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The prevention of these relapses hinges on the use of 8-aminoquinolines such as primaquine (PQ) and tafenoquine (TQ). However, the efficacy of these treatments is associated with Cytochrome P450 2D6 (\n                      <jats:italic toggle=\"yes\">CYP2D6<\/jats:italic>\n                      ) activity, which influences drug metabolism. This case-control study aimed to evaluate the relationship between\n                      <jats:italic toggle=\"yes\">CYP2D6<\/jats:italic>\n                      activity and the efficacy of TQ and PQ in preventing\n                      <jats:italic toggle=\"yes\">P. vivax<\/jats:italic>\n                      relapses. Patients with\n                      <jats:italic toggle=\"yes\">P. vivax<\/jats:italic>\n                      malaria were included in a nested case-control cohort study conducted at the Funda\u00e7\u00e3o de Medicina Tropical Dr. Heitor Vieira Dourado (Manaus, AM, Brazil). Participants were classified as cases (recurrent malaria within 180 days) or controls (patients without recurrence). They were treated with PQ or TQ. Epidemiological data were collected from participants, and blood samples were obtained for\n                      <jats:italic toggle=\"yes\">CYP2D6<\/jats:italic>\n                      genotyping by real-time PCR. The results showed that\n                      <jats:italic toggle=\"yes\">CYP2D6<\/jats:italic>\n                      polymorphisms did not affect TQ efficacy (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = 0.172). However, participants treated with PQ had a higher risk of recurrence until six months (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = 0.016). Those with a predicted intermediate or poor metabolizer phenotype (gIM + gPM) were more likely to experience recurrence compared to normal metabolizers (gNM) (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = 0.036). Our findings indicate that\n                      <jats:italic toggle=\"yes\">CYP2D6<\/jats:italic>\n                      does not impact the efficacy of TQ, whereas\n                      <jats:italic toggle=\"yes\">P. vivax<\/jats:italic>\n                      recurrence is associated with predicted metabolic phenotype, with increased risk among patients treated with PQ, suggesting that\n                      <jats:italic toggle=\"yes\">CYP2D6<\/jats:italic>\n                      variability influences treatment response, particularly in intermediate\/poor metabolizers.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.01797-25","type":"journal-article","created":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T09:07:37Z","timestamp":1777280857000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Differential impact of Tafenoquine and Primaquine on\n                    <i>Plasmodium vivax<\/i>\n                    recurrence: the role of\n                    <i>CYP2D6<\/i>\n                    variants"],"prefix":"10.1128","volume":"70","author":[{"given":"Vanessa Karina Castro","family":"Godinho","sequence":"first","affiliation":[{"name":"Programa de P\u00f3s-gradua\u00e7\u00e3o em Medicina Tropical da Universidade do Estado do Amazonas (PPGMT-UEA)","place":["Manaus, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2618-3816","authenticated-orcid":true,"given":"Victor Irungu","family":"Mwangi","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-gradua\u00e7\u00e3o em Medicina Tropical da Universidade do Estado do Amazonas (PPGMT-UEA)","place":["Manaus, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela Crispim","family":"Morais","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-gradua\u00e7\u00e3o em Medicina Tropical da 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