Single primaquine dose helps block malaria transmission in children

A single low primaquine dose appears to safely and efficaciously reduce transmission of Plasmodium falciparum in children, according to the results of a meta-analysis.

Researchers searched multiple online databases for relevant studies. The studies involved children younger than 15 years and examined the efficacy of a single dose of primaquine (≤0.75 mg/kg) plus artemisinin-based combination therapy (ACT) against falciparum malaria. Studies involving mass drug administration, healthy volunteers, or patients with severe malaria or mixed (with nonfalciparum) infections were excluded.

A total of 30 studies were identified for inclusion in the efficacy analysis. These studies provided data on transmission potential (as determined by gametocytaemia, infectivity, or both) at enrolment and follow-up (day 3, day 7, or day 14), with safety assessments. Investigators of 23 studies shared individual patient data including 6,056 patients from 16 countries. Of these patients, 1,171 (19.3 percent) were young children (aged <5 years), 2,827 (46.7 percent) were older children (aged 5 to <15 years), and 2,058 (34.0 percent) were adults (aged ≥15 years).

Pooled data showed that adding a single dose of primaquine (0.2–0.25 mg/kg) to ACTs was associated with reduced day 7 gametocyte positivity (adjusted odds ratio [aOR], 0.34, 95 percent confidence interval [CI], 0.22–0.52; p<0.001) and infectivity to mosquitoes over time (aOR per day, 0.02, 95 percent CI, 0.01–0.07; p<0.001). No difference was found in the effect of single low-dose primaquine both on gametocyte positivity in young children vs older children (aOR, 1.08, 95 percent CI, 0.52–2.23; p=0.84) and adults (aOR, 0.50, 95 percent CI, 0.20–1.25; p=0.14) and between low-transmission and moderate-to-high transmission settings (aOR, 1.07, 95 percent CI, 0.46–2.52; p=0.86).

Likewise, the effect of single low-dose primaquine on infectivity to mosquitoes was comparable between young children and older children (aOR, 1.36, 95 percent CI, 0.07–27.71; p=0.84) and adults (aOR, 0.31, 95 percent CI, 0.01–8.84; p=0.50) and between low-transmission and moderate-to-high transmission settings (aOR, 0.18, 95 percent CI, 0.01–2.95; p=0.23).

Gametocyte clearance was also similar with different ACTs (dihydroartemisinin–piperaquine vs artemether–lumefantrine) when combined with a primaquine target dose of 0.25 mg/kg (aOR, 1.56, 95 percent CI, 0.65–3.79; p=0.32 at day 7). However, patients who received a primaquine dose of <0.2 mg/kg with dihydroartemisinin–piperaquine were more likely to have gametocytaemia than those who received artemether–lumefantrine (aOR, 5.68, 95 percent CI, 1.38–23.48; p=0.016 at day 7).

At a primaquine dose of 0·25 mg/kg, no events related to anaemia-associated declines in haemoglobin concentration (>25 percent) were documented, regardless of age group, transmission setting, and glucose-6-phosphate dehydrogenase status. The incidence of adverse events (AEs) of grade 2 or higher and of serious adverse events did not differ between patients treated vs not treated with primaquine, including young children.