Associations,

London, England

International Leprosy Association (ILA)

Dr M. Virmond, President, International Leprosy Association, Bauru, BrazilRepresentative of Mr Y. Sasakawa, WHO Goodwill Ambassador for Leprosy Elimination

Professor K. Kiikuni, Chair, Sasakawa Memorial Health Foundation, Tokyo, Japan

Secretariat

Dr M.T. Htoon, Team Leader, WHO Global Leprosy Programme, WHO Regional Office for

South-East Asia, New Delhi, India (Secretary)

Dr V. Pannikar, Temporary International Professional, WHO Global Leprosy Programme,

WHO Regional Office for South-East Asia, New Delhi, India


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Declarations of interestMembers of the WHO Expert Committee on Leprosy reported the following:

Dr Y.A. Al-Qubati reported that he provides supervision to the Leprosy Control

Programme of Yemen. For these services, he receives an honorarium from the German

Leprosy and TB Relief Association (GLRA), which is a nongovernmental organization.

Professor S. Cole reported that, through his previous employment at Institut Pasteur, he

is a named inventor on a patent for antimycobacterial compounds that have antileprosy

activity in a murine model. The patent in question has been licensed to the company

Alere Technologies GmbH, for whom Professor Cole acts as a consultant, with anannual income of approximately 20 000. He currently teaches leprosy-related subjects

at the Ecole Polytechnique Fdrale de Lausanne.

Professor P.E.M. Fine reported that he is on the Editorial Board of the journal Leprosy

Review. He also reviews grants related to leprosy research for the Order of Malta, for

which he has received an honorarium payment for the past four years.

Professor J.H. Grosset reported that he is a member of the Scientific and Medical

Commission of Association Raoul Follereau of France as well of the United States

of America/Japan Panel for Leprosy and Tuberculosis Research. He receives no

remuneration for either position.

Dr H.J.S. Kawuma reported that he works as a Medical Adviser in Uganda for the

German Leprosy and TB Relief Association (GLRA), which is a nongovernmental

organization.

Dr S.K. Noordeen reported that he was involved in the preparation of the background

documents for this meeting under an Agreement for the Performance of Work (APW)

with WHO; this APW expired on 10 October 2010.

Mr J. Ramirez Jr reported that he serves as Managing Editor of The Star, an international

magazine put together by persons affected by leprosy. He also serves as the UnitedStates of America Coordinator for the International Association for Integration, Dignity

and Economic Advancement (IDEA), an organization comprising primarily persons

affected by leprosy. He receives no remuneration for either position.

Professor W.C.S. Smith reported that he is President of the Leprosy Mission International

and Chair of the Technical Commission of the International Federation of Anti-Leprosy

Associations. He receives no remuneration for either position.


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1. IntroductionTe WHO Expert Committee on Leprosy held its eighth meeting in Geneva,Switzerland, rom 12 to 19 October 2010. Opening the meeting on behal oDr Margaret Chan, WHO Director-General, and Dr Samlee Plianbangchang,Regional Director, WHO South-East Asia Region, which hosts the GlobalLeprosy Programme (GLP), Dr Hiroki Nakatani, Assistant Director-General,conveyed the appreciation o Dr Chan and Dr Samlee or the gracious supportbeing provided or GLP by WHO partners and experts.

Dr Nakatani noted the progress made towards elimination o leprosy

since the Committees previous (seventh) meeting in 1997. He recounted thecatalytic role played by World Health Assembly resolution WHA44.9 (1991)(1) in pushing orward the leprosy agenda. Te commitment to eliminateleprosy was reiterated by the World Health Assembly in 1998 throughresolution WHA51.15 (2), and the elimination target was reached globally atthe end o 2000 (3). Since the introduction o multidrug therapy (MD) in1981, an estimated 15 million patients have been cured and disabilities havebeen prevented in some 23 million individuals (4). Such an achievement,Dr Nakatani stated, had been made possible by the unique partnership betweengovernments, communities, WHO, academia, industry and nongovernmental

organizations (NGOs). Progress in the elimination o leprosy had been achievedthrough the synergistic efforts o all the supporting organizations.

It was acknowledged that, despite significant progress in controllingthe disease and reducing the disease burden, much still remained to be done tosustain the gains and urther reduce the impact o leprosy, especially in terms oits physical, mental and socioeconomic consequences or those affected and ortheir amilies.

Five-year initiatives or the elimination o leprosy were set out in WHOpublications o 2000 (5) and 2005 (6); the most recent initiative Globalstrategy for further reducing the disease burden due to leprosy 20112016 waspublished in 2009 (7). Te emphasis in these strategies has shifed to reducingthe occurrence o impairments and disabilities due to leprosy and to ways oensuring the sustainability and quality o leprosy services. Te strategies haveincluded such specific issues as gender equity and human rights and initiativesto reduce the stigma and discrimination aced by people affected by leprosy andtheir amilies.

Te purpose o this eighth meeting o the Expert Committee was:

to analyse the global leprosy situation;

to review the current status o developments in areas such as thetreatment o leprosy and its various complications;


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to consider the results o research and experience in leprosy control

since the previous meeting and to review existing indicators oprogress in order to determine whether better indicators could beintroduced;

to advise on technical and operational issues relating to efforts aimedat urther reducing the burden due to leprosy.


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2. Leprosy in the worldData on leprosy are reported to WHO routinely by most countries,

except those o the European Region, and published annually in the WeeklyEpidemiological Record (WER) (8). While such data are useul in providinga broad picture o leprosy patterns and trends, their interpretation is madedifficult by operational differences between different national programmes andthe act that the data cover different time periods.

In the past, the emphasis has been on prevalence data that is, dataon the numbers o cases registered or treatment at the beginning o the year.Because o the long duration o treatment, prevalence was considered anappropriate measure, as it reflected the burden on health services. Starting inthe early 1980s, prevalence declined dramatically throughout the world as aconsequence o the shortened treatment regimens that ollowed introduction oMD (9). Differences in treatment duration between countries, as a result eithero different programme policies or o different proportions o multibacillary(MB) cases (which require longer treatment than paucibacillary (PB) cases), havecomplicated the comparison o prevalence data between countries.

More recently, the emphasis has shifed to case detection, as this providesa more appropriate measure o recent transmission and current epidemiological

circumstances. Case-detection statistics are useul or measuring trends overtime provided that detection and registration policies remain constant. However,recent aggressive case-finding in many countries with higher leprosy burdenshas complicated the interpretation o trends. Te act that data rom somelow incidence countries may be influenced by an appreciable proportion ocases occurring in immigrants provides a urther challenge: these cases do notreflect autochthonous (local) transmission and may or may not be included innational statistics.

Nevertheless, several patterns are clear. Te disease remains endemicin all countries o the Arican and South-East Asia regions and in most

countries o the Eastern Mediterranean Region. In the Region o the Americas,autochthonous leprosy is ound in all countries with the exceptions o Canada,Chile and several island countries o the Caribbean. In the European Region,although data are not transmitted to WHO, autochthonous leprosy is knownto persist at low levels in several southern and eastern European countriesbut seems to have disappeared rom much o the northern and western parto the continent. In the Western Pacific Region, the disease persists in mostlarge countries apart rom New Zealand and with the exception o some smallisland nations. Tere is some evidence that transmission may have stopped inJapan, although small numbers o autochthonous cases still appear in older

individuals (8). Heterogeneity in leprosy requency and clinical maniestationsbetween populations is a prominent eature o the disease.


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2.1 Assessment of global dataSeveral broad trends over the past 30 years are evident. Te first is the

tremendous decline in registered prevalence since 1980, in all countries,which reflects the shif rom long-term dapsone monotherapy to shorter MD

regimens. Tis change was initiated by the WHO Study Group recommendationin 1981 (9) and was achieved through aggressive implementation o MD in all

countries during the 1990s. It has resulted in a major decline in the burden o

leprosy on health services in endemic communities. Te second broad trendrelates to incidence. Case-detection numbers and rates have allen in almostall countries, reflecting both improvements in socioeconomic conditions and

the effects o leprosy programmes. It is important to identiy and enhancethose measures that have been most successul in bringing about these alls.Te third trend is more difficult to demonstrate on the basis o available databut relates to the decline in numbers and proportions o cases with disabilitiesamong newly diagnosed patients. Tere are only rough estimates o the totalnumber o individuals with leprosy-attributable disabilities alive today (4).

2.2 Global leprosy situation in 2010A total o 141 Member States submitted reports to WHO at the beginning o

2010: 38 countries rom the Arican Region, 36 rom the Region o the Americas,10 rom the South-East Asia Region, 22 rom the Eastern MediterraneanRegion and 35 rom the Western Pacific Region (8). Tese data are shown,by WHO region, in able 1, which reveals considerable heterogeneity at theregional level, with highest numbers and rates in the South-East Asia Region. Atthe beginning o 2010, the global registered and reported point prevalence was211 903 cases; during 2009, 244 796 new cases were detected.

2.3 New case detection

Te reported trends in new case detection rom 2000 to 2009 are shown inable 2, by WHO region. Decline was evident in all regions, in particular inthe Arican and South-East Asia regions. Tese trends were influenced bychanges in case-detection policies and aggressive case-detection efforts insome large countries in the early years o this century. Figure 1 shows the case-detection rates reported or 2009 or all countries that provided data to WHO:geographical variation is clear.

2.4 Trends in case detection

able 2 shows that the global decline in case detection was dramatic (about58%) during the period 20002005 and much more limited (about 18%)


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Leprosy in the world

5

Table 1

Registered prevalence of leprosy and number of new cases detected, as reported byWHO region (excluding the European Region), 2010

WHO region Registered

prevalencea

(beginning

of 2010)

New cases

detectedb

during 2009

Grade 2 disabilities

during 2009c

Among

new cases

Rate per

1 000 000

populationNumber %

African 30 497 (0.40) 28 935 (3.75) 3 146 10 4.1

Americas 43 370 (0.49) 40 474 (4.58) 2 645 6 3.0

South-East Asia 120 456 (0.68) 166 115 (9.39) 7 286 4 4.1

Eastern

Mediterranean

8 495 (0.17) 4 029 (0.70) 608 15 0.11

Western Pacific 8 635 (0.05) 5 243 (0.29) 635 12 0.4

Total 211 903 (0.37) 244 796 (4.27) 14 320 6.7 2.5

a Prevalence rate is shown in parentheses as the number of cases per 10 000 population.b Case-detection rate is shown in parentheses as the number of cases per 100 000 population.c New-case grade 2 disability rate per 1 000 000 population.

during the period 20062009. It shows also that the dramatic decline observedduring 20002005 was largely the result o the 67% reduction in detected

cases in the South-East Asia Region over that period; during 20062009 thereduction as in other WHO regions was 18%. Because o the numerous

operational changes that have occurred at country and regional levels duringthe past 10 years, it is impossible to determine which actors were responsible

or the observed dramatic decline in case-detection rate or to assess the

epidemiological significance o the decline.Te steady all in case detection has not been uniorm, either among

countries or over the years, and fluctuations have occurred as a result ooperational actors, particularly during special case-detection campaignsorganized in certain countries (8).

Comparison o peak case-detection igures reached between 1992 and2009 with the igures or 2009 in the top 16 countries (i.e. those accountingor 93% o the global disease burden) reveals two very dierent trends.Detailed analysis identiies two groups o countries one group o eight

showing considerable decline, and another group o eight showing a verymodest decline.


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Table

2

Num

berofleprosycasesdetecteda

nnually,

byWHOregion(excludingtheEuropeanRegion),20002009

WHOregion

Annualcasedetection

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

African

54602

39612

48248

47006

46918

45179

34480

34468

29814

28935

Am

ericas

44786

42830

39939

52435

52662

41952

47612

42135

41891

40474

South-EastAsia

606703

668658

520632

405147

298603

201635

174118

171576

167505

166115

Eastern

Me

diterranean

5565

4758

4665

3940

3392

3133

3261

4091

3938

4029

We

sternPacific

7563

7404

7154

6190

6216

7137

6190

5863

5859

5243

Total

719219

763262

620638

514718

407791

299036

265661

258133

249007

244796


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7

Figu

re

1

Case-detectionratesreportedfor2009


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In the 16 top countries there was a decline (rom peak case-detection rate

to case detection in 2009) o 71.7% over a mean period o 9.2 years, indicatingan annual geometric decline o 12.9%.

In 8 o those 16 top countries, accounting or 64% o the global burdeno cases, the decline over a mean period o 9.2 years was 78% an annualgeometric decline o 15.2%. In the other 8 countries, with 29% o the globalburden o cases, the decline over a mean period o 9.9 years was only 27.7% anannual geometric decline o 3.2%.

2.5 Profiles of new cases

Statistics on age, sex, classification, disability status and relapse are collectedroutinely by many countries and reported to WHO. Tough potentially oconsiderable interest or monitoring trends, these statistics vary considerablybetween countries or reasons that include operational actors such as coverageand case-finding methods, which makes comparisons difficult.

Age is traditionally broken down in terms o child (under age 15)versus adult cases; the proportion o cases among children would be expectedto decrease as transmission declines. In the past, age patterns have beeninfluenced by BCG (bacille CalmetteGurin) vaccination, which shouldreduce cases among children, and by school surveys, which selectively increase

case detection among children. Te proportion o child cases in 2009 variedbetween 0.6% in Argentina and 32% in the Comoros Islands.

Data reported by sex should give some evidence o gender equity inpopulations, but are complicated by the act that males have a greater tendencyto MB disease and the proportion o MB disease varies between populations.Te reported proportion or emales in 2009 varied rom 6.5% in Ethiopiato 60% in the Central Arican Republic. Classification statistics have beeninfluenced by repeated changes in criteria or classification over the past 20years; new cases reported in 2009 ranged rom 32% MB in the Comoros to 95%MB in the Philippines.

Statistics on grade 2 disability (G2D) are o particular interest as theyprovide a potential indicator both o programme quality (a programme withearly case detection should be associated with a low proportion o G2D) and othe morbidity burden attributable to leprosy (8). Te act that the proportion onew cases with G2D ranged rom 1.5% (Liberia) to 23% (China) indicates thatcountries may differ considerably in terms o how disabilities are detected andreported as well as in the predominant clinical maniestations o the disease.

Tese differences in patient profiles between countries highlight ethnicand cultural differences between populations and differences in national leprosycontrol programmes. Tey could be valuable indicators o practices and trends

within countries and are thus important to national programme managers (seesection 6.13 on monitoring and evaluation).


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9

Table

3

Detectiontrendofleprosyin16cou

ntriesreporting1000newcasesduring19922000

Co

untry

N

umberofnewcasesdetected

19

92

1993

1994

1995

1996

1997

1998

1999

2000

Bangladesh

7307

6943

7983

8782

11225

11320

12351

14336

12135

Brazil

30094

34235

32515

3

2724

39792

43933

42055

43175

Ch

ina

3755

3755

2096

2109

1845

1854

2051

2051

1595

De

mocraticRep.o

fCongo

3247

3927

4195

4344

5526

3781

4221

3103

Eth

iopia

1936

4090

4790

5160

4747

4444

4457

4457

4931

Ind

ia

517000

456000

414894

39

1760

415302

519952

634901

537956

474286

Ind

onesia

13219

12638

17255

1

3492

15071

15337

18367

17477

13539

Ma

dagascar

2050

740

4701

4676

3921

11555

8957

8704

7689

Mo

zambique

1732

1930

2583

3430

4225

4195

3764

5488

6617

My

anmar

9816

12018

8303

6577

6935

9086

14357

30479

10262

Ne

pal

5953

6152

6169

4783

6602

7446

6570

18693

6661

Nigeria

4381

4381

7827

7147

6871

7176

7230

7918

7918

Philippines

7169

3442

4450

3988

4051

4942

3490

3390

2596

Sri

Lanka

944

1059

1897

1528

776

1376

1757

1700

Sudan

1980

1489

3100

1765

2126

2633

2077

2426

2045

Un

itedRep.o

fTanzania

2731

2596

2596

2747

2798

3535

5081

4640

Total

6096

39

555415

524516

49

5230

532514

651288

723483

706489

602892


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Table

3

(continued)

Detectiontrendofleprosyin16cou

ntriesreporting1000newcasesduring20012009

Co

untry

N

umberofnewcasesdetected

20

01

2002

2003

2004

2005

2006

2007

2008

2009

Bangladesh

10

740

9844

8712

8242

7882

6280

5357

5249

5239

Brazil

41

070

38365

49206

4

9384

38410

44436

39125

38914

37610

Ch

ina

1

726

1646

1404

1499

1658

1506

1526

1614

1597

De

mocraticRep.o

fCongo

4

980

5037

7165

1

1781

10737

8257

8820

6114

5062

Eth

iopia

4

523

4632

5193

4787

4698

4092

4187

4170

4417

Ind

ia

617

993

473658

367143

26

0063

169709

139252

137685

134184

133717

Ind

onesia

13

286

12377

14641

1

6549

19695

17682

17723

17441

17260

Ma

dagascar

8

599

5482

5104

3710

2709

1536

1521

1763

1572

Mo

zambique

5

713

5830

5907

4266

5371

3637

2510

1313

1191

My

anmar

9

684

7386

3808

3748

3571

3721

3637

3365

3147

Ne

pal

13

830

13830

8046

6958

6150

4235

4436

4708

4394

Nigeria

5

981

5078

4799

5276

5024

3544

4665

4899

4219

Philippines

2

669

2479

2397

2254

3130

2517

2514

2373

1795

Sri

Lanka

2

309

2214

1925

1995

1924

1993

2024

1979

1875

Sudan

1

299

1361

906

722

782

884

1706

1901

2100

Un

itedRep.o

fTanzania

4

656

6497

5279

5190

4237

3450

3105

3276

2654

Total

749

058

595716

491635

38

6424

285687

247022

240541

233263

227849


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11

3. Epidemiology3.1 Definition of a leprosy caseTe presence o classical clinical signs plays a major role in the diagnosis oleprosy, although demonstration o the causative organism by slit-skin smears,histopathology or polymerase chain reaction (PCR) is sometimes used tosupport the diagnosis. Since the availability o laboratory acilities or slit-skin smear or histopathology is restricted in many endemic countries, and thecurrent PCR technology is still not adequately reliable, diagnosis o most caseso leprosy in the field will continue to be based on clinical evidence, at least or

the time being. However, this situation may not be ideal when disease incidenceis declining and where more sensitive diagnostic tools and procedures may beneeded to ensure that all cases that need treatment are diagnosed and cured (10).

Leprosy should be suspected in people with any o the ollowingsymptoms or signs:

pale or reddish patches on the skin;

loss, or decrease, o eeling in the skin patches;

numbness or tingling o the hands or eet;

weakness o the hands, eet or eyelids;

painul or tender nerves; swelling o or lumps in the ace or earlobes;

painless wounds or burns on the hands or eet.

Although most leprosy patients have skin lesions that are visible,experienced field workers are aware that a great variety o skin lesions aremaniest in cases o the disease. Some are very diffused and difficult todistinguish rom the normal skin. In these cases, the other symptoms and signsbecome important or diagnosis.

Leprosy is diagnosed when at least one o the ollowing cardinal signs

is maniested:

definite loss o sensation in a pale (hypopigmented) or reddish skinpatch;

a thickened or enlarged peripheral nerve, with loss o sensation and/or weakness o the muscles supplied by that nerve;

the presence o acid-ast bacilli in a slit-skin smear.

Te quality o diagnosis should be monitored as part o regular technicalsupervision. I there are indications o substantial over-diagnosis, a validation

exercise on a representative sample o cases can be conducted to determine themagnitude o the problem.


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3.2 ClassificationLeprosy is a classic spectral disease, being maniest in a variety o clinicalorms related to the type and strength o the immune response. A strong cellularimmune response is effective in curtailing the multiplication o M. leprae andis thus associated with PB disease. A weak cellular response allows bacilli toreplicate reely in the body, leading to MB disease orms.

In 1981, the WHO Study Group on Chemotherapy o Leprosy orControl Programmes classified leprosy as MB and PB according to the degreeo skin-smear positivity (9). Tis was an essentially operational classification,intended to serve as the basis or chemotherapy. Multibacillary leprosy included

polar lepromatous (LL), borderline lepromatous (BL), and mid-borderline(BB) cases in the RidleyJopling classification, with a bacteriological index o2+ or more at any site in the initial skin smears. Paucibacillary leprosy includedindeterminate (I), polar tuberculoid () and borderline tuberculoid (B)cases in the RidleyJopling classification, with a bacteriological index o


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and other armadillo species, and its precise contribution to leprosy in the

Americas, is unknown and is a topic or research (13).Inection is thought to occur primarily by the respiratory route but there

is also evidence that it may occur through injured skin (14). Te mechanism odissemination rom the primary site to the final location in the skin and nervesis unclear. Te incubation period rom inection to clinical maniestations isvariable, but appears to be shorter or PB disease (in the order o 25 years) thanor MB (in the order o 510 years and sometimes much longer) (15).

3.4 Infectiousness of leprosy

Te inectiousness o leprosy patients is related to the size o the bacillarypopulation in the body. It has been shown that a single dose o riampicinreduces the load o viable bacilli to such low levels that it is no longer possibleto cultivate the organism in an animal model. In public health terms, it isreasonable to conclude that inectiousness becomes negligible afer the start oMD (16).

3.5 Risk factorsLeprosy cases occur at all ages in endemic populations, although the diseaseis rare among the very young because o the long incubation period beorethe appearance o clinical maniestations. Cases are more commonly reportedin males than emales in most populations. While this may be the result obiased case ascertainment or selective hiding o the disease in emales in somepopulations, the prevalence o MB disease is higher among males than emalesin all populations, which may reflect a gender difference in immune responseor exposure. Contact with a known (especially MB) case is recognized as a riskactor in all populations, as is the absence o a history o BCG vaccination. Lowsocioeconomic status is likewise associated with leprosy in all populations, orreasons that remain unclear. Although there is evidence that certain geneticactors may be associated with leprosy, the population-attributable risk is smalland leprosy should thereore not be considered a genetic disease. Familyclustering is determined predominantly by contact, not by shared genes. Itis useul to recollect that leprosy extended north o the Arctic Circle in thenineteenth century and is thus compatible with cold as well as warm climates.Te gradual disappearance o the disease rom high latitudes over the pastcentury is thought to be attributable largely to socioeconomic actors.

3.6 Interaction between HIV infection and leprosyIn the 1980s it was eared that the HIV pandemic might have the same effect on

leprosy as it has on tuberculosis. It was predicted that patients with leprosy andHIV coinection would be at increased risk o lepromatous disease and aster


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clinical evolution, and that leprosy would be more difficult to treat. None o these

ears has has been realized, and the interaction between HIV and M. leprae isknown to be ar more subtle than that between HIV and M. tuberculosis. Mosto the recent epidemiological, clinical and pathological studies show neither anincreased HIV prevalence among leprosy cases nor an alteration in the clinicalspectrum o leprosy among coinected patients. On the other hand, there is someevidence that immune-mediated reactions (particularly ype 1) occur moreofen in coinected patients (17).

Tere are several reports o leprosy presenting as an immunereconstitution disease among patients starting highly active antiretroviral

treatment (HAAR), probably as a result o the unmasking o an existingsubclinical inection or incubating disease (18). Histopathological observationsreveal a normal spectrum o appearance in biopsies o leprosy lesions romcoinected patients. Although no data indicate whether HIV inectionexacerbates nerve damage in leprosy, it may alter the immune response toM. leprae in nerves because o its neuropathic effect. LeprosyHIV coinectedpatients respond equally well to MD and experience similar side-effectprofiles. Some studies showed that patients with lepromatous disease andHIV coinection were at a higher risk o reversal reactions and neuritis butresponded as expected to steroid therapy.

In considering the relationship o HIV and leprosy it is also importantto recognize that HIV coinection may influence health-seeking behaviour andthis in turn may affect the chance o leprosy being diagnosed (19).

3.7 Geographical variationsGeographical variations are a striking eature o leprosy at every level. As shownin Figure 1, there are considerable differences between countries: among the141 countries reporting, just 7 countries accounted or 85% o all new casesdetected in 2009.

Geographical variations are also prominent within countries. In India in2009, or example, 12 out o 35 states (with 79% o the population) accountedor 94% o all new leprosy cases. In Brazil rom 2005 to 2007, 10 populationclusters with 17% o the population contributed 53% o all cases in that country.In Indonesia, in 2007, 14 out o 33 provinces (with 60% o the population)accounted or 83% o cases. In China, in 2009, 3 out o 31 provinces (with 12.4%o the population) had 54.5% o cases. Tese regional patterns have long beenrecognized, but their mechanism remains unclear.

Even at the local level, leprosy cases are ofen reported to be ar morecommon in certain villages or valleys than in others. In some circumstances

this may be the result o biased case ascertainment selective searching and ahigh diagnostic suspicion in certain areas but the observation is so common


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in leprosy-endemic populations that it is more likely to reflect important risk

actors that are not yet understood.Tese variations have two important implications. First, they indicate

the importance o risk actors that remain to be elucidated and whoserecognition could be useul in control o the disease. Second, they allowtargeting o leprosy control activities, which improves the costeffectivenesso control programmes. However, while targeting may be good policy in somecircumstances, the very wide distribution o the disease, ofen at very lowrequency, needs to be kept in mind i appropriate services are to be provided toall cases.


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4. Chemotherapy and management4.1 Chemotherapy4.1.1 Standard MDT regimens

Tree standard first-line drugs riampicin, cloazimine and dapsone areavailable or use in multidrug regimens o fixed duration, none o which shouldbe used as monotherapy.

Multibacillary leprosy

Te standard adult treatment regimen or MB leprosy is:

riampicin: 600 mg once a month

cloazimine: 300 mg once a month, and 50 mg daily

dapsone: 100 mg daily

Duration: 12 months.

Te standard child treatment regimen or MB leprosy is:


cloazimine: 150 mg once a month, and 50 mg every other day

dapsone: 50 mg dailyDuration: 12 months.

Paucibacillary leprosy

Te standard adult treatment regimen or PB leprosy is:



Duration: 6 months.

Te standard child treatment regimen or PB leprosy is:



Duration: 6 months.

Note: Children under 10 years o age should receive appropriatelyreduced doses o drugs, such as

riampicin: 10 mg/kg body weight once a month

dapsone: 2 mg/kg body weight per day

cloazimine: 1 mg/kg body weight to be given on alternate days,depending on the dosage.


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Tere may be occasional cases o dapsone hypersensitivity although the

drug is relatively non-toxic in the doses used. In the event o hypersensitivity,dapsone must be stopped immediately and the adverse reaction reported(dapsone syndrome).

4.1.2 Existing second-line antileprosy drugs

Since the mid-1980s, the bactericidal activities o the new fluoroquinolones

(pefloxacin and ofloxacin), a new macrolide (clarithromycin) and a tetracycline(minocycline) have been demonstrated (2023). In the limited experimental

tests carried out in mouse models, all these drugs were able to render the

mouse inoculums non-inective afer only 1 month o treatment. Te newdrugs showed greater bactericidal activity than dapsone and cloazimine. In thenude mouse model o leprosy, a single dose o a minocycline+clarithromycin

combination killed 96% o viableM. lepraeand a single dose o a minocycline+clarithromycin+ofloxacin combination killed 98.4% a bactericidal effect close

to the 99.5% killing effect o a single dose o riampicin (24).

Tese drugs were also tested in humans with MB leprosy. Ofloxacin,given at a daily dose o 400 mg, killed more than 99.99% o the viable M. leprae

afer only 4 weeks o therapy (2527). Similar bactericidal activities were

demonstrated with minocycline and clarithromycin (28). Te bactericidalactivity o a single dose o minocycline+clarithromycin+ofloxacin was testedin patients with MB leprosy against a single dose o riampicin alone and

4 weeks o standard MD. Although the bactericidal effect o the three-drugcombination was similar to that observed in the mouse model, the severe

gastrointestinal side-effects related to the use o clarithromycin were sufficientto preclude the routine use o this drug in the field (29). A single dose o

ofloxacin 400 mg + minocycline 100 mg killed 6898% o viableM. lepraeanda single dose o riampicin 600 mg + ofloxacin 400 mg + minocycline 100 mg

killed more than 99%.

Ofloxacin

O the many fluoroquinolones that have been developed, ofloxacin was the

first o interest or leprosy. Te results o clinical trials have indicated that itsoptimal dosage or the treatment o leprosy is 400 mg daily. While a single

dose o ofloxacin displayed a modest bactericidal effect, 22 doses killed 99.99%o the viable M. leprae in lepromatous patients. Side-effects include nausea,diarrhoea and other gastrointestinal complaints, and a variety o central nervoussystem complaints including insomnia, headaches, dizziness, nervousness and

hallucinations. Most side-effects do not require discontinuation o ofloxacintreatment, and serious problems are rare (26).


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Minocycline

Minocycline, a member o the tetracycline group o antibiotics, has significantbactericidal activity against M. leprae greater than that o clarithromycinalthough much less than that o riampicin. Te standard dose o 100 mg dailygives a peak serum level that exceeds the minimum inhibitory concentration(MIC) o minocycline against M. leprae by a actor o 1020 and has shownpromising bactericidal activity in lepromatous patients. Te side-effects ominocycline include discolouration o teeth during their period o ormation,and the drug should thereore not be given during pregnancy or to inants andchildren. Other side-effects include occasional pigmentation o the skin and

mucous membranes, various gastrointestinal symptoms and central nervoussystem complaints, including dizziness and unsteadiness. Minocycline ismost commonly used or the long-term treatment o acne, indicating that itis generally well tolerated; however, some rare but serious side-effects suchas autoimmune hepatitis and lupus erythematosus-like syndrome have beenreported recently (30).

Clarithromycin

Clarithromycin is a member o the macrolide group o antibiotics and displayssignificant bactericidal effect againstM. lepraein mice and in humans (27, 28).

In lepromatous patients, a daily dose o 500 mg o clarithromycin kills 99% oviableM. lepraewithin 28 days and >99.9% in 56 days. Te most common side-effect is gastrointestinal irritation (including nausea, vomiting and diarrhoea),which is particularly requent when clarithromycin is given at a dose o2000 mg.

4.1.3 Promising new antileprosy drugs

In recent years moxifloxacin (a fluoroquinolone) and riapentine (a long-acting riamycin derivative) have been identified as having highly promisingantimycobacterial activities.

Moxifloxacin

Moxifloxacin is a ourth-generation synthetic fluoroquinolone with broad-spectrum antibiotic activity against both Gram-positive and Gram-negativebacteria. Like other fluoroquinolones it unctions by inhibiting bacterialtopoisomerase II (DNA gyrase) and topoisomerase IV enzymes that arerequired or bacterial DNA replication, transcription and repair and thusinhibits cell replication.

Moxifloxacin has shown potent bactericidal activity against M. leprae

in mice and humans. Given at 150 mg/kg in mice (equivalent to 400 mg inhumans), it is as active as riampicin. A single dose o moxifloxacin 150 mg/kg


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killed five times more M. leprae than a single dose o ofloxacin 150 mg/kg.

In humans, given at a dose o 400 mg daily, it killed more than 99% M. lepraewithin 7 days, and no viable bacilli were demonstrated rom day 28 onwards. Itis more potent than ofloxacin, minocycline and clarithromycin (31, 32).

Rifapentine

Riapentine is a semi-synthetic riamycin derivative with a prolonged action(serum hal-lie 15 hours) compared with riamycin (hal-lie 3 hours).Because o its long hal-lie, riapentine was investigated in the 1980s and1990s in combination with other medications or the once-weekly treatment

o tuberculosis.Like all riamycin derivatives, riapentine targets DNA-dependent RNA

polymerase, which is necessary or RNA synthesis and thus or production oproteins. Tis process is different in human (eukaryotic) cells and bacteria,and all riamycin derivatives, including riapentine, affect the process only inbacteria. Resistance to riapentine can develop during tuberculosis treatment byselection o pre-existing riamycin-resistant mutants within large populations otubercle bacilli. I resistance develops to one riamycin-type drug, the bacteriabecome resistant to all riamycin derivativess.

Riapentine can cause some body fluids such as saliva, urine, breast milk,

tears and sweat to become orangered in colour. Te skin, teeth and tongue mayalso change colour and dentures and contact lenses can be permanently stained.Riapentine may reduce the effectiveness o contraceptive pills, and other ormso contraception should thereore be used during treatment with this drug.

In leprosy treatment, riapentine exhibited more potent bactericidalactivity than riampicin in both in mice and humans. In the mouse oot-padmodel, a single riapentine dose o 10 mg/kg killed 20 times more M. lepraethana single riampicin dose o 10 mg/kg. A single dose o a riapentine+moxifloxacin+minocycline combination killed 50 times moreM. lepraethan a single dose oriampicin+ofloxacin+minocycline (32).

Diarylquinoline (R207910)

Diarylquinoline offers a new mechanism o antituberculosis action byinhibiting mycobacterial adenosine triphosphate (AP) synthase. Te drugpotently inhibits drug-sensitive and drug-resistant M. tuberculosisin vitro andshows bactericidal activity both in patients with drug-susceptible pulmonarytuberculosis and in those with multidrug-resistant (MDR) pulmonarytuberculosis (3336).

AgainstM. lepraein mice, a single dose o 25 mg/kg is bactericidal. Te

drug is as active as riampicin, riapentine and moxifloxacin and more activethan minocycline. In mice, multiple doses o 1 mg/kg five times a week were as


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active as a single dose o 25 mg/kg. Similarly, a dose o 25 mg/kg once a month

was as active as the same dose given five times a week. Diarylquinoline has along hal-lie (1 week in humans). Te drug may be used to replace minocyclinein the new combined regimens or once-a-month treatment or leprosy.

Other new drugs active against Mycobacterium tuberculosis complex

Te activities o PA-824 (a nitroimidazopyran) and linezolid (an oxazolidinone)against M. leprae are rather modest (37). A single 100 mg/kg dose o PA-824showed no significant bactericidal activity; afer five consecutive days otreatment the bactericidal effect was significantly weaker than that o a single

dose o diarylquinoline or o moxifloxacin. Tus, PA-824 has a narrow spectrumo activity, limited primarily to theM. tuberculosiscomplex (37). Neither PA-824nor linezolid which yielded similar results is a promising drug or thetreatment o leprosy.

4.1.4 Study on the uniform multidrug therapy regimen

In order to shorten the duration o treatment and simpliy drug supplylogistics, a multicentre study has been launched to assess the efficacy o theWHO-recommended 6-month MD regimen or MB leprosy in new cases oall types o o leprosy, both MB and PB. Patients are to be actively ollowed

or a minimum period o 8 years afer completion o treatment to monitorreactions and relapses. Tis study aims to recruit a total o 5000 newlydetected, previously untreated patients (2500 PB and 2500 MB). It is designed asa multicentre, open field study; some 3400 patients have been recruited so arand about 2000 patients have completed their treatment. Te preliminary reportis avourable (38), but no conclusions can yet be drawn.

4.1.5 Combined therapy with four weeks of daily ofloxacin and rifampicin

Te possibility o urther shortening the duration o MD was evaluated in ariampicinofloxacin field trial. Tis was a multicentre, double-blind trialorganized by the Steering Committee on Chemotherapy o MycobacterialDiseases (HEMYC), a component o the UNDP/World Bank/WHO SpecialProgramme or Research and raining in ropical Diseases (DR). Multibacillaryleprosy patients were randomized into our groups and treated with:

24 months o standard WHO-MD or MB leprosy (as positivecontrol);

12 months o WHO-MD or MB leprosy;

12 months o WHO-MD or MB leprosy with riampicin 600 mg

plus ofloxacin 400 mg daily during the initial 4 weeks; and riampicin 600 mg plus ofloxacin 400 mg daily or 4 weeks.


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Te published results (39) showed that the trial regimen o daily

riampicin and ofloxacin or 4 weeks resulted in an unacceptable relapse rate o13%. Tus, daily treatment with riampicin and ofloxacin or 4 weeks is not aviable option.

4.1.6 Treatment regimens for special situations

Patients who cannot take rifampicin

Special treatment regimens are required or individual patients who cannottake riampicin because o side-effects or intercurrent diseases, such as chronichepatitis, or who have been inected with riampicin-resistant M. leprae. Te

ollowing 24-month regimen is recommended: Daily administration o 50 mg cloazimine, together with two o the

ollowing drugs 400 mg ofloxacin, 100 mg minocycline or 500 mgclarithromycin or 6 months, ollowed by daily administration o50 mg cloazimine, together with 100 mg minocycline or 400 mgofloxacin or an additional 18 months (40). I available, ofloxacin maybe replaced by moxifloxacin 400 mg, which has stronger bactericidalactivity againstM. leprae.

Patients who cannot take rifampicin

Multibacillary leprosy patients who reuse to take cloazimine because o skindiscolouration also need a sae and effective alternative treatment. In suchpatients, cloazimine in the normal 12-month MD may be replaced by ofloxacin,400 mg daily, or by minocycline, 100 mg daily, or 12 months. Similarly, ofloxacinmay be replaced by moxifloxacin, 400 mg.

In 1997, the WHO Expert Committee on Leprosy (41) alsorecommended the ollowing alternative 24-month regimen or adult MBleprosy patients who reuse to take cloazimine: riampicin, 600 mg oncea month, ofloxacin, 400 mg once a month, and minocycline, 100 mg once amonth, or 24 months.

Patients who cannot take dapsone

I dapsone produces severe toxic effects in any PB or MB leprosy patient, it mustbe stopped immediately. No urther modification o the regimen is required orpatients with MB leprosy. For PB leprosy, however, cloazimine in the dosageused in the standard MD or MB leprosy should be substituted or dapsonein the 6-month treatment regimen.

4.1.7 Relapses after multidrug therapy

Relapse afer MD remains low, even afer almost 30 years o widespread use.Some reports suggest that the risk o relapse is higher in a subset o patients


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with a pre-MD average bacterial index (BI) o 4 or more. Recently published

WHO operational guidelines recommend that it may be advisable to treat anMB patient with high BI or more than 12 months, taking careul considerationo the clinical and bacteriological evidence. A number o studies have reportedthat retreatment o relapses ollowing dapsone monotherapy or MD withanother course o standard MD regimens is highly successul (4143).

Although demonstration o organisms resistant to dapsone is relativelycommon, probably because o pre-existing dapsone-resistant strains, there arereports on organisms resistant to riampicin, cloazimine or quinolones afercompletion o treatment with MD. Most investigators consider that a relapseafer MD is most likely to be due to persisters and only rarely to resistance.

Tis is borne out by the results o molecular tests on biopsies rom a smallnumber o relapsed cases.

Several risk actors or relapses in leprosy have been suggested, includingpersisters, re-inection, drug resistance, inadequate/irregular therapy, use omonotherapy, high initial BI, number o skin lesions and lepromin negativity.Te risk o relapse in patients coinected with HIV is a possibility and needsurther investigation. Currently, diagnosis o relapse is based mainly on clinicaleatures such as appearance o a new lesion and a significantly increased BI.Some studies have demonstrated the utility o histopathological changesand simple serological tests in confirming the diagnosis o relapse. Tere is a

possibility o developing molecular tests based on PCR or early identificationo relapses (44).

4.2 Management of leprosy reactions and neuritis4.2.1 Neuritis and nerve function impairment

Nerve unction impairment (NFI) results rom a variety o pathological andimmunological processes taking place in the peripheral nerves. Te presence olongstanding NFI at the time o registration and MB classification are the mainrisk actors or subsequent development o serious nerve damage in leprosy.

Te proportion o new cases with NFI at diagnosis may be as high as 20%.Leprosy reactions, particularly ype 1 or reversal reactions, are regardedas the leading cause o NFI. Most patients, particularly those with MB disease,develop NFI events and reactions during the first 6 months afer startingtreatment: these events diminish over time (including time afer MD) and veryew patients develop such events afer the second year ollowing completiono MD. However, nerves can be unctionally impaired in the absence o anyobvious signs or symptoms o reactions (silent neuropathy) (45, 46).

4.2.2 Leprosy reactions

ogether, the two major clinical types o leprosy reactions ype 1 or reversalreaction, and ype 2 or erythema nodosum leprosum (ENL) reaction may


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affect 3050% o all MB leprosy patients (47). Because M. leprae inects

peripheral nerves, the inflammation associated with reactions is a medicalemergency: severe nerve injury may develop rapidly, with subsequent losso sensation, paralysis and deormity (48). No clinical or laboratory tests areavailable that can accurately predict either which patients are the most likely todevelop a reaction or when such a reaction might occur.

ype 1 reactions are recognized by swelling and redness o skin patchesand are regarded as severe when associated with loss o nerve unction (losso sensation or muscle weakness), pain or tenderness in one or more nerves,when the red swollen skin patches are on the ace or overlying another major

nerve trunk, when skin lesion anywhere becomes ulcerated and when there ismarked oedema o the hands, eet or ace. ype 1 reactions occur across thewhole leprosy spectrum.

ype 2 or ENL reactions are characterized by the appearance o tender,erythematous nodules in MB patients. Tey are regarded as severe whennumerous ENL nodules occur in association with high ever and neuritis orbecome ulcerated and when other organs (e.g. eyes, testes, lymph nodes andjoints) are involved. A severe ENL reaction can be recurrent and chronic andmay vary in its presentation.

Promising new markers to identiy patients at high risk o developing

reactions have been demonstrated but additional studies are needed todetermine their sensitivity and specificity (49).

4.2.3 Treatment of leprosy reactions

Te mainstay o treatment o both types o reaction is corticosteroids becauseo their anti-inflammatory effects. Some studies have demonstrated betterresults when steroids are administered or longer than 12 weeks, particularlyin the treatment o neuritis. o ensure that due attention is given to the risk oserious side-effects o long-term use o steroids, such as weight gain, pepticulcer, diabetes, hypertension, reactivation o tuberculosis, osteoporosis andpsychiatric disorders, these drugs should be prescribed only by someoneproperly trained in their use. rials o prophylactic steroids have demonstratedonly a shortterm effect on prevention o NFI. Several studies have indicatedthat NFI improves to some extent without steroid therapy, which may beattributable to MD (45).

Cyclosporine has been used to treat ype 2, or ENL, reactions with mixedresults (50). Azathioprine and methotrexate have been used in combinationwith prednisolone or treatment o ype 2 reactions and may offer a steroid-sparing regimen or treatment (51). Pentoxyylline, a NF-alpha inhibitor, has

shown no significant benefit. Inhibition o lymphocyte prolieration by severalpotent antimetabolites has had little or no consistent effect in the treatment o


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either type o leprosy reaction. Similarly, clinical inhibitors o NF-alpha, IL-2,

and other cytokines have had minimal effects on reactions (52, 53).Although several studies have demonstrated the useulness o

thalidomide in the treatment o acute ENL reactions, its use is restrictedbecause o its teratogenic effects and o ethical and legal considerations. Inaddition, thalidomide availability is limited by restrictions on its import andsupply in many endemic countries. WHO thereore recommends its use onlyunder strict medical supervision in specialized reerral acilities.

It is important to educate all patients about the signs and symptoms oreactions and NFI and to encourage them to return to health centres immediatelyin case o such events even those that occur afer completion o MD.

National leprosy programmes should continue to ensure that an efficientreerral system exists within the general health services to allow timely nerveunction assessment and diagnosis and treatment o patients experiencingreactions, neuritis and related complications such as iritis. Regular availability oantireaction drugs should be ensured.

Guidelines for the management of severe reactions

Severe ype 1 or reversal reaction

Severe reversal (ype1) reactions should be treated with a courseo steroids usually lasting 36 months. Patients still on antileprosytreatment should continue the standard course o MD.

Severe ype 2 or ENL reaction

Severe ENL reaction should be treated with a standard course oprednisolone (daily dosage not exceeding 1 mg/kg body weight)or 12 weeks. Patients who experience reactions while still onMD should continue the standard treatment with MD. I MDhas been completed, the management o ENL should not includerestarting o MD. Adequate doses o analgesics to control everand pain should be prescribed.

A combination o cloazimine and corticosteroids is indicated ormanagement o patients with severe ENL who are not respondingsatisactorily to treatment with corticosteroids alone or or whomthe risk o corticosteroid toxicity is high. Prednisolone should begiven in daily dosage not exceeding 1 mg/kg body weight. reatmentwith cloazimine should start with 100 mg three times a day or amaximum o 12 weeks, with the dose then tapering to 100 mg twice aday or 12 weeks and to 100 mg once a day or 1224 weeks.

Management o ENL reaction with cloazimine alone is indicatedin cases o severe ENL when the use o corticosteroids is


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contraindicated. reatment with cloazimine should ollow the same

guidelines as when it is used in combination with prednisolone.However, the total duration o treatment with high-dose cloazimineshould not exceed 12 months.

It should be noted that it takes about 46 weeks or cloazimineto take ull effect in controlling ENL. Management o severe ENLreaction is complex and should be undertaken only by physiciansat reerral acilities, who will adjust the dose and duration o anti-reaction drugs according to patients individual needs.

4.3 Disability and rehabilitationDisability in new patients as well as in people who have completed treatment remains a challenge. Addressing the problem o disability alls within thebroad scope o public health but requires support rom social services, thecommunity and the voluntary sector.

4.3.1 Magnitude of the problem

Currently there is no robust inormation on the numbers o people affected bydisability due to leprosy at either global or national level. While inormation

on G2D among new cases is regularly collected, only limited inormation isavailable on disability among people who have completed MD.For planning and implementation o rehabilitation measures or people

with leprosy-related disabilities, it is important to estimate the total prevalenceo G2D in the population. It would thereore be useul to include, in all nationalprogrammes, a new measure o total prevalence o G2D in the population asone o the main indicators or monitoring urther reduction in disease burden.As well as inormation on total prevalence o G2D, more detailed inormationwill be needed at the local level on the specific rehabilitation needs, includingphysical, social and economic needs, o leprosy-affected communities.

4.3.2 Disability grading for leprosy

Te three-grade WHO disability grading system (0, 1, 2) has been in use orseveral years and has proved to be a good basis or measuring the magnitude othe problem and organizing physical rehabilitation activities at both individualand community levels.

4.3.3 Prevention, limitation and management of disabilities

Prevention o disabilities begins with early diagnosis o leprosy, recognition

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Although or programme purposes statistics are compiled only or G2D, it is

important that inormation on grade 1 disability is also made available at theclinic level so that such patients are supported by preventive measures suchas provision o ootwear and protective devices and advice on sel-care. Tesepreventive measures are equally relevant or individuals who are cured and donot normally present themselves at clinics except as part o an active ollow-up. Management o disabilities should be an integral part o routine treatmentservices at the clinic level and should also cover people who have been cured.Available services should include the provision o aids and appliances, specialistmedical care, and surgical reconstruction and rehabilitation acilities.

4.3.4 Self-care

Sustaining the prevention and management o disabilities requires greateremphasis on sel-care and sel-help through counselling o those in need, aswell as o their amilies and community members. Sel-care measures shouldinclude care o dry, denervated skin o palms and soles in order to preventwounds, ulcers and skin cracks. Prevention o occupational injuries, such asburns caused by handling hot objects, should be an important aspect o thecounselling o individuals with sensory loss in the limbs, as should care o theeyes where indicated.

4.3.5 Community-based rehabilitation

Following the Declaration o Alma-Ata (1978), stating that health is aundamental human right, and in consideration o the constraints o scope,expertise and resources imposed on specialized medical rehabilitation services,WHO introduced the strategy o community-based rehabilitation (CBR). Tiswas intended to enhance the quality o lie or people with disabilities throughcommunity initiatives, promoting the concept o the inclusive communityand using local resources to support the rehabilitation o people with disabilities

within their own communities. However, stigma and lack o knowledge meantthat specialized rehabilitation services and many CBR programmes ailed torecognize people with leprosy-related disabilities as equal members o thecommunity requiring rehabilitation.

In recent years there has been a change in attitude towards leprosy.Stigma has lessened in many countries and people affected by leprosy nowmore ofen remain within their amilies and communities. As a result,involvement o amily and community members is now seen as critical orempowering people affected by leprosy, encouraging them to play an activerole in their rehabilitation and urther reducing the stigma o the disease. Te

central strategy o CBR is to acilitate community action to ensure that peoplewith disabilities including those disabled by leprosy have the same rights


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and opportunities as all other community members, including, or example,

equal access to health care, education, skills training, employment, amily lie,social mobility and political empowerment. Tus CBR has become a legitimatestrategy or meeting the needs o people affected by leprosy and enhancingtheir quality o lie.

Community-based rehabilitation calls or a comprehensive, rights-basedapproach, involving sectors other than health. Te recently published WHO/ILEP Technical guide on community-based rehabilitation and leprosy: meetingthe rehabilitation needs of people affected by leprosy and promoting quality of life(54) highlights the importance o the CBR approach, and the WHO/UNESCO/ILO/IDDC Communitybased rehabilitation: CBR guidelines (55) includes asupplementary section on leprosy and CBR that urther promotes the inclusiono leprosy-affected persons in broader CBR and development programmes.


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5. Social issuesTe Seventh Meeting o the Expert Committee on Leprosy did not addresssocial issues except in reerence to the meeting held in 1952 (40), whichrecommended that the issue o human rights be acknowledged, especially withregard to the particularly negative impact o leprosy on women.

In June 2010, WHO hosted a meeting o regional managers, individualsaffected by leprosy and various experts with the aim o developing guidelinesor increasing the participation o leprosy-affected persons in leprosy controlactivities (56). Te meeting identified several areas, with correspondingstrategies, or enhancing the empowerment o those affected. Te empowerment

strategies aim to increase the inclusion o persons affected by leprosy indifferent aspects o community lie, including health, housing, social welare,education and decision-making, as well as in socioeconomic activities. Teresult o this enhanced participation and empowerment is threeold: greaterwillingness o individuals affected by leprosy to seek diagnosis; completion othe prescribed treatment plans; and improved quality o lie.

5.1 Equity, social justice and human rightsTe principle o equity is based on the premise that disparities or inequalities in

the levels o health enjoyed by different populations are unnecessary, avoidableand unjust. It is the right o individuals enshrined in the Universal Declarationo Human Rights (57). In 2008, the United Nations Convention on the Rightso People with Disabilities came into orce. Tis Convention represents a majornew international legal instrument and, with its greater ocus on inclusivity indevelopment, is o critical importance in protecting the rights o all personswith disabilities, including those affected by leprosy.

Further potential or improving the condition o persons affected byleprosy and promote their rights to quality o lie was enshrined in the UnitedNations Human Rights Council resolution on the Elimination o discriminationagainst persons affected by leprosy and their amily members, which receivedunanimous approval in June 2008 (58). Tis has been urther strengthenedwith the adoption by the Human Rights Council in September 2010 o a set oprinciples and guidelines on the elimination o discrimination against personsaffected by leprosy and their amilies (59).

Equity, social justice and human rights in the world o leprosy aredifficult to attain without continually challenging those who label this populationin pejorative terms; consistent respect or those affected is essential.

5.2 Gender

Te sociocultural norms in many societies discriminate against girls andwomen, ofen consigning them to a lower status and value and placing them at


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considerable disadvantage in terms o access to resources and goods, decision-

making power, and choices and opportunities in all spheres o lie. Since womenappear to suffer more negative health consequences o leprosy than men (60),the topic o women in the world o leprosy is a cross-cutting issue.

Health systems need to give greater emphasis to gender in the trainingo health proessionals and health-care workers in order to improve awareness oand sensitivity to gender concerns and disparities (61).

Programmes need to identiy patterns o service use, levels oparticipation in decision-making and perceptions o quality o care. Whendefining priorities in leprosy control services, it is critical to increase womensinvolvement in health action at all levels. Tere is evidence that integration oleprosy services into general health services, coupled with decentralization, hasimproved the accessibility o services or all population groups in general andor the emale population in particular (62).

5.3 Enhancing the involvement of affected personsPersons affected by leprosy have a major role to play in leprosy services,especially in the areas o advocacy, awareness, rehabilitation and case-finding.Organized efforts by these individuals are vital to promoting a positive publicperception o and attitude to the disease; to effecting change in any legal

measures that are discriminatory in nature; and to ensuring that leprosycontrol continues to occupy an important place in the health policy rameworko the country.

Persons affected by leprosy also have a clear role and responsibility inthe area o community involvement or social action. Teir involvement canlead to country-specific definitions o the quality o service to be provided, aswell as help the programme in setting the standard or quality. Tey can provideregular inormation to programme managers, supervisors or sponsors onthe quality o services. Teir participation in research and evaluation can assistin identiying needs, particularly with respect to the accessibility and quality o

services being provided. Tey can contribute to reorming leprosy services andprovide a ocus on issues o discrimination and stigma. As role models, theyare the major contributors to cultivating positive attitudes.

5.4 Stigma and stigmatizationLeprosy has a strong social and psychological impact on all individualsaffected by the disease (including amily members) and the societies in whichthey live. Te disease carries significant stigma: communities respond withear, rejection, insensitivity, use o pejorative terms, and general devaluation

o the status o affected persons who, in turn, eel threatened by the rest osociety. Socioeconomic rehabilitation o affected people can play a major role in


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improving their quality o lie, increasing their social integration and reducing

leprosy-related stigma. Some reports suggest that stigmatization is in decline,particularly where integrated programmes are unctioning. Although stigmamay change in nature rom overt rejection o those affected by leprosy to theindividuals ear o what might happen as a result o having leprosy (6365) it ofen persists long afer the disease has ceased to be a public health problem.

Te response o the programme should be twoold. It is importantto address the community, responding to unanswered questions, dispellingmisunderstandings and myths, and helping people to acknowledge andaccept those affected by leprosy without prejudice. It is equally importantto empower persons affected by leprosy to deal with the daily challenges omisunderstanding and miscommunication.

Te treatment programme should also include counselling as animportant management strategy, and should introduce guidelines and protocolsor building the competence o health proessionals in three important areas:transorming knowledge into inormation that is easily understandable bypersons affected by leprosy; managing people and tasks; and communicationskills. A well-trained health person should be able to advise, support, guide,share inormation and empower others.

5.5 CounsellingTe purpose o counselling is to provide support to individuals in emotionaldistress in order to lessen their distress and allow them to unction optimallyin their everyday lives. Counselling by trained and experienced proessionalsis a critical resource that should be available to all persons affected by leprosyand that should ofen be extended to their amily members. It should becommunity-based and initiated at the time o diagnosis.

When provided by individuals who are amiliar with the community,knowledgeable about the emotional impact o leprosy and proessionally trainedcan have a positive impact on the social issues discussed in sections 4.14.4.

5.6 Residential carePersons newly diagnosed with leprosy should not be admitted or long-term institutional care. Te consequence o such institutionalization is ofensignificant difficulty in returning to independent living and in the evento institutions closing there is the problem o finding suitable alternativeaccommodation or inpatients.


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6. Leprosy control and preventionElimination o leprosy as a public health problem defined, in terms oprevalence, as ewer than 1 leprosy case registered or treatment per 10 000population was achieved at the global level at the end o 2000. Morerecent approaches, however, have ocused on monitoring new case detectionand working to reduce the burden o disease. Eradication o leprosy is notconsidered to be easible since there is no test or inection and the incubationis very long; moreover, many aspects o the natural history o the disease(such as subclinical inection and the role o carrier states) are unknown (or

example, there is at least one animal reservoir the armadillo o M. leprae).Te current approach targets reduction in disability in new cases based on earlycase detection, treatment with MD, and good-quality services that includeprevention o disability to reduce the burden o disease.

6.1 Improving the quality of leprosy servicesImproving the quality o care not only enables all the needs o the patient to bemet but also makes it possible to attract more people to come or examination,which results in improved case detection. Te elements o good-quality careinclude:

easy accessibility o health care;

availably o MD;

management o complications and side-effects;

disability care and prevention o disability (POD);

CBR;

respect or individual rights o patients; and

elimination o stigma and gender bias.

Tese elements can be ensured by improving:

the capacity o peripheral health services to deal with essential tasks(diagnosis, classification, MD, need or reerral, etc.);

availability o appropriate tools/protocols, resources and the necessarycompetence at reerral points;

the counselling o patients and their amilies; and

community awareness.

Patients should be reviewed at the end o MD treatment to confirmthe completion o treatment and to assess any new nerve unction impairments


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that may have developed during treatment. Patients should be counselled at this

point on the risks o uture reactions and relapses and on recommended actions.

Sel-care should be re-emphasized and advice given on prevention o disability.

6.2 Integrating leprosy control into general health servicesTe need to integrate leprosy control into general health services is based

largely on the principles o equity and sustainability. In addition, integration

allows issues o stigma and discrimination against persons affected by leprosy

and their amilies (66, 67) to be more effectively addressed. In an integrated

programme, leprosy control activities should be conducted in multipurpose

settings by health workers within the general health services. However,integration does not mean that specialized personnel no longer have a role.

Tey mustbe a part o the integrated programme at the national level; may also

be available at the intermediate (regional or provincial) or even district level;

and are expected to play a vital part in coordination, planning and technical

support and in monitoring o progress in leprosy control (68). Almost all

endemic countries have already involved general health workers, to a varying

extent, in antileprosy activities.

Te key issue is that o improving the perormance o the integrated

programme, which may be achieved by:

raising community awareness o the main eatures o leprosy its

curability and the availability o ree treatment and increasing

community participation in case-finding, case-holding, MD

delivery and POD;

building capacity within general health services;

ensuring regular supervision and technical support by workers

rom higher levels o the general health system and by specialized

leprosy workers;

ensuring adequate reerral services;

ensuring availability o the necessary quantities o MD drugs, o

other medical supplies and o materials or handling complications

and care at the peripheral level.

6.3 Referral systemAn ideal reerral system ensures that patients can receive appropriate, high-

quality care or their condition in the closest possible acility and at the lowest

cost given the resources available to the health system (69). Improving theeffective unctioning o reerral systems requires progress in three areas: reerral


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system design, acilitation o the transer o both patients and inormation

between levels, and effective reerral discipline.

Improving the design o the reerral system requires identification o the

services that can appropriately be provided at each level o care in both rural and

urban settings, including community- and home-based care and primary health

care at district, secondary and tertiary levels and in specialized hospitals (70).

Te development o effective transportation arrangements is critical to

ensure that patients rom remote areas have a air chance o being reerred

to specialists. When the patients treatment has finished at the higher-level

acility, back-reerral to the original acility must include inormation regarding

treatment, investigations already done and ollow-up expected at the lower level.Te bypassing o lower-level services by patients is a common problem

that leads to overcrowding o higher-level acilities. Effective reerral discipline

demands improvements in the quality o care at lower levels and in the

availability o resources in order to strengthen primary health care services,

giving them greater credibility and making them more attractive to patients.

A reerral system will unction effectively i all services providers adhere to the

reerral discipline, reerring appropriately and ollowing the agreed protocols o

care (71).

Te reerral system has a crucial role in defining the quality o carethat a programme can provide to persons affected by leprosy; it should include

identification o the primary-, secondary- and tertiary-level services that are

available to meet a whole range o needs (72). An integrated leprosy control

programme thus needs the support o an efficient reerral system to be effective.

Currently, the reerral system in most programmes is either non-existent or is

very weak as regards meeting programme needs. Strengthening existing reerral

acilities and, where necessary, establishing an adequate number o such acilities

to orm the national reerral network should be one o the key priorities or

integrated leprosy control programmes.

Te reerral system should include a network o individuals andinstitutions capable o providing services. Teir tasks and responsibilities should

be clearly defined, along with procedures and protocols or good, standardized

clinical practices, including protocols or the flow o patients and inormation

to and rom different levels. Te system should build partnerships, coordinating

the work o all care providers to maximize care and reduce cost. An effective

reerral system requires good communication and coordination between

levels o care: a range o options are available or effective communication and

transer o inormation, including personal visits, telephone, post, e-mail, and

telemedicine). It is also important to ensure that persons affected by leprosy areprovided with support or travel rom remote areas when needed.


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Besides direct patient care, reerral hospitals has other roles within the

health system, such as teaching and research, as well as technical support andquality assurance to lower levels o health services (70). Tey may also be closelyinvolved in other public health interventions such as disease-specific healthpromotion and education activities.

6.4 Building and maintaining national capacityCapacity building assumes greater importance against the backdrop o adeclining disease burden, shrinking resources, competing interests and prioritiesand, most importantly, loss o clinical expertise in leprosy. Te Enhanced Global

Strategy envisages a two-pronged approach,

Documents

8th Expert Comm 2012