Severe Hemolysis during Primaquine Radical Cure of Plasmodium vivax Malaria: Two Systematic Reviews and Individual Patient Data Descriptive Analyses.

"The funders of the study had no role in study design, data collection, analysis, interpretation of data, or writing of the report.: Original studies received ethical approval via the relevant approval authorities. Ethical approval for this study was obtained from the Human Research Ethics Committee of the Northern Territory Department of Health and Menzies School of Health Research (HREC reference no. 2020-3935)."

"Financial support: The research was funded in whole, or in part, by the Bill & Melinda Gates Foundation (SEPRA-INV-024389). D. Y. was funded by a WHO-TDR Clinical Research and Development Fellowship. R. N. P. was funded by an Australian National Health and Medical Research (NHMRC) Leadership Investigator Grant (2008501). R. J. C. was funded by an NHMRC Investigator Grant (1194702). K. T. was funded by a CSL Fellowship. M. L. and W. M. were funded by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq productivity scholarships). J. D. B. S. was funded by the Research Support Foundation of the State of Amazonas."

"The first systematic review used data from the Worldwide Antimalarial Resistance Network (WWARN) “vivax surveyor.” This repository contains details of all P. vivax antimalarial clinical efficacy studies done between January 1960 and August 23, 2021 (registered previously at PROSPERO [CRD42016053228]). To be eligible for inclusion in the current review, trials had to have been done since 1990 and include one or more treatment arms in which patients were treated with either partial or fully supervised PQ therapy for at least 5 days (Supplemental Appendix S1, Box S1). Primaquine administration had to commence within 7 days of starting blood schizontocidal therapy. Data from non-PQ–containing arms in these studies were also extracted for comparative purposes. Studies meeting these criteria, but not reporting the presence or absence of adverse effects of treatment, were excluded. In the second systematic review, all articles in any language reporting at least one case of severe PQ-associated hemolysis were identified. To be eligible for inclusion, works had to report data attributable to individual patients receiving PQ for P. vivax radical cure or terminal prophylaxis. The review was registered at PROSPERO (CRD42020196604). The term severe hemolysis was used to define a clinical event requiring hospitalization, blood transfusion, or renal replacement therapy, or death, which the original investigators attributed to hemolysis or anemia. Children younger than 6 months of age, and pregnant or lactating women were excluded from the analysis as both are ineligible for PQ treatment."