High versus low dose of 14 days treatment of primaquine in Plasmodium vivax infected patients in Cambodia: a randomised open-label efficacy study

作者：Virak Eng, Dysoley Lek, Sitha Sin, Lionel Brice Feufack-Donfack, Ágnes Orbán, Jeremy Salvador, Dynang Seng, S. Heng, Nimol Khim, Kieran Tebben, Claude Flamand, Cécile Sommen, Rob W. van der Pluijm, Michael White, Benoît Witkowski, David Serre, Jean Popovici · 发表于：medRxiv · 年份：2025 · DOI：10.1101/2025.01.01.25319862 · 被引用次数：3 · 研究领域：Malaria Research and Control、Parasites and Host Interactions、Diverse Scientific Research Studies

Summary Background The WHO malaria treatment guidelines recommend a total dose in the range of 3·5 to 7·0 mg/kg of primaquine to eliminate Plasmodium vivax ( P. vivax ) hypnozoites and prevent relapses. There are however indications that for tropical P. vivax isolates, notably from Southeast Asia, the lower dose of 3·5 mg/kg is insufficient. Determining the most effective regimen to eliminate P. vivax hypnozoites is needed to achieve elimination of this malaria parasite. Methods We conducted an open-label randomised controlled trial in Kampong Speu province, Western Cambodia. P. vivax infected patients with uncomplicated malaria, diagnosed at the community level or in health centres of the province, were offered to participate. Patients aged less than 15 years old, and pregnant or breastfeeding women were excluded. Enrolled patients were treated with a blood schizonticidal artesunate regimen of 2 mg/kg/day for 7 days. Upon enrolment, patients’ glucose-6-phosphate dehydrogenase (G6PD) activity was determined. G6PD normal patients were randomly assigned (2:2:1) to receive either (i) 3·5 mg/kg (low dose as 0·25 mg/kg/day) or (ii) 7·0 mg/kg (high dose as 0·5 mg/kg/day) of primaquine over 14 days or (iii) no primaquine as comparator arm. G6PD deficient patients were assigned to the no-primaquine comparator arm. Randomisation was done by blocks of 5 using sealed envelopes. Upon enrolment, patients were relocated to the study site in Aoral town where no malaria transmission occurs t...