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It also has an effect on the gametocytes of\n              <jats:italic>Plasmodium falciparum<\/jats:italic>\n              ; however, it is unclear to what extent PQ affects\n              <jats:italic>P. vivax<\/jats:italic>\n              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\n              <jats:italic>P. vivax<\/jats:italic>\n              malaria. To determine gametocyte density, we measured the levels of\n              <jats:italic>pvs25<\/jats:italic>\n              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\n              <jats:italic>CPR<\/jats:italic>\n              mutation showed a smaller decrease in gametocyte transcript levels on D3 compared to those without the mutation (\n              <jats:italic>P<\/jats:italic>\n              = 0.02, by GEE). Consistent with this, higher PQ blood levels on D3 were associated with a lower reduction in\n              <jats:italic>pvs25<\/jats:italic>\n              transcripts. Based on our findings, the\n              <jats:italic>CPR<\/jats:italic>\n              variant plays a role in the persistence of gametocyte density in\n              <jats:italic>P. vivax<\/jats:italic>\n              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\u2013PQ treatment, particularly in settings and seasons of high\n              <jats:italic>Anopheles<\/jats:italic>\n              human-biting rates.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/aac.01204-23","type":"journal-article","created":{"date-parts":[[2024,2,27]],"date-time":"2024-02-27T14:01:44Z","timestamp":1709042504000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":5,"title":["Delayed gametocyte clearance in\n            <i>Plasmodium vivax<\/i>\n            malaria is associated with polymorphisms in the cytochrome P450 reductase (CPR)"],"prefix":"10.1128","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5084-7707","authenticated-orcid":false,"given":"Yanka Evellyn Alves Rodrigues","family":"Salazar","sequence":"first","affiliation":[{"name":"Molecular Biology and Malaria Immunology Research Group, Instituto Ren\u00e9 Rachou, Funda\u00e7\u00e3o Oswaldo Cruz (FIOCRUZ), Belo Horizonte, Minas Gerais, Brazil"}]},{"given":"Jaime","family":"Louzada","sequence":"additional","affiliation":[{"name":"Universidade Federal de Roraima, Boa Vista, Roraima, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2580-2275","authenticated-orcid":false,"given":"Maria Carolina Silva de Barros","family":"Pu\u00e7a","sequence":"additional","affiliation":[{"name":"Molecular Biology and Malaria Immunology Research Group, Instituto Ren\u00e9 Rachou, Funda\u00e7\u00e3o Oswaldo Cruz (FIOCRUZ), Belo Horizonte, Minas Gerais, Brazil"}]},{"given":"Luiz Felipe Ferreira","family":"Guimar\u00e3es","sequence":"additional","affiliation":[{"name":"Molecular Biology and Malaria Immunology Research Group, Instituto Ren\u00e9 Rachou, Funda\u00e7\u00e3o Oswaldo Cruz (FIOCRUZ), Belo Horizonte, Minas Gerais, Brazil"}]},{"given":"Jos\u00e9 Luiz Fernandes","family":"Vieira","sequence":"additional","affiliation":[{"name":"Universidade Federal do Par\u00e1, Bel\u00e9m, Par\u00e1, Brazil"}]},{"given":"Andr\u00e9 Machado de","family":"Siqueira","sequence":"additional","affiliation":[{"name":"Instituto Nacional de Infectologia Evandro Chagas, Funda\u00e7\u00e3o Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, Rio de Janeiro, Brazil"}]},{"given":"Jos\u00e9 Pedro","family":"Gil","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Tumor and Cell biology, Karolinska Institutet, Solna, Sweden"}]},{"given":"Cristiana Ferreira Alves de","family":"Brito","sequence":"additional","affiliation":[{"name":"Molecular Biology and Malaria Immunology Research Group, Instituto Ren\u00e9 Rachou, Funda\u00e7\u00e3o Oswaldo Cruz (FIOCRUZ), Belo Horizonte, Minas Gerais, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6874-9427","authenticated-orcid":false,"given":"Tais Nobrega de","family":"Sousa","sequence":"additional","affiliation":[{"name":"Molecular Biology and Malaria Immunology Research Group, Instituto Ren\u00e9 Rachou, Funda\u00e7\u00e3o Oswaldo Cruz (FIOCRUZ), Belo Horizonte, Minas Gerais, Brazil"},{"name":"Department of Microbiology, Tumor and Cell biology, Karolinska Institutet, Solna, Sweden"}]}],"member":"235","reference":[{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1590\/0102-311X00020218"},{"key":"e_1_3_4_4_2","first-page":"625","article-title":"Gametocytocidal and Sporontocidal effects of Primaquine and of Sulfadiazine with Pyrimethamine in a chloroquine-resistant strain of Plasmodium Falciparum","author":"Rieckmann KH","year":"1968","unstructured":"Rieckmann KH, McNamara JV, Frischer H, Stockert TA, Carson PE, Powell RD. 1968. 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