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

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 Calcutta1

Sachin Chaudhury, Sunil Kumar Hajra, Ashutosh Mukerjee, Bibbuti Saha, Vibek Majumdar, Debasis Chattapadhya, and Kunal Saha2

Recently, we reported from Calcutta a promising and safe method for the treatment of lepromin-negative, advanced lepromatous leprosy (LL) patients with low-dose Convit vaccine [1.6 x 107 killed Mycobacterium leprae (human) and 1.5 x 105 M. bovis BCG] ('o) as an adjunct to the standard multidrug therapy (MDT) in place of the Convit vaccine containing 6.4 x lOs killed M. leprae (armadillo) supplemented by 0.1 mg BCG used in the Venezuelan trial (7), They were given one to six inoculations of the mixed vaccines at 3-month intervals until lepromin conversion. Thereafter, the patients were followed up for a period of 2 years for clinical, bacteriological and immunological outcome. Within 18 months of starting chemo-immunotherapy all patients showed remarkable clinical improvement and bacterial negativity but, even after six inoculations of the mixed vaccine, 33% of the patients failed to show lepromin conversion and 50% of the patients remained negative in the leukocyte migration inhibition (LMI) test using M. leprae sonicate. During the course of the vaccine therapy, no severe reversal reaction (RR) or nerve damage was encountered in any patient. On the contrary, the LL patients treated with MDT alone showed delayed bacterial clearance, prolonged clinical recovery, only 5% lepromin conversion, and none of them became LMI positive (10).

Being encouraged by the above results with the low-dose Convit vaccine, in the present study we extended our investigations on the same immunotherapy for the treatment of all types of lepromin-negative, borderline leprosy patients. Moreover, despite the success of the MDT regimen of the World Health Organization (WHO) in the treatment of leprosy patients, the occurrence of some degree of inflammatory reactions (types 1 and 2) in 50% of the borderline leprosy patients still remains a problem (Il). In view of the fear of severe RR and nerve damage that may occur in borderline leprosy patients during immunostimulation with vaccine therapy and in the light of their much lower bacterial load and less severe lepromin anergy than LL patients, the number of inoculations of the low-dose Convit vaccine was restricted to four instead of six as were given to our LL patients.

MATERIALS AND METHODS

One-hundred-fifty, untreated borderline leprosy patients (87 males and 63 females) were taken from the Outpatient Department, School of Tropical Medicine, Calcutta. Their mean age was 37.8 years; mean duration of illness, 36.6 months. The diagnosis was based on clinical, bacteriological and histological findings as well as lepromin testing with 0.1 ml standard lepromin containing 1.6 x 107 killed M. leprae (human). The criteria of lepromin reactivity was based on that described by Harboe (9). A slit-skin smear test was done for all patients at the beginning and at the end of the study (3). Of all the 150 borderline leprosy patients, 100 were Mitsuda negative and their mean bacterial index (BI) was 2.45+. The remaining 50 patients were Mitsuda positive (spontaneous) with a mean BI of 1.05+. The patients were histologically classified on the Ridley and Jopling scale (8).

Grouping of patients. All of the 150 borderline patients were divided into three well-matched groups: Group I (test) included 50 lepromin-negative patients, and they were given a mixed vaccine plus MDT. Group II (lepromin-negative controls) consisted of 50 lepromin-negative patients. They were subdivided into two groups: a) 25 patients were given killed M. leprae (human) vaccine plus MDT; b) the other 25 patients were given BCG vaccine plus MDT. Group III (lepromin-positive controls) included 50 Mitsuda-positive (spontaneous) patients who required no immunostimulation and were treated with only MDT (Table 1) (5).

Vaccines. Three types of vaccines were used: a) Convit vaccine: Each dose had 1.6 x 10^sup 7^heat-killed M. leprae (human) supplemented by 1.5 x 105 M. bovis BCG (Japan) suspended in 0.1 ml saline and mixed before injection. Human M. leprae were obtained from human lepromas routinely processed in our laboratory. The preparation of the vaccine has been described elsewhere (5). b) Killed M. leprae (human) vaccine: Each dose contained 1.6 x 107 heatkilled M. leprae (human) in 0.1 ml saline. c) M. bovis BCG vaccine: Each dose had 1.5 x 10^sup 5^ BCG (Japan) in 0.1 ml saline.

Before the administration of each inoculation, all of the patients were tested for lepromin reactivity with standard lepromin (human) (routinely made in our laboratory) ('o). Only those patients remaining lepromin negative after inoculation received subsequent inoculations. The interval between the two successive inoculations was about 12 weeks. Depending on the severity of lepromin anergy, the number of vaccinations given to the test and control patients varied from one to four. The schedule of vaccinations is shown in Table 1.