Field randomized trial to evaluate the efficacy of the Leish - Tec vaccine against canine visceral leishmaniasis in anendemic area of Brazil.

Abstract

Background: A 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 recombi-nant vaccine, based on the Leishmania A2 antigen, against canine VL (CVL). It is, since 2014, the singlecommercial vaccine licensed in Brazil. Here, Leish-Tec®efficacy was estimated through a randomizedfield trial (RFT), in a highly VL endemic area.Methods: The RFT was conducted from 2008 to 2010 in an endemic area of southeastern Brazil, presentinga CVL seroprevalence of 41.9%. Eight hundred forty-seven seronegative dogs were randomly selected toreceive Leish-Tec®(n = 429) or placebo (n = 418). Animals were followed up by clinical, serological, andparasitological exams for 18 months. The CVL incidence in both groups was compared through proportionanalysis.Results: A significant reduction in the number of cases of CVL was observed in the vaccine group, ascompared 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 parasito-logical exams (58.1%; 95% CI: 26.0–76.3%; p = 0.002; risk ratio = 0.419). Among the animals that convertedto 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 vaccinatedanimals presenting anti-A2 positive serology.Conclusion: The Leish-Tec®vaccine proved significantly effective for prophylaxis of CVL, after naturalchallenge assured by transmission of Leishmania parasites, in a highly endemic area. Noteworthy, thisreport has unveiled the complexity of performing a RFT for anti-CVL vaccines in Brazil, which may behelpful for designing of future studies.