Parasite clearance of two commonly administered artemisinin-based combination therapies in under-five children with uncomplicated malaria in a comprehensive healthcare facility in South-Western Nigeria: a randomised controlled trial

Abstract

This research work aimed to study the parasite clearance of two commonly prescribed artemisinin-based combination therapies (ACTs) in under-five children with uncomplicated malaria in a comprehensive healthcare facility in Southwestern Nigeria. An open-label, randomised controlled clinical trial was conducted. The participants were randomised into two treatment groups using simple randomisation by computer-generated random numbers. Children between the ages of six and 59 months with uncomplicated malaria in a comprehensive healthcare facility in southwestern Nigeria were enrolled after fulfilling the study criteria between July 2020 and December 2020. They had either artemether-lumefantrine (AL) or dihydroartemisinin-piperaquine phosphate (DHAPQ) for three days. The participants were monitored for 42 days by examining blood films for malaria parasite density on days 1, 2, 3, 7, 14, 21, 28, 35, and 42. Malaria parasite genotyping by polymerase chain reaction (PCR) was done to differentiate between reinfection and recrudescence. The main outcome measures were malaria parasite clearance, adequate clinical and parasitological response on days 28 and 42 (ACPR28 and ACPR42), and tolerability. A total of 122 participants were randomised to receive either AL (61 participants) or DHAPQ (61) with a mean age of 23.6 ± 13.0 (months) and 27.6 ± 16.6 (months), respectively. Day 42 per protocol analysis included 113 participants – 57 in the AL group and 56 in the DHAPQ group after excluding the nine that were lost to follow-up. Although not statistically significant, the median baseline malaria parasite density of participants in AL group was higher than that in the DHAPQ group (3,600.0 parasite/µL, lower quartile (LQ) 2,420 parasite/µL, upper quartile (UQ) 5,399 parasite/µL versus 3,440.0 parasite/µL, LQ 2,640 parasite/µL, UQ 5,597 parasite/µL; p = 0.636). The mean fever clearance time was significantly lower in the AL group compared to the DHAPQ group (46.16 ± 3.31 h vs. 48.83 ± 8.95 h; p = 0.032). Parasite clearance time was shorter in the AL treatment group compared to DHAPQ (61.30 ± 23.75 h vs. 63.97 ± 23.42 h; p = 0.541), but this difference was not statistically significant. The day 42 PCR uncorrected cure rate in the AL group and DHAPQ group was 94.7% and 92.9% respectively (p = 0.679). The cure rate increased to 100% in both groups after PCR correction. Five participants in the DHAPQ group reported mild adverse events compared to none of those in the AL group. The study concluded that both DHAPQ and AL had good parasite clearance. Registered on 10/07/2020 with the Pan African Clinical Trials Registry, Cochrane South Africa (PACTR202007553348930).