DATA-MEDICOS 
DERMAGIC/EXPRESS 2-(96) 
4 Octubre 2.000  4 October 2.000 
 
~ Hansen para Siempre...??? ~ 
~ Hansen forever...??? ~ 
 

============================================================ 
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. [email protected] 

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. [email protected] 
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. 
[email protected] 

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. 
[email protected] 

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 

================================================ 
67.) Leprosy Elimination 
================================================ 
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. 
 
================================================ 
70.) Leprosy in Venezuela, 1.998 
================================================ 
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) 4 Octubre 2.000  4 October 2.000 Dr. JOSE LAPENTA R.
=================================================================