Background: Primaquine is the only drug approved for use in children for treatment of P vivax hypnozoites. The standard 14-day regimen is limited by poor adherence and optimal timing of administration in relation to artemisinin-combination therapy. We aim to assess the safety and efficacy of an ultra-short (3.5 days), high dose (1 mg/kg twice daily) primaquine regimen.
Methods: We performed an open label, randomised controlled trial where children between the ages of 6 months and 12 years with uncomplicated malaria and normal glucose-6-phosphate-dehydrogenase were recruited. They were given artemether-lumefantrine and randomly assigned to receive primaquine either immediately after completion of artemether-lumefantrine (early group, primaquine given at day 3) or 21 days later (delayed group, primaquine given at day 24). The primary endpoint was appearance of any P vivax parasitaemia within 42 days following treatment of uncomplicated malaria.
Findings: 219 children (110 children in the early group and 109 children in the delayed group) were recruited. 70% of children had P falciparum and 24% had P vivax at enrolment. Gastrointestinal symptoms (abdominal pain, vomiting and diarrhoea) were more common in the early group compared to the delayed group (24.5% vs 4.6%, p<0.001). No haemolysis or other severe adverse reactions were reported. At day 42 follow-up, P. vivax parasitaemia was 13.2% in the early group and 7.8% in the delayed group (p=0.26).
Interpretation: An ultra-short (3.5 days), high-dose primaquine regimen was well tolerated and could markedly improve adherence to primaquine treatment and its efficacy. Although there were fewer gastrointestinal symptoms in the delayed group, there was no difference in appearance of P vivax parasitaemia when primaquine is given early or delayed after artemether-lumefantrine at day 42 follow-up. In co-endemic regions, universal primaquine treatment given to all patients with uncomplicated malaria for radical cure could lead to improved malaria control efforts.