Allopurinol therapy provides long term clinical improvement, but additional immunotherapy is required for sustained parasite clearance, in L. infantum-infected dogs

Detalhes bibliográficos
Autor(a) principal: Nascimento, Leopoldo Fabrício Marçal do
Data de Publicação: 2019
Outros Autores: Miranda, Dayane Francisca Higino, Moura, Luana Dias de, Pinho, Flaviane Alves de, Werneck, Guilherme Loureiro, Cunha, Antonio Ricardo Khouri, Reed, Steven G., Duthie, Malcolm S., Barral, Aldina Maria Prado, Barral Netto, Manoel, Cruz, Maria do Socorro Pires e
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/38646
Resumo: Artigo encontra-se disponível em acesso aberto no site do Editor.
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spelling Nascimento, Leopoldo Fabrício Marçal doMiranda, Dayane Francisca HiginoMoura, Luana Dias dePinho, Flaviane Alves deWerneck, Guilherme LoureiroCunha, Antonio Ricardo KhouriReed, Steven G.Duthie, Malcolm S.Barral, Aldina Maria PradoBarral Netto, ManoelCruz, Maria do Socorro Pires e2019-12-17T13:28:47Z2019-12-17T13:28:47Z2019NASCIMENTO, 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. 2019.0264-410Xhttps://www.arca.fiocruz.br/handle/icict/3864610.1016/j.jvacx.2019.100048Artigo encontra-se disponível em acesso aberto no site do Editor.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.Universidade Federal do Piauí. Departamento de Morfofisiologia Veterinária. Teresina, PI, Brasil.Universidade Federal do Piauí. Departamento de Morfofisiologia Veterinária. Teresina, PI, Brasil.Universidade Federal do Piauí. Departamento de Morfofisiologia Veterinária. Teresina, PI, Brasil.Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Estudos em Saúde Coletiva. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil.Infectious Diseases Research Institute. Seattle, WA, USA.Infectious Diseases Research Institute. Seattle, WA, USA / HDT Biotech Corporation. Seattle, WA, USA.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.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.Universidade Federal do Piauí. Departamento de Morfofisiologia Veterinária. Teresina, PI, Brasil.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.engElsevierhttps://www.arca.fiocruz.br/handle/icict/41238Leishmaniose visceral caninaVacinaParasitaDrogaSinais clínicosCanine visceral leishmaniasisVaccineParasiteDrugClinical signsAllopurinol therapy provides long term clinical improvement, but additional immunotherapy is required for sustained parasite clearance, in L. infantum-infected dogsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/38646/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALNascimento FM. Allopurinol....pdfNascimento FM. 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dc.title.pt_BR.fl_str_mv Allopurinol therapy provides long term clinical improvement, but additional immunotherapy is required for sustained parasite clearance, in L. infantum-infected dogs
title Allopurinol therapy provides long term clinical improvement, but additional immunotherapy is required for sustained parasite clearance, in L. infantum-infected dogs
spellingShingle Allopurinol therapy provides long term clinical improvement, but additional immunotherapy is required for sustained parasite clearance, in L. infantum-infected dogs
Nascimento, Leopoldo Fabrício Marçal do
Leishmaniose visceral canina
Vacina
Parasita
Droga
Sinais clínicos
Canine visceral leishmaniasis
Vaccine
Parasite
Drug
Clinical signs
title_short Allopurinol therapy provides long term clinical improvement, but additional immunotherapy is required for sustained parasite clearance, in L. infantum-infected dogs
title_full Allopurinol therapy provides long term clinical improvement, but additional immunotherapy is required for sustained parasite clearance, in L. infantum-infected dogs
title_fullStr Allopurinol therapy provides long term clinical improvement, but additional immunotherapy is required for sustained parasite clearance, in L. infantum-infected dogs
title_full_unstemmed Allopurinol therapy provides long term clinical improvement, but additional immunotherapy is required for sustained parasite clearance, in L. infantum-infected dogs
title_sort Allopurinol therapy provides long term clinical improvement, but additional immunotherapy is required for sustained parasite clearance, in L. infantum-infected dogs
author Nascimento, Leopoldo Fabrício Marçal do
author_facet Nascimento, Leopoldo Fabrício Marçal do
Miranda, Dayane Francisca Higino
Moura, Luana Dias de
Pinho, Flaviane Alves de
Werneck, Guilherme Loureiro
Cunha, Antonio Ricardo Khouri
Reed, Steven G.
Duthie, Malcolm S.
Barral, Aldina Maria Prado
Barral Netto, Manoel
Cruz, Maria do Socorro Pires e
author_role author
author2 Miranda, Dayane Francisca Higino
Moura, Luana Dias de
Pinho, Flaviane Alves de
Werneck, Guilherme Loureiro
Cunha, Antonio Ricardo Khouri
Reed, Steven G.
Duthie, Malcolm S.
Barral, Aldina Maria Prado
Barral Netto, Manoel
Cruz, Maria do Socorro Pires e
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Nascimento, Leopoldo Fabrício Marçal do
Miranda, Dayane Francisca Higino
Moura, Luana Dias de
Pinho, Flaviane Alves de
Werneck, Guilherme Loureiro
Cunha, Antonio Ricardo Khouri
Reed, Steven G.
Duthie, Malcolm S.
Barral, Aldina Maria Prado
Barral Netto, Manoel
Cruz, Maria do Socorro Pires e
dc.subject.other.pt_BR.fl_str_mv Leishmaniose visceral canina
Vacina
Parasita
Droga
Sinais clínicos
topic Leishmaniose visceral canina
Vacina
Parasita
Droga
Sinais clínicos
Canine visceral leishmaniasis
Vaccine
Parasite
Drug
Clinical signs
dc.subject.en.pt_BR.fl_str_mv Canine visceral leishmaniasis
Vaccine
Parasite
Drug
Clinical signs
description Artigo encontra-se disponível em acesso aberto no site do Editor.
publishDate 2019
dc.date.accessioned.fl_str_mv 2019-12-17T13:28:47Z
dc.date.available.fl_str_mv 2019-12-17T13:28:47Z
dc.date.issued.fl_str_mv 2019
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
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status_str publishedVersion
dc.identifier.citation.fl_str_mv 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.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/38646
dc.identifier.issn.pt_BR.fl_str_mv 0264-410X
dc.identifier.doi.pt_BR.fl_str_mv 10.1016/j.jvacx.2019.100048
identifier_str_mv 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.
0264-410X
10.1016/j.jvacx.2019.100048
url https://www.arca.fiocruz.br/handle/icict/38646
dc.language.iso.fl_str_mv eng
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dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
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