Field randomized trial to evaluate the efficacy of the Leish-Tec® vaccine against canine visceral leishmaniasis in an endemic area of Brazil

Abstract

BackgroundA canine vaccine remains a promising approach for effective control of visceral leishmaniasis (VL), given its complex epidemiology in areas where zoonotic VL is prevalent. Leish-Tec® is a recombinant vaccine, based on the Leishmania A2 antigen, against canine VL (CVL). It is, since 2014, the single commercial vaccine licensed in Brazil. Here, Leish-Tec® efficacy was estimated through a randomized field trial (RFT), in a highly VL endemic area. MethodsThe RFT was conducted from 2008 to 2010 in an endemic area of southeastern Brazil, presenting a CVL seroprevalence of 41.9%. Eight hundred forty-seven seronegative dogs were randomly selected to receive Leish-Tec® (n=429) or placebo (n=418). Animals were followed up by clinical, serological, and parasitological exams for 18 months. The CVL incidence in both groups was compared through proportion analysis. ResultsA significant reduction in the number of cases of CVL was observed in the vaccine group, as compared with the placebo group, whether efficacy was estimated according to parasitological results (71.4%; 95% CI: 34.9–87.3%; p=0.001; risk ratio=0.287), by adding results of xenodiagnosis and parasitological exams (58.1%; 95% CI: 26.0–76.3%; p=0.002; risk ratio=0.419). Among the animals that converted to a positive anti-A2 serology, efficacy reached 80.8% (95% CI: 37.6–94.1%, p=0.001; risk ratio=0.192). Xenodiagnosis has detected a reduction of 46.6% (p=0.05) in transmission to sand flies from vaccinated animals presenting anti-A2 positive serology. ConclusionThe Leish-Tec® vaccine proved significantly effective for prophylaxis of CVL, after natural challenge assured by transmission of Leishmania parasites, in a highly endemic area. Noteworthy, this report has unveiled the complexity of performing a RFT for anti-CVL vaccines in Brazil, which may be helpful for designing of future studies.