In vivo Efficacy and Safety of Artemether-Lumefantrine and Amodiaquine-Artesunate for Uncomplicated Plasmodium Falciparum Malaria in Mozambique, 2018

Abstract Background : Artemisinin-based combination therapy has been the recommended treatment for uncomplicated malaria in Mozambique since 2006, with artemether-lumefantrine (AL) and amodiaquine-artesunate (AS-AQ) as first-line treatments. To assess efficacy of currently used artemisinin-based combination therapy, an in vivo therapeutic efficacy study was conducted. Methods : The study was conducted in four sentinel sites: Montepuez, Moatize, Mopeia and Massinga. Patients between 6 to 59 months old with uncomplicated Plasmodium falciparum malaria (2,000–200,000 parasites/µl) were enrolled between February and September of 2018, assigned to either an AL or AS-AQ treatment arm, and monitored for 28 days. A Bayesian algorithm was applied to differentiate recrudescence from new infection using genotyping data of seven neutral microsatellites. Uncorrected and PCR-corrected efficacy results at day 28 were calculated. Results : Totals of 368 and 273 patients were enrolled in the AL and AS-AQ arms, respectively. Of these, 9.5% (35/368) and 5.1% (14/273) were lost to follow-up in the AL and AS-AQ arms, respectively. There were 48 and 3 recurrent malaria infections (late clinical and late parasitological failures) in the AL and AS-AQ arms, respectively. The day 28 uncorrected efficacy was 85.3% (95% CI: 81.1–88.9%) for AL and 98.8% (95% CI: 96.7–99.8%) for AS-AQ, whereas day 28 PCR-corrected efficacy was 97.9% (95% CI: 95.6–99.2%) for AL and 99.6 % (95% CI: 97.9–100%) for AS-AQ. Molecular testing confirmed that 87.4% (42/48) and 33.3% (1/3) of participants with a recurrent malaria infection in the AL and AS-AQ arms were new infections; an expected finding in a high malaria transmission area. Adverse events were documented in less than 2% of participants for both drugs. Conclusion : Both AL and AS-AQ have therapeutic efficacies well above the 90% WHO recommended threshold and remain well-tolerated in Mozambique. Routine monitoring of therapeutic efficacy should continue to ensure the treatments remain efficacious. Trial registration: Clinicaltrials.gov: NCT04370977