Severe Hemolysis during Primaquine Radical Cure of Plasmodium vivax Malaria: Two Systematic Reviews and Individual Patient Data Descriptive Analyses
Issued Date
2023-10-04
Resource Type
eISSN
14761645
Scopus ID
2-s2.0-85173562846
Pubmed ID
37604475
Journal Title
The American journal of tropical medicine and hygiene
Volume
109
Issue
4
Start Page
761
End Page
769
Rights Holder(s)
SCOPUS
Bibliographic Citation
The American journal of tropical medicine and hygiene Vol.109 No.4 (2023) , 761-769
Suggested Citation
Yilma D., Groves E.S., Brito-Sousa J.D., Monteiro W.M., Chu C., Thriemer K., Commons R.J., Lacerda M.V.G., Price R.N., Douglas N.M. Severe Hemolysis during Primaquine Radical Cure of Plasmodium vivax Malaria: Two Systematic Reviews and Individual Patient Data Descriptive Analyses. The American journal of tropical medicine and hygiene Vol.109 No.4 (2023) , 761-769. 769. doi:10.4269/ajtmh.23-0280 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/90568
Title
Severe Hemolysis during Primaquine Radical Cure of Plasmodium vivax Malaria: Two Systematic Reviews and Individual Patient Data Descriptive Analyses
Author's Affiliation
WorldWide Antimalarial Resistance Network
Faculty of Tropical Medicine, Mahidol University
Mahidol Oxford Tropical Medicine Research Unit
Jimma University
Fundacao de Medicina Tropical do Amazonas
Christchurch Hospital New Zealand
Menzies School of Health Research
Fiocruz Amazônia
Nuffield Department of Medicine
Universidade do Estado do Amazonas
University of Otago, Christchurch
University of Cape Town
Grampians Health
Faculty of Tropical Medicine, Mahidol University
Mahidol Oxford Tropical Medicine Research Unit
Jimma University
Fundacao de Medicina Tropical do Amazonas
Christchurch Hospital New Zealand
Menzies School of Health Research
Fiocruz Amazônia
Nuffield Department of Medicine
Universidade do Estado do Amazonas
University of Otago, Christchurch
University of Cape Town
Grampians Health
Other Contributor(s)
Abstract
Primaquine (PQ) kills Plasmodium vivax 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 P. vivax 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 ≥ 0.5 mg/kg/day. Overall, 101 patients were categorized as having probable or possible severe PQ-associated hemolysis, 96.8% of whom were G6PD deficient (< 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.