| Autor | Salazar, Yanka Evellyn Alves Rodrigues | |
| Autor | Louzada, Jaime | |
| Autor | Puça, Maria Carolina Silva de Barros | |
| Autor | Guimarães, Luiz Felipe Ferreira | |
| Autor | Vieira, José Luiz Fernandes | |
| Autor | Siqueira, André Machado de | |
| Autor | Gil, José Pedro | |
| Autor | Brito, Cristiana Ferreira Alves de | |
| Autor | Sousa, Tais Nobrega de | |
| Data de acesso | 2024-04-01T13:26:19Z | |
| Data de disponibilização | 2024-04-01T13:26:19Z | |
| Data do publicação | 2024 | |
| Citação | SALAZAR, Yanka Evellyn Alves Rodrigues et al. Delayed gametocyte clearance in <i>Plasmodium vivax</i> malaria is associated with polymorphisms in the cytochrome P450 reductase (CPR). Antimicrob Agents Chemother, 2024, e0120423, 2024. doi: 10.1128/aac.01204-23 | en_US |
| ISSN | 0066-4804 | en_US |
| URI | https://www.arca.fiocruz.br/handle/icict/63274 | |
| Idioma | eng | en_US |
| Editor | American Society for Microbiology | en_US |
| Direito Autoral | restricted access | |
| Título | Delayed gametocyte clearance in <i>Plasmodium vivax</i> malaria is associated with polymorphisms in the cytochrome P450 reductase (CPR) | en_US |
| Tipo do documento | Article | |
| Resumo em Inglês | Primaquine (PQ) is the main drug used to eliminate dormant liver stages and prevent relapses in Plasmodium vivax malaria. It also has an effect on the gametocytes of Plasmodium falciparum; however, it is unclear to what extent PQ affects P. vivax gametocytes. PQ metabolism involves multiple enzymes, including the highly polymorphic CYP2D6 and the cytochrome P450 reductase (CPR). Since genetic variability can impact drug metabolism, we conducted an evaluation of the effect of CYP2D6 and CPR variants on PQ gametocytocidal activity in 100 subjects with P. vivax malaria. To determine gametocyte density, we measured the levels of pvs25 transcripts in samples taken before treatment (D0) and 72 hours after treatment (D3). Generalized estimating equations (GEEs) were used to examine the effects of enzyme variants on gametocyte densities, adjusting for potential confounding factors. Linear regression models were adjusted to explore the predictors of PQ blood levels measured on D3. Individuals with the CPR mutation showed a smaller decrease in gametocyte transcript levels on D3 compared to those without the mutation (P = 0.02, by GEE). Consistent with this, higher PQ blood levels on D3 were associated with a lower reduction in pvs25 transcripts. Based on our findings, the CPR variant plays a role in the persistence of gametocyte density in P. vivax malaria. Conceptually, our work points to pharmacogenetics as a non-negligible factor to define potential host reservoirs with the propensity to contribute to transmission in the first days of CQ–PQ treatment, particularly in settings and seasons of high Anopheles human-biting rates. | en_US |
| Afiliação | Universidade Federal de Roraima. Boa Vista, RO, Brazil | en_US |
| Afiliação | Universidade Federal de Roraima. Boa Vista, RO, Brazil | en_US |
| Afiliação | Universidade Federal de Roraima. Boa Vista, RO, Brazil | en_US |
| Afiliação | Universidade Federal de Roraima. Boa Vista, RO, Brazil | en_US |
| Afiliação | Universidade Federal do Pará. Belém, PA, Brazil | en_US |
| Afiliação | Fundação Oswaldo Cruz Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brazil | en_US |
| Afiliação | Department of Microbiology. Tumor and Cell biology. Karolinska Institutet. Solna, Sweden | en_US |
| Afiliação | Fundação Oswaldo Cruz. Instituto René Rachou. Molecular Biology and Malaria Immunology Research Group. Belo Horizonte, MG, Brazil | en_US |
| Afiliação | Fundação Oswaldo Cruz. Instituto René Rachou. Molecular Biology and Malaria Immunology Research Group. Belo Horizonte, MG, Brazil/ Department of Microbiology. Tumor and Cell biology. Karolinska Institutet. Solna, Sweden | en_US |
| Palavras-chave em inglês | malaria | en_US |
| Palavras-chave em inglês | Plasmodium vivax | en_US |
| Palavras-chave em inglês | gametocytes | en_US |
| Palavras-chave em inglês | primaquine | en_US |
| Palavras-chave em inglês | pharmacogenetics | en_US |
| Palavras-chave em inglês | cytochrome P450 reductase | en_US |
| Palavras-chave em inglês | CYP2D6 | en_US |
| Data de embargo | 2025-12-31 | |
