Abstract
BackgroundArtemisinin-based combination therapy (ACT) has been the recommended first-line treatment for uncomplicated malaria in Mozambique since 2006, with artemether–lumefantrine (AL) and amodiaquine–artesunate (AS–AQ) as the first choice. To assess efficacy of currently used ACT, an in vivo therapeutic efficacy study was conducted.MethodsThe study was conducted in four sentinel sites: Montepuez, Moatize, Mopeia and Massinga. Patients between 6 and 59 months old with uncomplicated Plasmodium falciparum malaria (2000–200,000 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.ResultsTotals 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 85.6% (95% confidence interval (CI) 81.3–89.2%) 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.ConclusionBoth 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
Highlights
Artemisinin-based combination therapy (ACT) has been the recommended first-line treatment for uncomplicated malaria in Mozambique since 2006, with artemether–lumefantrine (AL) and amodiaquine–artesunate (AS–AQ) as the first choice
The main reasons for exclusion were the absence of malaria parasites at the time of recruitment, parasitaemia outside the inclusion range, and living outside the study area
Of the 48 participants with recurrent parasitaemia detected during the study, only six cases were classified as recrudescent infections, making the day 28 PCR-corrected efficacy 97.9% (285/291; 95% CI 95.6–99.2) for AL
Summary
Artemisinin-based combination therapy (ACT) has been the recommended first-line treatment for uncomplicated malaria in Mozambique since 2006, with artemether–lumefantrine (AL) and amodiaquine–artesunate (AS–AQ) as the first choice. According to the World Health Organization (WHO), approximately 229 million cases of malaria and 409,000 deaths from malaria occurred globally in 2019. The majority of malaria cases (94%) occurred in sub-Saharan Africa, where more than 71 million children aged 1–59 months had malaria in 2019 [1]. In Mozambique, about 9 million malaria cases and about 16,000 malaria deaths (~ 4% of global deaths) were estimated to have occurred in 2019 [1]. According to the 2018 Malaria Indicator Survey (MIS), the prevalence of Plasmodium falciparum infection in children under 5 years of age was 39% [2]. Resistance of P. falciparum to commonly used anti-malarials represents a major obstacle, in Southeast Asia, where evidence for the emergence of resistance to artemisinin derivatives is well-documented [3,4,5,6,7]; recently, emergence of partial resistance to artemisinin was reported in East Africa [8]
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