High dose, short coure of Primaquine safely offers radical cure against P.Vivax in patients with G6PD activity: Lancet

An increased risk of P vivax parasitaemia following P falciparum malaria was seen in areas co-endemic for Plasmodium vivax and Plasmodium falciparum. Currently, the radical cure is recommended only for patients presenting with P vivax malaria. Expanding the indication for a radical cure to patients presenting with P falciparum malaria could lower their risk of subsequent P vivax parasitaemia.

Therefore, Kamala Thriemer, Menzies School of Health Research and Charles Darwin University, Darwin, NT, Australia, and colleagues aimed to assess the efficacy of a universal radical cure to lower the risk of subsequent P vivax episodes versus the current standard treatment for P falciparum, which entails schizontocidal treatment of blood-stage parasites plus a single dose of primaquine to eliminate the sexual parasite stages.

For this purpose, the researchers performed an open-label, multicentre, superiority randomised controlled trial (RCT) across five health clinics in Ethiopia, Indonesia, and Bangladesh.

Patients with uncomplicated P falciparum mono-infection having fever or a history of fever in the 48 h preceding clinic visit were eligible for enrolment and were required to have a glucose-6-dehydrogenase (G6PD) activity of 70% or greater. Patients received blood schizontocidal treatment (artemether–lumefantrine in Ethiopia and Bangladesh and dihydroartemisinin–piperaquine in Indonesia).

500 patients were enrolled and randomly assigned in a ratio of 1:1 to receive either high-dose short-course oral primaquine (intervention arm, n=246; total dose 7 mg/kg over 7 days) or standard care (standard care arm, n=249; single dose oral primaquine of 0·25 mg/kg). The study's primary endpoint was determined as the incidence risk of P vivax parasitaemia on day 63.

Based on the study, the researchers reported the following findings:

• The incidence risk of P vivax parasitaemia at day 63 was 11·0% in the standard care arm compared with 2·5% in the intervention arm (hazard ratio 0·20).
• The effect size differed with blood schizontocidal treatment and site.
• Routine symptom reporting on day 2 and day 7 were similar between groups.
• In the first 42 days, there were a total of four primaquine-related adverse events reported in the standard care arm and 26 in the intervention arm; 92% of the adverse events were mild.
• There were two serious adverse events in the intervention arm, which were considered unrelated to the study drug.
• None of the patients developed severe anaemia (defined as haemoglobin <5 g/dL).

"The findings showed that in patients who have a G6PD activity of 70% or greater, high-dose short-course primaquine radical cure was safe and led to a significant reduction in the risk of subsequent P vivax parasitaemia," the researchers wrote.

"Universal radical cure therefore potentially offers substantial public health, clinical and operational benefits, but these benefits will vary with endemic settings," they concluded.

Reference:

"Primaquine radical cure in patients with Plasmodium falciparum malaria in areas co-endemic for P falciparum and Plasmodium vivax (PRIMA): a multicentre, open-label, superiority randomised controlled trial," was published in The Lancet. DOI: https://doi.org/10.1016/S0140-6736(23)01553-2