REFERENCIAS BIBLIOGRÁFICAS / BIBLIOGRAPHICAL REFERENCES

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1.) Leprosy: the Disease 

2.) The Global Alliance for Elimination of Leprosy 

3.) Leprosy in a child of less than two months of age. 

4.) 7th WHO Expert Committee on leprosy June 1997 

5.) The US-Japan Joint Leprosy Research Program Meeting, San Francisco, June 2830, 1999 

6.) Another View of the Therapy of Leprosy 

7.) Rifampicin/minocycline and ofloxacin (ROM) for single lesions--what is the evidence? 

8.) What are the new antileprosy drugs - ROM - now available for the treatment of leprosy? 

9.)What are the types of leprosy that can be treated by ROM ? 

10.)What is the reason for introducing single dose treatment for paucibacillary leprosy presenting with a single skin lesion? 

11.) What is the basis for the recommended alternative regimen for the treatment of paucibacillary leprosy presenting with a single skin lesion? 

12.)Does WHO recommend that all programmes should treat single lesion paucibacillary leprosy cases with one dose of ROM? 

13.) Efficacy of single dose multidrug therapy for the treatment of single-lesion paucibacillary leprosy. Single-lesion Multicentre Trial Group. 

14.) Minocycline in lepromatous leprosy. 

15.) Efficacy of minocycline in single dose and at 100 mg twice daily for lepromatous leprosy. 

16.) Field trial on efficacy of supervised monthly dose of 600 mg rifampin, 400 mg ofloxacin and 100 mg minocycline for the treatment of leprosy; first results. 

17.) Bactericidal activity of a single-dose combination of ofloxacin plus minocycline, with or without rifampin, against Mycobacterium leprae in mice and in lepromatous patients. 

18.) Bactericidal activity of single dose of clarithromycin plus minocycline, with or without ofloxacin, against Mycobacterium leprae in patients. 

19.) WHO Expert Committee on Leprosy. 

20.) Experimental evaluation of possible new short-term drug regimens for treatment of multibacillary leprosy. 

21.) Powerful bactericidal activities of clarithromycin and minocycline gainst Mycobacterium leprae in lepromatous leprosy. 

22.) Leprosy resistant to multi-drug-therapy (MDT) successfully treated with ampicillin-sulbactam combination--(a case report). 

23.) Differential protective effect of bacillus calmette-guerin vaccine against multibacillary and paucibacillary leprosy in nagpur, india. 

24.) Protective effect of Bacillus Calmette Guerin (BCG) against leprosy: a population-based case-control study in Nagpur, India. 

25.) Patient contact is the major determinant in incident leprosy: implications for future control. 

26.) The clinical use of fluoroquinolones for the treatment of mycobacterial diseases. 

27.) A case of relapsed leprosy successfully treated with sparfloxacin. 

28.) Active leprosy treated effectively with ofloxacin. 

29.) Reactional states and neuritis in multibacillary leprosy patients following MDT with/without immunotherapy with Mycobacterium w antileprosy vaccine. 

30.) Mycobacterium w vaccine, a useful adjuvant to multidrug therapy in multibacillary leprosy: a report on hospital based immunotherapeutic clinical trials with a follow-up of 1-7 years after treatment. 

31.) What is WHO MDT? 

32.) Is WHO-recommended multidrug therapy (MDT) the best combination available for treatment of multibacillary (MB) and paucibacillary (PB) leprosy in leprosy control today? 

33.) WHY MULTIDRUG THERAPY FOR MULTIBACILLLARY LEPROSY CAN BE 

SHORTENED TO 12 MONTHS 

34.) Supervised Multiple Drug Therapy Program, Venezuela 

35.) Search for newer antileprosy drugs. 

36.) Mycobacterium leprae--millennium resistant! Leprosy control on the threshold of a new era. 

37.) The impact of multidrug therapy on the epidemiological pattern of leprosy in Juiz de Fora, Brazil. 

38.) Serologic response to mycobacterial proteins in hansen's patients during multidrug treatment. 

39.) HLA linked with leprosy in southern China: HLA-linked resistance alleles to leprosy. 

40.) A Mycobacterium leprae-specific human T cell epitope cross-reactive with an HLA-DR2 peptide. 

41.) Association of HLA antigens with differential responsiveness to Mycobacterium w vaccine in multibacillary leprosy patients. 

42.) HLA antigens and neural reversal reactions in Ethiopian borderline tuberculoid leprosy patients. 

43.) Evidence for an HLA-DR4-associated immune-response gene for Mycobacterium 

tuberculosis. A clue to the pathogenesis of rheumatoid arthritis? 

44.) Diaminodiphenylsulfone resistance of Mycobacterium leprae due to mutations in the dihydropteroate synthase gene. 

45.) Resolution of lepromatous leprosy after a short course of amoxicillin/clavulanic acid, followed by ofloxacin and clofazimine. 

46.) Studies on risk of leprosy relapses in China: relapses after treatment with multidrug therapy. 

47.) An immunotherapeutic vaccine for multibacillary leprosy. 

48.) Nasal mucosa and skin of smear-positive leprosy patients after 24 months of fixed duration MDT: histopathological and microbiological study. 

49.) Induction of lepromin positivity following immuno-chemotherapy with Mycobacterium w vaccine and multidrug therapy and its impact on bacteriological clearance in multibacillary leprosy: 

report on a hospital-based clinical trial with the candidate antileprosy vaccine. 

50.) SIMLEP: a simulation model for leprosy transmission and control. 

51.) Detection of viable organisms in leprosy patients treated with multidrug therapy. 

52.) An immunotherapeutic vaccine for multibacillary leprosy. 

53.) Addition of immunotherapy with Mycobacterium w vaccine to multi-drug therapy benefits multibacillary leprosy patients. 

54.) Immunotherapy with Mycobacterium w vaccine decreases the incidence and severity of type 2 (ENL) reactions. 

55.) A follow-up study of multibacillary Hansen's disease patients treated with multidrug therapy (MDT) or MDT + immunotherapy (IMT). 

56.) Immunotherapy of lepromin-negative borderline leprosy patients with low-dose Convit vaccine 

as an adjunct to multidrug therapy; a six-year follow-up study in Calcutta. 

57.) Immunotherapy of far-advanced lepromatous leprosy patients with low-dose convit vaccine 

along with multidrug therapy (Calcutta trial). 

58.) A longitudinal study of immunologic reactivity in leprosy patients treated with immunotherapy. 

59.) BCG vaccination protects against leprosy in Venezuela: a case-control study. 

60.) Immunoprophylactic trial with combined Mycobacterium leprae/BCG vaccine against leprosy: preliminary results. 

61.) Why relapse occurs in PB leprosy patients after adequate MDT despite they are Mitsuda reactive: lessons form Convit's experiment on bacteria-clearing capacity of lepromin-induced granuloma. 

62.) A lost talisman: catastrophic decline in yields of leprosy bacilli 

from armadillos used for vaccine production. 

63.) RESEARCH IN LEPROSY - ( H.D.)/ LEPROSY - RESEARCH AND BEYOND THE  YEAR 2000 

64.)THE CHALLENGE OF LEPROSY” at :- INDIA APPROVES LEPROSY VACCINE ( Ganapati Madur, New Delhi ) 

65.) A vaccine for leprosy 

66.) FREQUENTLY ASKED QUESTIONS about Leprosy / Hansen’s Disease 

67.) Leprosy Elimination 

68.) 'LEPROSY' IN THE BIBLE - WHAT WAS IT? 

69.) TI  - Thalidomide's effectiveness in erythema nodosum leprosum is 

associated with a decrease in CD4+ cells in the peripheral blood. 

70.) Leprosy in Venezuela, 1.998 

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1.) Leprosy: the Disease 

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Leprosy is a chronic infectious disease caused by 

Mycobacterium leprae, an acid-fast, rod-shaped bacillus. The 

disease mainly affects the skin, the peripheral nerves, mucosa of the upper respiratory tract and also 

the eyes, apart from some other structures. Leprosy has afflicted humanity since time immemorial. It 

once affected every continent and it has left behind a terrifying image in history and human memory - 

of mutilation, rejection and exclusion from society. 

Leprosy has struck fear into human beings for thousands of 

years, and was well recognized in the oldest civilizations of China, Egypt and India. A cumulative 

total 

of the number of individuals who, over the millennia, have suffered its chronic course of incurable 

disfigurement and physical disabilities can never be calculated. 

Since ancient times, leprosy has been regarded by the community as a contagious, mutilating and 

incurable disease. There are many countries in Asia, Africa and Latin America with a significant 

number of leprosy cases. As of 1997 around 2 100 000 000 people live in countries where the 

prevalence of leprosy is more than one case per 10 000 population. It is estimated that there are 

between one and two million people visibly and irreversibly disabled due to past and present 

leprosy 

who require to be cared for by the community in which they live. 

When M.leprae was discovered by G.A. Hansen in 1873, it was the first bacterium to be identified 

as causing disease in man. However, treatment for leprosy only appeared in the late 1940s with the 

introduction of dapsone, and its derivatives. Leprosy bacilli resistant to dapsone gradually appeared 

and became widespread. 

In 1997, there were an estimated 1.2 million cases in the world, most of them concentrated in 

South-East Asia, Africa and the Americas. The number of new cases detected worldwide each year 

is about half a million. 

 

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2.) The Global Alliance for Elimination of Leprosy 

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source: THE WHO on leprosy 

The Final Push 

An Alliance to eliminate leprosy. . . 

On November 15 th 1999, representatives of leprosy endemic countries, the World Health 

Organisation (WHO), the Nippon Foundation, Novartis and the International Federation of the 

Anti-Leprosy Associations (ILEP) announced a Global Alliance to eliminate leprosy as a public 

health problem from every country by the year 2005.TheAlliance will work closely with patients, 

communities and all agencies interested in leprosy such as the Danish International Development 

Agency (DANIDA) and the World Bank. 

The Alliance and its partners aim to detect and cure all the remaining leprosy cases in the world – 

currently estimated at 2.5–2.8 million – over this six year period. Efforts will focus on generating 

"demand" for treatment through improved awareness of leprosy in conjunction with better access to 

diagnosis and treatment. 

Is it really possible to do away with a disease that has afflicted humanity since time immemorial? It is 

no simple matter, since leprosy is an insidious, slowly-developing disease which flourishes mainly in 

the 'poverty belt' of the globe. It once affected every continent and it has etched a terrifying image in 

history and human memory, of mutilation, rejection and exclusion from society. Leprosy has always 

and everywhere been regarded as a special disease. 

India, Indonesia and Myanmar account for 70% of all the cases in the world. 

In Africa, the second most affected area, the situation is more difficult for the moment.The AIDS 

epidemic, the resurgence of the major tropical diseases, weaknesses in health infrastructure, social 

unrest and armed conflict make leprosy elimination seem like a luxury, an impracticable one at that. 

The situation remains worrying in Latin America. Brazil is particularly badly affected, accounting for 

over 80% of cases in that continent. 

In Central and Eastern Europe, there are sporadic cases; it is impossible at present to tell how many 

such cases go unreported. 

 

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3.) Leprosy in a child of less than two months of age. 

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Benerjee, K, Meyers W.M., 

Clinical Dermatology,  The CMD Case collection, World Congress Of Dermatology 

Berlin (West), 

May 24-29-1.987,: 149. 

History. Patient was a less than 2 months oid male baby belonging to one of the trained  nurses of 

our Institute. The chud had close, intimate contact with arelative who suffered 

from dimorphous leprosy and who had taken treatment for only 6 months before discontinuing it on 

his own. 

Examination. A round, elevated, red-dish lesion was detected on the face. 

Investigations. KOH mount of scrap-ings showed no fungus. A slit smear for acid fast  bacilli was 

negative. 

Histopathology. Skin biopsy material was sent to 4 different centres. Ah of them confirmed it to be 

Hansen's disease of a tuberculoid nature. 

Treatment. The lesion resolved com-pletely within three months' treatment with D.D.S. 2.5 mg for 5 

days each week. 

Conclusion. To my knowledge leprosy at less than 2 months of age has not yet been 

reported and may be disputed. Two cases of leprosy at 6 months of age were reported  by Bruce 

Baker et al. The precise mode of natural transmission, the incuba-tion period 

and clinical manifestation have not yet been established. Early signs and diagnosis may be missed in 

the mistaken belief that leprosy is non-existent in the very young. 

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4.) 7th WHO Expert Committee on leprosy June 1997 

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MAJOR CONCLUSIONS AND RECOMMENDATIONS 

The major conclusions and recommendations of the Expert Committee are summarized below: 

The Global Strategy for the Elimination of Leprosy, based on the implementation of MDT with 

case-finding, is working extremely well in reducing the prevalence of leprosy and should be 

continued. 

There is an important need to detect and treat the remaining undetected cases, for which special 

approaches, along with the extension of MDT services to all general health facilities, are required. 

The progressive simplification of diagnostic and treatment technologies has continued to facilitate 

reaching more leprosy patients. 

Based on a multicentre trial, it is considered that a single dose of a combination of rifampicin, 

ofloxacin and minocycline is an acceptable and cost-effective alternative regimen for the treatment of 

single-lesion PB leprosy. Furthermore, based on available information, it is possible that the duration 

of the current MDT regimen for MB leprosy could be shortened further to 12 months. 

A fresh strategy for the implementation of disability prevention and rehabilitation is called for to 

ensure a practical, community-oriented approach aimed at reaching the largest number of persons in 

need with-cost effective interventions. 

The monitoring of elimination through essential indicators should continue. Information reported 

should be validated and analysed further through independent monitors in order to identify in good 

time problem situations needing action. 

Anti-leprosy activities should become, and should remain beyond the year 2000, an integral part of 

general health services everywhere, and should also involve the communities to the fullest extent 

possible. Coordination between various agencies, including local and international nongovernmental 

organizations, should be consolidated. 

It is recommended that research in leprosy be continued, especially in improving patient care and in 

addressing post-elimination issues. 

It is important to sustain anti-leprosy activities beyond the year 2000 in order to deal with the 

remaining problems, including new cases and persons with disability. 

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Executive Summary 

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The WHO Expert Committee on Leprosy met in Geneva from 26 May to 3 June 1997 to review the 

global state of leprosy and the technology for dealing with it, to identify the remaining obstacles to 

reaching the goal of elimination, and to make technical and operational recommendations related to 

elimination and beyond. 

Definition of a case of leprosy: 

A case of leprosy is a person having one or more of the following features, and who has yet to 

complete a full course of treatment: 

- hypopigmented or reddish skin lesion(s) with definite loss of sensation; 

- involvement of the peripheral nerves, as demonstrated by definite thickening with loss of sensation; 

- skin smear positive for acid-fast bacilli. 

The case definition includes retrieved defaulters having signs of active disease as well as relapsed 

cases who have previously completed a full course of treatment, but does not include cured persons 

with late reactions or residual disabilities. 

Clinical classification for control programmes 

Since single-lesion leprosy may be cured by a shorter regimen than the standard MDT for PB 

leprosy, the Committee suggested that patients be classified into three groups: 

(a) PB single-lesion leprosy (one skin lesion); 

(b) PB leprosy (2-5 skin lesions); and (c) MB leprosy (more than 5 skin lesions). 

BCG re-vaccination 

The widespread application of BCG is likely to be a contributing factor to the decline in leprosy 

incidence observed in certain populations. However, repeated doses of BCG to prevent leprosy are 

not recommended on the grounds of poor cost-effectiveness, lack of acceptability to recipients, 

operational difficulties, and the fact that BCG is contraindicated in symptomatic HIV individuals. 

Shortening duration of MDT regimen for MB leprosy 

The results from both nude mouse experiments and a clinical trial have demonstrated that the 

rifampicin-resistant mutants in an untreated lepromatous patient are likely to be eliminated by 3 to 6 

months of treatment with the dapsone-clofazimine component in MDT regimen. From the 

operational point of view, the duration of MDT for MB leprosy is still very long, which adversely 

affects the implementation of MDT among all patients in need of treatment. When the Study Group 

(1981) designed the MDT regimens, MB leprosy referred to those patients who had a BI of 2 at any 

site in the initial skin smears. Currently MB leprosy includes all smear-positive patients, as well as 

patients with more than five lesions. Among the newly detected cases, the skin-smear positive 

patients represent only 12.5% of the total number. Based on all the available information, the 

Committee accepted that it is possible to reduce the duration of the current MDT regimen for MB 

leprosy to 12 months without significantly compromising its efficacy. 

Flexible MDT delivery system 

Due to poor coverage of the health services in most of the leprosy-endemic countries, supervision of 

the monthly administered drugs by health workers may not always be possible. In that case, more 

than one month's supply of MDT blister packs may be given to the patient, provided he or she is 

given appropriate information and guidance regarding the dosage, rhythm and necessary duration of 

treatment, and is advised to report any untoward signs/symptoms promptly. 

Regimen for single skin lesion PB leprosy 

Based on the results of a large multicentre randomized double-blind controlled clinical trial the 

Committee considered that a single dose of rifampicin 600 mg plus ofloxacin 400 mg and 

minocycline 100 mg, is an acceptable and cost-effective alternative regimen for the treatment of 

single skin lesion PB leprosy. 

Other regimens for special situations 

The Committee suggested that patients who do not accept clofazimine can be treated with a monthly 

administration of a combination consisting of 600 mg of rifampicin, 400 mg of ofloxacin and 100 mg 

of minocycline (ROM) for 24 months. For adult MB patients who cannot take rifampicin, the 

Committee recommended the daily administration of 50 mg of clofazimine, together with 400 mg of 

ofloxacin and 100 mg of minocycline for 6 months; followed by daily administration of 50 mg of 

clofazimine, together with 100 mg of minocycline or 400 mg of ofloxacin for at least an additional 18 

months. 

Drug resistance 

Rifampicin is by far the most bactericidal drug against M. leprae, and will still be the backbone of the 

MDT regimens in the foreseeable future. Consequently, all efforts should be made to prevent the 

emergence of rifampicin-resistant leprosy. To improve the surveillance of rifampicin-resistance, it 

may be useful to establish the genetic method for rapid detection of rifampicin-resistant strains at 

certain regional reference centres. 

Defaulter: definition and management 

A defaulter is a patient who started MDT but who has not received treatment for 12 consecutive 

months despite all attempts to trace the patient. If a defaulter patient returns to the health centre for 

treatment and shows signs of active disease such as new skin lesions, new nerve involvement or new 

nodules, he/she should be given a new course of MDT. In the absence of these, there is no need to 

restart MDT. 

Drug supply logistics 

The provision of an uninterrupted supply of high quality MDT drugs in blister packs, free of charge, 

to all patients is essential, including those living in difficult-to-access areas. To ensure the availability 

of MDT drugs and their proper distribution, a coordination mechanism between the government, 

WHO and donor agencies at the country level is needed. 

Management of reactions 

The crucial elements in the management of leprosy reactions and, thereby, the prevention of 

disabilities are early diagnosis of reactions together with prompt and adequate treatment. Most 

reactions, and neuritis, can be treated successfully under field conditions by a standard 12-week 

course of prednisolone. If patients do not respond to corticosteroid therapy in the field, they should 

be sent to an appropriate referral centre. 

WHO disability grading for leprosy 

At its last meeting in 1987, the WHO Expert Committee on Leprosy had substantially simplified the 

grading into a three-grade (0, 1, 2) system. This Committee endorsed this grading with the 

amendment that lagophthalmos, iridocyclitis and corneal opacities be considered as Grade 2. For 

safety reasons the Committee does not recommend the testing of touch sensibility of the cornea 

under field conditions. 

Reaching pockets of high prevalence 

In most endemic countries, MDT services are able to reach those patients who can easily contact the 

health care system. However, certain areas in some endemic countries have patients with only limited 

access to health care, or have MDT services that are not operating or not being utilized. In such 

areas, leprosy elimination campaigns (LEC) will be able to clear up undetected cases which have 

accumulated over a period of time in the community. Under LEC, three major activities are grouped 

as a new package: capacity building measures for local health workers to improve MDT services; 

increasing community participation; and diagnosing and curing patients, particularly MB cases. 

Reaching special population groups 

To reach patients living in difficult-to-access areas, or those belonging to underserved population 

groups, special action projects for the elimination of leprosy (SAPEL) constitute an important 

initiative to ensure the fullest MDT coverage. The essential elements of SAPEL are, firstly, to find 

cases living in difficult areas or situations who are in need of treatment and, secondly, to cure them. 

Innovative and practical strategies involving mainly operational solutions will be used in order to 

provide MDT to these patients. Since the project operates in situations where the health 

infrastructure is weak or does not exist, the strategies used should promote self-reliance and 

self-help, and must involve the community so that the activities begun under SAPEL can be 

sustained. 

Leprosy and human rights 

Patients on MDT, and those cured of disease, should not suffer from restrictions in areas such as 

employment, education and travel. Any special legal measures that might increase prejudice against 

leprosy or prevent early cases from presenting themselves for diagnosis and treatment should be 

abolished. In some countries, the human rights problem is particularly serious among female patients, 

firstly, because of their gender, and secondly, because of the stigmatization associated with leprosy. 

Strategy beyond elimination 

After the year 2000, simplifying MDT services and strengthening the process of integration into the 

general health services are the keys to sustaining anti-leprosy activities, especially in low prevalence 

situations. The uneven distribution of leprosy makes it possible to have significant endemicity in some 

parts of a country, particularly for larger countries, even though the national elimination target has 

been attained. It is important to focus elimination activities at the most peripheral levels and to plan to 

reach the elimination goal at sub-national levels. 

Monitoring leprosy elimination 

The validity of the essential indicators, reported by the programmes, should be assessed by 

independent monitors in collaboration with the national programmes, through special activities such 

as leprosy elimination monitoring (LEM) and Geographic information systems (GIS). 

Integration of anti-leprosy activities 

Programmes fully-integrated into the general health services would be more appropriate for 

strengthening leprosy elimination activities than vertical or combined programmes. 

Community action and participation 

The local community and its leaders will play a key role in improving public awareness about the 

disease and about the availability of free and effective treatment. Indeed, in some situations they may 

be the only possibility for delivering MDT drugs, supervising the monthly drug administration and 

retrieving defaulters, thereby ensuring that the patients complete their treatment. In addition, the 

prevention of dehabilitation and the rehabilitation of individual persons affected by leprosy depends 

on the community. 

Research priorities 

Due to the great success of implementing MDT, there has been a tendency in recent years for 

support for leprosy research to decline, and this may hamper the development of new technologies 

which are needed for leprosy elimination and beyond. The Committee recommends that national 

governments, scientific communities, international organizations and NGOs continue their support to 

leprosy research, particularly operational research in major endemic countries. 

 

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5.) The US-Japan Joint Leprosy Research Program Meeting, San Francisco, June 28-30, 1999 

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PATRICK J. BRENNAN 

Department of Microbiology, Colorado State University, Fort Collins, CO 80523-1677, USA 

Accepted for publication 1 August 1999 

The US-Japan Cooperative Medical Sciences Program was founded in the 1960s by the 

then-President of the United States and the Prime Minister of Japan and, since then, has had the 

highest political support from both governments. Leprosy was among the first disease entities named 

as part of the overall program, and the US and Japanese leprosy research panels and their guests 

have met in the alternating countries every year for the past 34 years (in 1995, the separate leprosy 

and tuberculosis panels were amalgamated). These meetings of the joint US-Japan panels in the form 

of scientific conferences have become a highlight of the annual leprosy research agenda. Some of the 

major fundamental research developments in leprosy over the past 30 years have been first reported 

at this conference. These include: the early development of the drug regimens leading to present-day 

MDT and ROM; the early development of the mouse footpad; the recognition of sylvian leprosy in 

the armadillo and the development of this model of leprosy and, later, the Mangabey monkey model; 

the original work on the extension of hybridoma technology to leprosy and the development of banks 

of monoclonal antibodies; the first research on the application of genetic recombinant technology to 

Mycobacterium leprae and the production of 15-20 recombinant protein antigens; the discovery of 

the heat-shock proteins and of PGL-I, and the synthesis of corresponding neoglycoproteins and the 

development of ELISA systems; the major developments in the definition of the genome and 

proteome of M. leprae; all major developments in defining the cellular immune response in leprosy; 

the application of thalidomide to leprosy reactions and elucidation of its action mechanism etc. 

The 34th US-Japan Leprosy Research Conference was held in San Francisco in conjunction with 

the US-Japan Tuberculosis Research Conference, June 28-30, 1999. Some of the highlights are as 

follows. 

A. Rambukkana (Rockefeller University, New York, USA) described the latest chapter in his 

important work on the molecular basis of the interaction between the Schwann cell and M. leprae. 

Previously, he had described how the G domain of the laminin a 2 chain in the basal lamina that 

surrounds the Schwann cell-axon unit serves as an initial neural target for M. leprae. This time, he 

addressed the nature of the M. leprae surface molecules that bind to a 2 laminin. By using human a 2 

laminins as a probe, a major 28 kDa protein in the M. leprae cell wall fraction was identified. 

Immunofluorescence and immunoelectron microscopy on intact M. leprae, using monoclonal 

antibodies against the recombinant protein, demonstrated that the protein is surface-exposed. Also, 

the recombinant protein was shown to bind avidly to a 2 laminins, the recombinant G domain of the 

laminin-a 2 chain, and the native peripheral nerve laminin. Thus, these data suggest that this 28 kDa 

protein functions as a critical surface adhesin that facilitates the entry of M. leprae into Schwann 

cells. 

In subsequent discussion of this work, it was revealed that Dr Cristina Pessolani (Fio-Cruz, Rio de 

Janeiro) had also described a 28 kDa protein as a key bacterial ligand in M. leprae-Schwann cell 

interaction and had shown that this is a member of the histone-like protein family. It thus seems that 

the protein described by Dr Rambukkana is this HLP. 

Dr Takeshi Yamada and colleagues (Nagasaki University, Japan) have also focused on this protein 

from a different perspective. They have been investigating the molecular basis of the slow growth of 

M. leprae and other mycobacteria and identified a 28 kDa protein (which they called MDPI) as the 

most abundant protein in M. bovis BCG. The protein was highly polymerized and localized in the 

nucleoid, 50S ribosomal subunit and cell surface. It interfered with replication, transcription and 

translation in E. coli cell-free systems, and was capable of transforming E. coli to slow growth. 

Sequence analysis also indicated a member of the HLP family. Thus, the 28 kDa HLP is apparently 

a major player in the pathogenesis and physiology of M. leprae. Its immunogenicity and diagnostic 

potential should now be examined. 

Efforts to 'cultivate' M. leprae continue, but this time through genetic augmentation of the organism, a 

sensible plan in light of a genome that is small and very defective in gene density. Drs Scott G. 

Franzblau (GWL Hansen's Disease Center, Baton Rouge, LA, USA) and William R. Jacobs (Albert 

Einstein College of Medicine, New York, USA) have used a combination of freshly harvested, 

viable nude mouse-propagated M. leprae and a modified D29 mycobacteriophage vector to achieve 

phage infection of M. leprae and foreign gene expression. Therefore, the key preliminary work has 

been achieved as a prelude to constructing a shuttle cosmid vector, carrying DNA libraries from 

slow growing cultivable mycobacteria and capable of stable expression of foreign DNA in M. 

leprae, allowing, in future, perhaps, in vitro growth competence. 

Widespread resistance to dapsone in the 1970s was the catalyst for the development of multiple 

drug therapy (MDT) for the treatment of leprosy. However, to date, researchers have not been 

successful in characterizing the molecular basis of dapsone resistance. Two laboratories have now 

conducted crucial preliminary experiments (Dr Y. Kashiwabara, Leprosy Research Center, Tokyo, 

Japan, and Dr Diana Williams, GWL Hansen's Disease Center). An analysis by others of 

sulphonamide resistance in E. coli has shown an association with dihydropteroate synthase (DHPS), 

a key enzyme in the folate biosynthetic pathway, encoded by the folp gene. Dr Williams has shown 

that M. leprae possesses two folp homologs (folP1 and folP2). DDS resistance was not associated 

with mutations in folP2 from two high-level DDS-resistant strains of M. leprae. However, mutations 

were observed within a highly conserved region of folP1 in two of these high-level DDS-resistant M. 

leprae clinical isolates. In addition, this folP1 homolog has been shown to encode a functional DHPS 

which itself is highly sensitive to DDS. These new data thus support early predictions that DDS 

resistance in M. leprae is associated with alterations in folate metabolism and that one possible 

mechanism of resistance is due to mutations in folP1. 

Resistance to fluoroquinolones is becoming widespread, at a time when ofloxacin, one of the 

fluoroquinolones, is being used more and more frequently in the form of ROM (rifampin, ofloxacin, 

and minocycline) in leprosy control programs. Dr Y. Kashiwabara has determined the sequences of 

the QRDR (quinolone resistance determining region) of gyrA (the gene encoding the A subunit of 

gyrase, the site of action of the fluoroquinolones) in 13 clinical isolates of M. leprae, and 

demonstrated that eight of them showed mutations in this region. Importantly, five of the eight also 

showed mutations in the rpoB gene (the gene encoding the B subunit of RNA polymerase, the site of 

action of the rifamycins), suggesting that exposure to one or the other of the two drugs can lead to 

resistance to both, a new worry as we develop alternative drug regimens for leprosy. 

The type of molecular epidemiology that is now being applied to M. tuberculosis isolates and 

tuberculosis in general has not been possible with leprosy, because M. leprae is devoid of the type of 

variable but relatively stable genetic polymorphism associated with the IS6110 insertion sequences in 

the M. tuberculosis chromosome. If other forms of DNA polymorphism could be identified in the M. 

leprae genome, the lessons that could be derived from its application would be profound in terms of 

tracking sources of infection, examining the relationship between non-symptomatic carriage of M. 

leprae and disease, probing the possibility of environmental sources of M. leprae, and differentiating 

between reactivation and new infection. Dr Y. Kashiwabara has now found some evidence of such 

polymorphism, albeit limited. The sequences of the rpoT gene from many M. leprae isolates were 

compared, allowing the classification of isolates into two broad categories. One group had three 

tandem repeats of a six-base-pair (AGATCG) sequence, and the other group had four tandem 

repeats. Isolates from Japan and Korea had the four-tandem repeat profile, whereas isolates from 

South-East Asian and Latin American countries had the three-repeat pattern, indicating that this 

genetic characteristic could be used to trace the origins of infections and the evolution of disease. 

The role of various cytokines and different T-cell subsets in leprosy pathogenesis and immunity to 

leprosy has long been a favorite topic of US-Japan participants. The curious balance between 

acquired resistance and pathogenesis is seen in granulomatous infiltration, a consequence of the 

marshalling of the acquired response to essentially contain bacilli, but with pathological sequelae. In 

the hands of Dr Linda Adams (GWL Hansen's Disease Center), mice genetically incapable of 

producing a functional inducible NO synthase (iNOS) showed markedly enhanced granuloma 

formation, and these types of granulomas were composed primarily of CD4+ cells and 

multinucleated giant cells. Thus, iNOS has an unexpected role in leprosy granulomatosis. Among the 

newer cytokines to be involved in the leprosy immune response are IL-12 and IL-10. According to 

Dr Robert Modlin (University of California, Los Angeles, CA, USA), some key lipoprotein ligands 

of M. leprae bind to the toll-like receptors in macrophages, evoking the dual response of NO 

production and IL-12 evocation, two new major players in counteracting infection. We have long 

been very conscious of the role of IFN-g in the type-1 protective immune response in leprosy. 

Apparently, part of the mechanism of this effect is to up-regulate type-1 cytokine expression and 

down-regulate IL-10, one of the type-2 cytokines (Drs Y. Fukutomi and M. Matsuoka, Leprosy 

Research Center, Tokyo, Japan). The newest players in these events are the chemokines. M. leprae 

induces elevated levels of MCP-I, MIP-1a , and MIP-1b expression, and it is now believed that 

chemokines will prove to be important in regulating granuloma formation and other immune 

responses in leprosy (Dr Linda Adams). 

Preliminary results were also reported by Dr T.P. Gillis (GWL Hansen's Disease Center) on the 

application of DNA vaccines to an animal model of leprosy. A recombinant construct of the antigen 

85A injected intradermally proved to be the most promising with strong IgG1 and Ig2a antibody 

responses and increased IFN-g and IL-2 production. However, protection studies in the mouse 

footpad infection model were disappointing. 

With the amalgamation of the US-Japan Leprosy and Tuberculosis Panels in 1995, a fear of leprosy 

research workers within the US-Japan Cooperative Medical Sciences Program was that leprosy 

research would be engulfed by the tuberculosis research juggernaut. This fear has proved to be 

unfounded. Basic research in leprosy is thriving, notably in Japan, where the Leprosy Research 

Center has been incorporated into the prestigious, well-endowed National Institute of Infectious 

Diseases. The formal combination of both panels is clearly benefiting leprosy research. 

============================================================= 

6.) Another View of the Therapy of Leprosy 

============================================================= 

Antimicrobial Agents and Chemotherapy, December 1998, p. 3334-3336, Vol. 42, No. 12 

LETTER/ Dr. Gelber's 

From 1943 until 1982 the standard treatment for lepromatous leprosy was lifelong dapsone 

monotherapy. Though dapsone is bacteriostatic and lepromatous leprosy has the highest bacterial 

burden of all human diseases, as well as an impairment in protective cellular immunity, dapsone 

monotherapy proved surprisingly effective. Only 10% of patients developed resistance (19), and on 

cessation after 18 years of treatment only an additional 10% clinically relapsed (21). In the 1970s 

Freekson and Rosenfeld (3) in Malta treated leprosy patients, many treated previously with dapsone 

alone for many years, with a regimen of daily rifampin, prothionamide, dapsone, and isoniazid (not 

active against Mycobacterium leprae) for 2 years and found that patients were regularly cured. In 

1982 the World Health Organization (WHO) (22, 23) recommended another 2-year regimen of 

multidrug therapy (MDT) (monthly rifampin, 600 mg, plus clofazimine, 300 mg, and daily dapsone, 

100 mg, plus clofazimine, 50 mg). This regimen has been widely implemented, largely in patients 

previously treated with dapsone for prolonged periods, many of whom no longer harbored 

detectable M. leprae, and successfuly (20). However, the one clinical study in previously untreated 

lepromatous patients followed up for a sufficient time found an unacceptably high relapse rate of 20 

to 40%, depending on the initial bacterial burden (12). 

Having discovered that minocycline was bactericidal for M. leprae in mice (5) and in a clinical trial 

(7) and having conducted several studies of the three antimicrobials utilized by Ji et al. (16) in mice 

and patients, I was naturally interested in their findings and conclusions. Against an alternative view 

of the reliability of WHO MDT and the further desirability of a once-monthly supervised regimen, Ji 

et al. (16) report that in leprosy patients single doses of minocycline plus ofloxacin with and without 

rifampin are bactericidal and side effects are acceptable; thus, further clinical application of 

intermittent therapy (monthly) is indicated. I do not believe their results in fact merit these 

conclusions. 

In their introduction the authors state that further applications of regimens to be used with rifampin 

must prove themselves to be bactericidal. However, the single dose of minocycline plus ofloxacin 

used was entirely inactive in 3 of the 10 studied patients, and 68 and 69% bactericidal in two others, 

considered by the authors moderately bactericidal. However, the prototype bacteriostatic agent 

dapsone was previously found by me (4) and others (1), by using these techniques in mice, to be 72 

to 87% bactericidal, and thus, we would consider, 68 to 69% primarily bacteriostatic. In any case 

whether this regimen was bactericidal in 7 of 10 or 5 of 10 of patients, it certainly was not reliably so 

and also far less active in mice than daily dapsone-clofazimine, a combination which together with 

monthly rifampin appears inadequate to effect a cure in previously untreated lepromatous leprosy 

patients (12). Also, in the current studies, 4 of the 10 patients receiving rifampin, minocycline, and 

ofloxacin had gastrointestinal side effects; however mild, this is consequential and likely would 

preclude large-scale utilization of such therapy. Thus, I would conclude, single doses of ofloxacin 

plus minocycline both in mice and in a clinical trial are not reliably bactericidal, and side effects are 

significant. 

Monthly therapy for bacterial disease would be unique if found effective against leprosy. Contrary to 

the opinion of Ji et al. (16), the literature does not support a case for intermittent therapy for each of 

three agents utilized, either in experimental mouse infections or in leprosy patients, particularly the 

monthly regimen they envisage. 

(i) In an established mouse footpad infection monitored by subpassage of M. leprae in serial 10-fold 

dilutions in mice, Grosset et al. (10) found that daily treatment with rifampin was significantly more 

bactericidal than weekly, fortnightly, or monthly treatment. An analysis of relapse rates in 

lepromatous leprosy patients treated with finite chemotherapy regimens which included several 

different frequencies of rifampin administration found that equivalent amounts of rifampin daily 

resulted in significantly lower relapse rates than more intermittent rifampin therapy (18). 

(ii) My colleagues and I (9) found in mice that once-monthly minocycline was unreliable, and in 

clinical trials we (8) (contrary to the interpretation of Ji et al. [16]) and others (2) found single doses 

to be without activity. Though Ji et al. (16) are correct in saying that we (8) found that in six of eight 

patients single doses of minocycline resulted in a fall of the proportion of viable M. leprae, only in 

one patient was this statistically significant, and two of these six had a higher proportion of viable 

bacilli after an additional week of daily minocycline than was found prior to the beginning of 

treatment. Our data thus hardly support the suggestion that single doses of minocycline afford 

bacterial killing. 

(iii) Though pefloxacin in mice was active when administered three times weekly, it was inactive even 

twice weekly, as well weekly and monthly (17). A single dose of ofloxacin was entirely inactive in 

five of eight treated patients (11). Even the study of Ji et al. (16) itself provides evidence against 

monthly therapy: in mice, together with rifampin, daily dapsone plus clofazimine, which are each far 

less active than either minocycline and ofloxacin, were vastly superior to single doses of minocycline 

plus ofloxacin. Though I (6) have also suggested alternative methodological explanations, the Ji et al. 

(16) claim that their case for the bactericidal activity of a single monthly dose, not found by others, is 

a result of the more sensitive "titration" methods they used. However, several of these other studies 

(10, 11, 17) utilized just those methods, and as has been mentioned, titration results have the pitfall 

of labeling activity which is primarily bacteriostatic "bactericidal." In any event there appears to be a 

compelling case favoring daily, as opposed to intermittent, therapy of leprosy. 

Studies of potential synergism or anatagonism of combined treatment against M. leprae are difficult 

to perform and interpret, and the limited results available provide mixed findings for the agents 

proposed by Ji et al. (16). It is noteworthy, however, that the authors' published literature on mice 

(15) and leprosy patients (14) suggests that ofloxacin anatagonizes the killing provided by 

minocycline plus clarithromycin. 

Finally, Ji et al. (16) appear now to advocate a duration of monthly supervised rifampin, minocycline, 

and ofloxacin of 2 years, the major bactericidal activity being provided by rifampin. Such a regimen 

includes less rifampin than what was used by them previously in a 1-month regimen of daily rifampin 

plus ofloxacin, which resulted in a very high rate of clinical relapse (13). 

An effective regimen for the cure of lepromatous leprosy is still needed. Combinations of daily 

rifampin and newer bactericidal drugs (minocycline, clarithromycin, and fluorquinolones), each having 

been demonstrated to be more active than dapsone and clofazimine, appear to be reasonable 

treatments. 

    REFERENCES 

1.  Colston, M. J., G. R. F. Hilson, and D. K. Banerje. 1978. The `proportional bactercidal test': a 

method for assessing bactercidal activity of drugs against Mycobacterium leprae in mice. Lepr. Rev. 

49:7-15[Medline]. 

2.  Fajardo, T. T., Jr., L. G. Villahermosa, E. G. dela Cruz, R. M. Abalos, S. G. Franzblau, and P. 

Walsh. 1995. Minocycline in lepromatous leprosy. Int. J. Lepr. 63:8-17. 

3.  Freerksen, E., and M. Rosenfeld. 1977. Leprosy eradication project of Malta. Chemotherapy 

(Basel) 23:356-386[Medline]. 

4.  Gelber, R. H. 1986. The killing of Mycobacterium leprae in mice by various dietary 

concentrations of dapsone and rifampin. Lepr. Rev. 57:347-353[Medline]. 

5.  Gelber, R. H. 1987. Activity of minocycline in Mycobacterium leprae-infected mice. J. Infect. 

Dis. 156:236-239[Abstract]. 

6.  Gelber, R. H. 1997. Regimens to treat lepromatous leprosy. Antimicrob. Agents Chemother. 

41:1618-1620[Abstract]. 

7.  Gelber, R. H., K. Fukuda, S. Byrd, L. P. Murray, P. Siu, M. Tsang, and T. H. Rea. 1995. A 

chemical trial of minocycline in lepromatous leprosy. Br. Med. J. 304:91-92. 

8.  Gelber, R. H., L. P. Murray, P. Siu, M. Tsang, and T. H. Rea. 1994. Efficacy of minocycline in 

single dose and at 100 mg twice daily for lepromatous leprosy. Int. J. Lepr. 58:568-573[Abstract]. 

9.  Gelber, R. H., P. Siu, M. Tsang, P. Alley, and L. P. Murray. 1991. Effect of low-level and 

intermittent minocycline therapy on the growth of Mycobacterium leprae in mice. Antimicrob. Agents 

Chemother. 35:992-994[Abstract/Full Text]. 

10.  Grosset, J. H., and C. C. Guelpa-Lauras. 1987. Activity of rifampin in infections of normal mice 

with Mycobacterium leprae. Int. J. Lepr. 55:847-851. 

11.  Grosset, J. H., B. Ji, C. C. Guelpa-Lauras, E. G. Perani, and L. N'Deli. 1990. Clinical trial of 

pefloxacin and ofloxacin in the treatment of lepromatous leprosy. Int. J. Lepr. 58:281-295. 

12.  Jamet, P., B. Ji, and the Marchoux Chemotherapy Study Group. 1995. 

Relapse after long-term follow up of multibacillary patients treated by WHO multidrug regimen. Int. 

J. Lepr. 63:195-201[Medline]. 

13.  Ji, B., Jamet, S. Sow, E. G. Perani, I. Traore, and J. H. Grosset. 1997. High relapse rate 

among lepromatous leprosy patients treated with rifampin plus ofloxacin daily for 4 weeks. 

Antimicrob. Agents Chemother. 41:1953-1956[Abstract]. 

14.  Ji, B., P. Jamet, E. G. Perani, S. Sow, C. Lienhardt, C. Petinon, and J. H. Grosset. 1996. 

Bactericidal activity of single dose of clarithromycin plus minocycline, with or without ofloxacin, 

against Mycobacterium leprae in patients. Antimicrob. Agents Chemother. 

40:2137-2141[Abstract]. 

15.  Ji, B., E. G. Perani, C. Petinon, and J. H. Grosset. 1996. Bactericidal activities of combinations 

of new drugs against Mycobacterium leprae in nude mice. Antimicrob. Agents Chemother. 

40:393-399[Abstract]. 

16.  Ji, B., S. Sow, E. Perani, C. Lienhardt, V. Diderot, and J. Grosset. 1998. Bactericidal activity 

of a single-dose combination of ofloxacin plus minocycline, with or without rifampin, against 

Mycobacterium leprae in mice and in lepromatous patients. Antimicrob. Agents Chemother. 

42:1115-1120[Abstract/Full Text]. 

17.  Pattyn, S. R. 1987. Activity of ofloxacin and pefloxacin against Mycobacterium leprae in mice. 

Antimicrob. Agents Chemother. 31:671-672[Medline]. 

18.  Pattyn, S. R. 1993. Search for effective short-course regimens for the treatment of leprosy. Int. 

J. Lepr. 62:72-81. 

19.  Pearson, J. M. H., R. J. W. Rees, and M. F. R. Waters. 1975. Sulphone resistance in leprosy. 

A review of one hundered proven cases. Lancet ii:69-72. 

20.  Rajendran, V., C. Vellut, and C. Pushpadass. 1993. Profile of relapse cases in field trial of 

combined therapy in multibacillary leprosy. Int. J. Lepr. 61(Suppl.):4A. 

21.  Waters, M. F. R., R. J. W. Rees, A. B. G. Laing, K. F. Khoo, T. W. Meade, W. Parikshah, 

and W. R. S. North. 1986. The rate of relapse in lepromatous leprosy following completion of 

twenty years of supervised sulphone therapy. Lepr. Rev. 57:101-109. 

22.  World Health Organization. 1994. Chemotherapy of leprosy. Technical report series no. 847. 

World Health Organization, Geneva, Switzerland. 

23.  World Health Organization Study Group. 1982. Chemotherapy of leprosy for control 

programmes. Technical report series, no. 675. World Health Organization, Geneva, Switzerland. 

     Robert H. Gelber 

Departments of Medicine and Dermatology/ University of California/ San Francisco, California 

 

Dr. Gelber's letter covered many important aspects of chemotherapy of leprosy, which would be 

impossible to address in a single reply. However, his view on the seriousness of dapsone-resistant 

leprosy and the efficacy and achievement of World Health Organization (WHO)-recommended 

multidrug therapy (MDT) for leprosy are beyond the scope of our articles (5, 6, 8, 9) and have been 

clearly addressed in the report of the latest WHO Expert Committee on Leprosy (14); in addition, 

some of the issues, such as a detectable bactericidal effect of single-dose minocycline (MINO) or 

ofloxacin (OFLO) treatment had been raised in his previous letter to the editor (3) and responded to 

by us (7). Therefore, we will focus only on those of his comments that were not covered by the 

previous correspondence. 

In one of our pilot trials, 20 lepromatous patients were randomly allocated to two groups (10 each) 

and treated with a single dose of either 600 mg of rifampin (RMP) plus 400 mg of OFLO and 100 

mg of MINO or 400 mg of OFLO plus 100 mg of MINO (9). Because the treatment was inactive 

in three patients receiving OFLO-MINO and mild gastrointestinal adverse events were observed in 

two (not four, as wrongly quoted in the letter) patients of this group, Dr. Gelber concludes that a 

single dose of OFLO-MINO is not reliably bactericidal and the side effects are significant. We 

disagree with the conclusion based on the following reasons. (i) By definition (11), any antibacterial 

effect detected by the "proportional bactericidal test" (1) should be bactericidal, and there is no 

reason to consider the 68 to 69% killing of viable organisms as bacteriostatic. (ii) Bactericidal effect 

was observed in a great majority (7 of 10) of patients treated with a single dose of OFLO-MINO, 

and even with RMP, by far the most bactericidal drug against Mycobacterium leprae (5), 

single-dose treatment may not display detectable bactericidal effect in all patients; e.g., no 

bactericidal effect was observed in 1 of 10 patients receiving a single dose of RMP-OFLO-MINO 

(9). Finally, (iii) the adverse events in a clinical trial are not necessarily equivalent to the side effects 

caused by actual treatment, particularly when the events are mild and transitory (without significant 

findings on physical examination). Whether such degree of mild adverse events is significant is a 

matter of judgement. Nevertheless, more and more patients are treated with a single dose of 

RMP-OFLO-MINO in the field with excellent tolerance (12), indicating that Dr. Gelber's prediction 

precluding large-scale utilization of such therapy was wrong. 

Besides OFLO and MINO, Dr. Gelber also challenges the justification for treating leprosy with 

monthly administration of RMP, despite the fact that it is the backbone of the MDT regimens for 

both paucibacillary and multibacillary leprosy since 1981. More than 8 million leprosy patients have 

been cured by the beginning of 1997 with a very low relapse rate (14). Numerous publications, 

including one by Dr. Gelber himself (2), have indicated that RMP displays very powerful and rapid 

bactericidal activity against M. leprae in experimental animals and in patients. Immediately after RMP 

treatment is begun, the great majority of viable M. leprae organisms are killed. No one has been able 

to convincingly demonstrate that after a few doses of RMP-containing regimens, daily administration 

is more bactericidal than monthly treatment. On the contrary, we have observed that, in nude mice 

with established M. leprae infection (5), monthly administration of RMP-containing regimens always 

produced significantly greater bactericidal activities than the same number of doses of daily 

treatment. To prove that daily treatment with RMP was significantly more bactericidal than weekly, 

fortnightly, or monthly treatment, Dr. Gelber quotes one of our earlier results for immunocompetent 

mice with established M. leprae infection (4). However, we have already pointed out that because of 

the rapid spontaneous killing of M. leprae in untreated controls, established infection in 

immunocompetent mice is not a suitable system for comparing the activities of different drug 

regimens, and the results must be interpreted with caution (4). Furthermore, the duration of treatment 

in the quoted experiments was only 8 to 12 weeks, and the differences in bactericidal effects 

between daily and monthly administrations were marginal though statistically significant; based on our 

experience with infection in nude mice (5), it is likely that the differences may not exist after a longer 

duration, e.g., 6 months, of treatment. To support his argument, Dr. Gelber also cites studies on 

relapse rates for lepromatous patients treated with various RMP-containing regimens, which 

concluded that equivalent amounts of daily RMP resulted in significantly lower relapse rates than 

those in patients treated with intermittent RMP (10). Nonetheless, one has to be extremely cautious 

in drawing conclusions from such an analysis, because the pretreatment characteristics of the patients 

in the different groups may not be comparable. Association between relapse rate and frequency of 

RMP administration was not confirmed for patients treated with the same regimens by an Institut 

Marchoux study after a longer follow-up period (13). 

Finally, we would like to point out that, based on the considerations of cost-effectiveness and 

operational feasibility, the main objective of our research activities is to develop a minimal but not 

suboptimal regimen(s) that is effective, simple, and affordable. To eradicate leprosy, such minimal 

regimens are badly needed in many countries of endemicity, particularly in areas where the health 

infrastructure is poor and/or accessibility is difficult. On the other hand, it is understandable that the 

regimen for the treatment of a handful leprosy patients in developed countries may be far more 

sophisticated, as long as it can be justified by the physicians, tolerable by the patients, and affordable 

by the community. 

    REFERENCES 

1.  Colston, M. J., G. R. F. Hilson, and D. K. Banerjee. 1978. The "proportional bactericidal test," 

a method for assessing bactericidal activity of drugs against Mycobacterium leprae in mice. Lepr. 

Rev. 49:7-15[Medline]. 

2.  Gelber, R. H., and L. Levy. 1987. Detection of persisting Mycobacterium leprae by inoculation 

of the neonatally thymectomized rat. Int. J. Lepr. 55:872-878. 

3.  Gelber, R. H. 1997. Regimens to treat lepromatous leprosy. Antimicrob. Agents Chemother. 

41:1618-1619[Medline]. (Letter to the editor.) 

4.  Grosset, J. H., and C. C. Guelpa-Lauras. 1987. Activity of rifampin in infections of normal mice 

with Mycobacterium leprae. Int. J. Lepr. 55:847-851[Medline]. 

5.  Ji, B., E. G. Perani, C. Petinom, and J. H. Grosset. 1996. Bactericidal activities of combinations 

of new drugs against Mycobacterium leprae in nude mice. Antimicrob. Agents Chemother. 

40:393-399[Abstract]. 

6.  Ji, B., P. Jamet, E. G. Perani, S. Sow, C. Lienhardt, C. Petinon, and J. H. Grosset. 1996. 

Bactericidal activity of single dose of clarithromycin plus minocycline, with or without ofloxacin, 

against Mycobacterium leprae in patients. Antimicrob. Agents Chemother. 

40:2137-2141[Abstract]. 

7.  Ji, B., E. G. Perani, C. Petinon, J. H. Grosset, P. Jamet, S. Sow, and C. Lienhardt. 1997. 

Regimens to treat lepromatous leprosy. Antimicrob. Agents Chemother. 41:1619-1620. (Letter to 

the editor.) 

8.  Ji, B., P. Jamet, S. Sow, E. G. Perani, I. Traore, and J. H. Grosset. 1997. High relapse rate 

among lepromatous leprosy patients treated with rifampin plus ofloxacin daily for 4 weeks. 

Antimicrob. Agents Chemother. 41:1953-1956[Abstract]. 

9.  Ji, B., S. Sow, E. Perani, C. Lienhardt, V. Diderot, and J. Grosset. 1998. Bactericidal activity of 

a single dose combination of ofloxacin plus minocycline, with or without rifampin, against 

Mycobacterium leprae in mice and in lepromatous patients. Antimicrob. Agents Chemother. 

42:1115-1120[Abstract/Full Text]. 

10.  Pattyn, S. R. 1993. Search for effective short-course regimens for the treatment of leprosy. Int. 

J. Lepr. 61:76-81. 

11.  Shepard, C. C. 1982. Statistical analysis of results obtained by two methods for testing drug 

activity against Mycobacterium leprae. Int. J. Lepr. 50:96-101. 

12.  Single-Lesion Multicentre Trial Group. 1997. Efficacy of single dose multidrug therapy for the 

treatment of single-lesion paucibacillary leprosy. Indian J. Lepr. 69:121-129[Medline]. 

13.  Sow, S., B. Ji, and Marchoux Chemotherapy Study Group. 1998. Intervals between stopping 

rifampin-containing regimens and occurrence of relapse in multibacillary leprosy, abstr. CH19. In 

Program and abstracts of the 15th International Leprosy Congress, Beijing, China, 7 to 12 

September 1998. 

14.  WHO Expert Committee on Leprosy. 1998. Seventh report. WHO Technical Series, no. 874. 

World Health Organization, Geneva, Switzerland. 

     Baohong Ji 

Jacques H. Grosset 

Faculté de Médecine Pitié-Salpêtrière/ Paris/ France 

 

============================================================= 

7.) Rifampicin/minocycline and ofloxacin (ROM) for single lesions--what is the evidence? 

============================================================= 

Lepr Rev 1997 Dec;68(4):299-300 Related Articles, Books, LinkOut 

Earlier this year the results of a double-blind randomized controlled trial comparing a potential new 

treatment (single dose rifampicin/ofloxacin and minocycline (ROM)) for monolesion paucibacillary 

leprosy with the current 6-month treatment with rifampicin and dapsone (WHO-PB-MDT) were 

published. The executive report of the 7th WHO Expert Committee on Leprosy (Geneva, 26 May-3 

June 1997) noted that the Committee considered the single-dose ROM an acceptable and 

cost-effective regimen for the treatment of single skin lesion PB leprosy. The paper and report have 

been highly influential and already strategic planners in several countries, notably India and Brazil, 

have introduced ROM treatment for single-lesion disease into their national programmes. We are 

reprinting this important paper in this issue of Leprosy Review (p. 299-300) by kind permission of 

the Editor of the Indian Journal of Leprosy since we feel that readers may wish to study the original 

publication for themselves. 

The introduction of single-dose treatment for a subset of leprosy patients is obviously attractive from 

an operational standpoint and will make a significant impact in reducing prevalence in some areas. 

However it is also fraught with dangers, and hence the evidence for its effectiveness should be 

considered in some depth. 

The trial involved nine different centres, each recruiting between 103 and 400 patients over a 

10-month period to give a total of 1483 patients. Follow-up over an 18-month period was good 

with a 93% completion rate. 

There are a number of difficulties in interpreting the data. The first of these relates to the diagnosis of 

leprosy in these patients. It is not clear how lesions were tested for anaesthesia nor which modalities 

of sensation were examined. Much of the initial testing (skin biopsy, histamine testing, lepromin 

testing and even detailed neurological examination) was optional. Hence it is not possible to know 

how many patients in the trial had definite evidence of leprosy. The system used in the Karonga trial, 

of grading patients on a scale of diagnostic certainty for leprosy is a useful way of addressing the 

problem of diagnosis.1 From an operational point of view it would be helpful to know how many 

patients were evaluated and prepared for entry to the trial but then proved to be slit-skin smear 

positive and so ineligible for treatment with ROM. There is no information on how many patients had 

skin biopsies with microscopic evidence of leprosy. 

Children above the age of 5 were eligible for the trial but no details are given of numbers of children 

treated nor the drug doses used. The side-effects observed in the trial patients are briefly discussed. 

No mention is made of monitoring for specific side-effects and no details are given of potential 

side-effects such as tooth discoloration in children given minocycline. 

The major outcome measure was derived from a scoring system based on five different clinical 

observations of the lesions. No details of how this scale was constructed nor what weights were 

given to the five components nor how scoring was standardized between centres are provided. This 

makes interpretation of the results difficult. Of the 1381 patients who completed the trial only 12 

patients failed to improve, and of these 2 deteriorated. The investigators set an improvement of 13 

points in the clinical score as their definition of marked clinical improvement; their other outcome 

measure was complete cure. Patients treated with the conventional WHO-PB-MDT regimen 

showed statistically significantly better results on both these measures when compared with the 

patients treated with the ROM regimen. The significance level for the difference in complete cure 

rates is incorrectly given in Table V as P = 0 04, the correct figure is actually even more significant at 

P = 0 004 as given in the text. It is not possible from the data given to discern which modalities 

improved most. A more detailed analysis of the data such as an analysis of covariance would have 

allowed examination of the effect of age, sex or type of improvement on response to treatment. This 

would be valuable in determining which patients would benefit most from treatment with ROM. 

These details are important because this trial was designed to be a gold standard trial of ROM 

showing its medical effectiveness, not an operational trial showing that it is an easy treatment to 

administer. 

The follow-up period of 18 months for ROM treated patients and 12 months for WHOPB-MDT 

treated patients is too short to detect relapses with a relapse rate for paucibacillary disease of 1% 

per year. It is to be hoped that the patients will continue under active surveillance so that this 

important figure can be determined. 

ROM is undoubtedly an attractive treatment. It is operationally easy to administer and is probably 

suitable for some patients. If it is to be incorporated into treatment schedules then it is important that 

workers follow good practice guidelines. It is vital that all patients should be examined carefully to 

ensure that there really is only a single lesion. Women may be reluctant to be examined fully and if 

so, should not be prescribed ROM. It is also vital that a careful neurological examination is done to 

ensure that no nerve thickening or impairment of motor or sensory function is present. There was no 

statistical difference in the number of reactions or neuritis in each of the treatment groups. This serves 

as a reminder that even patients with monolesions can suffer reactions and so need to be kept under 

follow-up even after single dose treatment when it will be very tempting to have less stringent 

follow-up. 

In conclusion this trial as published leaves many doubts: how many of the patients treated in this trial 

actually had leprosy, which outcome measure improved, did sensation in the lesions improve, what 

side-effects were monitored? The analysis reveals few details but the two measures reported 

showed significant superiority for the existing WHO-PB-MDT regimen. Thus it is inaccurate to claim 

on the basis of the published data, as the authors did in their abstract that ROM is 'almost as 

effective as WHO-PB-MDT'. The implementation of single dose ROM should be undertaken with 

care; it is likely to be of value for some patients, but the attraction of operational expediency could 

easily result in misuse. 

DIANA N. J. LOCKWOOD 

============================================================= 

8.) What are the new antileprosy drugs - ROM - now available for the treatment of leprosy? 

============================================================= 

Recently three more drugs have shown bactericidal activity against M. leprae. These are 

ofloxacin-a fluoroquinolone, 

minocycline-a tetracycline 

clarithromycin-a macrolide 

Several experimental and clinical studies have demonstrated that these drugs either alone or in 

combination with other antileprosy drugs have significant bactericidal activity. 

WHO started supplying quantities of special ROM blister packs in late 1997 to India, Bangladesh, 

Nepal and Brazil for the treatment of single lesion PB leprosy. 

============================================================ 

9.)What are the types of leprosy that can be treated by ROM ? 

============================================================ 

The 7th WHO Expert Committee on Leprosy recommended the use of a combination of rifampicin 

600 mg, ofloxacin 400 mg and minocycline 100 mg (ROM) for the treatment of two categories of 

leprosy patients: 

patients presenting with single skin lesion paucibacillary leprosy can be treated with only one dose of 

ROM 

multibacillary leprosy patients who do not accept clofazimine can be treated with monthly 

administration of 24 doses of ROM. 

============================================================= 

10.)What is the reason for introducing single dose treatment for paucibacillary leprosy presenting with a single skin lesion? 

============================================================= 

Most of the paucibacillary leprosy cases presenting with only one skin lesion have a high tendency to 

heal without any specific antileprosy treatment. However, today it is not possible to identify those 

who will develop progressive disease and all such cases need to be treated. In some programmes 

(especially vertical programmes which have a strong active case finding component) such patients 

constitute a significant proportion of newly detected cases. The six-month MDT regimen puts a 

heavy burden both on patients and the health services as a large proportion of such patients are 

children and the compliance to treatment is usually less than satisfactory. 

============================================================= 

11.) What is the basis for the recommended alternative regimen for the treatment of paucibacillary leprosy presenting with a single skin lesion? 

============================================================= 

The discovery of effectiveness of ofloxacin and minocycline in the treatment of leprosy encouraged 

WHO to assess the efficacy of single dose treatment for this group of patients. A large multicentre, 

double-blind study was organized. The results demonstrated that single dose of a combination of 

rifampicin 600 mg, ofloxacin 400 mg and minocycline 100 mg (ROM) is as effective as the standard 

6-month WHO MDT for paucibacillary leprosy. 

============================================================= 

12.)Does WHO recommend that all programmes should treat single lesion paucibacillary leprosy cases with one dose of ROM? 

============================================================= 

No, as such patients are detected in large numbers mainly by vertical programmes having a strong 

active case finding component. The introduction of this regimen in programmes detecting very few 

single-lesion leprosy cases will only add to the logistic problems of catering to a third regimen and 

also complicate the information system. Such programmes should continue to treat these cases with 

the standard WHO MDT for paucibacillary leprosy for six months. Therefore, WHO recommends 

that this regimen may be used only by programmes detecting a large number of (1 000 or more) such 

cases annually. 

 

============================================================= 

13.) Efficacy of single dose multidrug therapy for the treatment of single-lesion paucibacillary leprosy. Single-lesion Multicentre Trial Group. 

============================================================= 

Source 

Indian J Lepr, 69(2):121-9 1997 Apr-Jun 

Abstract 

A multicentre double-blind controlled clinical trial was carried out to 

compare the efficacy of a combination of rifampicin 600 mg plus ofloxacin 

400 mg plus minocycline 100 mg (ROM) administered as single dose with that 

of the standard six-month WHO/MDT/PB regimen. The subjects included 1483 

cases with one skin lesion who were previously untreated, were 

smear-negative, and had no evidence of peripheral nerve trunk involvement, 

and they were randomly divided into study and control groups. The total 

duration of the study from the day of intake was 18 months, and 1381 

patients completed study. Only 12 patients were categorized as treatment 

failure and no difference was observed between the two regimens. Occurrence 

of mild side-effects and leprosy reactions were minimal (less than 1%) in 

both groups. This study showed that ROM is almost as effective as the 

standard WHO/MDT/PB in the treatment of single lesion PB leprosy. 

============================================================= 

14.) Minocycline in lepromatous leprosy. 

============================================================= 

Author 

Fajardo TT Jr; Villahermosa LG; dela Cruz EC; Abalos RM; Franzblau SG; 

Walsh GP 

Address 

Clinical Research Branch, Leonard Wood Memorial Center, Cebu City, The 

Philippines. 

Source 

Int J Lepr Other Mycobact Dis, 63(1):8-17 1995 Mar 

Abstract 

Twelve patients were treated with three dose levels of minocycline for 30 

days, primarily to detect the dose-related effects on Mycobacterium leprae 

viability, followed by another 5 months of daily minocycline for overall 

efficacy and persistence of clinical and antibacterial effects. 

Subsequently, the patients were given standard WHO/MDT chemotherapy for 

multibacillary leprosy. Clinical improvement was recognizable during the 

first month, occurring much earlier among those on minocycline 200 mg daily 

than those who received minocycline 100 mg daily. A similar change also was 

observed in one patient 11 days after three daily doses of 100 mg of 

minocycline. At the end of 6 months, all patients were clinically improved 

with a slight reduction in the average bacterial index (BI) and logarithmic 

index of bacilli in biopsy (LIB). The effects of minocycline on viability 

by mouse foot pad inoculation and palmitic acid oxidation assays were noted 

beginning at 10 to 14 days of daily dosing and becoming more definite after 

30 days of treatment. Both tests correlated fairly well. Doses of 200 mg 

daily did not appear to be more efficient than minocycline 100 daily. 

Phenolic glycolipid-I (PGL-I) antigen determinations done on some patients 

during the first month remained positive and did not correlate with changes 

in viability results. At the end of 6 months, after 5 months of 100 mg of 

minocycline monotherapy, no viable organisms could be demonstrated by mouse 

foot pad inoculation and palmitic acid oxidation assays; assays for PGL-I 

antigen were all negative.(ABSTRACT TRUNCATED AT 250 WORDS) 

============================================================= 

15.) Efficacy of minocycline in single dose and at 100 mg twice daily for lepromatous leprosy. 

============================================================= 

Int J Lepr Other Mycobact Dis  (United States), Dec 1994, 62(4) p568-73 

AUTHOR(S):  Gelber RH; Murray LP; Siu P; Tsang M; Rea TH 

AUTHOR'S ADDRESS:  San Francisco Regional Hansen's Disease Program, CA 94115. 

PUBLICATION TYPE:  CLINICAL TRIAL; JOURNAL ARTICLE 

ABSTRACT:  A clinical trial of minocycline in a total of 10 patients with 

previously untreated lepromatous leprosy was conducted in order to evaluate 

the efficacy of a single, initial, 200-mg dose and 100 mg twice daily of 

minocycline for a total duration of up to 3 months. Patients improved 

remarkably quickly. Although single-dose therapy did not result in a 

significant killing of Mycobacterium leprae, viable M. leprae were cleared 

from the dermis regularly by 3 months of twice-daily therapy, a rate 

similar to that achieved by minocycline 100 mg once daily. Because more 

side effects were noted herein than previously with 100 mg daily, we 

recommend that minocycline, when applied, be administered at 100 mg daily 

to leprosy patients. 

============================================================= 

16.) Field trial on efficacy of supervised monthly dose of 600 mg rifampin, 400 mg ofloxacin and 100 mg minocycline for the treatment of leprosy; first results. 

============================================================= 

Author 

Mane I; Cartel JL; Grosset JH 

Address 

Institut de Leprologie Appliquee, Dakar CD Annexe, Senegal. 

Source 

Int J Lepr Other Mycobact Dis, 65(2):224-9 1997 Jun 

Abstract 

In 1995, a field trial was implemented in Senegal in order to evaluate the 

efficacy of a regimen based on the monthly supervised intake of rifampin 

600 mg, ofloxacin 400 mg and minocycline 100 mg to treat leprosy. During 

the first year of the trial, 220 patients with active leprosy (newly 

detected or relapsing after dapsone monotherapy) were recruited: 102 

paucibacillary (PB) (60 males and 42 females) and 118 multibacillary (MB) 

(71 males and 47 females). All of them accepted the new treatment (none 

requested to be preferably put under standard WHO/MDT), no clinical sign 

which could be considered as a toxic effect of the drug was noted, and none 

of the patients refused to continue treatment because of any clinical 

trouble. The compliance was excellent: the 113 patients (PB and MB) 

detected during the first 6 months of the trial have taken six monthly 

doses in 6 months, as planned. The rate of clearance and the progressive 

decrease of cutaneous lesions was satisfactory. Although it is too soon to 

give comprehensive results, it should be noted that no treatment failure 

was observed in the 56 PB patients who have completed treatment and have 

been followed up for 6 months. The long-term efficacy of the new regimen is 

to be evaluated on the rate of relapse during the years following the 

cessation of treatment. If that relapse rate is acceptable (similar to that 

observed in patients after treatment with current standard WHO/ MDT), the 

new regimen could be a solution to treat, for instance, patients very 

irregular and/or living in remote or inaccessible areas since no selection 

of rifampin-resistant Mycobacterium leprae should be possible (a monthly 

dose of ofloxacin and minocycline being as effective as a dose of dapsone 

and clofazimine taken daily for 1 month). Nevertheless, until longer term 

results of this and other trials become available, there is no 

justification for any change in the treatment strategy, and all leprosy 

patients should be put under standard WHO/MDT. 

============================================================= 

17.) Bactericidal activity of a single-dose combination of ofloxacin plus minocycline, with or without rifampin, against Mycobacterium leprae in mice and in lepromatous patients. 

============================================================= 

Author 

Ji B; Sow S; Perani E; Lienhardt C; Diderot V; Grosset J 

Address 

Facult´e de M´edecine Piti´e-Salp^etri`ere, Paris, France. 

bacterio@biomath.jussieu.fr 

Source 

Antimicrob Agents Chemother, 42(5):1115-20 1998 May 

Abstract 

To develop a fully supervisable, monthly administered regimen for treatment 

of leprosy, the bactericidal effect of a single-dose combination of 

ofloxacin (OFLO) and minocycline (MINO), with or without rifampin (RMP), 

against Mycobacterium leprae was studied in the mouse footpad system and in 

previously untreated lepromatous leprosy patients. Bactericidal activity 

was measured by the proportional bactericidal method. In mouse experiments, 

the activity of a single dose of the combination OFLO-MINO was dosage 

related; the higher dosage of the combination displayed bactericidal 

activity which was significantly inferior to that of a single dose of RMP, 

whereas the lower dosage did not exhibit a bactericidal effect. In the 

clinical trial, 20 patients with previously untreated lepromatous leprosy 

were treated with a single dose consisting of either 600 mg of RMP plus 400 

mg of OFLO and 100 mg of MINO or 400 mg of OFLO plus 100 mg of MINO. The 

OFLO-MINO combination exhibited definite bactericidal activity in 7 of 10 

patients but was less bactericidal than the RMP-OFLO-MINO combination. Both 

combinations were well tolerated. Because of these promising results, a 

test of the efficacy of multiple doses of ROM in a larger clinical trial 

appears justified. 

============================================================= 

18.) Bactericidal activity of single dose of clarithromycin plus minocycline, with or without ofloxacin, against Mycobacterium leprae in patients. 

============================================================= 

Author 

Ji B; Jamet P; Perani EG; Sow S; Lienhardt C; Petinon C; Grosset JH 

Address 

Facult´e de M´edecine Piti´e-Salp^etri`ere, Paris, France. 

Source 

Antimicrob Agents Chemother, 40(9):2137-41 1996 Sep 

Abstract 

Fifty patients with newly diagnosed lepromatous leprosy were allocated 

randomly to one of five groups and treated with either a month-long 

standard regimen of multidrug therapy (MDT) for multibacillary leprosy, a 

single dose of 600 mg of rifampin, a month-long regimen with the dapsone 

(DDS) and clofazimine (CLO) components of the standard MDT, or a single 

dose of 2,000 mg of clarithromycin (CLARI) plus 200 mg of minocycline 

(MINO), with or without the addition of 800 mg of ofloxacin (OFLO). At the 

end of 1 month, clinical improvement accompanied by significant decreases 

of morphological indexes in skin smears was observed in about half of the 

patients of each group. A significant bactericidal effect was demonstrated 

in the great majority of patients in all five groups by inoculating the 

footpads of mice with organisms recovered from biopsy samples obtained 

before and after treatment. Rifampin proved to be a bactericidal drug 

against Mycobacterium leprae more potent than any combination of the other 

drugs. A single dose of CLARI-MINO, with or without OFLO, displayed a 

degree of bactericidal activity similar to that of a regimen daily of doses 

of DDS-CLO for 1 month, suggesting that it may be possible to replace the 

DDS and CLO components of the MDT with a monthly dose of CLARI-MINO, with 

or without OFLO. However, gastrointestinal adverse events were quite 

frequent among patients treated with CLARI-MINO, with or without OFLO, and 

may be attributed to the higher dosage of CLARI or MINO or to the 

combination of CLARI-MINO plus OFLO. In future trials, therefore, we 

propose to reduce the dosages of the drugs to 1,000 mg of CLARI, 100 mg of 

MINO, and 400 mg of OFLO. 

========================================================================= 

19.) WHO Expert Committee on Leprosy. 

========================================================================= 

Source: World Health Organ Tech Rep Ser, 874():1-43 1998 

Abstract 

Considerable progress has been made in the fight against leprosy during the 

past 10-15 years, following the introduction of multidrug therapy (MDT) 

regimens and the establishment of the goal of eliminating leprosy as a 

public health problem by the year 2000. Current estimates indicate that 

there are about 1.15 million cases of leprosy in the world, compared with 

10-12 million cases in the mid-1980s. This report presents the conclusions 

of a WHO Expert Committee convened to review the global leprosy situation 

and the technology available for eliminating the disease, to identify the 

remaining obstacles to reaching the goal of eliminating leprosy as a public 

health problem, and to make appropriate recommendations for the future on 

technical and operational matters. The current status of leprosy 

elimination is discussed, and the various antileprosy drugs are reviewed, 

including the most recently available drugs. On the basis of field trials 

and clinical studies, the Committee concludes that a single dose of a 

combination of rifampicin, ofloxacin and minocycline is an acceptable and 

cost-effective alternative regimen for the treatment of single-lesion 

paucibacillary leprosy, and that the duration of the current MDT regimen 

for multibacillary leprosy could possibly be shortened to 12 months. The 

Committee points out the need for improved management of reactions and 

neuritis and prevention of leprosy-related disabilities and impairments, 

and recommends that antileprosy activities should become an integral part 

of general health services and should involve communities to the fullest 

extent possible. 

========================================================================= 

20.) Experimental evaluation of possible new short-term drug regimens for  treatment of multibacillary leprosy. 

========================================================================= 

Author 

Banerjee DK; McDermott-Lancaster RD; McKenzie S 

Address 

Department of Medical Microbiology, St George's Hospital Medical School, 

London, United Kingdom. banerjee@sghms.ac.uk. 

Source 

Antimicrob Agents Chemother, 41(2):326-30 1997 Feb 

Abstract 

Groups of nude mice, with both hind footpads infected with 10(8) 

Mycobacterium leprae organisms, were treated with 4-week courses of 

different drug combinations. The effect treatment on each group was 

evaluated by subinoculating footpad homogenates from the treated mice into 

groups of normal and nude mice for subsequent regrowth, assessed 1 year 

later. A combination of rifampin (RMP) with clarithromycin (CLARI), 

minocycline (MINO), and ofloxacin (OFLO) resulted in the complete killing 

of M. leprae after 3 weeks of treatment. A combination of sparfloxacin 

(SPAR) and RMP also resulted in a similar bactericidal effect after 3 weeks 

of treatment. Other drug combinations showed variable effects. Very little 

or no effect was observed with any regimen if the treatment was given for 

less than 2 weeks. World Health Organization (WHO) multidrug therapy (MDT) 

given for 8 weeks was as effective as the two combinations described above. 

The results suggest that multidrug combinations consisting of RMP-OFLO (or 

SPAR)-CLARI (and/or MINO) are as effective as the WHO MDT for the treatment 

of experimental leprosy. Moreover, they imply that these combinations, 

which were found to be active in a 4-week experimental treatment protocol, 

could be administered as treatment to patients for a period of time shorter 

than the present 2-year regimen without a loss of effectiveness. 

========================================================================= 

21.) Powerful bactericidal activities of clarithromycin and minocycline  against Mycobacterium leprae in lepromatous leprosy. 

========================================================================= 

ARTICLE SOURCE:  J Infect Dis  (United States), Jul 1993, 168(1) p188-90 

AUTHOR(S):  Ji B; Jamet P; Perani EG; Bobin P; Grosset JH 

AUTHOR'S ADDRESS:  Faculte de Medecine Pitie-Salpetriere, Paris, France. 

PUBLICATION TYPE:  CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED 

CONTROLLED 

TRIAL 

ABSTRACT:  Thirty-six patients with newly diagnosed lepromatous leprosy 

were allocated randomly to three groups and treated for 56 days with 

minocycline (100 mg daily), clarithromycin (500 mg daily), or 

clarithromycin (500 mg) plus minocycline (100 mg daily). All groups had 

rapid and remarkable clinical improvement and significant decline of the 

bacterial and morphologic indices in skin smears during treatment. More 

than 99% and 99.9% of the viable Mycobacterium leprae had been killed by 28 

and 56 days of treatment, respectively, as measured by inoculation of 

organisms recovered from skin samples, taken before and during treatment, 

into the footpads of immunocompetent and nude mice. Clinical improvement 

and bactericidal activity did not differ significantly among the three 

groups. Adverse reactions were rare and mild, and no laboratory abnormality 

was detected during the trial. Both clarithromycin and minocycline 

displayed powerful bactericidal activities against M. leprae in leprosy 

patients and may be considered important components of new multidrug 

regimens for the treatment of multibacillary leprosy. 

============================================================ 

22.) Leprosy resistant to multi-drug-therapy (MDT) successfully treated  with ampicillin-sulbactam combination--(a case report). 

============================================================ 

  Mehta VR 

  L.T.M.M. College, Bombay. 

  Indian J Med Sci  (INDIA)  Nov 1996  50 (11) p305-7  ISSN: 0019-5359 

  Language: ENGLISH 

Document Type:   JOURNAL ARTICLE 

  Journal Announcement: 9707 

  Subfile: INDEX MEDICUS 

  A 50 year male developed a discoid lesion of leprosy on the face. 

Inspite of Dapsone 100 mg/day and Rifampicin 600 mgm per day the disease 

spread to both sides of the face and forehead.  It became worse with 

Prednisolone and Clofazimine.  It cleared completely when Sultamicillin was 

added to the latter.  This seems to be the first patient of leprosy to be 

treated with this combination and reported. 

========================================================================= 

23.) Differential protective effect of bacillus calmette-guerin vaccine  against multibacillary and paucibacillary leprosy in nagpur, india. 

========================================================================= 

Public Health 1999 Nov;113(6):311-3 

Kulkarni HR, Zodpey SP 

Department of Preventive and Social Medicine and Clinical Epidemiology 

Unit, Government Medical College, Nagpur, India. 

For this paper we conducted a secondary data analysis to test the 

hypothesis that a linear trend exists in the protective effect of bacillus 

Calmette-Guerin (BCG) vaccine against types of leprosy. We used data from 

two previous case-control studies to perform an unmatched test for linear 

trend. We observed that both the studies revealed a significant linear 

trend (P<0.00001). One study that estimated an insignificant protective 

effect of BCG against paucibacillary leprosy showed a significant departure 

from linearity. We conclude that, the protective effect of BCG vaccination 

is differential across severity of leprosy as it brings about a shift in 

the immune response to a higher level of cell mediated immunity. We 

recommend that future studies dealing with the protective effect of BCG 

against leprosy should also conduct an analysis for trend. 

========================================================================= 

24.) Protective effect of Bacillus Calmette Guerin (BCG) against leprosy: a population-based case-control study in Nagpur, India. 

========================================================================= 

Lepr Rev 1999 Sep;70(3):287-94 

Zodpey SP, Bansod BS, Shrikhande SN, Maldhure BR, Kulkarni SW 

Clinical Epidemiology Unit, Govt Medical College, Nagpur, MS, India. 

A population-based pair-matched case-control study was carried out in an 

urban community, Nagpur, India, to estimate the effectiveness of BCG 

vaccination in the prevention of leprosy. The study included 212 cases of 

leprosy (diagnosed by WHO criteria), below the age of 35 years, detected 

during a leprosy survey conducted by the Government of Maharashtra over a 

population of 20,03,325. Each case was pair-matched with one neighbourhood 

control for age, sex and socioeconomic status. A significant protective 

association between BCG and leprosy was observed (OR = 0.40, 95% CI = 

0.23-0.68). The overall vaccine effectiveness (VE) was estimated to be 60% 

(95% CI = 32-77). The BCG effectiveness against multi-bacillary and 

paucibacillary leprosy was 72% (95% CI = 35-88) and 45% (95% CI = 3-73), 

respectively. Vaccine was more effective during the first decade of life, 

among females and in lower socioeconomic strata. The overall prevented 

fraction was 39% (95% CI = 16-58). In conclusion, this first ever 

population-based case control study performed in Central India, identified 

a beneficial role of BCG vaccination in prevention of leprosy in study 

population. 

========================================================================= 

25.) Patient contact is the major determinant in incident leprosy:  implications for future control. 

========================================================================= 

Int J Lepr Other Mycobact Dis 1999 Jun;67(2):119-28 

van Beers SM, Hatta M, Klatser PR 

Department of Biomedical Research, Royal Tropical Institute, Amsterdam, The 

Netherlands. 

Notwithstanding the elimination efforts, leprosy control programs face the 

problem of many leprosy patients remaining undetected. Leprosy control 

focuses on early diagnosis through screening of household contacts, 

although this high-risk group generates only a small proportion of all 

incident cases. For the remaining incident cases, leprosy control programs 

have to rely on self-reporting of patients. We explored the extent to which 

other contact groups contribute to incident leprosy. We examined 

retrospectively incident leprosy over 25 years in a high-endemic village of 

2283 inhabitants in Sulawesi, Indonesia, by systematically reviewing data 

obtained from the local program and actively gathering data through 

interviews and a house-to-house survey. We investigated the contact status 

in the past of every incident case. In addition to household contact, we 

distinguished neighbor and social contacts. Of the 101 incident cases over 

a 25-year period, 79 (78%) could be associated to contact with another 

leprosy patient. Twenty-eight (28%) of these 101 cases were identified as 

household contacts, 36 (36%) as neighbors, and the remaining 15 (15%) as 

social contacts. Three patients had not had a traceable previous contact 

with another leprosy patient, and no information could be gathered from 19 

patients. The median span of time from the registration of the primary case 

to that of the secondary case was 3 years; 95% of the secondary cases were 

detected within 6 years after the primary case. The estimated risk for 

leprosy was about nine times higher in households of patients and four 

times higher in direct neighboring houses of patients compared to 

households that had had no such contact with patients. The highest risk of 

leprosy was associated with households of multibacillary patients. The risk 

of leprosy for households of paucibacillary patients was similar to the 

risk of leprosy for direct neighboring houses of multibacillary patients, 

indicating that both the type of leprosy of the primary case and the 

distance to the primary case are important contributing factors for the 

risk of leprosy. Contact with a leprosy patient is the major determinant in 

incident leprosy; the type of contact is not limited to household 

relationships but also includes neighbor and social relationships. This 

finding can be translated into a valuable and sustainable tool for leprosy 

control programs and elimination campaigns by focusing case detection and 

health promotion activities not only on household contacts but also on at 

least the neighbors of leprosy cases. 

============================================================ 

26.) The clinical use of fluoroquinolones for the treatment of mycobacterial diseases. 

============================================================ 

Clin Infect Dis 1997 Nov;25(5):1213-21 Related Articles, Books, LinkOut  Alangaden GJ, Lerner 

SA 

Department of Biochemistry and Molecular Biology, Wayne State University School of Medicine, 

Detroit, Michigan, USA. 

Mycobacterial diseases often require prolonged therapy with multidrug regimens. Fluoroquinolones 

have excellent bactericidal activity against many mycobacteria; achieve effective serum, tissue, and 

intracellular levels following oral administration; and produce few adverse effects. These properties 

have led to the increasing use of fluoroquinolones for the treatment of mycobacterial infections. We 

reviewed clinical studies and reports involving the use of fluoroquinolones for mycobacterial 

diseases. Ofloxacin, ciprofloxacin, sparfloxacin, and pefloxacin exhibit clinical efficacy against 

mycobacterial diseases, especially tuberculosis and leprosy. Fluoroquinolones have generally been 

administered in regimens that include other agents. However, when a fluoroquinolone has been found 

to be the sole active agent in a multidrug regimen, the ready emergence of resistance to 

fluoroquinolones has been recognized, just as when they have been used as monotherapy. Therefore, 

to forestall the emergence of resistance to fluoroquinolones during the treatment of mycobacterial 

diseases, these drugs should always be used in combination with at least one other active agent, and 

they should be used only when effective alternative drugs are not available. 

============================================================ 

27.) A case of relapsed leprosy successfully treated with sparfloxacin. 

============================================================ 

Arch Dermatol 1996 Nov;132(11):1397-8 Related Articles, Books, LinkOut 

Sugita Y, Suga C, Ishii N, Nakajima H 

Publication Types: 

Letter 

============================================================ 

============================================================ 

28.) Active leprosy treated effectively with ofloxacin. 

============================================================ 

Intern Med 1996 Sep;35(9):749-51 Related Articles, Books, LinkOut 

Mochizuki Y, Oishi M, Nishiyama C, Iida T 

Department of Neurology, Nihon University School of Medicine, Tokyo. 

The patient is a 25-year-old Filipino who showed polymorphous eruptions over the whole body, 

right ulnar nerve paresis, polyneuropathy and hypalgesia in the area of eruptions. Because the biopsy 

specimen showed foam cells, histiocytes, epithelioid cells, many Mycobacterium leprae and no giant 

cells, the diagnosis of borderline-lepromatous (BL) type was made. The symptoms were improved 

by the administration of 300 mg/day ofloxacin. Because the monotherapy using ofloxacin has been 

reported to be effective in all 5 previously reported cases of BL type leprosy, it may be 

recommended for a larger number of leprosy cases. 

 

============================================================ 

29.) Reactional states and neuritis in multibacillary leprosy patients following MDT with/without immunotherapy with Mycobacterium w antileprosy vaccine. 

============================================================ 

Lepr Rev 2000 Jun;71(2):193-205 Related Articles, Books, LinkOut 

Sharma P, Kar HK, Misra RS, Mukherjee A, Kaur H, Mukherjee R, Rani R 

National Institute of Immunology, New Delhi, India. 

A vaccine based on autoclaved Mycobacterium w was administered, in addition to standard 

multidrug therapy (MDT), to 157 untreated, bacteriologically positive, lepromin negative 

multibacillary leprosy patients, supported by a well matched control group of 147 patients with 

similar type of disease, who received a placebo injection in addition to MDT. The MDT was given 

for a minimum period of 2 years and continued until skin smear negativity, while the vaccine/placebo 

was given at 3-monthly intervals up to a maximum of eight doses. The incidence of type 2 reaction 

and neuritis during treatment and follow-up showed no statistically significant difference in the 

vaccine and placebo groups. The incidence of type 1 reaction (mild in most cases), however, was 

higher in the vaccine group (P = 0.041, relative risk ratio 1.79), considering LL, BL and BB leprosy 

types together, and considerably higher (P = 0.009) in LL type, probably because of confounding 

due to higher number of patients with previous history of reaction in this group. The occurrence of 

reactions and neuritis in terms of single or multiple episodes was similar in the vaccine and placebo 

groups. The association of neuritis and reactions, as well as their timing of occurrence (during MDT 

or follow-up), was also similar in the two groups, with more than 90% of occurrences taking place 

during MDT. The incidence of reversal reaction was significantly higher among the males in the 

vaccine group (34.5% versus 8.3%, P = 0.019). Patients with high initial BI (4.1-6.0) showed higher 

incidence of reactions (70.3%) as compared to those with medium (2.1-4.0) and low (0.3-2.0) BI 

where the reactions were observed with a frequency of 56.1% and 38.8%, respectively. However, 

unlike reactions, neuritis incidence did not seem to be affected by initial BI to the same extent in the 

vaccine group, with frequencies of 35.3%, 36.3% and 25.9% in the three mentioned BI ranges. 

Overall, the vaccine did not precipitate reactional states and neuritis over and above that observed 

with MDT alone. 

============================================================ 

30.) Mycobacterium w vaccine, a useful adjuvant to multidrug therapy in multibacillary leprosy: a  report on hospital based immunotherapeutic clinical trials with a follow-up of 1-7 years after  treatment. 

============================================================ 

Lepr Rev 2000 Jun;71(2):179-92 Related Articles, Books, LinkOut 

Sharma P, Misra RS, Kar HK, Mukherjee A, Poricha D, Kaur H, Mukherjee R, Rani R 

National Institute of Immunology, New Delhi, India. 

A vaccine based on autoclaved Mycobacterium w was administered, in addition to standard 

multidrug therapy (MDT), to 156 bacteriologically positive, lepromin negative multibacillary leprosy 

patients compared to a well matched control group of 145 patients with a similar type of disease 

who received a placebo injection in addition to MDT. The MDT was given for a minimum period of 

2 years and continued until skin smear negativity, while the vaccine was given at 3-month intervals up 

to a maximum of eight doses. The fall in clinical scores and bacteriological indices was significantly 

more rapid in vaccinated patients, from 6 months onward until years 2 or 3 of therapy. However, no 

difference was observed in the fall in bacteriological index in the two groups from year 4 onwards. 

The number of LL and BL patients released from therapy (RFT) following attainment of skin smear 

negativity, after 24-29 months of treatment was 84/133 (63.1%) in vaccinated and 30/120 (25.0%) 

in the placebo group; the difference was highly statistically significant (P < 0.0001). In all, 90.2% 

patients (146/162) converted from lepromin negativity to positivity in the vaccine group, as against 

37.9% (56/148) in the placebo group. The average duration of lepromin positivity maintained 

following eight doses of vaccine administered over 2 years was 3.016 years in the vaccine and 0.920 

years in the placebo group. Histological upgrading after 2 years of treatment in the LL type was 

observed in 34/84 (40.5%) cases in the vaccine and 5/85 (5.9%) cases in the placebo group, the 

difference being statistically significant (P < 0.001). The incidence of type 1 reactions was 

significantly higher (30.5%) in the vaccine group than (19.7%) in the placebo group (P = 0.0413); 

the difference was mainly observed in LL type (P = 0.009). The incidence of type 2 reactions was 

similar (31.8 and 34.6%) in vaccine and placebo groups. The vaccine did not precipitate neuritis or 

impairments over and above that encountered with MDT alone. After 5 years of follow-up following 

RFT, no incidence of bacteriological or clinical relapses was observed in both groups. 

============================================================ 

31.) What is WHO MDT? 

============================================================ 

Multidrug therapy (MDT) is a key element of the elimination strategy 

The drugs used in WHO-MDT are a combination of rifampicin, clofazimine and dapsone for MB 

leprosy patients and rifampicin and dapsone for PB leprosy patients. Among these rifampicin is the 

most important antileprosy drug and therefore is included in the treatment of both types of leprosy. 

Treatment of leprosy with only one antileprosy drug will always result in development of drug 

resistance to that drug. Treatment with dapsone or any other antileprosy drug used as monotherapy 

should be considered as unethical practice. 

Rifampicin: The drug is given once a month. No toxic effects have been reported in the case of 

monthly administration. The urine may be coloured slightly reddish for a few hours after its intake, 

this should be explained to the patient while starting MDT. 

Clofazimine: It is most active when administered daily. The drug is well tolerated and virtually 

non-toxic in the dosage used for MDT. The drug causes brownish black discoloration and dryness 

of skin. However, this disappears within few months after stopping treatment. This should be 

explained to patients starting MDT regimen for MB leprosy. 

Dapsone: The drug is very safe in the dosage used in MDT and side effects are rare. The main side 

effect is allergic reaction, causing itchy skin rashes and exfoliative dermatitis. Patients known to be 

allergic to any of the sulpha drugs should not be given dapsone. 

============================================================ 

32.) Is WHO-recommended multidrug therapy (MDT) the best combination available for treatment 

of multibacillary (MB) and paucibacillary (PB) leprosy in leprosy control today? 

============================================================ 

Yes, it is the best combination available today, as proved by its successful application in leprosy 

control under varying conditions since 1982. The combination not only cures leprosy but is also 

highly cost-effective. The recommended standard regimen for multibacillary (MB) leprosy is: 

Rifampicin: 600 mg once a month Dapsone: 100 mg daily Clofazimine: 300 mg once a month, and 

50 mg daily Duration: 12 months. The recommended standard regimen for paucibacillary (PB) 

leprosy is: Rifampicin: 600 mg once a month Dapsone: 100 mg daily Duration: 6 months. Children 

should receive appropriately reduced doses of the above drugs. 

============================================================ 

33.) WHY MULTIDRUG THERAPY FOR MULTIBACILLLARY LEPROSY CAN BE 

SHORTENED TO 12 MONTHS 

============================================================ 

To overcome the serious threat posed by the widespread emergence of dapsone resistance,1 and to 

increase the therapeutic effect in chemotherapy of leprosy, a World Health Organization (WHO) 

Study Group in 1981 recommended multidrug therapy (MDT) for the treatmentof leprosy.2 It was 

recommended that, for the purpose of treating different categories of patients with various bacterial 

loads, leprosy be classified as paucibacillary (PB) and multibacillary (MB), and that two drugs, 

monthly rifampicin (RMP) and daily dapsone (DDS), be prescribed for the treatment of PB leprosy, 

and three drugs – daily DDS and clofazimine (CLO) together with monthly RMP plus a 

supplemental higher dose of CLO – for MB leprosy. The duration of MDT for PB leprosy is 6 

months; whereas for MB leprosy, it was recommended that MDT should be given at least 2 years 

and preferably be continued up to skin-smear negativity.2 Because of the promising results of 

24-month treatment, the WHO Study Group recommended, at its second meeting in 1994, that all 

MB leprosy should be treated for 24 months.3 The MDT regimens have proved to be highly 

effective and well tolerated by the patients.4,5 At the beginning of 1997, more than 84 million 

leprosy patients had been cured by MDT.5 

However, from the operational point of view, the duration of MDT is still too long, especially for MB 

leprosy. The long duration of treatment has become one of the major obstacles in implementing 

MDT, particularly in areas where the health infrastructure is poor or the accessibility is difficult. It 

would facilitate the implementation of MDT among all patients who need treatment if the duration of 

MDT could be further shortened without significantly compromising its efficacy. 

To avoid relapse caused by spontaneously occurring RMP-resistant mutants and to minimize the 

relapse due to drug-susceptibility organisms after stopping MDT, the appropriate duration of MDT 

for MB leprosy is the time required to reduce the size of viable bacterial population to such an extent 

that RMP-resistant mutants are completely eliminated and the great majority of drug-susceptible 

organisms are killed. To date, due to technical constraints, we are unable to determine directly, with 

any laboratory tool, whether or not the RMP-resistant mutants are still present in the hosts, or 

whether the drug-susceptible organisms are reduced to a negligible level. However, the following 

information may be useful to define the appropriate duration of MDT for MB leprosy. 

First of all, the definition of MB leprosy has become much broader since 1981, when the Study 

Group designed the MDT regimen. Originally, MB leprosy referred to those patients who had a 

bacterial index (UI) of ³ 2 at any site in the initial skin smears.2 A few years later, the WHO Expert 

Committee on Leprosy at its 6th Meeting modified the definition that all skin smear positive cases 

should be classified as MB leprosy;4 and the Second WHO Study Group further recommended 

that, when the classification is in doubt, the patients should be created as having MB leprosy.3 Then, 

because of the lack of dependable skin-smear facilities in most leprosy programmes, the WHO 

Expert Committee on Leprosy at its 7th Meeting proposed that patients could be classified on 

clinical grounds only, and that MB leprosy should refer to those having more than five skin lesions.5 

These modifications have resulted in the classification of many cases that would otherwise be PB 

leprosy as MB leprosy, and the proportion of MB leprosy among newly detected cases has 

increased from 20·8% in 1985 to 309% in 1996.6 A more important finding is that, unlike in the 

early 1980s when all newly detected MR cases were skin smear positive, the proportion of smear 

positive cases among newly detected MB leprosy cases in 1996 was less than half. Among 142,844 

newly detected MBN cases from the 16 major leprosy endemic countries, it was estimated that 

69,449 (486%) were skin smear positive, and only 24,216 (170%), or one-sixth, of MB cases have 

a BI of >3.7 Because the bacterial loads of the majority of MB patients currently classified are 

significantly smaller than those in the past, the overall requirements of chemotherapy for MB leprosy 

may also be less. 

Secondly, the results from both routine control programmes8 and from research projects9 have 

demonstrated that the relapse rates after MDT were very low, about 0·2% annually, among MB 

leprosy cases. Similar results have been obtained after 2-year fixed duration MDT.10–14 The low 

relapse rates indicate that there is enough room for further shortening the duration of MDT to less 

than 24 months. Although some reports suggested that relapse rates after MDT could be significantly 

higher among MB patients with a high initial BI, i.e. the average BI ³ 4.0,15,16 because such patients 

have become relatively scarce in the field,7 the total number of relapses by them contributed to a 

leprosy control programme will be small. The programmes should accept the few relapses that may 

occur from patients with a high initial BI and treat those patients who do relapse with a further course 

of MDT. 

Thirdly, the major role of the DDS-CLO component of the MDT regimen for MB leprosy is to 

ensure the elimination of the spontaneously occurring RMP-resistant mutants. estimated to be no 

greater than 104 organisms in an untreated patient with lepromatous leprosy,17 before stopping 

chemotherapy. The results from both nude mouse experiments18 and a clinical trial19 have 

demonstrated that the bactericidal effect of the DDS-CLO component was significantly greater than 

expected; 3 months of daily treatment with DDS-CLO component alone killed more than 99.999% 

of viable Mycobacterium leprae,18 suggesting that all the spontaneously occurring RMP-resistant 

mutants are likely to be eliminated by 3–6 months of treatment with the DDS-CLO component in the 

MDT regimen. 

Fourthly, in a multicentre, double-blind trial organized by the Steering Committee on Chemotherapy 

of Mycobacterial Diseases (THEMYC) of the UNDP/World Bank/WHO Special Programme for 

Research and Training in Tropical Diseases, MB patients with initial BI ³ 2 were randomized into 

four groups of about 500 patients each, and two of the four groups were treated, respectively, with 

24-month or 12-month MDT. After 4–6 years of follow-up from intake, or 3–5 years after stopping 

treatment with the 12-month regimen, not a single relapse has been detected among the two groups, 

which suggests that the 12-month MDT is as effective as the standard 24-month MDT regimen 

(THEMYC Steering Committee, unpublished data). The efficacy of various durations of MDT has 

also been compared in a clinical trial in Malawi, in which 305 MB cases were randomly allocated 

into two groups and treated, respectively, with 18 or 30 months of MDT.20 After stopping 

treatment, the mean duration of follow-up was 3 years, with a maximum of 6 years. In both groups, 

the BI continued to fall, and fell to 0 by 60 months of follow-up. No relapse was observed in either 

group and the percentage of patients who developed new disabilities was similar. It was concluded 

that 18-month MDT may be sufficient for the treatment of MB leprosy. 

Finally, information on the clinical and bacteriological progress of defaulted MB cases may shed 

some light on the efficacy of MDT with duration shorter than the standard one. In one study,21 41 

defaulted MB cases were retrieved. They had been treated with MDT for a mean duration of 7 

months (range 3–13 months), and had not taken treatment after defaulting. By the time the patients 

were retrieved, from less than 1 year to more than 5 years after drop-out, all 41 patients showed 

clinical improvement, and 29 (71%) became smear negative, while the BI was stationary in five 

(122%) cases. In another series of patients,7 who were skin smear positive before defaulting, 139 

and 95 of them had been treated, respectively, with <12 months and 13–23 months of MDT before 

defaulting. By the time the patients were retrieved, after a mean duration of drop-out for 7.6 and 7.5 

years, respectively, only 11 (7.9%) patients from the former and six (6.3%) patients from the latter 

group were still smear positive. Not only were the positive rates very similar between the two 

groups, but neither differed significantly from those (3·3%) of 761 patients who had completed 24 

months of MDT and were examined 4 years later. Although one has to be cautious in interpreting the 

information from the retrospective analyses, because the records are often incomplete, the sample 

size is relatively small and the pretreatment characteristics of the patients between the groups may 

not be comparable, they do suggest that treatment with less than 12 months of MDT exhibited 

promising therapeutic effects among the majority of MB patients. 

On the basis of all the available information, the WHO Expert Committee on Leprosy concluded, at 

its latest meeting in 1997, that it is possible that the duration of the MDT regimen for MB leprosy 

could be further shortened to 12 months.5 This conclusion has been well-accepted by almost all the 

leprosy control programmes of the major endemic countries and is being implemented. Of course, 

during the transitional period from 24-month MDT to 12-month, a series of operational issues should 

be addressed, such as providing guidelines for the transition, revising national manuals, introducing a 

new reporting system, and improving the detection and treatment of leprosy reactions after 

completion of treatment. However, compared with the earlier days when MDT was introduced, in 

most countries now the leprosy control programme managers and their field staffs are more 

experienced, and they are able to handle these operational issues without too much difficulty. 

B. Ji 

Faculté de Médecine Pitié-Salpétriére 

91 Boulevard de l'Hôpital 

75634 Paris Cedex 13 

France 

References 

1Ji B. Drug resistance in leprosy – a review. Lepr Rev, 1985; 56: 265–278. 

2WHO Study Group. Chemotherapy of leprosy for control programmes. WHO Technical Report 

Series No. 675. World Health Organization, Geneva, 1982. 

3WHO Study Group. Chemotherapy of leprosy. WHO Technical Report Series no. 847. World 

Health Organization, Geneva, 1994. 

4WHO Expert Committee on Leprosy. Sixth Report. WHO Technical Report Series, No. 768. 

World Health Organization, Geneva, 1988. 

5WHO Expert Committee on Leprosy. Seventh Report. WHO Technical Report Series, No. 874. 

World Health Organization, Geneva. 1998 (in press). 

6World Health Organization. Global case-detection trend in leprosy Weekly Epid Rec, 1997; 72: 

173–180. 

7World Health Organization. Shortening duration of treatment of multibacillary leprosy. Weekly Epid 

Rec, 1997; 72: 125–132. 

8WHO Leprosy Unit. Risk of relapse in leprosy. WHO document WHO/CTD/LEP/94.1). 

9Beck-Bleumink M. Relapses among leprosy patients treated with multidrug therapy, experience in 

the leprosy control program of the All Africa Leprosy and Rehabilitation Training Centre (ALERT) 

in Ethiopia; practical difficulties with diagnosing relapses; operational procedures and criteria for 

diagnosing relapses. Int J Lepr, 1992; 60: 421–435. 

10Vijayakumaran P, Jesudasan K. Manimozhi N. Fixed-duration therapy (FDT) in multibacillary 

leprosy: efficacy and complications. Int J Lepr, 1996; 64: 123–127. 

11Jesudasan Km Vijayakumaran P, Manimozhi N, Jeyarajan T, Rao PSS. Absence of relapse 

within 4 years among 34 multibacillary patients with high BIs treated for 2 years with MDT. Int J 

Lepr, 1996; 64: 133–135. 

12Li H, Hu L, Wu P, Luo J, Liu X. Fixed-duration multidrug therapy in multibacillary leprosy. Int J 

Lepr, 1997; 65: 230–237. 

13Li H, Hu L, Huang W, Liu G, Yuan I, Jin Z, Li X, Li J, Yang Z. Risk of relapse in leprosy after 

fixed-duration multidrug therapy. Int J Lepr, 1997; 65: 238–245. 

14Dasananjali K, Schreuder PAM, Pirayavaraporn C. A study on the effectiveness and safety of the 

WHO/MDT regimen in the Northeast of Thailand; a prospective study, 1984–1996. Int J Lepr, 

1997; 65: 28–36. 

15Jamet P, Ji B, and Marchoux Chemotherapy Group. Relapse after long-term follow-up of 

multibacillary patients to treated by WHO multidrug regimen. Int J Lepr, 1995; 63: 195–201. 

16Girdhar BK Personal communication, 1996. 

17Ji R, Grosset JH. Recent advances in the chemotherapy of leprosy (Editorial). Lepr Rev, 1990; 

61: 313–329. 

18Ji B, Perani EG, Petinom C, Grosset JH. Bactericidal activities of combinations of new drugs 

against Mycobacterium leprae in nude mice. Antimicrob Agents Chemother, 1996; 40: 393–399. 

19Ji B, Jamet P, Perani EG, Sow S, Liemhardt C, Petinom C, Grosset JH. Bactericidal activity of 

single dose of clarithromycin plus minocycline, with or without ofloxacin, against Mycobacterium 

leprae in patients. Antimicrob Agents Chemother, 1996; 40: 2137–2141. 

20Ponnighaus JM, Boerrigter G. Are 18 doses of WHO/MDT sufficient for multibacillary leprosy? 

Results of a trial in Malawi. Int J Lepr, 1995; 63: 1–7. 

21Ganapati R, Shroff HJ, Gandewar KL, Rao BRP, Pai RR, Kute AS, Fernandes TX, Revankar 

CR, Pawar PL. Five year follow-up of multibacillary leprosy patients after fixed duration 

chemotherapy. Quaderni di cooperazione sanitaria, 1992; 12: 223–229. 

============================================================ 

34.) Supervised Multiple Drug Therapy Program, Venezuela 

============================================================ 

Dr Jacinto Convit Director, Institute of Biomedicine, Caracas 

A supervised multiple drug therapy program (SMDT) for the treatment of leprosy has been in 

progress in our country since 1985. It has been supported by the Novartis Leprosy Fund since 

1991. In contrast to the WHO MDT regime, the SMDT program provides a single treatment regime 

for both multibacillary (MB) and paucibacillary (PB) leprosy, differing only in the duration of 

treatment (two years for MB; six months for PB). Twice a month, health workers visit patients at 

home to supervise the taking of medication–600 milligrams of clofazimine each visit and 600 

milligrams of rifampicine once a month. The daily 100 milligram dose of dapsone is checked 

indirectly with sulfone-in-urine tests done at random. 

The Venezuelan program also includes health education activities, examination of patients’ families, 

and a research program in connection with the quest for a leprosy vaccine. Once the treatment has 

been completed, former patients are kept under surveillance over a period of two (for PB) or five 

(for MB) years for a possible relapse of the disease. 

Our leprosy program in Venezuela has brought highly gratifying results. More than 4,200 patients 

have been cured and are now under post-treatment surveillance; a further 3,000 are still in treatment. 

Although the number of newly detected cases has scarcely changed, averaging around 450 a year, 

the number of patients undergoing treatment has gone down distinctly. The program’s activities have 

also brought about an improved public attitude to the disease. Most new patients seek treatment on 

their own initiative, and the manifest improvement in the condition of those who have been treated is 

the best publicity for the program. 

To secure the success of the leprosy program we have had to reorganize the Public Health 

Dermatology Services and reinforce their infrastructure and central data registration system. Carrying 

out the program of visits at patients’ homes necessitated providing the health workers with 

transportation and allowances to defray travel expenses. Finally, an extensive health education 

program had to be mounted so as to ensure that patients come regularly for follow-up examinations 

after they are cured. 

Not least thanks to the backing we have received from the Novartis Leprosy Fund, we have been 

able to solve all these problems or move them closer to a solution. 

Our future efforts will be directed toward integrating our leprosy work with the control of other 

endemic diseases such as tuberculosis, leishmaniasis, and Chagas’ disease. The training programs for 

this are now under way, and some are already completed. In future, MDT as recommended by the 

WHO will be used. We also plan to develop a vaccination program in conjunction with the current 

curative program and, through further research projects, to improve early diagnosis. 

============================================================ 

35.) Search for newer antileprosy drugs. 

============================================================ 

Indian J Lepr 2000 Jan-Mar;72(1):5-20 Related Articles, Books 

Dhople AM 

Department of Biological Sciences, Florida Institute of Technology, Melbourne 32901, USA. 

[Medline record in process] 

In 1991 World Health Organization proclaimed the goal of global elimination of leprosy as a public 

health problem by year 2000 by implementing multidrug therapy (MDT). Since then the prevalence 

rate has declined by 85%. However, during the same period the incidence rate of leprosy has 

remained constant or even has been increasing. This suggests that it will take a long time for the 

eradication of leprosy and that without in-vitro cultivation of M. leprae, eradication of leprosy is not 

likely to be achieved. While in-vitro cultivation is a long-term goal, as an immediate measure, there is 

an urgent need for the development of newer drugs and newer multidrug therapy regimens. Using the 

in-vitro system for screening potential antileprosy drugs and also using the mouse foot-pad system 

we have evaluated several compounds in four classes of drugs--dihydrofolate reductase inhibitors, 

fluoroquinolones, rifampicin analogues and phenazines--and identified at least two compounds that 

appear to be more potent than dapsone, rifampicin and clofazimine. Newer combinations of 

rifampicin analogues and fluoroquinolones have also been identified that seem to be better than the 

combination of rifampicin and ofloxacin. 

 

============================================================ 

36.) Mycobacterium leprae--millennium resistant! Leprosy control on the threshold of a new era. 

============================================================ 

Trop Med Int Health 2000 Jun;5(6):388-99 Related Articles, Books, LinkOut 

Visschedijk J, van de Broek J, Eggens H, Lever P, van Beers S, Klatser P 

Department of Health Care and Disease Control, Royal Tropical Institute, Amsterdam, The 

Netherlands. 

Over the past decades, the conditions of leprosy control implementation have changed dramatically. 

Introduction of multidrug therapy, together with the global effort of the World Health Organization to 

eliminate leprosy as a public health problem, had a tremendous impact on leprosy control, 

particularly by decreasing the registered prevalence of the disease. At the beginning of the new 

millennium, leprosy control programmes face several new challenges. These relate not only to 

changes in the prevalence of the disease, but also to changes in the context of leprosy control, such 

as those created by health sector reforms and other disease control programmes. This review 

discusses current knowledge on the epidemiology of Mycobacterium leprae and some important 

aspects of leprosy control. It is argued that our understanding is still insufficient and that, so far, no 

consistent evidence exists that the transmission of leprosy has been substantially reduced. Sustainable 

leprosy control, rather than elimination, should be our goal for the foreseeable future, which also 

includes care for patients on treatment and for those released from treatment. This, however, 

requires new strategies. 

 

============================================================ 

37.) The impact of multidrug therapy on the epidemiological pattern of leprosy in Juiz de Fora, 

Brazil. 

============================================================ 

Cad Saude Publica 2000 Apr-Jun;16(2):343-50 

Soares LS, Moreira Rd, Vilela VV, Alves MJ, Pimentel AF, Ferreira AP, Teixeira HC 

Departamento de Parasitologia, Microbiologia e Imunologia, Instituto de Ciencias Biologicas, 

Universidade Federal de Juiz de Fora, Juiz de Fora, MG, 36036-330, Brasil. 

We investigated the impact of multidrug therapy (MDT) on the epidemiological pattern of leprosy in 

Juiz de Fora, Brazil, from 1978 to 1995. Evaluation of 1,283 medical charts was performed 

according to the treatment regimen used in two different periods. Following the introduction of MDT 

in 1987, prevalence of leprosy decreased from 22 patients/10,000 inhabitants to 5.2 patients/10,000 

inhabitants in 1995. Incidence rate of leprosy was lower in period II (1987-1995) than in period I 

(1978-1986). Decreasing prevalence and incidence appear to be related to drug efficacy rather than 

decreased case identification, since both self-referred and professionally referred treatment increased 

markedly from period I to period II. For both periods, multibacillary leprosy was the most frequent 

clinical form of the disease (+/-68%), and the main infection risk factor identified was household 

contact. Leprosy is predominantly manifested in adults, but an increase in the number of very old and 

very young patients was observed in period II. The MDT program has been effective both in 

combating leprosy and in promoting awareness of the disease. 

 

============================================================ 

38.) Serologic response to mycobacterial proteins in hansen's patients during multidrug treatment. 

============================================================ 

Int J Lepr Other Mycobact Dis 1999 Dec;67(4):414-21 Related Articles, Books, LinkOut 

Rada E, Aranzazu N, Ulrich M, Convit J 

Instituto de Biomedicina, Caracas, Venezuela. erada@telcel.net.ve 

Humoral immune responses were studied in 24 leprosy patients treated with multidrug therapy 

(MDT) and 16 contacts. The patients were monitored for 2 to 3 years with repeated determination 

of IgG antibody levels directed to different mycobacterial proteins (Mycobacterium tuberculosis, 

Mt70; M. bovis, Mb65; M. leprae, Ml36, 28, 18, 10 kDa, and the complete protein M. leprae 

extract, MLSA). All recombinant antigens were used at 5 micrograms/ml concentration and the 

complete soluble M. leprae extract at 2 micrograms/ml. The results shown in this study reveal a clear 

decline in IgG antibodies directed toward mycobacterial proteins in the 12 multibacillary (MB) 

patients when they were submitted to MDT. Initially we found strong reactivity toward complete 

cytosolic protein and M. leprae membrane protein. The most reactive recombinant proteins in MB 

patients were Ml10, Ml36, Mt70 kDa and, finally, Ml18 kDa when compared to the paucibacillary 

(PB) group. After treatment was completed all lepromatous and borderline lepromatous patients 

showed low or undetectable levels as compared with their initial values before starting treatment. 

============================================================ 

39.) HLA linked with leprosy in southern China: HLA-linked resistance alleles to leprosy. 

============================================================ 

Int J Lepr Other Mycobact Dis 1999 Dec;67(4):403-8 Related Articles, Books, LinkOut 

Wang LM, Kimura A, Satoh M, Mineshita S 

Department of Preventive Medicine, Tokyo Medical and Dental University, Japan. 

According to the World Health Organization recommended multidrug therapy (WHO/MDT), we 

have carried out this study to investigate the presence of HLA-linked susceptibility or resistance to 

leprosy in a southern Chinese population. Sixty-nine leprosy patients and 112 healthy controls 

participated in the study. HLA-DR2 subtypes, HLA-B and MHC Class I chain-related A (MICA) 

alleles were typed at the DNA level using the polymerase chain reaction-single strand conformation 

polymorphism method. The frequencies of HLA-DR2-DRB1 alleles did not show any significant 

differences between the patient and the control groups, suggesting that the disease susceptibility was 

not associated with the DR2 subtypes in this southern Chinese population. On the other hand, in the 

multibacillary (MB) patients significantly decreased allele frequencies of HLA-B46 (0.040 in MB 

patients vs 0.129 in controls) and MICA-A5 (0.200 vs 0.380) were observed compared with the 

healthy controls. The calculated relative risk (RR) for B46 was 0.28; for MICA-A5, 0.52. In 

addition, on haplotype analysis the frequency of the HLA-B46/MICA-A5 haplotype was 

significantly decreased in the MB patients compared to controls (0.060 vs 0.233, RR = 0.22, p < 

0.01). These results suggest that an HLA-linked disease-resistant gene to MB leprosy in southern 

China is in strong linkage disequilibrium with the HLA-B46/MICA-A5 haplotype. In other words, 

the resistant gene may be located near the HLA-B/MICA region and not in the HLA-DR locus. 

============================================================ 

40.) A Mycobacterium leprae-specific human T cell epitope cross-reactive 

with an HLA-DR2 peptide. 

============================================================ 

ARTICLE SOURCE:  Science  (United States), Oct 14 1988, 242(4876) p259-61 

AUTHOR(S):  Anderson DC; van Schooten WC; Barry ME; Janson AA; Buchanan 

TM; 

de Vries RR 

PUBLICATION TYPE:  JOURNAL ARTICLE 

ABSTRACT:  Mycobacterium leprae induces T cell reactivity and protective 

immunity in the majority of exposed individuals, but the minority that 

develop leprosy exhibit various types of immunopathology. Thus, the 

definition of epitopes on M. leprae antigens that are recognized by T cells 

from different individuals might result in the development of an effective 

vaccine against leprosy. A sequence from the 65-kD protein of this organism 

was recognized by two HLA-DR2-restricted, M. leprae-specific helper T cell 

clones that were derived from a tuberculoid leprosy patient. Synthetic 

peptides were used to define this epitope as 

Leu-Gln-Ala-Ala-Pro-Ala-Leu-Asp-Lys-Leu. A similar peptide that was derived 

from the third hypervariable region of the HLA-DR2 chain, 

Glu-Gln-Ala-Arg-Ala-Ala-Val-Asp-Thr-Tyr, also activated the same clones. 

The unexpected cross-reactivity of this M. leprae-specific DR2-restricted T 

cell epitope with a DR2 peptide may have to be considered in the design of 

subunit 

============================================================ 

41.) Association of HLA antigens with differential responsiveness to 

Mycobacterium w vaccine in multibacillary leprosy patients. 

============================================================ 

ARTICLE SOURCE:  J Clin Immunol  (United States), Jan 1992, 12(1) p50-5 

AUTHOR(S):  Rani R; Zaheer SA; Suresh NR; Walia R; Parida SK; Mukherjee A; 

Mukherjee R; Talwar GP 

PUBLICATION TYPE:  JOURNAL ARTICLE 

ABSTRACT:  Leprosy patients undergoing phase II trials in two hospitals of 

New Delhi, India, were HLA typed to see the association of HLA with 

differential responsiveness to Mycobacterium w vaccine. The vaccine 

comprises an atypical, nonpathogenic mycobacterium, Mycobacterium w, which 

has cross-reactive antigens with M. leprae. Multibacillary patients who are 

lepromin negative are vaccinated at an interval of 3 months. Considerable 

improvement is evident in the patients in terms of a decline in bacterial 

indices and histopathological and immunological upgrading. But all the 

patients do not respond to the vaccine in the same manner; some are slow 

responders, while others are good responders. HLA-A28 and DQw3 (DQw8 + 9) 

were found to be associated with slow responsiveness, while DQw1 and DQw7 

were found to be associated with a more rapid responsiveness to the M. w 

vaccine. However, these associations were not significant after P 

correction for the number of antigens tested for each locus except for 

HLA-DQw3 (DQw8 and DQw9) and DQw7. DQw7, a new defined split of 

HLA-DQw3, 

seems to be associated with the responsiveness to M. w vaccine. 

============================================================ 

42.) HLA antigens and neural reversal reactions in Ethiopian borderline 

tuberculoid leprosy patients. 

============================================================ 

ARTICLE SOURCE:  Int J Lepr Other Mycobact Dis  (United States), Jun 1987, 

55(2) p261-6 

AUTHOR(S):  Ottenhoff TH; Converse PJ; Bjune G; de Vries RR 

PUBLICATION TYPE:  JOURNAL ARTICLE 

ABSTRACT:  Reversal reactions (RR) or acute neuritis episodes are 

frequently observed in borderline tuberculoid (BT) leprosy patients during 

the first year of treatment, and are associated with a rapid increase in 

cell-mediated immunity. Because HLA-linked genes have been shown to be an 

important factor in determining the type of leprosy that develops in 

susceptible individuals and because HLA molecules regulate cellular 

interactions in the immune system, we have investigated whether RR are 

associated with HLA antigens in Ethiopian patients. The data reported here 

indicate that this is not the case: no significant differences in the 

distribution of HLA class I and class II antigens were observed among three 

groups: 28 BT patients with a history of RR, 27 BT patients with no history 

of RR, and 33 healthy individuals. In contrast to these negative results, 

we observed that HLA-DR3 was associated with high skin-test responsiveness 

against Mycobacterium leprae antigens among RR patients. Since DR3 was not 

associated with RR per se, the observed DR3-associated high responsiveness 

to M. leprae may not be primarily 

============================================================ 

43.) Evidence for an HLA-DR4-associated immune-response gene for 

Mycobacterium 

tuberculosis. A clue to the pathogenesis of rheumatoid arthritis? 

============================================================ 

ARTICLE SOURCE:  Lancet  (England), Aug 9 1986, 2(8502) p310-3 

AUTHOR(S):  Ottenhoff TH; Torres P; de las Aguas JT; Fernandez R; van Eden 

W; de Vries RR; Stanford JL 

PUBLICATION TYPE:  JOURNAL ARTICLE 

ABSTRACT:  Antigens of Mycobacterium tuberculosis, M leprae, M 

scrofulaceum, and M vaccae were injected intradermally in 86 caucasoid 

leprosy patients, and skin responses (measured in mm of induration at 72 h) 

were analysed in relation to HLA class II phenotypes. HLA-DR4 was 

associated with high responsiveness to antigens specific to M tuberculosis 

but not to antigens shared with other mycobacteria (p = 0.0005). Because 

DR4 is associated with rheumatoid arthritis (RA) and because a role for M 

tuberculosis antigens has been suggested both in experimentally induced 

autoimmune arthritis in rats and in RA, the DR4 associated regulation of 

the immune response to M tuberculosis may be relevant to the pathogenesis 

of RA. 

============================================================ 

44.) Diaminodiphenylsulfone resistance of Mycobacterium leprae due to 

mutations in the dihydropteroate synthase gene. 

============================================================ 

Author 

Kai M; Matsuoka M; Nakata N; Maeda S; Gidoh M; Maeda Y; Hashimoto K; 

Kobayashi K; Kashiwabara Y 

Address 

Leprosy Research Center, National Institute of Infectious Diseases, Tokyo, 

Japan. mkai@nih.go.jp 

Source 

FEMS Microbiol Lett, 177(2):231-5 1999 Aug 15 

Abstract 

The nucleotide sequence analysis of the dihydropteroate synthase (DHPS) 

gene of six diaminodiphenylsulfone-resistant Mycobacterium leprae strains 

revealed that the mutation was limited at highly conserved amino acid 

residues 53 or 55. Though the mutation at amino acid residue 55 or its 

homologous site has been reported in other bacteria, the mutation at 

residue 53 is the first case in bacteria. This is the first paper which 

links the mutations in DHPS and sulfonamide resistance in M. leprae. This 

finding is medically and socially relevant, since leprosy is still a big 

problem in certain regions. 

========================================================================= 

45.) Resolution of lepromatous leprosy after a short course of 

amoxicillin/clavulanic acid, followed by ofloxacin and clofazimine. 

========================================================================= 

Int J Dermatol 1999 Jul;38(7):558-60 

Villahermosa LG, Walsh DS, Fajardo TT Jr, Abalos RM, dela Cruz EC, 

Veerasubramanian P, Walsh GP 

Publication Types: 

letter 

========================================================================= 

============================================================ 

46.) Studies on risk of leprosy relapses in China: relapses after treatment with multidrug therapy. 

============================================================ 

Int J Lepr Other Mycobact Dis 1999 Dec;67(4):379-87 Related Articles, Books, LinkOut 

Chen XS, Li WZ, Jiang C, Ye GY 

Department for Leprosy Research, Chinese Academy of Medical Sciences, Nanjing, China. 

epicams@jlonline.com 

Based upon the data from the Chinese National System for Leprosy Surveillance, this paper reports 

on the relapses in 47,276 leprosy patients cured by or released from WHO-recommended multidrug 

therapy (WHO/MDT). The overall relapse rate was 0.73/1000 patient-years (PY). There was a 

statistically significant difference in the relapse rates of WHO/MDT-MB (0.61/1000 PY) and 

WHO/MDT-PB (1.04/1000 PY) (chi 2 = 15.7, p < 0.01) patients. For multibacillary (MB) 

patients, the relapse rate in patients treated with fixed-duration MDT (0.56/1000 PY) was 

comparable with that in patients treated with MDT until skin-smear negativity (0.73/1000 PY) (chi 2 

= 2.20, p > 0.05). Our present study suggests that fixed-duration MDT is a cost-effective regimen 

for the treatment of leprosy in China. The present results also show that relapse of leprosy is 

acceptably low and has not yet become a serious clinical or public health problem but, based upon 

the incubation of relapse in MDT patients, it is necessary to encourage annual follow up for at least 5 

years for paucibacillary (PB) and 10 years for MB patients after being released from WHO/MDT. 

============================================================ 

47.) An immunotherapeutic vaccine for multibacillary leprosy. 

============================================================ 

Int Rev Immunol 1999;18(3):229-49 Related Articles, Books, LinkOut 

Talwar GP 

International Centre for Genetic Engineering & Biotechnology, New Delhi, India. 

On January 30, 1998, a vaccine for leprosy based on Mycobacterium w (the code word under 

which this species hitherto unspecified was investigated) was launched for public use for therapeutic 

purposes. The vaccine has completed phase III immunotherapeutic trials as an adjunct to 

chemotherapy in urban and rural leprosy control centres and has received the authorization from the 

Drugs Controller of India for industrial manufacture. It will be made available by M/s Cadila 

Pharmaceuticals, Ahmedabad. As an adjunct to chemotherapy, the vaccine expediates bacterial 

clearance and accelerates clinical regression of lesions. It shortens significantly the period for release 

from treatment (RFT) of patients. It is effective in inducing a fall of bacterial index (BI) in 

multibacillary patients who are either nonresponders or slow responders to the standard multidrug 

therapy and who have persistent BI over long periods. An additional benefit of immunization with this 

vaccine is the conversion of >60% of LL, 71% of BL and 100% of BB patients from lepromin 

negativity to lepromin positivity status. A significant number of vaccinated patients showed 

histopathological upgrading and eventually attainment of a state of nonspecific infiltration without 

dermal granulomas. The vaccine was well tolerated and the incidence of Type 2 reactions and their 

severity was less in combined immuno cum chemotherapy group than in the group receiving only 

chemotherapy. This review describes the nature of the vaccine and the way it was developed. 

============================================================ 

48.) Nasal mucosa and skin of smear-positive leprosy patients after 24 months of fixed duration 

MDT: histopathological and microbiological study. 

============================================================ 

Int J Lepr Other Mycobact Dis 1999 Sep;67(3):292-7 Related Articles, Books, LinkOut 

Ebenezer GJ, Job A, Abraham S, Arunthathi S, Rao PS, Job CK 

Department of Histopathology and Experimental Pathology, Schieffelin Leprosy Research and 

Training Center, Tamil Nadu, India. 

The skin and nasal mucosa of 10 lepromatous leprosy patients who had completed 24 doses of fixed 

duration multidrug therapy (MDT) but who continued to be skin-smear positive for acid-fast bacilli 

(AFB) were examined histopathologically. The nasal mucosa showed granuloma fractions that 

exceeded those seen in the skin specimens, signifying that activity in this region subsides much more 

gradually than the activity in the skin. Mouse foot pad studies done using T900r mice with an 

inoculum from the nasal mucosa biopsy specimens of these patients did not demonstrate any growth 

of Mycobacterium leprae, indicating that these bacilli were not viable. A skin specimen from one 

patient grew significant amounts of bacteria in the T900r mouse foot pad. These results show that 2 

years of treatment with MDT would prevent dissemination of M. leprae from the nasal mucosa and, 

therefore, should preclude further transmission of the disease. It also indicates that viable bacteria 

might persist in the skin of patients, especially those with an initial bacterial index of > or = 4+ who 

have completed 24 doses of regular MDT. Therefore, a more cautious approach to administering 

only 12 doses of MDT to highly positive multibacillary patients is suggested. 

============================================================ 

49.) Induction of lepromin positivity following immuno-chemotherapy with Mycobacterium w 

vaccine and multidrug therapy and its impact on bacteriological clearance in multibacillary leprosy: 

report on a hospital-based clinical trial with the candidate antileprosy vaccine. 

============================================================ 

Int J Lepr Other Mycobact Dis 1999 Sep;67(3):259-69 Related Articles, Books, LinkOut 

Sharma P, Kar HK, Misra RS, Mukherjee A, Kaur H, Mukherjee R, Rani R 

National Institute of Immunology, New Delhi, India. 

A vaccine based on autoclaved Mycobacterium w was administered, in addition to standard 

multidrug therapy (MDT), to 157 bacteriologically positive, lepromin-negative, multibacillary (LL, 

BL and BB) leprosy patients. The vaccinees were supported by a well-matched control group of 

147 patients with similar type of disease who received a placebo injection in addition to MDT. The 

MDT was given for a minimum period of 2 years and continued until skin-smear negativity, while the 

vaccine was given at 3-month intervals up to a maximum of 8 doses. The lepromin response 

evaluated in terms of percentage of subjects converting to positivity status, measurement in 

millimeters, and duration of lepromin positivity sustained, reflected a statistically significant better 

outcome in the vaccine group patients (especially LL and BL leprosy) in comparison to those in the 

placebo group. The data indicate that lepromin-positivity status seems to have an impact on 

accelerating the bacteriological clearance, as is evident by the statistically significant accelerated 

decline in the BI of those patients who converted to lepromin positivity as compared to those 

remaining lepromin negative throughout therapy and post-therapy follow up. To conclude, the 

addition of the Mycobacterium w vaccine to standard MDT induces a lepromin response of a 

statistically significant higher magnitude than that observed with MDT alone. 

============================================================ 

50.) SIMLEP: a simulation model for leprosy transmission and control. 

============================================================ 

Int J Lepr Other Mycobact Dis 1999 Sep;67(3):215-36 Related Articles, Books, LinkOut 

Meima A, Gupte MD, van Oortmarssen GJ, Habbema JD 

Department of Public Health, Faculty of Medicine, Erasmus University Rotterdam, The Netherlands. 

Meima@mgz.fgg.eur.nl 

SIMLEP is a computer program for modeling the transmission and control of leprosy which can be 

used to project epidemiologic trends over time, producing output on indicators such as prevalence, 

incidence and case-detection rates of leprosy. In SIMLEP, health states have been defined that 

represent immunologic conditions and stages of leprosy infection and disease. Three types of 

interventions are incorporated: vaccination, case detection and chemotherapy treatment. 

Uncertainties about leprosy have led to a flexible design in which the user chooses which of many 

aspects should be included in the model. These aspects include natural immunity, asymptomatic 

infection, type distribution of new cases, delay between onset of disease and start of chemotherapy, 

and mechanisms for leprosy transmission. An example run illustrates input and output of the program. 

The output produced by SIMLEP can be readily compared with observed data, which allows for 

validation studies. The support that SIMLEP can give to health policy research and actual decision 

making will depend upon the extent of validation that has been achieved. SIMLEP can be used to 

improve the understanding of observed leprosy trends, for example, in relation to early detection 

campaigns and the use of multidrug therapy, by exploring which combinations of assumptions can 

explain these trends. In addition, SIMLEP allows for scenario analysis in which the effects of control 

strategies combining different interventions can be simulated and evaluated. 

============================================================ 

51.) Detection of viable organisms in leprosy patients treated with multidrug therapy. 

============================================================ 

Acta Leprol 1999;11(3):89-92 Related Articles, Books, LinkOut 

Gupta UD, Katoch K, Singh HB, Natrajan M, Sharma VD, Katoch VM 

Central Jalma Institute for Leprosy (ICMR), Taj Ganj, Agra, India. 

Cutaneous biopsies were collected from multibacillary leprosy patients who attended the out-patient 

department of Jalma Institute for treatment at different time intervals, i.e. 6 months, 12 months, 18 

months, 24 months, 30 months, 36 months and 42 months after starting multidrug therapy (MDT) 

when they were still skin smear positive. Biopsies were processed for inoculation into mouse foot 

pad (MFP) and estimation of bacillary ATP levels by bioluminescent assay (ATP assay) by earlier 

established procedures. Viable bacilli were detectable after 1 year (25% cases by MFP and 31% 

cases by ATP assay), 2 years (8% cases by MFP and 12% cases by ATP assay) and 3 years (4% 

cases by both MFP and ATP assays). Overall, the percentage of the persisters was 10% by MFP 

and 13% by ATP assay. It would be important to carry out surveillance studies in larger number of 

BL/LL cases to know the trends and also the resultant relapses. 

 

============================================================ 

52.) An immunotherapeutic vaccine for multibacillary leprosy. 

============================================================ 

Int Rev Immunol 1999;18(3):229-49 Related Articles, Books, LinkOut 

Talwar GP 

International Centre for Genetic Engineering & Biotechnology, New Delhi, India. 

On January 30, 1998, a vaccine for leprosy based on Mycobacterium w (the code word under 

which this species hitherto unspecified was investigated) was launched for public use for therapeutic 

purposes. The vaccine has completed phase III immunotherapeutic trials as an adjunct to 

chemotherapy in urban and rural leprosy control centres and has received the authorization from the 

Drugs Controller of India for industrial manufacture. It will be made available by M/s Cadila 

Pharmaceuticals, Ahmedabad. As an adjunct to chemotherapy, the vaccine expediates bacterial 

clearance and accelerates clinical regression of lesions. It shortens significantly the period for release 

from treatment (RFT) of patients. It is effective in inducing a fall of bacterial index (BI) in 

multibacillary patients who are either nonresponders or slow responders to the standard multidrug 

therapy and who have persistent BI over long periods. An additional benefit of immunization with this 

vaccine is the conversion of >60% of LL, 71% of BL and 100% of BB patients from lepromin 

negativity to lepromin positivity status. A significant number of vaccinated patients showed 

histopathological upgrading and eventually attainment of a state of nonspecific infiltration without 

dermal granulomas. The vaccine was well tolerated and the incidence of Type 2 reactions and their 

severity was less in combined immuno cum chemotherapy group than in the group receiving only 

chemotherapy. This review describes the nature of the vaccine and the way it was developed. 

 

============================================================ 

53.) Addition of immunotherapy with Mycobacterium w vaccine to multi-drug therapy benefits 

multibacillary leprosy patients. 

============================================================ 

Vaccine 1995 Aug;13(12):1102-10 Related Articles, Books, LinkOut 

Zaheer SA, Beena KR, Kar HK, Sharma AK, Misra RS, Mukherjee A, Mukherjee R, Kaur H, 

Pandey RM, Walia R, et al 

National Institute of Immunology, New Delhi, India. 

Immunotherapy with a vaccine consisting of autoclaved Mycobacterium w, was given in addition to 

standard chemotherapy (multidrug therapy (MDT)) to 93 multibacillary (MB) leprosy patients. One 

hundred and seven patients with similar types of disease served as controls and received MDT + 

placebo injections. The study was a double-blind randomised trial. On opening the codes, results 

obtained were in concordance with those in a single-blind trial which has been extensively reported. 

Bacteriological clearances were significantly more rapid in vaccinated patients (p < 0.03). Thirty-five 

LL or BL patients with a high bacterial index (BI) of 6 were completely cleared of acid-fast bacilli 

(AFB) after eight doses of vaccine. Only 8 patients in the control group became bacteriologically 

negative in the same time period. They all had BIs < 4. Associated with decreasing BI was 

accelerated clinical regression of lesions after vaccination and lepromin conversion rates of 100% for 

BB, 71% for BL and 70% for LL. A significant number of immunised patients showed histological 

improvement (p < 0.004). Thirty-six showed a complete disappearance of dermal granulomas and a 

picture of non-specific infiltration. The vaccine did not precipitate neuritis or deformities; episodes 

were noted in vaccinated patients as were incidences of Type 2 reaction. The overall improvement 

was reflected by a shorter duration of treatment and faster release of vaccinated patients. 

============================================================ 

54.) Immunotherapy with Mycobacterium w vaccine decreases the incidence and 

severity of type 2 (ENL) reactions. 

============================================================ 

Zaheer SA, Misra RS, Sharma AK, Beena KR, Kar HK, Mukherjee A, Mukherjee R, Walia R, 

Talwar GP 

Microbiology Division, National Institute of Immunology, Jit Singh Marg, New Delhi, India. 

Immunotherapy with Mycobacterium w (M.w) vaccine was given to 45 patients with multibacillary 

(MB) leprosy; 41 similarly classified patients served as controls. All patients received standard 

multidrug therapy (MDT). Incidence, severity and frequency of type 2 (ENL) reactional episodes 

were monitored in both groups in a follow-up extending up to 4 years. Reactions were seen in fewer 

vaccinated (10/37) BL and LL patients than in the control group (12/34). A total of 20 episodes 

were recorded in the vaccine group as against 29 in the controls, 75% of reactions were mild in 

vaccinated and 51.72% were mild in the control group patients, and 3 patients in the control group 

had more than 3 reactional episodes. None of the vaccinated patients showed this. No additional 

incidence of neuritis were seen among vaccinated individuals during reactional episodes. 

============================================================ 

55.) A follow-up study of multibacillary Hansen's disease patients treated with multidrug therapy 

(MDT) or MDT + immunotherapy (IMT). 

============================================================ 

Int J Lepr Other Mycobact Dis 1997 Sep;65(3):320-7 Related Articles, Books, LinkOut 

Rada E, Ulrich M, Aranzazu N, Rodriguez V, Centeno M, Gonzalez I, Santaella C, Rodriguez M, 

Convit J 

Instituto de Biomedicina, Caracas, Venezuela. 

Multibacillary (MB) leprosy patients treated with multidrug therapy (MDT) or MDT + 

immunotherapy (IMT) with BCG + heat-killed Mycobacterium leprae were tested annually for their 

ability to proliferate in vitro to the mycobacterial antigens BCG, M. leprae soluble extract, and intact 

M. leprae. IgM antibody responses to phenolic glycolipid I (PGL-I) were measured, as well as 

serum nitrite levels in patients' sera, before, during and after treatment. Patients who received only 

MDT did not present cellular reactivity to intact M. leprae antigens, in contrast to the results 

obtained with BCG, which elicited reactivity at time zero, that increased after treatment. Regarding 

PGL-I antibody variations in relation to the initial value, we observed a statistically significant marked 

decrease at the end of 2 years which continued to fall in successive evaluations. MB patients showed 

high initial serum nitrite concentrations which dropped drastically with treatment. This decay was 

apparently associated with the bacillary load present in these patients. The group submitted to IMT 

+ MDT showed high and long-lasting T-cell responses to mycobacterial antigens in a significant 

number of initially unresponsive MB patients. There was a marked increase to M. leprae soluble 

extract and BCG, as well as a more variable response to whole bacilli. The antibody levels in this 

group of patients are sustained for a somewhat longer period and decreased more slowly during the 

5-year follow up. 

============================================================ 

56.) Immunotherapy of lepromin-negative borderline leprosy patients with low-dose Convit vaccine 

as an adjunct to multidrug therapy; a six-year follow-up study in Calcutta. 

============================================================ 

Int J Lepr Other Mycobact Dis 1997 Mar;65(1):56-62 Related Articles, Books, LinkOut 

Chaudhury S, Hajra SK, Mukerjee A, Saha B, Majumdar V, Chattapadhya D, Saha K 

School of Tropical Medicine, Calcutta, India. 

The present report, which describes management of lepromin-negative borderline leprosy patients 

with low-dose Convit vaccine, is an extension of our earlier study on the treatment of lepromatous 

leprosy patients with low-dose Convit vaccine as an adjunct to multidrug therapy (MDT). The test 

Group I, consisting of 50 lepromin-negative, borderline leprosy patients, were given low-dose 

Convit vaccine plus MDT. The control group II consisted of 25 lepromin-negative, borderline 

leprosy patients given BCG vaccination plus MDT and 25 lepromin-negative, borderline leprosy 

patients given killed Mycobacterium leprae (human) vaccine plus MDT. The control group III 

consisted of 50 lepromin-positive, borderline leprosy patients not given any immunostimulation but 

given only MDT. Depending upon the lepromin unresponsiveness, the patients were given one to 

four inoculations of the various antileprosy vaccines and were followed up every 3 months for 2 

years for clinical, bacteriological and immunological outcome. All patients belonging to the test and 

control groups showed clinical cure and bacteriological negativity within 2 years. However, 

immunologic potentiation, assessed by lepromin testing and the leukocyte migration inhibition test 

(LMIT), was better in the test patients receiving low-dose Convit vaccine plus MDT than in the 

control patients receiving BCG vaccine plus MDT or killed M. leprae vaccine plus MDT or MDT 

alone. But the capacity of clearance bacteria (CCB) test from the lepromin granuloma showed poor 

bacterial clearance in the test patients. However, there was no relapse during 6 years of follow up. 

Two mid-borderline (BB) patients had severe reversal reactions with lagophthalmos and wrist drop 

during immunotherapy despite being given low-dose Convit vaccine. 

============================================================ 

57.) Immunotherapy of far-advanced lepromatous leprosy patients with low-dose convit vaccine 

along with multidrug therapy (Calcutta trial). 

============================================================ 

Int J Lepr Other Mycobact Dis 1996 Mar;64(1):26-36 Related Articles, Books, LinkOut 

Majumder V, Mukerjee A, Hajra SK, Saha B, Saha K 

School of Tropical Medicine, Calcutta, India. 

This report describes a promising mode of treatment of lepromin-unresponsive, far-advanced, 

lepromatous (LL) leprosy patients with antileprosy vaccines as an adjunct to multidrug therapy 

(MDT). The Trial Groups included 50 highly bacilliferous, lepromin-negative, untreated LL patients. 

They were given MDT for 2 years. Of them, 30 patients were administered a mixed antileprosy 

vaccine containing killed Mycobacterium leprae of human origin plus M. bovis BCG. The remaining 

20 patients were given M. bovis BCG. Depending on the severity of lepromin unresponsiveness, 

they were given one to six inoculations at 3-month intervals. Another 20 similar LL patients were 

taken in the Control Group. They were given only MDT for 2 years. From the start of the study, all 

patients belonging to the Trial and Control Groups were followed every 3 months for clinical, 

bacteriological and immunological outcomes. Within 2 years all 50 patients of the Trial Groups and 

19 of the 20 patients of the Control Group became clinically inactive and bacteriologically negative. 

However, the clinical cure and the falls of the bacterial and morphological indexes were much faster 

in those patients receiving the mixed vaccine therapy than in those patients who were given BCG 

plus MDT or only MDT. The immunological improvements in the patients of the Trial and Control 

Groups were assessed by: a) lepromin testing at the beginning of the study and at 3-month intervals 

and also by b) the in vitro leukocyte migration inhibition (LMI) test at both the beginning and end of 

the study. As the patients were given more and more vaccinations, the incidence of lepromin 

conversion increased, more so in the patients receiving the mixed vaccine. Thus, 63%, 15% and 5% 

of the patients became lepromin positive in those patients receiving the mixed vaccine, BCG, and 

MDT only, respectively. Lamentably, the vaccine-induced lepromin positivity was temporary and 

faded away within several months. At the beginning of the study, the LMI test against specific M. 

leprae antigen was negative in all patients of both the Trial and Control Groups. After the end of the 

chemo-immunotherapy schedule, the LMI test became positive in 50% and 20% of LL patients 

receiving the mixed vaccine and BCG, respectively. None of the Control Group could show LMI 

positivity after completion of the MDT schedule. These results show that treatment of LL patients 

with the mixed vaccine and MDT could quickly reverse the clinical course of the disease, remove 

immunologic anergy in some patients, and induce a rapid decrease in the bacterial load in them. 

============================================================ 

58.) A longitudinal study of immunologic reactivity in leprosy patients treated with immunotherapy. 

============================================================ 

Int J Lepr Other Mycobact Dis 1994 Dec;62(4):552-8 Related Articles, Books, 

Rada E, Ulrich M, Aranzazu N, Santaella C, Gallinoto M, Centeno M, Rodriguez V, Convit J 

Instituto de Biomedicina, Caracas, Venezuela. 

More than 150 leprosy patients treated with multidrug therapy (MDT) plus immunotherapy (IMT) 

with a mixture of heat-killed Mycobacterium leprae plus live BCG were studied in relation to 

humoral and cell-mediated immune responses. Many previously had received prolonged sulfone 

monotherapy. Patients received 2 to 10 doses of IMT in a period of 1 to 3 years, depending upon 

their clinical form of leprosy. The patients were followed up for 5 to 10 years with repeated 

determinations of antibody levels to phenolic glycolipid-I; lymphoproliferative (LTT) responses to 

soluble extract of M. leprae, to whole bacilli and to BCG, skin-test responses and bacterial indexes 

(BIs). After MDT plus IMT there was a statistically significant decrease of antibody levels in the 

multibacillary (MB) group. The BI decreased proportionally to the ELISA results. LTT increased to 

M. leprae antigens, especially to soluble extract, in a high percentage of these patients (34% of LL 

patients positive). Lepromin positivity in MB patients increased from 5% initially positive to 75% at 

the cut-off during this follow up. These results show substantial early and persistent cell-mediated 

reactivity to M. leprae in many MB patients treated with MDT-IMT, confirming and expanding 

previously published data. 

============================================================ 

59.) BCG vaccination protects against leprosy in Venezuela: a case-control study. 

============================================================ 

Int J Lepr Other Mycobact Dis 1993 Jun;61(2):185-91 Related Articles, Books, LinkOut 

Convit J, Smith PG, Zuniga M, Sampson C, Ulrich M, Plata JA, Silva J, Molina J, Salgado A 

Instituto de Biomedicina, Caracas, Venezuela. 

A total of 64,570 household and other close contacts of about 2000 leprosy cases were screened 

for eligibility for entry into a trial of a new leprosy vaccine. The screening procedure included a 

clinical examination for leprosy and for the presence of BCG and lepromin scars. Ninety-five new 

cases of leprosy were identified, and the prevalence of BCG and lepromin scars among them was 

compared with similar data from matched controls selected from among those with no evidence of 

leprosy. The difference in the prevalence of BCG scars in the two groups was used to estimate the 

protection against leprosy conferred by BCG vaccination. One or more BCG scars was associated 

with a protective efficacy of 56% (95% confidence limits 27% to 74%). There was a trend of 

increasing protection with four or more BCG scars, but this was not statistically significant. There 

was no evidence that the efficacy of BCG varied with age or according to whether or not the contact 

lived in the same household as a case. The protective effect was significantly higher among males, 

and was significantly greater for multibacillary than for paucibacillary leprosy. 

============================================================ 

60.) Immunoprophylactic trial with combined Mycobacterium leprae/BCG vaccine against leprosy: 

preliminary results. 

============================================================ 

Lancet 1992 Feb 22;339(8791):446-50 Related Articles, Books, LinkOut 

Convit J, Sampson C, Zuniga M, Smith PG, Plata J, Silva J, Molina J, Pinardi ME, Bloom BR, 

Salgado A 

Instituto de Biomedicina, Caracas, Venezuela. 

In an attempt to find a vaccine that gives greater and more consistent protection against leprosy than 

BCG vaccine, we compared BCG with and without killed Mycobacterium leprae in Venezuela. 

Close contacts of prevalent leprosy cases were selected as the trial population since they are at 

greatest risk of leprosy. Since 1983, 29,113 contacts have been randomly allocated vaccination with 

BCG alone or BCG plus 6 x 10(8) irradiated, autoclaved M leprae purified from the tissues of 

infected armadillos. We excluded contacts with signs of leprosy at screening and a proportion of 

those whose skin-test responses to M leprae soluble antigen (MLSA) were 10 mm or more 

(positive reactions). By July, 1991, 59 postvaccination cases of leprosy had been confirmed in 

150,026 person-years of follow-up through annual clinical examinations of the trial population (31 

BCG, 28 BCG/M leprae). In the subgroup for which we thought an effect of vaccination was most 

likely (onset more than a year after vaccination, negative MLSA skin-test response before 

vaccination), leprosy developed in 11 BCG recipients and 9 BCG/M leprae recipients; there were 

18% fewer cases (upper 95% confidence limit [CL] 70%) in the BCG/M leprae than in the BCG 

alone group. For all cases with onset more than a year after vaccination irrespective of MLSA 

reaction the relative efficacy was 0% (upper 95% CL 54%; 15 cases in each vaccine group). 

Retrospective analysis of data on the number of BCG scars found on each contact screened 

suggested that BCG alone confers substantial protection against leprosy (vaccine efficacy 56%, 95% 

CL 27-74%) and there was a suggestion that several doses of BCG offered additional protection. 

There is no evidence in the first 5 years of follow-up of this trial that BCG plus M leprae offers 

substantially better protection against leprosy than does BCG alone, but the confidence interval on 

the relative efficacy estimate is wide. 

===================================================================== 

61.) Why relapse occurs in PB leprosy patients after adequate MDT despite they are Mitsuda 

reactive: lessons form Convit's experiment on bacteria-clearing capacity of lepromin-induced 

granuloma. 

===================================================================== 

Int J Lepr Other Mycobact Dis 1998 Jun;66(2):182-9 

Chaudhuri S, Hajra SK, Mukherjee A, Saha B, Mazumder B, Chattapadhya D, Saha K 

Department of Leprosy, School of Tropical Medicine, Calcutta, India. 

It is amazing how after years of scientific research and therapeutic 

progress many simple and basic questions about protective immunity against 

Mycobacterium leprae remain unanswered. Although the World Health 

Organization (WHO) has recommended short-term multidrug therapy (WHO/MDT) 

for the treatment of paucibacillary (PB) leprosy patients, from time to 

time several workers from different parts of the globe have reported 

inadequate clinical responses in a few tuberculoid and indeterminate 

leprosy patients following adequate WHO/MDT despite the fact that they are 

Mitsuda responsive. A few borderline tuberculoid patients harbor acid-fast 

bacilli (AFB) in their nerves for many years even though they become 

clinically inactive following MDT, a fact which has been ignored by many 

leprosy field workers. Keeping these patients in mind, we have attempted to 

investigate the cause of the persistence of AFB in PB cases and have looked 

into the question of why Mitsuda positivity in tuberculoid and 

indeterminate leprosy patients, as well as in healthy contacts, is not 

invariably a guarantee for protectivity against the leprosy bacilli. We 

have: a) analyzed the histological features of lepromin-induced granulomas, 

b) studied the bacteria-clearing capacity of the macrophages within such 

granulomas, and c) studied the in vitro leukocyte migration inhibition 

factor released by the blood leukocytes of these subjects when M. leprae 

sonicates have been used as an elicitor. The results of these three tests 

in the three groups of subjects have been compared and led us to conclude 

that the bacteria-clearing capacity of the macrophages within 

lepromin-induced granuloma (positive CCB test) may be taken as an indicator 

of the capability of elimination of leprosy bacilli and protective immunity 

against the disease. This important macrophage function is not invariably 

present in all tuberculoid and indeterminate leprosy patients or in all 

contacts even though they are Mitsuda responsive and are able to show a 

positive leukocyte migration inhibition (LMI) test. It is likely but not 

certain that this deficit of the macrophage is genetically predetermined 

and persists after completion of short-term WHO/MDT. Thus, after 

discontinuation of treatment slow-growing, persisting M. leprae multiply 

within macrophages leading to relapse. 

========================================================================= 

62.) A lost talisman: catastrophic decline in yields of leprosy bacilli 

from armadillos used for vaccine production. 

========================================================================= 

Int J Lepr Other Mycobact Dis 1999 Mar;67(1):67-70 

Storrs EE 

Publication Types: 

Letter 

========================================================================= 

=========================================== 

63.) RESEARCH IN LEPROSY - ( H.D.) 

=========================================== 

LEPROSY - RESEARCH AND BEYOND THE YEAR 2000 

Be sure to access - http://www.webspawner.com/users/SkilliIBS - with its many leprosy LINKS 

You are invited to subscribe to (FREE) and share in our Newsgroup - alt.support.leprosy If your 

ISP cannot help you, you may FIND the Group at :- http://dejanews.com using search-filter and 

create-filter buttons 

Leprosy (Hansen’s Disease) has been one of the most dreaded of all diseases because, even though 

one may recover clinically, both through the body’s own self-healing immune response and/or 

through chemotherapy, nerve damage can result in lifelong crippling deformities. In some 

communities, its sufferers are the victims of intense social prejudice, discrimination and stigma. For 

centuries, leprosy has been shrouded in mysteries, myths and religious superstitions to the point 

where it has been called “The Living Death”. 

Until the year 1950, when Diamino Diphenyl Sulphone (Dapsone or DDS) became available, there 

was no real cure for the disease. Chaulmoogra Oil / Hydnocarpus Oil or derivatives such as Sodium 

Hydnocarpate were the only hope the patients had of recovery. Even then, DDS, being a 

bacteriostatic drug, does not actually kill the leprosy bacilli but only prevents their multiplication. For 

many years, it did seem that Dapsone would eventually help us in eliminating leprosy, until resistant 

organisms began to appear. Fortunately, new and more potent drugs such as Rifampicin ( used also 

in treating T.B.) became available and, using this drug, in combination with other drugs (Multi Drug 

Therapy or MDT), has given real hope that, sometime in the future, the elimination of Hansen’s 

disease could possibly become a reality. 

After extensive trials, in 1981, the World health Organisation (W.H.O.) recommended the use of 

three drugs (Dapsone, Clofazamine and Rifampicin), in a two year course, against the more 

infectious lepromatous or multibacilliary forms of the disease and two drugs (Dapsone and 

Rifampicin), in a six months course in treating the less infectious Paucibacilliary forms. This treament 

(MDT) has brought new hope to millions of sufferers and, combined with more efficient means of 

diagnosis, has resulted in the prevention of much ulceration, crippling deformities and other 

disabilities. In addition to this, intensive health educational programmes have resulted in the curbing 

of much misunderstanding, superstition and stigma. 

So spectacular has been the control programmes , using MDT, that millions have been completely 

cured of the disease in recent years, enabling the W.H.O., in 1991, to give serious consideration to 

actually eliminating the disease as Smallpox has been eradicated. In 1991, the W.H.O. adopted a 

resolution in its International Assembly, setting the goal of -- “Eliminating Leprosy as a Public Health 

Problem by the year 2000”. “Elimination” was defined as attaining a level of prevalence below one 

case per 10,000 population in a given society. Today, almost every registered leprosy patient in the 

world has access to free MDT resulting in the curing, over the past 10 years, of nearly 8 million 

leprosy sufferers world-wide. It is true to say that this dreaded disease has been reduced by as much 

as 80%, thanks to the W.H.O. and the associated 20-odd non-govt. international Member 

Organisations of ILEP (International Federation of Anti-Leprosy Associations) . 

THE CHALLENGE to face the remaining 20% of the leprosy problem must save us from a spirit of 

complacency. Sadly, there are many people who imagine that, by the year 2000, no cases of leprosy 

will exist . In actual fact, LEPROSY, WITH ALL ITS SUFFERINGS, WILL BE AROUND FOR 

A LONG TIME TO COME - WELL INTO THE 21st. CENTURY. 

While the W.H.O. is to be applauded for undertaking this enormous effort, certain concerns remain 

and TLM is to be commended for highlighting the following:- :- 

1. MDT has not been implemented yet in all endemic areas. In some regions, because of political 

instability, it is virtually impossible for control teams to enter. 

2. Killing bacilli (M.leprae) by chemotherapy (MDT), is only one measure of successful treatment of 

leprosy. Nerve damage, which, being leprosy’s hall-mark, is not reversed by MDT. Many treated 

patients still need rehabilitation and others suffer from the enormous psychological stigma of the 

disease. 

3. Relapse rate may rise with time. This has been observed since the introduction of MDT. To 

control costs, WHO.’s MDT regimen is truncated. Early data suggests that relapse of clinical 

leprosy, years after completion of MDT, may become a greater problem than anticipated. 

4. Although the prevalence rate of leprosy is falling as patients are enrolled on MDT, the incidence of 

new cases has remained constant at > 650,000 new cases per year. 

5. Vertical leprosy control programs are being discontinued and integrated with primary health care 

programs. As dedicated field workers are declared unneeded and made redundant, they will not be 

available to detect new cases or relapsed disease. General public health personnel are not being 

adequately trained in differential diagnosis to detect the signs and symptoms of early leprosy. 

6. Funding sources for leprosy research already have begun to dry up and, in the face of this 

prophecy, causing a serious “brain-drain” of dedicated , productive researchers with the necessary 

expertise. 

7. While self-serving cries for the mere continuation of leprosy research must be avoided, there is a 

concern that we may be dismantling the very research and control measures needed to eventually, 

truly control leprosy around the globe, a costly mistake already made in relation to malaria and 

tuberculosis control efforts. 

Out there in Cyberspace, are there any who feel a call to study Microbiology - to help us find the 

elusive anti-leprosy vaccine? 

Please do not imagine that this is merely a “medical issue” . It has enormous social implications, 

particularly in view of the prevailing stigma, persistent misinformation and religious superstitions 

concerning the disease. 

Please don’t think that your country or your particular race are immune to the disease. Leprosy is no 

respecter of persons, whatever be your creed, culture or social status. It is an insidious disease, but 

one that, with early detection, proper diagnosis and adequate MDT, is totally curable with all its 

horrendous deformities, ulcerations, blindness and disfigurement, totally preventable. Just because 

funds are short, there is no need for us to become complacent. Until we have that anti-leprosy 

vaccine and eradicated the stigma of the disease, we must remain vigilant. To gain a glimpse of what 

the fate of leprosy sufferers could again possibly become, because of our apathy, please read :- 

============================================================ 

64.)THE CHALLENGE OF LEPROSY” at :- INDIA APPROVES LEPROSY VACCINE ( 

Ganapati Madur, New Delhi ) 

============================================================ 

(Reproduced from the British Medical Journal, Feb. 1998 ) 

A vaccine against leprosy has been approved by India’s drug control agency and is to be 

incorporated into the national eradication programme. The vaccine is designed to be used as an 

adjunct to standard Multi-Drug-Therapy to accelerate healing and reduce the duration and cost of 

treatment. 

The vaccine, developed at the National Institute of Immunology in New Delhi, is said to be the first 

in the world that stimulates the immune system to kill Mycobacterium leprae. The vaccine, 

administered intradermally, is prepared from a non-pathogenic strain of Mycobacterium, first isolated 

in the mid-1970’s from the sputum of a patient with tuberculosis in Madras. 

“Patients who receive the vaccine and standard anti-leprosy multi-drug-therapy, show faster clinical 

improvement and more rapid clearance of bacteria than those who receive only drugs”, said Dr. 

Rama Mukherjee, a senior scientist at the institute. “Whereas multi-drug-therapy, using Rifampicin 

and two other drugs, takes 12 - 24 months, the vaccine will help to reduce duration of treatment by 

at least six months in the most severe cases”, Dr. Mukherjee said. 

We expect this vaccine to provide a big boost to the leprosy eradication programmes”, said Dr. 

Manju Sharma, secretary of India’s department of biotechnology, which invested about 20 million 

rupees (approx. 300,000 pounds sterling or $480,000 ) in the project. 

Leprosy is prevalent across Asia, Africa and Latin America, but India accounts for 60% of the 

global pool of patients with leprosy, estimated to be about one million in 1996. One fifth of patients 

are below the age of 18 years. 

The vaccine is based on the concept of “cross reacting antigens”, in which the killed Mycobacterium 

strain is used used to stimulate the immune system into mounting an attack on M.leprae. “This is 

possible because the two bacilli have cross-matching antigens”, said Dr. Mukherjee. The first 

commercial batch is expected to be released by June 1998, and will be sold in India at Rupees six 

(10 British pence) a dose. 

Health Ministry officials, however, have expressed reservations about the impact of the vaccine in 

the leprosy eradication programme. “We don’t see any real advantage of using this adjunct. Patients 

who are on standard multidrug-therapy are not expected to feel any benefit from the faster clearance 

of the bacteria brought about by the vaccine. Drug treatment alone does lead to complete elimination 

of bacteria, although the process may be slower,” said a senior official. 

Others argue that the vaccine has been known to cure the disease and clear bacteria within six 

months in some patients. “It will also help prevent reactivation of the disease in the most severe 

cases”, said Gursaran Talwar, former Director of the National Institute of Immunology. India is 

nowhere near eradicating leprosy with the current treatment available. Last year, the health teams 

detected 400,000 new cases of leprosy. 

Institute scientists say that the immunoprophylactic role of the vaccine is also under investigation. 

Over the past eight years, nearly 23,000 healthy contacts of patients have received the vaccine. The 

results of this study are not expected for another three years because of the long gestation period of 

the leprosy bacteria. 

(Extract from a WHO document) 

......... While no specific vaccination has yet been identified, it has been recently shown that some 

protection is given after a second BCG injection. However, widespread vaccination campaigns are 

not considered worthwhile 

COMMENT ON THE NEW INDIAN VACCINE BY THE LEPROSY MISSION’s MEDICAL 

CONSULTANT, Dr. MICHAEL WATERS (12 March, 1998). 

(Extract from TLM’s “Newslink” Issue #32, April 1998 ) 

“It is clearly noted that this vaccine is being introduced as an adjunct to standard 

Multi-Drug-Therapy (MDT), for treatment (immunotherapy) of established cases of leprosy. 

Hansen was the first to attempt immunotherapy. After the introduction of Dapsone, the method fell 

into disuse, until 1982. Convit claimed that repeated injections of live BCG, plus dead M.leprae (the 

leprosy bacillus) produced clinical improvement, and a more rapid fall in the bacteriological index 

(B.I.) in lepromatous cases, and improved resistance (immunological status) in old, smear-negative 

lepromatous patients. 

A number of other workers have used vaccines prepared from non-pathogenic, easily grown, related 

Mycobacteria (the family of bacteria to which the leprosy bacillus belongs) and recently, 

immunological substances produced by genetic engineering. 

These studies, including those carried out using the Mycobacterium “W” - the Indian vaccine - have 

shown that the vaccines aid the removal of dead leprosy bacilli from the injection site, and, to a 

lesser extent, from further away, i.e. the B.I. falls faster. Improved patient resistance (produced by 

the vaccinations) is more variable, though the effect does occur certainly in some smear negative 

lepromatous patients. 

Whether or not the vaccines kill leprosy bacilli is much less certain, and whether or not they will 

allow the duration of treatment to be significantly shortened, without increasing relapse rate, can only 

be proved by long term studies, not yet completed. 

There are on-going studies which seek to identify the protective antigens of the leprosy bacillus. 

Once these have been identified, the genetic engineering technology is largely available, to allow a 

more specific “second generation” vaccine to be produced.“ (Michael Waters, 12 March, 

CONFLICTING REPORTS:- 

We often are asked to clarify what some people think are “Conflicting Reports”. It has been 

reported that there are now only 1.8 Million (or even less) leprosy sufferers world-wide. These are 

those patients who have been reported and who have been brought under treatment (MDT). 

However, many leprosy sufferers have yet to be detected and, because of the inefficiency in data 

collecting and reporting in some endemic countries, accurate statistics may not be available. A 

leprosy sufferer AFFECTED by leprosy may have been totally cured (bacteriologically or clinically) 

through MDT and so removed from the register, inspite of the fact that he/she may still be the victim 

of repeated ulceration and deformity etc., due to nerve damage and lack of health education. Further 

to that, due to society’s prejudice and the resultant stigma, the patient may have no job opportunity 

and no self-esteem. 

In some patriachal, male chauvinistic areas, women sufferers are sometimes hidden away and locked 

up. 

============================================================ 

65.) A vaccine for leprosy 

============================================================ 

From the publishers of THE HINDU 

Vol. 15 :: No. 06 :: Mar. 21 - Apr. 3, 1998 

The development of a vaccine to counter multibacillary leprosy is a significant event for India, which 

has the largest number of leprosy patients in the world. 

T.K. RAJALAKSHMI 

in New Delhi 

A VACCINE to "immunise" patients suffering from a severe type of leprosy, called the Multibacillary 

(M.B.) leprosy, has been developed by Dr. G.P. Talwar, founder-Director of the National Institute 

of Immunology. The vaccine, Mycobacterium w (the code name under which this species of bacteria 

was investigated), was launched in the market on January 30. The institute has also received from the 

Drugs Controller of India authorisation for its commercial production. "While research on a leprosy 

vaccine goes on in many parts of the world, this is one which has signalled the end of the search," 

Talwar told Frontline. 

The M.B. type is a severe type of leprosy. Patients afflicted with it serve as reservoirs of infection. 

They have failed to respond to lepromin, the antigen for ordinary cases of leprosy. 

S. ARNEJA 

 Dr. G.P. Talwar, founder-Director of the National Institute of Immunology. 

Nearly 99 per cent of all human beings are resistant to leprosy and are able to eliminate M.leprae 

infection, according to epidemiological studies. Among those who are afflicted with the disease, 

nearly a quarter contract the M.B. type. They are the ones who serve as a hospitable base from 

which the bacilli can spread, wrote Talwar in his paper titled 'An Immunotherapeutic Vaccine for 

Multibacillary Leprosy'. Only the administration of drugs for two to five years was found to cure 

patients of the M.B. grouping. "Multibacillary patients need a long period of treatment," Talwar 

says. 

In the clinical trials conducted so far, the Mw vaccine has been found to be effective when used in 

combination with chemotherapy and immunotherapy. The vaccine has gone through three phases of 

clinical trials in rural and urban leprosy control centres. While Phase I involved the administration of 

the vaccine to M.B. leprosy patients who had gone through chemotherapy, Phases II and III 

explored its preventive or immunoprophylactic potential. However, owing to the long latent period of 

the disease (two to 10 years), Talwar said that immunoprophylactic studies would need up to 12 or 

15 years to get conclusive results. However, he said that trials were being conducted in a community 

block of Kanpur Dehat in tandem with the National Leprosy Eradication Programme and in 

collaboration with the Uttar Pradesh Health Directorate. A similar trial was on at Chengalpattu in 

Tamil Nadu, he said. 

The vaccine's potential to confer immunity on M.B. leprosy patients was also explored. The vaccine 

was administered along with the standard multi-drug treatment (MDT) recommended by the World 

Health Organisation (WHO) to two groups, one in Delhi and the other in Kanpur Dehat. It was 

found that this shortened the treatment period. Besides, considerable clinical improvement was 

noticed with two or four doses of the vaccine. Talwar said that an independent study by the Leprosy 

Research Institute in Agra showed that the lepra bacilli in M.B. patients with a Bacillary Index were 

rendered non-viable within six months of combined treatment with multiple drugs and one or two 

injections of the Mw vaccine. It was found that M.leprae continued to thrive in patients who were 

not given the vaccine but were administered only chemotherapy with the recommended MDT. 

S. ARNEJA 

 A lepromatous leprosy patient at the time of enrolment in the trial. 

The advantages of the vaccine are that it expedites "bacterial clearance" and "accelerates clinical 

regression of lesions", according to Talwar. During clinical trials, a faster rate of decline of the 

bacteriological load was detected in patients who were given the vaccine, compared to those who 

received only the MDT and a placebo. The vaccine was found to upgrade immunity and help clear 

granulomas (lesions) quickly. No reactions were caused other than those noticed during MDT 

therapy. By killing the M.leprae within six months, the vaccine ensured that the disease did not 

spread from the patient. 

S. ARNEJA 

 The same patient after four doses of Mw vaccine and standard MDT for one year. 

Talwar said that while the prevalence of leprosy had gone down in some countries, the incidence of 

the disease continued to be alarming in many others, including India. He said that this was because of 

the continuing existence of a foyer of infection. 

The development of the vaccine is a significant achievement. Since the 1970s, when there were 

around four million leprosy patients in India, it was felt that the eradication of the disease was 

impossible unless its spread from the principal reservoir, that is, human beings, was controlled. The 

disease is prevalent in several states of India, which has the largest number of leprosy patients in the 

world. What is alarming is the latent gestation of the disease. The M.B. type was found to be 

non-auto-regressive unlike other forms such as tuberculoid leprosy, Talwar said. 

In a paper published in 1978, Talwar, who was then the head of the Indian Council of Medical 

Research(ICMR)-WHO Training Centre in Immunology at the All India Institute of Medical 

Sciences, New Delhi, pointed out that the latent period of the disease was long and many patients 

could be agents of transmission even before they were spotted and treated. The research on the 

vaccine began then. Although the research began at the AIIMS, it was during his tenure as the 

Director of the NII that clinical trials with the Mw vaccine were conducted. 

"This vaccine will play a very important role in the eventual eradication of leprosy," said Talwar, a 

recipient of the Padma Bhushan. He is currently Professor of Eminence and Senior Consultant at the 

International Centre for Genetic Engineering and Biotechnology. 

================================================ 

66.) FREQUENTLY ASKED QUESTIONS about Leprosy / Hansen’s Disease 

================================================ 

THE LEPROSY MISSION INTERNATIONAL 

80 Windmill Road, Brentford, Middlesex, 

Britain, U.K. TW8 OQH 

1. WHAT IS LEPROSY ? - Leprosy is a slightly contageous disease caused by a tiny rod-like germ 

called Mycobacterium Leprae (M.leprae) . It was first discovered by Dr. G.A. Hansen in 1873. 

2. HOW MANY PEOPLE SUFFER FROM LEPROSY TODAY ? Nobody knows exactly, 

because figures from countries where leprosy is a problem are both incomplete and unreliable. 

Approximately 6.5 million is a conservative estimate of the number affected by leprosy and only one 

in four is getting regular, effective treatment. 

3. WHERE DOES LEPROSY OCCUR ? In practically every country in the world. However, most 

of the sufferers are to be found in the populous countries of South East Asia, Africa and South 

America. There are 3.5 million in India. 

4. IS LEPROSY HEREDITARY ? No, but infants may catch the disease from a parent and show 

the first signs of infection after an incubation period of from two to five years. 

5. SHOULD LEPROSY SUFFERERS BE SEGREGATED ? It is not necessary, advisable or even 

possible to segregate sufferers from leprosy. A high percentage of cases are unable to pass the 

disease on and the most contageous types are the hardest to recognise. Forcible segregation usually 

leads to concealment which makes early, effective treatment impossible and aggravates the problem. 

6. ARE THERE DIFFERENT KINDS OF LEPROSY ? Yes. But this depends on a person’s 

resistance to the disease, not the type of germ. There is only one leprosy germ, but people react to it 

in different ways. Many people resist leprosy so well that they will never develop clinical signs even 

though exposed to active cases for long periods. If a person has no resistance, the germ multiplies 

freely in the skin, the lining of the nose and even deep in organs like the liver. This is lepromatous, 

“multibacilliary” leprosy. Other types are:- tuberculoid, borderline, indeterminate and polyneuritic, 

which are “paucibacilliary”, and each with their own set of symptoms. 

7. WHAT ARE THE EARLY SIGNS OF LEPROSY ? The early signs and symptoms can vary 

considerably, depending on the patient’s resistance to the disease. They can be easily missed or 

mistaken for some other disease by the untrained person. People with lepromatous leprosy usually 

develop a skin rash or nodules while tuberculoid leprosy might first show itself as an area of 

numbness or “pins and needles”. Dark-skinned people sometimes have patches which are paler in 

colour than their normal skin. There is no one “first sign” of leprosy and careful examination by a 

competent doctor with the examination of skin smears under a microscope are necessary for correct 

diagnosis 

3. HOW IS LEPROSY CAUGHT ? Scientifically speaking, it is almost impossible to prove how the 

leprosy germ gets from one person to another, but people with lepromatous leproy expel large 

numbers of germs from their nose and mouth. It may be that they get into the body the same way. 

Other theories are that blood-sucking insects and close skin to skin contact could be ways of 

transmitting the disease. The discharge from ulcers on the hands and feet very rarely contains live 

leprosy germs. 

4. CAN LEPROSY BE CURED ? Yes, it can and the earlier the treatment is begun, the better the 

hope of a complete recovery. The most severe kinds of leprosy take much longer to cure than those 

of types which occur in people with some degree of resistance. However, even after a few days of 

multi-drug treatment, all patients are rendered non-contageous and they can no longer pass the 

disease on to others. 

5. WHAT MEDICINES ARE USED FOR LEPROSY TREATMENT ? Until recently, the most 

commonly used drug has been “diamino-diphenyl-sulphone” (DDS or Dapsone) . But because of the 

widespread incidence of Dapsone resistance over recent years, the World Health Organisation now 

recommends using several drugs in combination for the treatment of leprosy. The most useful of 

these are - Rifampicin, Clofazamine and Dapsone. This multi-drug-therapy (MDT) greatly increases 

the cost of treatment, but also considerably reduces the length of time a patient needs treatment. 

6. CAN LEPROSY BE PREVENTED ? So far, no specific vaccine against leprosy is available. 

The best way of preventing the transmission of the disease is to reduce the infectivity of all 

contageous cases as quickly as possible. 

7. WHY DO PATIENTS WITH LEPROSY BECOME CRIPPLED ? Not all patients become 

crippled. Many become healed without any treatment at all and others who have been diagnosed 

and treated in the early stages of the disease suffer no deformity. The main cause of deformity in 

leprosy patients is nerve damage. This occurs because the leprosy germs have a peculiar liking for 

nerve tissue and multiply freely between nerve fibres. When the leprosy germs die or are killed by 

the medicines, the resulting inflammation compresses and destroys these delicate fibres with more or 

less complete loss of function. So feeling is lost and muscles are paralysed. The end result is 

ulceration and deformity. 

8. CAN ANYTHING BE DONE FOR THE DEFORMITIES THAT ARISE FROM 

NEGLECTED LEPROSY ? Yes, the techniques of reconstructive surgery may be used to help 

restore function and appearance to tissue damaged by leprosy. Deformities of hands, feet and face 

may be corrected, but no operation can restore lost sensation. Even when nerves are partly 

destroyed, the patients must be educated in the careful use of their insensitive hands and feet so that 

they do not injure themselves. 

9. ARE OTHER FORMS OF TREATMENT USED IN LEPROSY ? Physiotherapy is employed 

to maintain the mobility and strength of partly paralysed muscles, and to educate the patients in the 

prevention of deformities. Occupational therapy can teach patients how to gain their livlihood without 

damaging their hands and feet 

10. WHAT HAPPENS WHEN PATIENTS ARE CURED ? If, as is now usually the case, they 

have been receiving treatment at an outpatient clinic, they carry on with normal daily activities, 

reporting for re-examination at prescribed intervals. If they have been in hospital for a long time, they 

may face a difficult period of social and domestic re-adjustment. In a few favoured countries, they 

may be able to obtain work in some kind of sheltered workshop. 

11. WHAT IF PATIENTS ARE UNABLE TO EARN A LIVING ? Many former leprosy patients 

are so crippled permanently that they will need food and shelter for their remaining days. The size of 

this problem is such that all available resources could, in some countries, be swallowed up in simply 

caring for this large group of unfortunate people. If this course were taken, then, many suffering from 

untreated leprosy would, in time, develop crippling deformities. However, Christians cannot neglect 

those who, having caught leprosy before treatment became available, are now hopelessly crippled. 

The opportunity for compassionate service constitutes a real challenge to Christians. 

12. HOW DID THE LEPROSY MISSION (TLM) BEGIN ? In 1874, a group of Christians in 

Dublin pledged to support a young schoolmaster in India. Wellesley Bailey was giving his spare time 

in service to a group of leprosy sufferers in Ambala, in the Punjab. Soon, he was giving all his time to 

this work and more money was coming from the homeland in support of this and allied ventures. So 

the work grew, and today, support for the Mission’s work in over thirty countries comes from all 

over the world. 

13. HOW DOES THE LEPROSY MISSION WORK ? Besides maintaining its own centres or 

personnel in India, Africa, Bhutan, Bangladesh, Nepal, Papua New Guinea, Indonesia, Korea and 

China, the Mission also aids substantially the leprosy work in many Christian churches and 

missionary societies in Africa, India and other parts of Asia. 

14. WHAT ARE THE NEEDS OF T.L.M. ? It requires such trained and dedicated workers as 

doctors, nurses, physiotherapists and administrators, to serve in the centres owned and aided by 

TLM. It also relies on men and women who, by their prayers and generous giving, enable the work 

to continue and expand. 

THIS SITE WAS LAST UPDATED ON 25th. JUNE 1999 

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67.) Leprosy Elimination 

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Shortening Duration of Treatment 

Leprosy Elimination 

What is meant by eliminating leprosy as a public health problem? 

This means reducing the proportion of leprosy patients in the community to very low levels, 

specifically below one case per 10 000 population. 

Why has a prevalence of below one case per 10 000 population been chosen as the level of 

elimination? 

There are indications that around the prevalence level of one in 10 000, there is a tendency for the 

disease to die out, and any resurgence of the disease is highly improbable. 

At what level of population cluster is elimination expected to be achieved? 

Ideally elimination should be attained at all levels - regionally and nationally. However, in view of the 

uneven distribution of the disease, it is not always possible to envisage attaining the targeted 

prevalence level of one in 10 000 population for every local population cluster by 2000. At the 

minimum, we will attain elimination levels at the national level, and for larger countries at the first 

sub-national level (province or state). 

Will new cases of leprosy continue to occur beyond the year 2000? 

New cases will continue to occur in small numbers beyond the year 2000 as a result of the disease 

making an appearance in individuals who acquired their infection several years earlier as is usual in 

leprosy: the incubation of leprosy germs is exceptionally long (from 3 to 10 years or more). The new 

cases cannot be immediately detected in the community and it has been shown that they usually start 

infecting their contacts before they become aware of any change in their own health or their 

appearance. 

If we can interrupt the transmission of infection with leprosy organisms in the community, will that be 

enough to eliminate the disease as a public health problem? 

With very high coverage of MDT, it is expected that the pool of infectious sources will be wiped out 

in the course of time, and transmission of infection with M. leprae will cease. 

Is there a risk of re-emergence of the disease after its elimination (less than one case per 10 000)? 

Transmission of the disease is low and available observation indicate that there is no chance for the 

disease to spread again provided that the elimination target has been achieved even in small 

communities. 

What epidemiological advantages over other diseases does leprosy have that make elimination 

possible? 

1. We have a curative treatment for leprosy that is short, simple and provided to all. 

2. the infected human being is the only reservoir and source of infection; 

3. below a certain level of prevalence, any resurgence of the disease is very unlikely; 

4. unlike tuberculosis, where HIV-positive individuals have lower resistance to the disease, the 

leprosy situation does not appear to be adversely affected by HIV infection 

Will new cases of leprosy continue to occur beyond the year 2000? Will the attainment of the goal of 

elimination mean the end of leprosy work? What actions will be needed in the post-elimination 

period? 

Elimination leprosy will not mark the end of leprosy activities. Special strategies will have to be 

developed for both situations, towards elimination and after elimination phases. 

1. When a country reaches the point of elimination, the management of the few cases occurring 

afterwards will be addressed by a simplified surveillance system 

2. It will be necessary to keep up the level of interest and involvement from the policy makers. 

3. Training of health workers in leprosy work will have to be pursued 

4. Awareness of leprosy in the community should be kept at a reasonable level 

5. The task of rehabilitation of the former leprosy patients will have to be addressed in all countries 

with the assistance of Governments and NGOs. 

In some countries leprosy patients are being isolated from the rest of society. Is WHO doing 

something about this? 

Since the 1960s WHO advertise and support ambulatory treatment of leprosy patients and 

recommend that the patient stay with his family. Currently, with Leprosy Elimination Campaign 

(WHO initiative), leprosy has become a skin disease as any other. Treatment is provided by any 

health facility. 

Shortening Duration of Treatment 

What is the reason for shortening the duration of MDT to Multibacillary or MB patients to 12 

months? 

The most important component of the MDT regimens is rifampicin. The majority of 

rifampicin-susceptible M. leprae are killed by a few monthly doses of rifampicin. Recently it has been 

shown that the daily combination of dapsone and clofazimine is highly bactericidal. This combination 

is capable of eliminating any rifampicin-resistant mutants in an untreated MB leprosy patient within 

three to six months. Several studies have demonstrated that MB leprosy patients who received less 

than 24 monthly doses of MDT, responded as favourably as those who received 24 or more doses 

of MDT. Therefore, the Seventh WHO Expert Committee considered that the duration of treatment 

of MB leprosy can be reduced to 12 months without compromising the efficacy of the MDT 

regimen. 

Is there any problem foreseen in treating MB patients with a high bacteriological index (BI) with 

12-month MDT regimen? 

Multibacillary patients starting with a high bacterial index (BI) may have a higher risk of developing 

reactions and nerve damage during the second year than those patients starting with a low bacterial 

index. Secondly, this group of patients starting with high bacteriological index are likely to show 

clearance of skin lesions more slowly and are likely to have a significant level of bacterial index at the 

end of 12 months compared with those starting with lower BI. While most of the high BI patients will 

continue to improve even after stopping the 12 months of treatment, some may show evidence of 

deterioration and will need an additional 12 months of MDT for multibacillary leprosy. 

Will shortening the duration of MDT for multibacillary leprosy increase the risk of M. leprae 

developing resistance to rifampicin? 

No, there is no risk, if the patient takes all the drugs prescribed in the MDT. Several studies have 

demonstrated that even a few doses of rifampicin kill all organisms susceptible to rifampicin. The 

naturally occurring rifampicin-resistant mutants are killed by the clofazimine/ dapsone combination. 

Therefore, the chances of finding any live bacilli after 12 doses of MDT are almost nil. 

How can we minimize this risk to MB patients with high bacterial index? 

Fortunately MB (multibacillary) patients with high bacterial index are becoming rare in most of the 

leprosy programmes. WHO estimates that their proportion among newly detected cases is less than 

15%. There is evidence that three to six months administration of MDT kills all live organisms. 

Secondly more and more programmes are classifying leprosy patients on clinical criteria as skin 

smear services are either not available or not reliable. If a programme can identify patients with high 

bacterial index and those at the risk of developing reactions/neuritis by clinical and/or bacteriological 

examination, then such selected patients may be kept on surveillance for one to two years to 

diagnose deterioration and reactions as early as possible. Any patient showing signs of deterioration 

can be given one more course of 12 month MDT. Patients with reactions can be successfully 

managed by a standard course of prednisolone. The most important activity will be to educate the 

patients at the time of stopping treatment about the signs/symptoms of relapse and request them to 

report immediately to the nearest health centre when such problems arise. 

How should we deal with MB leprosy patients who are currently on treatment and have completed 

12 or more monthly doses of MDT? 

According to the recommendation, all MB (multibacillary) patients who have completed 12 or more 

doses of WHO MDT for multibacillary leprosy should be regarded as cured and removed from the 

registers. However, as usual, all patients should be educated about the signs/symptoms of reactions 

and relapse and asked to report immediately to the nearest health centre when such problems arise. 

In some control programmes, after completion of MDT, patients continue with a single drug, usually 

dapsone, for various lengths of time. Is this necessary? 

The continuation of dapsone monotherapy after a course of MDT is totally unnecessary. Some 

control programmes may be using this to ensure regular follow-up; to satisfy patients who are not 

willing to discontinue treatment; or in situations where the physician may not be convinced of the 

efficacy of MDT. Whatever the reason, this approach puts an unnecessary burden on the patient and 

on the field workers and is not recommended. 

Is post-MDT surveillance of patients essential? 

Because the risk of relapses after completion of the WHO MDT regimens has been negligible, it is 

no longer necessary to continue active post-MDT surveillance. Instead, patients should be taught at 

the time of release from treatment to recognize early signs of possible relapses or reactions and to 

report promptly for treatment. 

 

 

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68.) 'LEPROSY' IN THE BIBLE - WHAT WAS IT? 

================================================ 

Superstition and false religious beliefs can have devastating PSYCHOLOGICAL effects 

Be sure to access http://www.webspawner.com/users/SkilliIBS/ with its many leprosy LINKS 

Leprosy is a very enigmatic subject. Often it is associated with the Bible but only in the older 

versions. Most of the later translations render the Hebrew and Greek words as “Terrible Skin 

Disease” etc. and yet, paradoxically, “Leprosy”, as we know it today, basically is not a skin disease. 

Essentially, it is a disease which affects the nerves, although not the central nervous system. Only the 

peripheral nerves and their cutaneous branches are involved. What then was the “leprosy” of the 

Bible? Was it what we call “Hansen’s Disease” today? The answer is No. The Hebrew word 

“Tsara’ath” may have included Hansen’s Disease or what is called True Leprosy today, but even this 

is doubted 

That Hebrew word is not a precise medical term referring to a specific disease . Rather does is seem 

to refer to a whole range of disfiguring conditions that resulted in rejection by a society that, in its 

ignorance, attributed such afflictions to punishment from God. Today, there are about thirty 

conditions which can be confused with early and late Hansen’s Disease and these are discussed in 

“Differential Diagnosis”, which I could email to you, if you wish. 

Some references to “leprosy” in the Bible obviously refer to conditions other than Hansen’s Disease. 

“Naaman the Leper”, (2 Kings 5:27) for example, was said to be “leprous” - as white as snow” . 

This, clearly, is not what we call leprosy (Hansen’s Disease) today because Hansen’s Disease does 

not cause the skin to become white. The condition which can be confused with leprosy and which 

causes a whitening of the skin, is Leucaderma or Vitiligo. In true leprosy or Hansen’s Disease, there 

can be some loss of pigment in the skin but it never becomes white because of the disease. Similarly, 

in Exodus 13:44, we read of a person with a hand “leprous and white as snow” . In Leviticus 13:10 

and 20, Biblical “leprosy” even resulted in the hair turning white. This does not happen in patients 

with Hansen’s Disease, nor is their scalp (except in vary rare cases) affected by the disease as in 

Leviticus 13:42. However, there can be loss of eyebrows (Madarosis) because that is one of the 

COOLER areas of the body. Other patches, in cooler areas, also can suffer hair loss. 

Biblical ”leprosy” could also involve clothing and leather garments (Leviticus 13:37-48); maybe it 

was a form of mildew . In Lev.14:37 it could even affect walls of buildings. Dr Stanley Browne 

believes that in Lev.13 v.18, it could be a form of boil; v:24 - an infection complicating a burn; v:29 - 

ringworm or sycosis of the scalp; v:36 a form of pustular dermatitis; v:42 - a favus or desert sore. 

Biblical “leprosy” also had a religious connotation. It was such a repulsive condition that it was 

imagined that God used it as an instrument of divine punishment - See the punishment suffered by 

Miriam in the Bible’s Book of Numbers 12:9 , also in 2 Chronicles, where King Uzziah was said to 

have been “Smitten” by God with “leprosy”. 

In the book of the Prophet Isaiah chapter 53:4, it stated that the coming Suffering Servant would be 

“Smitten of God and Afflicted” . In the Greek Septuagent translation of the Hebrew Old Testament, 

the word “Leprosum” is used. It is the adjectival form of the Greek word “lepra”, translated 

“leprosy” . The germ responsible for leprosy is Mycobacterium leprae or, for short - M.leprae. Was 

Jesus Christ a “leper”? Incidently, we should never call a person a “leper” but rather a “leprosy 

patient” or a “leprosy sufferer”. 

Clinically, Jesus was not a “leper” but, if we understand that Biblical leprosy was more than just a 

disease - it was a “condition” - there is truth in claiming that he was a “leper”., “Lepers” were those 

who were rejected by society and this is the most devastating thing about neglected, untreated 

Hansen’s Disease. It can result in rejection where there are no treatment facilities and no health 

education by which people may be freed from superstition and ignorance. There is a sense in which 

Jesus was a “leper” because we rejected him. Every time we reject a person in real need, virtually, 

we are rejecting Jesus - making him a “leper” - because, in the Christian faith, we really come into 

contact with God through people and particularly people in real need (Matthew 25 34-40) 

The first religious exercise of the fundamentalist Pharisees in Biblical times was to thank God that 

they were not born in any of the four following categories, and they prayed :- “I thank you God that I 

was not born a Gentile (a foreigner) a slave, a ‘leper’ or a woman! In their ignorance and in a society 

dominated by patriachal prejudice , they believed that the God Yahweh or Jehovah had placed a 

“curse” on these four groups of people! Therefore, in a spiritual sense, from this point of view, it is 

tragic that there are a lot of “lepers” out there in society - people whom we REJECT for whatever 

cause. Sadly, we tend to reject people because they are different in some way or other - too fat, too 

short, of a different race, culture, creed, gender or speak a different language etc.. Jesus rejected no 

one. To really experience the dynamism of the Christian faith, we have to go with Christ - “outside 

the camp”( Hebrews 13:13 - terminology referring to the place where “lepers” were isolated”), 

“bearing the stigma” or empathising with people rejected by society. Sadly, most religions are male 

dominated, are prejudiced in some way against women and have male gods when, in fact, the Great 

Supreme Spirit of the Universe, called God, is beyond gender, and racial prejudice. 

The Christian faith becomes meaningful only when we identify with Christ in caring for those who, in 

our society today, are rejected for whatever reason. In our modern era, Biblical “leprosy” could 

even include AIDS because some of its victims are rejected by society. This is the reason why so 

many caring organisations, with a concern for leprosy sufferers, are Christian . They feel the call not 

only to medically treat people with some exotic disease, but to help rejected people develop a sense 

of self esteem and, once more, feel accepted by the human race. From this point of view, AIDS has 

a close relationship with Leprosy (Hansen’s Disease) . Victims of both these conditions need an 

extra portion of human compassion. 

=================================================================== 

69.) TI  - Thalidomide's effectiveness in erythema nodosum leprosum is 

associated with a decrease in CD4+ cells in the peripheral blood. 

=================================================================== 

SO  - Lepr Rev  1992 Mar;63(1):5-11 

AU  - Shannon EJ; Ejigu M; Haile-Mariam HS; Berhan TY; Tasesse G 

AD  - Pharmacology Research Department, G.W. Long Hansen's Disease Center, 

Carville, La 70721. 

MJ  - CD4-CD8 Ratio; Erythema Nodosum [drug therapy]; Leprosy, Lepromatous 

[drug therapy]; Thalidomide [therapeutic use] 

MN  - Adult; Erythema Nodosum [immunology]; Leprosy, Lepromatous [immunology] 

MT  - Human; Male; Support, Non-U.S. Gov't 

PT  - JOURNAL ARTICLE 

AB  - Thalidomide is well documented as being an effective drug in the 

treatment of erythema nodosum leprosum (ENL). The mechanism of action of 

thalidomide in ENL as well as the pathogenesis of ENL are yet to be fully 

determined. Lepromatous leprosy patients experiencing ENL have been 

reported to have an increase in the ratio of CD4+ to CD8+ cells in their 

blood and ENL skin lesions. Thalidomide has been shown to cause a decrease 

in the ratio of CD4+ to CD8+ lymphocytes in the blood of healthy males. 

This decrease was due to a significant reduction in the numbers of Cd4+ 

lymphocytes and an apparent increase in the numbers of CD8+ lymphocytes. In 

this study, thalidomide's effectiveness in halting chronic ENL and 

arresting a relapse into ENL was consistently associated with a decrease in 

the numbers of CD4+ lymphocytes in the blood of 2 male lepromatous leprosy 

patients. 

 

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70.) Leprosy in Venezuela, 1.998 

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Source: The WHO 

Prevalence  prevalence rate per       detection    detection rate per   Coverage with 

                     10.0000                                           100.000                  MTD 

 1384              0.60                           534               2.30                      99.49 2

================================================ 

================================================================= 

DERMAGIC/EXPRESS 2-(96) 04/OCTOBER/2001 DR. JOSÉ LAPENTA R. 

UPDATED 24 SEPTEMBER 2025

=================================================================== 

Produced by Dr. José Lapenta R. Dermatologist

Venezuela 1.998-2.025

Producido por Dr. José Lapenta R. Dermatólogo Venezuela 1.998-2.025

Tlf: 0414-2976087 - 04127766810