ReviewThe role of BCG in prevention of leprosy: a meta-analysis
Introduction
Although eliminated from most of the countries where it was considered a public-health problem, leprosy—a chronic infection caused by Mycobacterium leprae—is still present in countries in Africa, Asia, and Latin America. With the introduction of multidrug therapy in 1982 as a response to resistance to dapsone,1, 2 the duration of treatment for leprosy reduced, and lower relapse rates were observed.3, 4, 5 However, the WHO estimated that there were 290 000 registered cases worldwide at the beginning of 2005 and that about 52% of these cases were from India.6 Efforts to reduce the prevalence of leprosy below the elimination target of less than one case per 10 000 need to be stepped up in target countries like Brazil (figure 1) and India.7, 8 The primary public-health strategy for the control of leprosy has been the diagnosis and treatment of symptomatic patients to make them less infectious to susceptible individuals. The different methods considered for primary prevention of leprosy are chemoprophylaxis and immunoprophylaxis.9
Apart from dapsone and multidrug therapy as methods of treatment and secondary prevention, vaccination of susceptible individuals has often been an area of discussion for primary prevention efforts. Some of the potential vaccines for prevention of leprosy are BCG alone, BCG and killed Mycobacterium leprae, Indian Cancer Research Centre (ICRC) bacillus, Mycobacterium ‘w’, and Mycobacterium vaccae.10, 11, 12, 13 Among these potential vaccines, studies with BCG are most common. BCG is recommended by WHO's Expanded Programme on Immunization for protection against tuberculosis caused by a mycobacterium closely related to M leprae. Thus it is routinely used in the vaccination of children in countries where leprosy still continues to be a public-health problem and is currently also recommended for the household contacts of leprosy patients in Brazil.14
In 1939, Fernandez15 was the first to demonstrate the induction of a positive Mitsuda reaction—a marker for improved cell-mediated immunity against leprosy—following vaccination with BCG, a finding later discussed by others.16, 17 Subsequently studies were done to assess the protective effect of BCG in leprosy and controlled clinical trials to examine the role of BCG in leprosy were initiated in the 1960s. The studies done in endemic areas in different countries have demonstrated varying protective effects against leprosy. BCG is the world's most widely used vaccine, yet its role in the prevention of tuberculosis and leprosy is controversial. Given that BCG is easily available and widely used compared with the other vaccines useful in leprosy, we did a meta-analysis of existing published work to determine the protective effect of BCG in leprosy and the factors that impact its efficacy by doing a subgroup analysis.
Section snippets
Search strategy and identification of studies
We assessed the role of BCG in protection of clinical leprosy, our study hypothesis being that rates of leprosy cases were different in BCG vaccinated and unvaccinated populations. We did a search of Medline, limited to human studies, using the index terms “BCG and leprosy”, “leprosy vaccines”, “BCG and Hansen's disease”, and “BCG and hanseniasis”. All papers until February 2005 were included in the meta-analysis. Other sources searched for relevant articles using the same index terms included
Search results
We scanned 986 articles obtained from all the electronic searches and reviewed 115 complete articles (including studies, reviews, editorials, case reports, and WHO reports). Of the articles reviewed in detail, we found 26 studies eligible for inclusion in our meta-analysis, which included seven experimental studies (clinical trials) and 19 observational studies (cohort and case-control studies). Table 1 describes all the studies that were included in the meta-analysis, along with the relative
Discussion
The meta-analysis of these studies provides useful information on the overall protective effect of BCG in the prevention of leprosy. The results from the experimental studies indicate that BCG vaccination offered an average protection of 26% (95% CI 14–37%) against leprosy, with significant heterogeneity between the trials (p<0·00001). The overall average protective effect of BCG estimated by the observational studies was 61% (95% CI 51–70%), also with significant heterogeneity between these
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