{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T11:36:12Z","timestamp":1774611372914,"version":"3.50.1"},"reference-count":19,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2024,6,13]],"date-time":"2024-06-13T00:00:00Z","timestamp":1718236800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004901","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de Minas Gerais","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004901","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"publisher","award":["200075\/2022-5"],"award-info":[{"award-number":["200075\/2022-5"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Programa PrInt-Fiocruz-CAPES"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Primaquine is essential for the radical cure of Plasmodium vivax malaria and must be metabolized into its bioactive metabolites. Accordingly, polymorphisms in primaquine-metabolizing enzymes can impact the treatment efficacy. This pioneering study explores the influence of monoamine oxidase-A (MAO-A) on primaquine metabolism and its impact on malaria relapses.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Samples from 205 patients with P. vivax malaria were retrospectively analysed by genotyping polymorphisms in MAO-A and cytochrome P450 2D6 (CYP2D6) genes. We measured the primaquine and carboxyprimaquine blood levels in 100 subjects for whom blood samples were available on the third day of treatment. We also examined the relationship between the enzyme variants and P. vivax malaria relapses in a group of subjects with well-documented relapses.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The median carboxyprimaquine level was significantly reduced in individuals carrying low-expression MAO-A alleles plus impaired CYP2D6. In addition, this group experienced significantly more P. vivax relapses. The low-expression MAO-A status was not associated with malaria relapses when CYP2D6 had normal activity. This suggests that the putative carboxyprimaquine contribution is irrelevant when the CYP2D6 pathway is fully active.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>We found evidence that the low-expression MAO-A variants can potentiate the negative impact of impaired CYP2D6 activity, resulting in lower levels of carboxyprimaquine metabolite and multiple relapses. The findings support the hypothesis that carboxyprimaquine may be further metabolized through CYP-mediated pathways generating bioactive metabolites that act against the parasite.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkae196","type":"journal-article","created":{"date-parts":[[2024,6,14]],"date-time":"2024-06-14T10:51:45Z","timestamp":1718362305000},"page":"1985-1989","source":"Crossref","is-referenced-by-count":4,"title":["Monoamine oxidase-A (MAO-A) low-expression variants and increased risk of <i>Plasmodium vivax<\/i> malaria relapses"],"prefix":"10.1093","volume":"79","author":[{"given":"Maria Carolina Silva De Barros","family":"Pu\u00e7a","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":"Danielle Fonseca","family":"Rodrigues","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":"Yanka Evellyn Alves Rodrigues","family":"Salazar","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":"Jaime","family":"Louzada","sequence":"additional","affiliation":[{"name":"Universidade Federal de Roraima , Boa Vista, Roraima , Brazil"}]},{"given":"Cor Jesus Fernandes","family":"Fontes","sequence":"additional","affiliation":[{"name":"Universidade Federal do Mato Grosso , Faculdade de Medicina, Departamento de Medicina Interna, Cuiab\u00e1, Mato Grosso , Brazil"}]},{"given":"Andr\u00e9","family":"Daher","sequence":"additional","affiliation":[{"name":"Vice Presidency of Research and Biological Collections, Funda\u00e7\u00e3o Oswaldo Cruz (FIOCRUZ), Rio de Janeiro , Rio de Janeiro , Brazil"}]},{"given":"Dh\u00e9lio Batista","family":"Pereira","sequence":"additional","affiliation":[{"name":"Centro de Pesquisa em Medicina Tropical de Rond\u00f4nia, CEPEM , Porto Velho, Rond\u00f4nia, Brazil"}]},{"given":"Jos\u00e9 Luiz","family":"Fernandes Vieira","sequence":"additional","affiliation":[{"name":"Universidade Federal do Par\u00e1 , Faculdade de Farm\u00e1cia, Laborat\u00f3rio de Toxicologia, Bel\u00e9m, Par\u00e1 , Brazil"}]},{"given":"Luzia Helena","family":"Carvalho","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":"Cristiana Ferreira","family":"Alves de 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"}]},{"given":"Jos\u00e9 Pedro","family":"Gil","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Tumor and Cell biology, Karolinska Institutet , Solna , Sweden"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6874-9427","authenticated-orcid":false,"given":"Tais","family":"Nobrega de 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":"286","published-online":{"date-parts":[[2024,6,13]]},"reference":[{"key":"2024073123522782500_dkae196-B1","author":"WHO"},{"key":"2024073123522782500_dkae196-B2","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/s12936-018-2190-z","article-title":"Primaquine ineligibility in anti-relapse therapy of Plasmodium 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