Efficacy of artesunate-amodiaquine for the treatment of uncomplicated Plasmodium falciparum malaria among children aged 2–11 years in the Asante Akim North Municipality, Ghana: a single-arm open trial

Abstract Background The burden of malaria in Ghana is significantly high. The emergence of resistance to artemisinin-based combination therapy (ACT), the primary treatment for malaria, necessitates constant surveillance. In this study the efficacy of artesunate-amodiaquine (AS-AQ), a first-line treatment for uncomplicated malaria in Ghana since 2005, and the prevalence of single nucleotide polymorphisms (SNPs) in resistance markers associated with this antimalarial drug were assessed. Methods This prospective single-arm trial was conducted between July 2018 and June 2019 at two health facilities. A total of 173 children aged 2–11 years who presented with fever or a history of fever and tested positive by rapid diagnostic test (RDT) were recruited for the study. The participants were prescribed AS-AQ based on their body weight. The study followed the 2009 World Health Organization (WHO) protocol for monitoring antimalarial drug efficacy, with adequate clinical and parasitological response (ACPR) assessed on day 28. A total of 155 samples were successfully analysed for mutations in the pfk13, pfcrt, and pfmdr1 genes. Results A total of 164 participants completed the three-day treatment regimen while adhering to the study protocol. During directly observed treatment, 8.1% of participants experienced vomiting after at least one dose. By day 3, all treated participants achieved total parasite clearance. Thirteen (7.9%) participants were either lost to follow-up, non-compliant or withdrew voluntarily. The ACPR on day 28 was 92.07% and 100% by the modified intention to treat and Kaplan–Meier methods, respectively. No treatment, clinical or parasitological failure was observed during the 28-day follow-up period. Whole-genome sequencing (WGS) analysis did not detect any pfk13 gene mutations linked to artemisinin resistance. The pfmdr1 NFD haplotype (86 + 184 + 1246) was identified in 27.1% of isolates, while the pfcrt K76T mutation was found in 1.9% of the isolates. Conclusions The study confirmed that artesunate (AS) combined with amodiaquine (AQ) remains an effective treatment for uncomplicated Plasmodium falciparum malaria in children aged 2–11 years in Ghana. Additionally, a high prevalence of a haplotype associated with reinfection following artemether-lumefantrine treatment, one of Ghana’s first-line antimalarial therapies, was observed.