Efficacy and gametocyte carriage in Plasmodium falciparum cases treated with artemether-lumefantrine alone versus with single-dose primaquine in Ethiopia: A randomized controlled study.

This study evaluated the efficacy of adding primaquine (PQ) to artemether-lumefantrine (AL) for treating uncomplicated Plasmodium falciparum malaria in Ethiopia. Asexual parasite clearance was monitored with microscopy and molecular techniques, while gametocyte clearance was observed solely through microscopy. Genotyping to distinguish recrudescence from reinfection was performed using nested polymerase chain reaction (PCR). A parallel, two-arm, randomized controlled trial with a 1:1 allocation ratio was conducted involving 146 symptomatic patients, with 106 included in the final analysis. The study compared the outcomes of AL plus PQ with those of AL alone over 28 days. PQ treatment was initiated simultaneously with AL therapy. Both treatment groups showed no asexual parasites by day 2 when assessed by microscopy. However, PCR testing detected parasite DNA in 5.8 % (3/52) of the patients in the AL plus PQ group, compared to 18.5 % (10/54) in the AL alone group by day 7 (P = 0.09). PCR-uncorrected cure rate was 100 % for the AL alone and 98.1 % for the AL plus PQ groups (P = 0.31). Gametocyte clearance was faster in the AL plus PQ group, with 100 % clearance by day 7, compared to day 14 in the AL alone group. Notably, only 9.4 % (10/106) of cases had gametocytes at baseline, while this percentage increased to 11.3 % (12/106) by day 1 of post-treatment. The recrudescence rate was 2.8 % (3/106). Although AL alone was as effective as AL plus PQ in eliminating asexual parasites, adding PQ may accelerate gametocyte clearance. However, the low prevalence of gametocyte carriers among symptomatic cases at the study site, combined with the restriction of PQ administration to only those seeking treatment, may limit its overall impact on malaria transmission. Trial registration number: PACTR202502642820967.