Randomised vaccine trial of single dose of killed Leishmania major plus BCG against anthroponotic cutaneous leishmaniasis in Bam, Iran

Background A vaccine consisting of a single dose of whole-cell autoclave-killed Leishmania major (ALM) mixed with BCG was assessed in comparison with BCG alone against anthroponotic (human to human transmission) cutaneous leishmaniasis in a randomised double-blind trial in Bam, Iran. Methods 3637 schoolchildren, aged 6-15 years, with no history of cutaneous leishmaniasis and no response to a leishmanin skin test, were randomly assigned to receive 1 mg ALM mixed with BCG (n=1839), or BCG alone (n=1798). Safety of the vaccine and the incidence of confirmed-cases of cutaneous leishmaniasis were followed up for 2 years. Findings Side-effects were those usually associated with BCG vaccination, but-tended to persist longer in the ALM+BCG group. After exclusion of four cases occurring within 80 days of vaccination tone in the ALM+BCG group and three in the BCG group), the 2-year incidence of cutaneous leishmaniasis did not differ significantly between vaccine and BCG groups: 2-8% vs 3-3%, respectively (total cases 112). A sex-stratified analysis showed that in boys the vaccine conferred a protective efficacy of 18% and 78% for the first and second years, respectively-a crude 2-year overall protection of 55% (95% CI 19-75%, p<0.01). In the first 9 months after vaccination, there was a non-significant excess of cases in the ALM+BCG group (25 vs 16), whereas the incidence of cutaneous leishmaniasis-thereafter was significantly reduced in the ALM+BCG group (27 vs 44, p<0.05). Interpretation A single dose of ALM+BCG was safe and more immunogenic than BCG alone, as measured by leishmanin shin test. The exact reason-for the apparent protective effect of the vaccine in boys is unknown, and maybe a chance finding. However, since boys are more exposed to the infection, which is indicated-by higher disease prevalence in boys in this study population, the preferential protective effect in boys may have resulted from a greater booster effect produced by repeated exposure to infected sandflies. Booster injections or alternative adjuvants should be tried to improve the potential efficacy of this vaccine.