{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T21:48:05Z","timestamp":1788904085036,"version":"build-2803163510"},"reference-count":28,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2025,4,2]],"date-time":"2025-04-02T00:00:00Z","timestamp":1743552000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,4,2]],"date-time":"2025-04-02T00:00:00Z","timestamp":1743552000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2025,4,2]]},"abstract":"ABSTRACT<\/jats:title>\n \n \n \n Primaquine is the only widely available drug to prevent relapses of\n Plasmodium vivax<\/jats:italic>\n malaria. Primaquine is underused because of concerns over oxidant hemolysis in glucose-6-phosphate dehydrogenase (G6PD) deficiency. A pharmacometric trial showed that ascending-dose radical cure primaquine regimens causing \u2018slow burn\u2019 hemolysis were safe in G6PD-deficient Thai and Burmese male volunteers. We developed and calibrated a within-host model of primaquine hemolysis in G6PD deficiency, using detailed serial hemoglobin and reticulocyte count data from 23 hemizygote deficient volunteers given ascending-dose primaquine (1,523 individual measurements over 656 unique time points). We estimate that primaquine doses of ~0.75 mg base\/kg reduce the circulating lifespan of deficient erythrocytes by ~30 days in individuals with common Southeast Asian\n G6PD<\/jats:italic>\n variants. We predict that 5 mg\/kg primaquine total dose can be administered safely to G6PD-deficient individuals over 14 days with expected hemoglobin drops of 18 to 43% (2.7 to 6.5 g\/dL drop from a baseline of 15 g\/dL).\n <\/jats:p>\n \n CLINICAL TRIALS<\/jats:title>\n \n This study is registered with the Thai Clinical Trials Registry (TCTR) as\n TCTR20170830002<\/jats:related-object>\n a\n \n nd\n TCTR20220317004<\/jats:related-object>\n \n .\n <\/jats:p>\n <\/jats:sec>\n <\/jats:sec>","DOI":"10.1128\/aac.01549-24","type":"journal-article","created":{"date-parts":[[2025,2,24]],"date-time":"2025-02-24T14:00:26Z","timestamp":1740405626000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["Within-host modeling of primaquine-induced hemolysis in hemizygote glucose-6-phosphate dehydrogenase deficient healthy volunteers"],"prefix":"10.1128","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5524-0325","authenticated-orcid":true,"given":"James A.","family":"Watson","sequence":"first","affiliation":[{"name":"Infectious Diseases Data Observatory","place":["Oxford, United Kingdom"]},{"name":"Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford","place":["Oxford, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parinaz","family":"Mehdipour","sequence":"additional","affiliation":[{"name":"Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne","place":["Melbourne, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4568-2012","authenticated-orcid":false,"given":"Robert","family":"Moss","sequence":"additional","affiliation":[{"name":"Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne","place":["Melbourne, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1020-2760","authenticated-orcid":true,"given":"Podjanee","family":"Jittamala","sequence":"additional","affiliation":[{"name":"Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University","place":["Bangkok, Thailand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8253-8896","authenticated-orcid":true,"given":"Sophie","family":"Zaloumis","sequence":"additional","affiliation":[{"name":"Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne","place":["Melbourne, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0076-3123","authenticated-orcid":false,"given":"David J.","family":"Price","sequence":"additional","affiliation":[{"name":"Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne","place":["Melbourne, Australia"]},{"name":"Department of Infectious Diseases, Peter Doherty Institute for Infection and Immunity, University of Melbourne","place":["Melbourne, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4613-3672","authenticated-orcid":true,"given":"Saber","family":"Dini","sequence":"additional","affiliation":[{"name":"Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne","place":["Melbourne, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8729-1442","authenticated-orcid":false,"given":"Borimas","family":"Hanboonkunupakarn","sequence":"additional","affiliation":[{"name":"Mahidol Oxford Tropical Medicine 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Thailand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6533-6811","authenticated-orcid":true,"given":"Kesinee","family":"Chotivanich","sequence":"additional","affiliation":[{"name":"Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University","place":["Bangkok, Thailand"]},{"name":"Medical Therapeutics Unit, Faculty of Tropical Medicine, Mahidol University","place":["Bangkok, Thailand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4550-0431","authenticated-orcid":false,"given":"Germana","family":"Bancone","sequence":"additional","affiliation":[{"name":"Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford","place":["Oxford, United Kingdom"]},{"name":"Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University","place":["Mae Sot, Thailand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Commons","sequence":"additional","affiliation":[{"name":"Global Health Division, Menzies School of Health Research and Charles Darwin University","place":["Darwin, Australia"]},{"name":"General and Subspecialty Medicine, Grampians Health-Ballarat","place":["Ballarat, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2309-1171","authenticated-orcid":false,"given":"Nicholas P. 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