T-lymphocyte clones from leprosy skin lesions.
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This study was performed in order to analyse whether the immune unresponsiveness to Mycobacterium leprae, largely seen in lepromatous patients, persisted after discharge from treatment. Lymphoproliferation and skin tests were performed using two mycobacterial antigens (M. leprae and BCG) in three groups of lepromatous patients grouped by treatment status. Forty-seven per cent of the lepromatous patients tested acquired reactivity to M. leprae after long-term treatment.
Immunotherapy with Mycobacterium w was given, in addition to standard multidrug therapy (MDT) to a lepromatous leprosy (LL) patient with a bacteriological index (BI) of 6. After 15 months of treatment this patient attained bacteriological negativity and clinical inactivity. Histopathologically the patient upgraded to borderline-tuberculoid at 12 months, and at 15 months showed features of nonspecific infiltration in the dermis. The rapid immunological upgrading seen in the patient is highlighted in this paper.
The reliability of methods of testing nerve function is important, since diagnostic decision making is a direct function of the quality of the test. Three methods of nerve function testing were investigated at the Danish Bangladesh Leprosy Mission (DBLM) in north Bangladesh, and assessed for inter-observer reliability. The three methods were 1) ballpoint pen test (BPT) for sensory function; 2) graded Semmes Weinstein monofilament test (SWM) for sensory function and 3) voluntary muscle testing (VMT) for motor function. The weighted kappa (kappa w) statistic was used to express inter-observer reliability. Using this statistic, 0 represents agreement no better than random, and 1.0 complete agreement. kappa w values of > or = 0.80 are reckoned to be adequate for monitoring and research. Fifty-three patients were tested, a Senior physiotechnician acting as 'gold standard' against whom four other staff physiotechnicians were assessed. All three testing methods were found to have minimal inter-observer variation, with the kappa w for inter-observer agreement using BPT being 0.86, the SWM 0.92, and VMT 0.94. It is concluded that in trained and experienced hands, all three methods are reliable and repeatable to a level allowing confident use of results obtained in monitoring and research.
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Immunologic responses were measured in 46 patients with lepromatous leprosy. These patients were not distinguishable from controls on the basis of responses to soluble intradermal antigens, sensitization to contactants, peripheral blood T- and B-cell percentages, in vitro lymphocyte responses to a mitogen, or the prevalence of autoantibodies. Generalized immunologic abnormalities in patients with lepromatous leprosy are neither predisposing causes nor necessary accompaniments of lepromatous leprosy, but are probably remote sequellae of the illness. By implication, the generalized immunologic abnormalities reported in other diseases are likely to be remote sequellae of the particular illness.
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The author describes the progress made in our knowledge of tuberculoid leprosy since the original case of Jadassohn in 1898. The numerical importance of T patients in different parts of the world is reviewed and their role in the transmission of the disease discussed. An analysis is made of the subgroups into which T leprosy is divided according to the clinical symptoms, bacteriology, histopathology and immunology in the Madrid classification as well as in the Souza-Lima-Souza Campos and Ridley-Jopling studies. The author concludes that a majority of T patients are immunologically stable and belong to two well defined groups, the first called T annular in the Souza-Lima-Souza Campos study and TT in the Ridley-Jopling classification and the second called T reactional by S.L.-S.C. and BT by R.J. Taking into account the high proportion of T cases in most epidemiological situations, their generally accepted good prognosis under treatment and the present availability of several drugs of proved efficacy, the author suggests to carry out in T leprosy under controlled conditions a trial of a number of therapeutic regimens of not more than 12 months duration. Follow-up periods will make possible medium and long-term evaluation of results after 3 and 5 years respectively of the initiation of the chemotherapeutic regimens. The practical implications of effective and well tolerated short-term therapy in T leprosy is stressed. Its widespread use in field programmes will represent among other advantages a considerable economy in personnel and drugs costs. The use of a single protocol is recommended. The one worked out by THELEP for therapeutic trials in lepromatous leprosy could be adopted with a few changes made necessary because of the morphological and bacteriological differences between L and T leprosy. It is suggested that, if the results of the trial are successful, similar regimens could be tried in indeterminate leprosy.
Thirty sib-pairs were ascertained through unrelated lepromatous probands. They consisted of 22 healthy individuals and 8 leprosy patients. The Mitsuda reactions of all sibs were evaluated both macroscopically and histologically, and high molecular weight genomic DNA was extracted from the white blood cells of all sib-pairs. Three DNA polymorphisms identified by polymerase chain reaction (274C/T, D543N, 1729 + 55del4) were used as chromosome markers at the NRAMP1 locus. Sib-pair comparisons did not disclose any sign of close linkage between the Mitsuda reaction and the genetic markers.
Thirty eight patients with indeterminate leprosy (HI), at least 4 to 6 years after discharge from multibacillary (MB) or paucibacillary (PB) schemes of anti leprosy multidrug therapy (MDT), were submitted to traditional diagnostic procedures for leprosy and to polymerase chain reaction (PCR) analysis of different clinical samples for detection of Mycobacterium leprae DNA. No significant difference was observed for any of the parameters analyzed between PB or MB schemes of treatment and no indications were found for more efficient outcome of HI using the MB scheme. Remarkably, 18 (54.5%) of the individuals were PCR positive in at least one of the samples: positivity of PCR was highest in blood samples and four individuals were PCR positive in blood and some other sample. Upon comparison of PCR results with clinical and histopathological parameters, no correlation was found between PCR-positivity and eventual relapse. This is the first report on detection of M. leprae DNA in PB patients, more than half a decade after completion of MDT, suggesting that live bacilli are present and circulating much longer than expected, although reinfection of the individuals can not be excluded. Overall, we feel that because of the high sensitivity of the assay, extreme care should be taken about association of PCR results, efficacy of treatment and disease status.
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The course of leprosy in patients with HIV infection has been a controversial issue for a long time. It is still a matter of debate whether the HIV status of an individual has any impact on the natural history of leprosy and response to anti-leprosy treatment. We report here three HIV-positive leprosy cases (two BT and one BB) along with their CD4 counts and HIV staging with anti-leprosy therapeutic response. Both BT cases responded well to conventional WHO MDT (PB) for 6 months, whereas the BB case relapsed 3 months after completion of MDT (MB) for one year. However, he became inactive again following a further one-year course of MDT (MB).
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