Effect of higher dose primaquine for the radical cure of <i>Plasmodium vivax</i> malaria in Indonesia: a systematic review and individual patient data meta-analysis.
meta_analysis · Level I
Where this comes from
- Record sourced from PubMed, PMID 42375875.
- Also identified by DOI 10.1016/j.lanwpc.2026.101908 and PMC identifier 13310647.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
<i>Plasmodium vivax</i> malaria has diverse transmission and relapse patterns in Indonesia. The optimal dose of primaquine to prevent relapses across the country is unknown. We evaluated the anti-relapse efficacy, gastrointestinal tolerability, and haematological safety (G6PD activity ≥30%) of different primaquine regimens in varied endemic settings in Indonesia. We systematically searched for studies published between 1 January 2000 and 23 July 2024 prospectively enrolling patients with acute uncomplicated <i>P. vivax</i> malaria where some patients were treated with primaquine. Individual patient data (IPD) from eligible studies were pooled and harmonised. We fitted one-stage IPD multivariable regression models to estimate the causal relationship between the body weight-adjusted primaquine dose with three separate primary outcomes: (i) the time to first <i>P. vivax</i> recurrence (days 7-180), (ii) any gastrointestinal discomfort (days 5-7), and (iii) ≥25% reduction relative to baseline haemoglobin and a reduction to <7 g/dL (days 1-14). Of ten eligible studies, seven were available for inclusion. Compared with a total dose of 3.5 mg/kg primaquine, patients treated with a total dose of 7 mg/kg had a lower rate of recurrence over 6 months (adjusted hazard ratio 0.53; 95% confidence interval [CI] 0.45-0.63; n = 1797); the relative efficacy was consistent across regions, but the absolute benefit varied. Gastrointestinal discomfort was more frequent with higher doses (adjusted risk ratio 1.32 per 0.25 mg/kg daily dose; 95% CI 1.15-1.51; n = 952). In 822 patients available to be assessed for haematological safety (788 [96%] with G6PD activity ≥70% and 34 [4%] with activity 30% to <70%), only one patient developed clinically relevant haemolysis. Across all transmission settings in Indonesia, a total dose of 7 mg/kg halved the rate of recurrent <i>P. vivax</i> malaria over a 6-month period compared with the low dose of 3.5 mg/kg. However, increased daily doses slightly increased risks of gastrointestinal discomfort and haemolysis. NDM Tropical Network Fund, Bill and Melinda Gates Foundation.