{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T04:18:25Z","timestamp":1785557905168,"version":"3.56.0"},"reference-count":30,"publisher":"American Society of Tropical Medicine and Hygiene","issue":"4","license":[{"start":{"date-parts":[[2023,10,4]],"date-time":"2023-10-04T00:00:00Z","timestamp":1696377600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,10,4]]},"abstract":"<jats:title>ABSTRACT.<\/jats:title>\n<jats:p>Primaquine (PQ) kills <jats:italic>Plasmodium vivax<\/jats:italic> hypnozoites but can cause severe hemolysis in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. We conducted two systematic reviews. The first used data from clinical trials to determine the variety of definitions and frequency of hematological serious adverse events (SAEs) related to PQ treatment of vivax malaria. The second used data from prospective studies and case reports to describe the clinical presentation, management, and outcome of severe PQ-associated hemolysis necessitating hospitalization. In the first review, SAEs were reported in 70 of 249 clinical trials. There were 34 hematological SAEs among 9,824 patients with <jats:italic>P. vivax<\/jats:italic> malaria treated with PQ, nine of which necessitated hospitalization or blood transfusion. Criteria used to define SAEs were diverse. In the second review, 21 of 8,487 articles screened reported 163 patients hospitalized after PQ radical cure; 79.9% of whom (123 of 154) were prescribed PQ at \u2265 0.5\u2009mg\/kg\/day. Overall, 101 patients were categorized as having probable or possible severe PQ-associated hemolysis, 96.8% of whom were G6PD deficient (&lt; 30% activity). The first symptoms of hemolysis were reported primarily on day 2 or 3 (45.5%), and all patients were hospitalized within 7 days of PQ commencement. A total of 57.9% of patients (77 of 133) had blood transfusion. Seven patients (6.9%) with probable or possible hemolysis died. Even when G6PD testing is available, enhanced monitoring for hemolysis is warranted after PQ treatment. Clinical review within the first 5 days of treatment may facilitate early detection and management of hemolysis. More robust definitions of severe PQ-associated hemolysis are required.<\/jats:p>","DOI":"10.4269\/ajtmh.23-0280","type":"journal-article","created":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T14:57:41Z","timestamp":1692629861000},"page":"761-769","source":"Crossref","is-referenced-by-count":27,"title":["Severe Hemolysis during Primaquine Radical Cure of Plasmodium vivax Malaria: Two Systematic Reviews and Individual Patient Data Descriptive Analyses"],"prefix":"10.4269","volume":"109","author":[{"given":"Daniel","family":"Yilma","sequence":"first","affiliation":[{"name":"Jimma University Clinical Trial Unit, Department of Internal Medicine, Jimma University, Jimma, Ethiopia;"},{"name":"WorldWide Antimalarial Resistance Network, Oxford, United Kingdom;"},{"name":"Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily S.","family":"Groves","sequence":"additional","affiliation":[{"name":"Division of Global and Tropical Health, Menzies School of Health Research and Charles Darwin University, Darwin, Casuarina, Northern Territory, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose Diego","family":"Brito-Sousa","sequence":"additional","affiliation":[{"name":"Instituto de Pesquisa Cl\u00ednica Carlos Borborema, Fundac\u00e3o de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Brazil;"},{"name":"Escola Superior de Ci\u00eancias da Saude, Universidade do Estado do Amazonas, Manaus, Brazil;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wuelton M.","family":"Monteiro","sequence":"additional","affiliation":[{"name":"Instituto de Pesquisa Cl\u00ednica Carlos Borborema, Fundac\u00e3o de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Brazil;"},{"name":"Escola Superior de Ci\u00eancias da Saude, Universidade do Estado do Amazonas, Manaus, Brazil;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cindy","family":"Chu","sequence":"additional","affiliation":[{"name":"Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medical Research Unit, Faculty of Tropical Medicine, Mahidol University, MaeSot, Tak, Thailand;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamala","family":"Thriemer","sequence":"additional","affiliation":[{"name":"Division of Global and Tropical Health, Menzies School of Health Research and Charles Darwin University, Darwin, Casuarina, Northern Territory, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Commons","sequence":"additional","affiliation":[{"name":"Division of Global and Tropical Health, Menzies School of Health Research and Charles Darwin University, Darwin, Casuarina, Northern Territory, Australia;"},{"name":"General and Subspecialty Medicine, Grampians Health, Ballarat, Victoria, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus V. G.","family":"Lacerda","sequence":"additional","affiliation":[{"name":"Instituto de Pesquisa Cl\u00ednica Carlos Borborema, Fundac\u00e3o de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Brazil;"},{"name":"Instituto Le\u00f4nidas & Maria Deane, Fundac\u00e3o Oswaldo Cruz, Manaus, Brazil;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ric N.","family":"Price","sequence":"additional","affiliation":[{"name":"Division of Global and Tropical Health, Menzies School of Health Research and Charles Darwin University, Darwin, Casuarina, Northern Territory, Australia;"},{"name":"Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, United Kingdom;"},{"name":"Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas M.","family":"Douglas","sequence":"additional","affiliation":[{"name":"Division of Global and Tropical Health, Menzies School of Health Research and Charles Darwin University, Darwin, Casuarina, Northern Territory, Australia;"},{"name":"Department of Medicine, University of Otago, Christchurch, New Zealand;"},{"name":"Department of Infectious Diseases, Christchurch Hospital, Christchurch, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2795","reference":[{"key":"b1","series-title":"Guidelines for the Treatment of Malaria","year":"2015"},{"key":"b2","series-title":"Blood","first-page":"1225","article-title":"Glucose-6-phosphate dehydrogenase deficiency","volume":"136","author":"Luzzatto","year":"2020"},{"key":"b3","series-title":"Malar J","first-page":"418","article-title":"Primaquine: the risks and the benefits","volume":"13","author":"Ashley","year":"2014"},{"key":"b4","series-title":"Safety of 8-Aminoquinoline Antimalarial Medicines.","author":"Recht","year":"2014"},{"key":"b5","series-title":"PLoS 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