Association of vitamin D receptor genotype with leprosy type.

Host genetic factors including major histocompatibility complex (MHC) polymorphisms influence both susceptibility to leprosy per se and also to leprosy type. Non-MHC genes may play an important role, but such genes remain undefined. The influence of two non-MHC candidate genes was assessed in a case-control study of Bengali leprosy patients from Calcutta. Recent studies have implicated variation in the vitamin D receptor (VDR) gene in susceptibility to several diseases, including osteoporosis and pulmonary tuberculosis. In this population, homozygotes for the alternate alleles of the VDR polymorphism are associated, respectively, with lepromatous and tuberculoid leprosy. The NRAMP1 (natural resistance associated macrophage protein 1) gene may influence human mycobacterial disease susceptibility based on studies with the murine homologue Nramp1. However, no significant association was found between NRAMP1 and leprosy susceptibility. This study suggests that the VDR polymorphism may influence susceptibility to some diseases by affecting the type and the strength of the host immune response.

Tumor necrosis factor promoter polymorphism and susceptibility to lepromatous leprosy.

Genetically determined differences in immune responses to environmental agents may underlie susceptibility to many autoimmune and infectious diseases. Leprosy provides an example of a polarity in the type of immune response made to an infectious agent, and there is evidence that the major histocompatibility complex is genetically linked to leprosy type. It was found that HLA-DR2 is associated with both tuberculoid and lepromatous types of leprosy; however, a variant at position -308 of the promoter of the neighboring tumor necrosis factor (TNF) gene was increased in frequency in lepromatous (odds ratio = 3.0, P = .02) but not tuberculoid leprosy. Some studies have found higher serum levels of TNF in lepromatous than tuberculoid leprosy, and high TNF levels are found in malaria and leishmaniasis, which are also associated with this TNF allele. It is speculated that this association reflects genetic variability in cytokine production, which influences the immune response to and clinical outcome of leprosy.

An eight-year field trial on antileprosy vaccines among high-risk household contacts in the Calcutta metropolis.

One-hundred-seventy-nine lepromin-negative household contacts were vaccinated with heat-killed Mycobacterium leprae, BCG, or a combination of the two. Vaccination induced lepromin positivity in 131 of these contacts. Over an 8-year follow-up period, 12 lepromin-positive contacts developed leprosy, all tuberculoid; while 2 lepromin-negative vaccinated contacts developed leprosy, both lepromatous. Overall, 7.8% of the vaccinated contacts developed the disease. Seven-hundred-fourteen household contacts were not vaccinated, and served as controls. Among the 504 who were lepromin positive, leprosy developed in 35, all tuberculoid, over the 8-year follow up. Among the 210 lepromin-negative unvaccinated contacts, 61 developed leprosy: tuberculoid in 29, borderline in 4, lepromatous in 8, and indeterminate in 20. Overall, 13.5% of the 714 unvaccinated contacts and 29.0% of the 210 unvaccinated, lepromin-negative contacts developed leprosy. Vaccination could not induce lepromin positivity in all contacts. The three vaccines were equally effective in inducing lepromin positivity. Vaccination reduced the overall incidence of leprosy from 13.5% to 7.8% among household contacts but did not reduce the incidence of lepromatous leprosy (1.2% of all the vaccinated and 1.1% of all the unvaccinated contacts).

Immunomodulation with corticosteroids and levamisole in leprosy as gauged by in vivo lepromin and in vitro CMI responses.

Corticosteroids and Levamisole are known to be immuno suppressive and immuno stimulating agents respectively. Their effects on polar types of leprosy, tuberculoid and lepromatous have been studied using in vivo lepromin and in vitro lymphocyte count, rosette formation, L.T.T. and L.M.I.T. parameters. Immunosuppressive effect of corticosteroids on tuberculoid leprosy is marked with reduced and negative lepromin sensitivity but same does not hold true with other in vitro C.M.I. tests. Similar results are obtained with levamisole exhibiting its ineffectiveness in lepromin conversion in lepromatous cases although some improvement is observed in other in vitro C.M.I. tests. Evaluation of the results showed: lack of correlation between in vivo lepromin and in vitro other C.M.I. parameters with corticosteroids and levamisole lepromin sensitivity has some unknown influence other than thymic factors, prolonged corticosteroid therapy may produce permanent immunosuppression in tuberculoid cases making them more vulnerable towards lepromatous pole and lepromin sensitivity is more reliable, stable and easy to perform.

Prothionamide and dapsone therapy in leprosy--a clinical study.

Combined therapy with prothionamide and dapsone was instituted in fifteen active untreated lepromatous leprosy cases for a period of 18 months. Clinical improvement was good with attainment of zero morphological index in about 66% cases. Bacteriological improvement was rather unsatisfactory as one case only reached zero level. Side effects were observed in few cases necessitating withdrawal of combined therapy and patients' prothionamide compliance was rather unimpressive.

Evaluation of multidrug therapy with rifampicin, clofazimine and D.D.S. in multibacillary leprosy cases.

Rifampicin, Clofazimine and D.D.S. have been tried in fifteen active untreated lepromatous cases for a period of two years. Compared to dapsone monotherapy remarkable clinical and bacteriological improvement was observed with this combined therapy with attainment of negative BI in ten cases. Use of this combination therapy is thus advocated to achieve noninfectivity in a shorter period and to prevent emergence of dapsone resistance thereby causing the path of leprosy control before it becomes unmanageable due to dapsone resistance.

Corticosteroids and lepromin sensitivity.

Corticosteroids are known to influence the hypersensitivity reaction in a number of diseases involving hypersensitivity of tissues and alter the antigen antibody reactions in vivo. Corticosteroids administered in thirty tuberculoid cases for a period of 3 weeks showed negative response in the lepromin positive cases uniformly thereby proving suppression of cell mediated immunity in tuberculoid cases under the influence of corticosteroids; hence polar concept of tuberculoid type may be under question with continuous and prolonged corticosteroid therapy under necessity.

Nature and familial character of lepromin sensitivity in 27 families and their siblings.

A group of 27 families consisting of 176 individuals had been investigated for the lepromin sensitivity (with Dharmendra antigen). The families were arranged under group A (9 families) in whom either of the parents or both were suffering from Lepromatous type of leprosy, group B numbering 4 families, of whom either of the parents or both were suffering from non-lepromatous type of leprosy and group C comprising 14 families where none of the parents was suffering from leprosy but some of the each family had the disease in their siblings. The present study points towards the possible genetic influence on lepromin sensitivity but at times may be influenced by the environmental factors. However the study does not permit to reach any valid conclusions; further elaborate investigations alone could prove the useful role of genetic influence in the propagation of lepromin sensitivity to the subsequent sibs.

EMS-induced reversion studies in the white locus of Drosophila melanogaster.

5 white-locus mutants of Drosophila melanogaster, respresenting 5 different sub-sites, were treated with EMS and tested for reversion to wild-type. 4 of them were genuine mutants and one was not. Moreover, the ability of the 4 mutants to revert to wild-type differed from one another which therefore reflects a qualitatively distinct alteration in the genetic material delimited by each mutant.

Clinical trial with rifampicin in the treatment of leprosy (final report).

A controlled trial of Rifampicin plus Dapsone had been in progress for two years in the Department of Leprology, School of Tropical Medicine, Calcutta. Interim results of this trial after six months treatment were reported in 1976. The present paper is the final report of the study after two years of treatment. The study reveals that with Rifampicin, MI falls rapidly after six months, but changes in BI are not better than in the DDS group. As a matter of fact, regarding BI, treatment with DDS has given better results as two cases have become negative in the DDS group while no case has become negative in the Rifampicin group. It is, therefore, concluded that clinical improvement with Rifampicin is similar to that with DDS.