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

International Journal of Leprosy and Other Mycobacterial Diseases, Mar 1997 by Sachin Chaudhury, Sunil Kumar Hajra, Ashutosh Mukerjee, Bibbuti Saha, et al

Clinical outcome. After starting chemoimmunotherapy all of the patients were followed at 3-month intervals for a period of 2 years to study their clinical course, any RR and other clinical complications.

Bacteriological negativity. The bacterial index (BI) of each patient was recorded at the start and at the end of the study by employing the standard technique (3).

Immunological testing. All of the patients were tested twice (once at the beginning and again at the end of treatment) to study any augmentation of specific cell-mediated immunity against M. leprae (human) antigen following chemo-immunotherapy. Three methods were employed: a) the invivo standard lepromin test (described earlier); b) the capacity of clearing bacteria (CCB) test. This in-vivo test was performed at the end of the study in all patients. The method was described by Convit, et al. (6). In brief, a massive dose of autoclaved human M. leprae (6.4 x 10^sup 7^ in 0.1 ml saline) was injected intradermally. Biopsies of the injected sites were taken 6 weeks after injection and histopathological studies were done; c) the in-vitro leukocyte migration inhibition (LMI) test against sonicated M. leprae (human) antigen was done for all patients at the start and at the end of the treatment. The method has been described elsewhere (1).

RESULTS AND DISCUSSION

An inter-laboratory study of armadilloderived M. leprae vaccine revealed striking differences between the preparations of M. leprae provided by the WHO for use in leprosy vaccine trials (13). We used humanderived M. leprae vaccine which obviated those differences.

Table 2 shows the clinical, bacteriological and immunological outcome of the borderline leprosy patients following administration of the three types of currently popular antileprosy vaccines. all patients belonging to the test and control groups showed clinical cure and bacteriological negativity within the 2-year study period. However, 80% of the test patients, immunostimulated by low-dose Convit vaccine (Group I), and another 80% of the control patients, receiving BCG vaccination (Group IIb), had undergone a clinical upgrading reaction and had shown a histological shift of polarity toward the tuberculoid end. Clinically upgrading (reversal) reactions were manifested by exacerbation of existing lesions, neuritis of already involved nerves, the appearance of new lesions and involvement of new nerves within 6 weeks of starting immunotherapy. On the contrary, only 40% of the control patients receiving immunologic stimulation with the killed M. leprae (human) vaccine (Group IIa) had undergone a clinical upgrading reaction and had shown a shift of histological polarity (Table 2). Fifty spontaneously lepromin-responsive, control borderline leprosy patients (Group III), who had a low mean BI (1.OS ) (Table 1), received no antileprosy vaccine. Curiously, only 40% of these patients showed a clinical upgrading reaction (Table 2). The reaction was so severe in two mid-borderline (BB) leprosy patients receiving low-dose Convit vaccine therapy (Group I) that one developed facial paralysis with lagophthalmos and another developed bilateral foot and wrist drop which necessitated steroid therapy. This perhaps diluted out the gain of immunostimulation offered by the vaccine therapy. However, up to now there is no suitable method to predict such disaster before starting immunotherapy. These results, thus, show that vaccine-driven, leprominreactive, borderline leprosy patients (Group I) can show better clinical and histological reversal reactions than the spontaneously lepromin-positive, borderline leprosy patients with a low bacterial load (Group III), who were not given any vaccine therapy. Also, low-dose Convit vaccine was more effective than the killed M. leprae (human) vaccine in terms of clinical and histological reversal reactions. This needs explanation: Perhaps killed M. leprae (human) in the mixed vaccine could stimulate M. lepraespecific T-helper cells, vis-a-vis, it could also activate M. leprae-specific T-suppressor cells (12), while BCG in the mixed vaccine could, in addition, activate M. lepraeloaded macrophages and eliminate intracellular bacteria.