{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T15:36:54Z","timestamp":1791992214215,"version":"4.4.0"},"reference-count":36,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T00:00:00Z","timestamp":1693958400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/K007424\/1"],"award-info":[{"award-number":["MR\/K007424\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["OPP1054404"],"award-info":[{"award-number":["OPP1054404"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["B9RJIXO"],"award-info":[{"award-number":["B9RJIXO"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Australian NHMRC Leadership Investigator Grant","award":["1196068"],"award-info":[{"award-number":["1196068"]}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>The World Health Organization recommends that primaquine should be given once weekly for 8-weeks to patients with <jats:italic>Plasmodium vivax<\/jats:italic> malaria and glucose-6-phosphate dehydrogenase (G6PD) deficiency, but data on its antirelapse efficacy and safety are limited.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>Within the context of a multicentre, randomised clinical trial of two primaquine regimens in <jats:italic>P<\/jats:italic>. <jats:italic>vivax<\/jats:italic> malaria, patients with G6PD deficiency were excluded and enrolled into a separate 12-month observational study. They were treated with a weekly dose of 0.75 mg\/kg primaquine for 8 weeks (PQ8W) plus dihydroartemisinin piperaquine (Indonesia) or chloroquine (Afghanistan, Ethiopia, Vietnam). G6PD status was diagnosed using the fluorescent spot test and confirmed by genotyping for locally prevalent G6PD variants. The risk of <jats:italic>P<\/jats:italic>. <jats:italic>vivax<\/jats:italic> recurrence following PQ8W and the consequent haematological recovery were characterized in all patients and in patients with genotypically confirmed G6PD variants, and compared with the patients enrolled in the main randomised control trial.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Between July 2014 and November 2017, 42 male and 8 female patients were enrolled in Afghanistan (6), Ethiopia (5), Indonesia (19), and Vietnam (20). G6PD deficiency was confirmed by genotyping in 31 patients: Viangchan (14), Mediterranean (4), 357A-G (3), Canton (2), Kaiping (2), and one each for A<jats:sup>-<\/jats:sup>, Chatham, Gaohe, Ludhiana, Orissa, and Vanua Lava. Two patients had recurrent <jats:italic>P<\/jats:italic>. <jats:italic>vivax<\/jats:italic> parasitaemia (days 68 and 207). The overall 12-month cumulative risk of recurrent <jats:italic>P<\/jats:italic>. <jats:italic>vivax<\/jats:italic> malaria was 5.1% (95% CI: 1.3\u201318.9) and the incidence rate of recurrence was 46.8 per 1000 person-years (95% CI: 11.7\u2013187.1). The risk of <jats:italic>P<\/jats:italic>. <jats:italic>vivax<\/jats:italic> recurrence was lower in G6PD deficient patients treated with PQ8W compared to G6PD normal patients in all treatment arms of the randomised controlled trial. Two of the 26 confirmed hemizygous males had a significant fall in haemoglobin (&gt;5g\/dl) after the first dose but were able to complete their 8 week regimen.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>PQ8W was highly effective in preventing <jats:italic>P<\/jats:italic>. <jats:italic>vivax<\/jats:italic> recurrences. Whilst PQ8W was well tolerated in most patients across a range of different G6PD variants, significant falls in haemoglobin may occur after the first dose and require clinical monitoring.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec005\">\n<jats:title>Trial registration<\/jats:title>\n<jats:p>This trial is registered at ClinicalTrials.gov (<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT01814683\" xlink:type=\"simple\">NCT01814683<\/jats:ext-link>).<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pntd.0011522","type":"journal-article","created":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T17:29:40Z","timestamp":1694021380000},"page":"e0011522","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":13,"title":["Weekly primaquine for radical cure of patients with Plasmodium vivax malaria and glucose-6-phosphate dehydrogenase deficiency"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6236-0464","authenticated-orcid":true,"given":"Walter R. 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