Immunoprophylactic effects of the anti-leprosy Mw vaccine in household contacts of leprosy patients: clinical field trials with a follow up of 8-10 years.

We report here a large scale, double blind immunoprophylactic trial of a leprosy vaccine based on Mycobacterium w (Mw) in an endemic area of Kanpur Dehat, Uttar Pradesh, India. A population of 420,823 spread over 272 villages was screened where 1226 multibacillary (MB) and 3757 paucibacillary (PB) cases of leprosy were detected. A total of 29,420 household contacts (HHC) of these patients were screened for evidence of active or inactive leprosy. After exclusion of 1622 contacts for any of the different exclusion criteria, a total of 24,060 HHC could be vaccinated for vaccine or placebo under coding (20,194 administered two doses and 3866 received single dose). The vaccine consisted of 1 x 10(9) heat killed bacilli (Mw) in normal saline for the first dose and half of the first dose, i.e. 5 x 10(8) bacilli for the second dose, given 6 months after the first dose. The placebo consisted of 1/8th dose of the normal dose of tetanous toxoid. Both placebo and vaccine were given under double-blind coding, The contacts were followed up during three surveys at 3, 6 and 9 years after the initial vaccination, for detection of post-vaccination cases (PVCs) and observing any side-effects caused as a result of vaccination. The codes were opened on 24th January 2001, after the analysis of the data following completion of the third and final follow-up survey. When only contacts received the vaccine, Mw vaccine showed a protective efficacy (PE) of 68-6% at the end of first, 59% at the end of the second and 39.3% at the end of the third follow-up survey. When both patients and contacts received the vaccine, the protective efficacy observed was 68%, 60% and 28% at the end of the first, second and third surveys, respectively. When patients, and not the contacts, received the vaccine, a PE of 42.9% in the first, 31% in the second and 3% in the third survey was shown. These results suggest that the vaccination of the contacts is more valuable in achieving the objective of immunoprophylaxis than that of patients, and the vaccine effects are noted maximally in children (as compared to adolescents and adults) who constitute the most responsive group The effect of vaccine is sustained for a period of about 7-8 years, following which there is a need to provide a booster vaccination for the sustained protection.

Field trials on the use of Mycobacterium w vaccine in conjunction with multidrug therapy in leprosy patients for immunotherapeutic and immunoprophylactic purposes.

A double blind field trial was started with a candidate anti-leprosy vaccine, Mycobacterium w as an immunotherapeutic and immunoprophylactic agent against leprosy in a highly endemic region with a prevalence rate of over 18 per 1000 population. By 31 August 1992, 224 villages have been surveyed, covering a population of 307,981 (1981 census). A total of 979 MB patients and 2801 PB patients have been registered. A total of 19,453 household contacts of leprosy patients have been examined for clinical signs of disease, of which 16,519 have received the initial dose while 10,434 have also received the booster dose of vaccine/placebo. The aims and objectives, study design of the trial, present status as well as the socio-cultural aspect involved are highlighted in this paper.

Reversal reaction in multibacillary leprosy patients following MDT with and without immunotherapy with a candidate for an antileprosy vaccine, Mycobacterium w.

Immunotherapy with a candidate for an antileprosy vaccine, Mycobacterium w, was given in addition to standard multidrug therapy (MDT) to 53 multibacillary lepromin negative patients belonging to BB, BL and LL types of leprosy (vaccine group). An equal control group received MDT and injections of micronized starch as placebo. Both the vaccine and placebo were administered intradermally every 3 months. The patients were evaluated at determined intervals by clinical, bacteriological and histopathological parameters and lepromin testing. Reactional episodes were analysed with reference to incidence, onset, frequency and severity during and after release from treatment (RFT). Incidence of reversal reaction (RR) was marginally higher in the vaccine group (22.6% vaccine group vs 15% control group). All cases with a history of downgrading type 1 reaction developed RR during therapy. Most episodes occurred within the 1st year of the commencement of therapy--50% developing within 3 months. Late reversal reaction (after RFT) were observed in 3.8% of cases in both groups, and 50% of the reactors in the control group and 33% in the vaccine group had repeated reactional episodes. Incidence of neuritis associated with RR as well as isolated neuritis was similar in both groups.

Serum tumor necrosis factor and interleukin 1 in leprosy and during lepra reactions.

Tumor necrosis factor--alpha (TNF), one of the mediators of septic shock, has a role in the immunopathological complications of several infections. However, its role in leprosy is yet unclear. In this study, serum TNF and IL-1 levels in 64 patients spread over the spectrum of leprosy [lepromatous leprosy (LL), 30; borderline lepromatous, 12; borderline borderline, 8; and borderline tuberculoid-tuberculoid leprosy, 14] were measured at the time of admission. Elevated levels of TNF ranging from 15 to 4500 pg/ml were detected in lepromatous leprosy cases (399 +/- 189) and low levels ranging from 15 to 160 pg/ml were detected in the tuberculoid form of leprosy. Patients undergoing type 1 and type 2 lepra reactions also exhibited high TNF levels of 15-2100 pg/ml. Of the 14 clinically healthy individuals studied, 3 showed TNF levels of 15, 50, and 58 pg/ml. Interleukin 1-beta (IL-1) levels were found to be significantly higher in LL cases (70-5000 pg/ml) (328 +/- 184) in comparison to other groups or normal controls (9 +/- 3). The coefficient of correlation between TNF and IL-1 levels was statistically significant in LL and reaction cases (r = 0.96, P less than 0.001). These patients were followed up as outpatients for a period of 1 year. It was observed that 4 out of 8 patients with TNF levels greater than 100 pg/ml went into lepra reactions between 2 and 6 months after entry into the study, whereas only 5 out of 56 with less than 100 pg/ml went into mild lepra reactions (chi 2 = 9.7, P less than 0.01). Determination of TNF and IL-1 levels thus seems to have a prognostic significance in terms of lepra reaction in patients.

Association of HLA antigens with differential responsiveness to Mycobacterium w vaccine in multibacillary leprosy patients.

Leprosy patients undergoing phase II trials in two hospitals of New Delhi, India, were HLA typed to see the association of HLA with differential responsiveness to Mycobacterium w vaccine. The vaccine comprises an atypical, nonpathogenic mycobacterium, Mycobacterium w, which has cross-reactive antigens with M. leprae. Multibacillary patients who are lepromin negative are vaccinated at an interval of 3 months. Considerable improvement is evident in the patients in terms of a decline in bacterial indices and histopathological and immunological upgrading. But all the patients do not respond to the vaccine in the same manner; some are slow responders, while others are good responders. HLA-A28 and DQw3 (DQw8 + 9) were found to be associated with slow responsiveness, while DQw1 and DQw7 were found to be associated with a more rapid responsiveness to the M. w vaccine. However, these associations were not significant after P correction for the number of antigens tested for each locus except for HLA-DQw3 (DQw8 and DQw9) and DQw7. DQw7, a new defined split of HLA-DQw3, seems to be associated with the responsiveness to M. w vaccine.

Immunotherapeutic effects of a vaccine based on a saprophytic cultivable mycobacterium, Mycobacterium w in multibacillary leprosy patients.

Immunotherapy with a vaccine consisting of autoclaved Mycobacterium w was given in addition to chemotherapy in 54 multibacillary, lepromin negative patients belonging to BB, BL and LL types of leprosy. Thirty-seven patients with similar types of diseases received chemotherapy and placebo injections. The 'vaccine' was repeated every 3 months. Bacterial clearance was more rapid in the vaccinated patients. Two lepromatous leprosy patients with initial bacterial index (BI) of 1.8 and 2.8 became bacteriologically negative in 1 year. One LL patient with BI of 6.0 had a BI fall to 0.16 after four doses of the vaccine. None of the LL patients belonging to placebo group during the same time period became bacteriologically negative. Rapid bacterial clearance was accompanied by distinct signs of clinical improvement. One hundred percent of BB, 85.7% of BL patients and 61.5% of LL patients converted to lepromin positivity after four doses of the vaccine. A significant number of vaccinated patients demonstrated an upgrading in skin lesions histopathologically.