Author | Nascimento, Leopoldo Fabrício Marçal do | |
Author | Miranda, Dayane Francisca Higino | |
Author | Moura, Luana Dias de | |
Author | Pinho, Flaviane Alves de | |
Author | Werneck, Guilherme Loureiro | |
Author | Cunha, Antonio Ricardo Khouri | |
Author | Reed, Steven G. | |
Author | Duthie, Malcolm S. | |
Author | Barral, Aldina Maria Prado | |
Author | Barral Netto, Manoel | |
Author | Cruz, Maria do Socorro Pires e | |
Access date | 2019-12-17T13:28:47Z | |
Available date | 2019-12-17T13:28:47Z | |
Document date | 2019 | |
Citation | NASCIMENTO, Leopoldo Fabrício Marçal do et al. Allopurinol therapy provides long term clinical improvement, but additional immunotherapy is required for sustained parasite clearance, in L. infantum-infected dogs. Vaccine, p. 1-31, Nov. 2019. | pt_BR |
ISSN | 0264-410X | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/38646 | |
Description | Artigo encontra-se disponível em acesso aberto no site do Editor. | pt_BR |
Sponsorship | National Council for Scientific and
Technological Development – CNPq under Award Number 4674463/2014-0 and Coordination of
Superior Level Staff Improvement - CAPES. IDRI has been funded by for leishmaniasis vaccine
development through grant support from the Bill and Melinda Gates Foundation (#631) and
National Institute of Allergy And Infectious Diseases of the National Institutes of Health under
Award Number R01AI025038. | pt_BR |
Language | eng | pt_BR |
Publisher | Elsevier | pt_BR |
Later version | https://www.arca.fiocruz.br/handle/icict/41238 | |
Rights | open access | pt_BR |
Subject in Portuguese | Leishmaniose visceral canina | pt_BR |
Subject in Portuguese | Vacina | pt_BR |
Subject in Portuguese | Parasita | pt_BR |
Subject in Portuguese | Droga | pt_BR |
Subject in Portuguese | Sinais clínicos | pt_BR |
Title | Allopurinol therapy provides long term clinical improvement, but additional immunotherapy is required for sustained parasite clearance, in L. infantum-infected dogs | pt_BR |
Type | Preprint | pt_BR |
DOI | 10.1016/j.jvacx.2019.100048 | pt_BR |
Abstract | There is little evidence that current control strategies for canine leishmaniosis (CanL), the veterinary disease caused by L. infantum infection, are having a positive impact. This is of critical importance because dogs are a primary reservoir for L. infantum and a significant source of parasite transmission to humans. Drugs intended primarily for human use are prohibited for the treatment of CanL because of concerns over the propagation of resistant parasites. Although allopurinol effectively decreases parasite burden in CanL the treatment needs to be maintained for life. We hypothesized that during the allopurinol-induced parasite reduction dogs may become capable of developing a more robust immune response that may permit more effective control of parasites. To test this, we investigated the clinical and parasitological impact of shortterm treatment with allopurinol, either alone or in combination with a defined subunit vaccine, on dogs naturally infected with L. infantum. A total of 28 dogs were distributed as follows: untreated; oral allopurinol alone (20 mg/kg, once each day for 90 days); or allopurinol with immunization with the Leish-F2 antigen formulated with the Toll-like receptor (TLR) 4 agonist Second generation Lipid Adjuvant (SLA) in stable emulsion (SE; SLA-SE). Dogs that did not receive treatment had a progressive decline in their clinical condition and an increase in their infection levels, while treatment with allopurinol alone alleviated the clinical symptoms of CanL but did not generate sustained reduction in parasites. Concomitant immunization with Leish-F2 + SLA-SE, however, improved clinical condition while also providing long-term clearance of L. infantum from lymphoid tissues and systemic organs. These results have important implications for both the management of CanL and for limiting L. infantum transmission to humans. | pt_BR |
Affilliation | Universidade Federal do Piauí. Departamento de Morfofisiologia Veterinária. Teresina, PI, Brasil. | pt_BR |
Affilliation | Universidade Federal do Piauí. Departamento de Morfofisiologia Veterinária. Teresina, PI, Brasil. | pt_BR |
Affilliation | Universidade Federal do Piauí. Departamento de Morfofisiologia Veterinária. Teresina, PI, Brasil. | pt_BR |
Affilliation | Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Estudos em Saúde Coletiva. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil. | pt_BR |
Affilliation | Infectious Diseases Research Institute. Seattle, WA, USA. | pt_BR |
Affilliation | Infectious Diseases Research Institute. Seattle, WA, USA / HDT Biotech Corporation. Seattle, WA, USA. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil / Instituto Nacional de Ciência e Tecnologia. Instituto de Investigação em Imunologia. São Paulo, SP, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil / Instituto Nacional de Ciência e Tecnologia. Instituto de Investigação em Imunologia. São Paulo, SP, Brasil. | pt_BR |
Affilliation | Universidade Federal do Piauí. Departamento de Morfofisiologia Veterinária. Teresina, PI, Brasil. | pt_BR |
Subject | Canine visceral leishmaniasis | pt_BR |
Subject | Vaccine | pt_BR |
Subject | Parasite | pt_BR |
Subject | Drug | pt_BR |
Subject | Clinical signs | pt_BR |
xmlui.metadata.dc.subject.ods | 03 Saúde e Bem-Estar | |