Abstract
BACKGROUND: Malaria, caused by Plasmodium falciparum and Plasmodium vivax, is commonly reported in Ethiopia. The World Health Organization (WHO) recommends treating P. vivax malaria with a schizonticidal drug and a 14-day course of primaquine (0.25-0.5 mg/kg body weight daily) to prevent relapses. In 2018, Ethiopia adopted a policy of primaquine radical cure (0.25 mg/kg for 14 days), with close monitoring for adverse events, but without prior glucose-6-phosphate dehydrogenase (G6PD) testing. This study aimed to assess the safety of this policy by monitoring the risk of haemolysis and other adverse events following the administration of primaquine. METHODS: A prospective observational study was conducted from May 2019 to June 30, 2021, enrolling patients with P. vivax and mixed malaria at four health centres. The clinics were chosen based on their P. vivax malaria patient volume and the expected prevalence of G6PD deficiency. Clinical, laboratory, and treatment data were gathered from patients at baseline and again on days 3, 7, 13, and 27. On day 13, all patients were evaluated for G6PD deficiency using the CareStart qualitative or SD Biosensor quantitative tests. RESULTS: A total of 879 patients were enrolled; none had G6PD deficiency. Among the 298 female patients tested with the SD Biosensor, 3 (1.0%) were found to have intermediate deficiency. On day three, the median fractional fall in haemoglobin was - 0.9% (range - 51.9-61.3). Nine patients had a drop in haemoglobin of more than 25% from baseline, of whom two patients had a haemoglobin level below 8 g/dL. On day 7, the median fractional drop was 0.8% (range - 51.9-48.3%). Five patients had a > 25% decline in haemoglobin between day three to day 7. None of the patients with the haemoglobin drop exhibited clinical symptoms attributable to haemolytic anaemia. By day 13, 91.9% of the patients had haematological recovery. No serious adverse events were reported. CONCLUSIONS: In this study, conducted in a population with a low prevalence of G6PD deficiency, a 14-day regimen of low-dose primaquine was well tolerated and resulted in few mild adverse events only. These findings support the current national policy for low-dose primaquine in Ethiopia without prior G6PD testing, if systems for monitoring adverse events are in place.