title: Treatment of canine visceral leishmaniasis by the vaccine Leish-111f+MPL-SE.
abstract: Immunotherapy of canine visceral leishmaniasis (CVL) may provide an alternative to both marginally effective chemotherapy and undesired euthanasia of infected dogs and could have a great impact not only on animal welfare, but also on control of human disease. Therefore, we examined the potential immunotherapeutic efficacy of the subunit vaccine Leish-111f+MPL-SE, which has undergone rigorous preclinical testing and been demonstrated safe in human clinical trials. Two separate trials were performed in Salvador, Brazil, to evaluate the vaccine for therapeutic efficacy against CVL caused by natural infection: an Open Trial and a Blinded Trial. In the Open Trial 59 dogs with clinically active CVL were sequentially allocated to four groups: group 1 received Leish-111f+MPL-SE; group 2 was treated with Glucantime; group 3 received a combination of the vaccine and Glucantime; and group 4 was given no treatment. At the 6-month assessment, the 13 non-treated dogs had either died or showed no clinical improvement. In contrast, most dogs in groups 1-3 showed initial improvement (100%, 80%, and 92%, respectively). Upon evaluation for a mean of 36 months after therapy, the following cure rates were observed: 75% for group 1 dogs (exact 95% confidence interval [CI] 43-95%), 64% for group 2 dogs (exact 95% CI 31-89%), and 50% for group 3 dogs (exact 95% CI 19-81%). Therapeutic efficacy of the Leish-111f+MPL-SE vaccine was reconfirmed in a subsequent Blinded Trial. The vaccine was effective for mild cases of CVL and was compromised in dogs with severe disease. Although further studies are required to understand mechanisms of action, the Leish-111f+MPL-SE vaccine is a promising tool to control VL in both dogs and humans.
authors.affiliation: Canil Avançado em Monte Gordo de Pesquisa em Leishmanioses, Camaçari, Bahia-Clinvet, Brazil.
authors.forename: Joelma
authors.initials: J
authors.lastname: Trigo
authors.forename: Melissa
authors.initials: M
authors.lastname: Abbehusen
authors.forename: Eduardo M
authors.initials: EM
authors.lastname: Netto
authors.forename: Maria
authors.initials: M
authors.lastname: Nakatani
authors.forename: Geraldo
authors.initials: G
authors.lastname: Pedral-Sampaio
authors.forename: Robson Silva
authors.initials: RS
authors.lastname: de Jesus
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Goto
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Guderian
authors.forename: Randall F
authors.initials: RF
authors.lastname: Howard
authors.forename: Steven G
authors.initials: SG
authors.lastname: Reed
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000008:administration & dosage; D001938:Brazil; D004285:Dogs; D007167:Immunotherapy / Q000379:methods*; D054332:Leishmaniasis Vaccines / Q000008:administration & dosage*; D007898:Leishmaniasis, Visceral / Q000628:therapy* / Q000662:veterinary*; D008536:Meglumine / Q000008:administration & dosage; D000077485:Meglumine Antimoniate; D009942:Organometallic Compounds / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D000981:Antiprotozoal Agents; D054332:Leishmaniasis Vaccines; D009942:Organometallic Compounds; D008536:Meglumine; D000077485:Meglumine Antimoniate