RANDOMIZED CONTROLLED TRIAL OF SINGLE BCG, REPEATED BCG, OR COMBINED BCG AND KILLED MYCOBACTERIUM-LEPRAE VACCINE FOR PREVENTION OF LEPROSY AND TUBERCULOSIS IN MALAWI

Background Repeat BCG vaccination is standard practice in many countri es for prevention of tuberculosis and leprosy, but its effectiveness h as not been evaluated. The addition of Mycobacterium leprae antigens t o BCG might improve its effectiveness against leprosy. A double-blind, randomised, controlled trial to evaluate both these procedures was ca rried out in Karonga District, northern Malawi, where a single BCG vac cine administered by routine health services had previously been found to afford greater than 50% protection against leprosy, but no protect ion against tuberculosis. Methods Between 1986 and 1989, individuals l acking a BCG scar were randomly assigned BCG alone (27 904) or BCG plu s killed M leprae (38 251). Individuals with a BCG scar were randomly allocated placebo (23 307), a second BCG (23 456), or BCG plus killed M leprae (8102). Incident cases of leprosy and tuberculosis were ascer tained over the subsequent 5-9 years. Findings 139 cases of leprosy we re identified by May, 1995; 93 of these were diagnostically certain, d efinitely postvaccination cases. Among scar-positive individuals, a se cond BCG vaccination gave further protection against leprosy (about 50 %) over a first BCG vaccination. The rate ratio for all diagnostically certain, definitely postvaccination cases, all ages, was 0.51 (95% CI 0.25-1.03, p=0.05) for BCG versus placebo. This benefit was apparent in all subgroups, although the greatest effect was among individuals v accinated below 15 years of age (RR=0.40 [95% CI 0.15-1.01], p=0.05). The addition of killed M leprae did not improve the protection afforde d by a primary BCG vaccination. The rate ratio for BCG plus killed M l eprae versus BCG alone among scar-negative individuals was 1.06 (0.62- 1.82, p=0.82) for all ages, though 0.37 (0.11-1.24, p=0 09) for indivi duals vaccinated below 15 years of age. 376 cases of postvaccination p ulmonary tuberculosis and 31 of glandular tuberculosis were ascertaine d by May, 1995. The rate of diagnostically certain tuberculosis was hi gher among scar-positive individuals who had received a second BCG (1. 43 [0.88-2.35], p=0.15) than among those who had received placebo and there was no evidence that any of the trial vaccines contributed to pr otection against pulmonary tuberculosis. Interpretation In a populatio n in which a single BCG vaccination affords 50% or more protection aga inst leprosy, but none against tuberculosis, a second vaccination can add appreciably to the protection against leprosy, without providing a ny protection against tuberculosis.