The role of BCG in prevention of leprosy: a meta-analysis

Summary

The present meta-analysis investigates the role of BCG—a widely used yet controversial vaccine—in the prevention of leprosy. The electronic databases Medline, Embase, the Cochrane Library, and LILACS were searched to identify studies assessing the protective effect of BCG against leprosy. We included seven experimental studies and 19 observational studies. The experimental studies demonstrated an overall protective effect of 26% (95% CI 14–37%). At 61% (95% CI 51–70%), the observational studies overestimated the protective effect. The age at vaccination did not predict the protective effect of BCG. An additional dose of BCG was more protective in the prevention of leprosy compared with a single dose. An additional dose of BCG may be warranted for contacts of leprosy patients in areas where leprosy continues to be a public-health problem.

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.