{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T01:01:05Z","timestamp":1760576465725,"version":"build-2065373602"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T00:00:00Z","timestamp":1755561600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2016\/18740-9","2020\/03611-4","2022\/11963-3"],"award-info":[{"award-number":["2016\/18740-9","2020\/03611-4","2022\/11963-3"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U19 AI089681"],"award-info":[{"award-number":["U19 AI089681"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia, Portugal","doi-asserted-by":"publisher","award":["UID\/04413\/2020","LA\/P\/0117\/2020"],"award-info":[{"award-number":["UID\/04413\/2020","LA\/P\/0117\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004901","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de Minas Gerais","doi-asserted-by":"publisher","award":["APQ-00516-21"],"award-info":[{"award-number":["APQ-00516-21"]}],"id":[{"id":"10.13039\/501100004901","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Swedish Research Council Grant","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":[[2025,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>The CYP2D6 enzyme plays a critical role in the metabolism of primaquine, the most widely used drug for the radical cure of Plasmodium vivax malaria. Impaired CYP2D6 activity has been associated with an increased risk of relapse. However, the overall impact of CYP2D6 on infection dynamics is still not fully understood. We hypothesized that individuals with impaired CYP2D6 activity develop partial immunity more rapidly due to the ineffective clearance of hypnozoites.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>To test this hypothesis, we conducted a community-based study involving \u223c1300 individuals genotyped for CYP2D6 and assessed repeatedly for P. vivax using molecular diagnosis. This approach allowed us to detect and monitor submicroscopic and asymptomatic infections over a 4-year follow-up period.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>In our cohort, children with impaired CYP2D6 activity exhibited a higher frequency of P. vivax infections compared with those with normal enzyme activity. This pattern changed during the second decade of life, as the prevalence of P. vivax infection increased in adolescents with normal enzyme activity (P = .0008, Generalized additive mixed model). Consistent with this, parasite densities were lower in adults with impaired CYP2D6 activity compared with younger individuals with normal enzyme activity (P = .0383, Linear mixed model).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>These findings underscore the potential role of CYP2D6 in shaping infection dynamics and malaria immunity in endemic areas.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/infdis\/jiaf412","type":"journal-article","created":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T13:01:38Z","timestamp":1755608498000},"page":"e571-e579","source":"Crossref","is-referenced-by-count":0,"title":["How <i>CYP2D6<\/i> Polymorphism Modulates the Community-Wide Risk of <i>Plasmodium vivax<\/i> Infection: A Panel Study in Amazonian Brazil"],"prefix":"10.1093","volume":"232","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2580-2275","authenticated-orcid":false,"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 ,","place":["Brazil"]},{"name":"Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet , Solna ,","place":["Sweden"]}]},{"given":"Isabela Marques","family":"Naziazeno","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 ,","place":["Brazil"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3965-6037","authenticated-orcid":false,"given":"Viviane Cristina Fernandes dos","family":"Santos","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 ,","place":["Brazil"]}]},{"given":"Priscila Thihara","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Sciences, University of S\u00e3o Paulo , S\u00e3o Paulo ,","place":["Brazil"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0018-5936","authenticated-orcid":false,"given":"Priscila Rodrigues","family":"Calil","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Sciences, University of S\u00e3o Paulo , S\u00e3o Paulo ,","place":["Brazil"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8815-5773","authenticated-orcid":false,"given":"Winni Alves","family":"Ladeia","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Sciences, University of S\u00e3o Paulo , S\u00e3o Paulo ,","place":["Brazil"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6107-9379","authenticated-orcid":false,"given":"Jos\u00e9 Pedro","family":"Gil","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet , Solna ,","place":["Sweden"]},{"name":"Clinical Tropical Medicine, Global Health and Tropical Medicine (GHTM), Institute of Hygiene and Tropical Medicine, NOVA University of Lisbon , Lisbon ,","place":["Portugal"]}]},{"given":"Marcelo Urbano","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Sciences, University of S\u00e3o Paulo , S\u00e3o Paulo ,","place":["Brazil"]},{"name":"Global Health and Tropical Medicine (GHTM) Associate Laboratory in Translation and Innovation Towards Global Health (LA-REAL), Institute of Hygiene and Tropical Medicine , NOVA University of Lisbon, Lisbon ,","place":["Portugal"]}]},{"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 ,","place":["Brazil"]},{"name":"Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet , Solna ,","place":["Sweden"]}]}],"member":"286","published-online":{"date-parts":[[2025,8,19]]},"reference":[{"volume-title":"World malaria report 2024","year":"2024","author":"WHO","key":"2025101515143051500_jiaf412-B1"},{"volume-title":"Secretaria de vigil\u00e2ncia em sa\u00fade e ambiente","year":"2024","author":"Ministerio da Saude Boletim 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