A comparative study on the Mitsuda type response to antigens of chemoautotrophic nocardioform bacteria and to standard lepromin in leprosy patients.

Anergy, or contrarily, Mitsuda-type responses towards 4 chemoautotrophic nocardioform antigens (CAN-Ags) and a control standard lepromin were tested in 73 LL, TT and borderline cases of leprosy. The antigens injected per patient varied from a maximum of 5 to a minimum of 2. Complete anergy to CAN-Ags was seen in 92/92 instances tested on 24 LL cases. The anergy was weakly modified or unmodified in 3 other LL cases which had been vaccinated before. Concurrent studies with the same antigens tested on 33 TT cases showed clear-cut, dose-dependent, Mitsuda-type late responses in 80/81 instances. The CAN bacteria, therefore, despite their origin from different unrelated leprous human, mouse footpad (MFP) and armadillo tissues, appeared to be identical with each other and also probably related to the leprosy bacillus, on the basis of these parameters.

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.

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.

Microflora in the trophic ulcers of the foot in leprosy.

Out of 25 cases of trophic ulcers of the foot, 10 (40%) were both aerobic and anaerobic, 14 (56%) only aerobic and one (4%) showed no growth of bacteria. With the exception of two cases (8%) in the aerobic group, all others showed mixed infections. A wide range of bacteria is reported. Topical application of gentamicin and chloramphenicol is recommended, based on the results of in vitro sensitivity.

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.

Lepromin conversion in repeatedly lepromin negative BL/LL patients after immunization with autoclaved Mycobacterium w.

Thirty-two clinically, histopathologically confirmed cases of BL/LL leprosy were rendered bacteriologically negative by prolonged chemotherapy. All of them were negative to Mitsuda and Dharmendra lepromin at the start of study. They were immunized with a single intradermal injection of 5 X 10(7) autoclaved Mycobacterium w and were retested for lepromin reaction 4-6 weeks later. Twenty subjects gave at this time a positive reaction with both Dharmendra and Mitsuda lepromins. The histology of biopsies from converted cases showed mononuclear infiltration in all and granuloma formation in 12 of the 20 positive cases. The stability of the conversion of the patients' lepromin positivity was investigated 6-11 months after immunization with Mycobacterium w. Patients who were earlier converted to a positivity status remained positive in the skin test response to M. leprae. The leukocytes of these patients produced lymphokines on culture with lepromin, causing leukocyte migration inhibition. Patients who did not convert earlier continued to remain anergic to lepromin. These results suggest a conversion, stable for several months, to lepromin positivity caused by immunization with Mycobacterium w in about 60% of BL/LL leprosy patients.

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.