In vivo efficacy and safety of artemether–lumefantrine and amodiaquine–artesunate for uncomplicated Plasmodium falciparum malaria in Mozambique, 2018

• Published in: Malaria Journal
• Main Authors: Abel Nhama, Lídia Nhamússua, Eusébio Macete, Quique Bassat, Crizolgo Salvador, Sónia Enosse, Baltazar Candrinho, Eva Carvalho, Arsénio Nhacolo, Arlindo Chidimatembue, Abuchahama Saifodine, Rose Zulliger, Naomi Lucchi, Samaly S. Svigel, Leah F. Moriarty, Eric S. Halsey, Alfredo Mayor, Pedro Aide
• Format: Article in Journal/Newspaper
• Language: English
• Published: BMC 2021
• Subjects: Efficacy; Artemether–lumefantrine; Artesunate–amodiaquine; Uncomplicated malaria; Children; Mozambique; Arctic medicine. Tropical medicine; RC955-962; Infectious and parasitic diseases; RC109-216; Arctic
• Online Access: https://doi.org/10.1186/s12936-021-03922-9; https://doaj.org/article/d7fcf41e715d4331a632b40ce0e89937

Abstract Background 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. To assess efficacy of currently used ACT, 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 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. 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 85.6% (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. 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 ...