A COMPREHENSIVE analysis has confirmed that a single low dose of primaquine, when added to artemisinin-based combination therapy (ACT), is both effective and safe for reducing Plasmodium falciparum transmission across age groups and transmission settings.
Researchers conducted a systematic review and individual patient data meta-analysis of studies published up to April 2024. Eligible studies had to include patients under 15 years old and assess the efficacy or safety of a single dose of primaquine (≤0.75 mg/kg) combined with ACT. Exclusions were applied for studies involving severe malaria, healthy volunteers, or non-falciparum infections. Data were gathered from 23 studies across 16 countries, totalling 6,056 patients, and analysed using regression models that accounted for variation between study sites. Efficacy was evaluated via gametocyte carriage and infectivity up to day 14, while safety was measured by haemoglobin levels and adverse events through day 28.
The addition of primaquine at a dose of 0.20–0.25 mg/kg significantly reduced day 7 gametocyte carriage (adjusted odds ratio [aOR] 0.34, 95% CI: 0.22–0.52; P<0.001) and infectivity to mosquitoes over time (aOR per day 0.02, 0.01–0.07; P<0.001). The treatment effect was consistent across age groups and transmission settings, with no statistically significant differences in efficacy or safety. Similarly, no increased risk of anaemia or serious adverse events was found at the 0.25 mg/kg dose, even in young children or glucose-6-phosphate dehydrogenase-deficient individuals. However, gametocyte clearance was reduced when dihydroartemisinin-piperaquine was paired with a suboptimal primaquine dose (<0.2 mg/kg), indicating the importance of accurate dosing.
These findings support the routine use of 0.25 mg/kg primaquine alongside ACT for P. falciparum malaria, including in children and high-transmission regions. Developing paediatric formulations will be crucial to fully realise the public health potential of this approach.
Reference
Yilma D et al; WWARN Paediatric Primaquine for P falciparum Transmission Blocking Study Group. Safety and efficacy of single-dose primaquine to interrupt Plasmodium falciparum malaria transmission in children compared with adults: a systematic review and individual patient data meta-analysis. Lancet Infect Dis. 2025; DOI:10.1016/S1473-3099(25)00078-7.
