title: Field randomized trial to evaluate the efficacy of the Leish-Tec® vaccine against canine visceral leishmaniasis in an endemic 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 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.
  
  
  METHODS
  The 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.
  
  
  RESULTS
  A 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.
  
  
  CONCLUSIONS
  The 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.
authors.affiliation: Centro de Pesquisas René Rachou, Fiocruz, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Shara
authors.initials: S
authors.lastname: Regina-Silva
authors.affiliation: Inova Biotecnologia Saúde Animal Ltda, Juatuba, Minas Gerais, Brazil.
authors.forename: Ana Maria Leonardi Tibúrcio
authors.initials: AM
authors.lastname: Feres
authors.affiliation: Departamento de Parasitologia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: João Carlos
authors.initials: JC
authors.lastname: França-Silva
authors.affiliation: Centro de Pesquisas René Rachou, Fiocruz, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Edelberto Santos
authors.initials: ES
authors.lastname: Dias
authors.affiliation: Centro de Pesquisas René Rachou, Fiocruz, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Érika Monteiro
authors.initials: ÉM
authors.lastname: Michalsky
authors.affiliation: Departamento de Parasitologia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Hélida Monteiro
authors.initials: HM
authors.lastname: de Andrade
authors.affiliation: Setor de Patologia Clínica, Colégio Técnico, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Eduardo Antonio Ferraz
authors.initials: EA
authors.lastname: Coelho
authors.affiliation: Escola de Medicina, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil.
authors.forename: Gustavo Meirelles
authors.initials: GM
authors.lastname: Ribeiro
authors.affiliation: Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Fernandes
authors.affiliation: Escola de Medicina, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil. Electronic address: gmcoelho@medicina.ufop.br.
authors.forename: George Luiz Lins
authors.initials: GL
authors.lastname: Machado-Coelho
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D000953:Antigens, Protozoan / Q000276:immunology*; D001938:Brazil; D004283:Dog Diseases / Q000469:parasitology / Q000517:prevention & control*; D004285:Dogs; D056724:Immunity, Humoral; D054332:Leishmaniasis Vaccines / Q000627:therapeutic use*; D007898:Leishmaniasis, Visceral / Q000517:prevention & control / Q000662:veterinary*; D015800:Protozoan Proteins / Q000276:immunology*; D011576:Psychodidae / Q000469:parasitology; D020525:Xenodiagnosis
chemical_list: C107645:A2 protein, Leishmania donovani; D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D054332:Leishmaniasis Vaccines; D015800:Protozoan Proteins
keywords: A2 antigen; Canine visceral leishmaniasis; Efficacy; Leish-Tec(®); Randomized field trial; Vaccine