Amodiaquine-Artesunate versus Artemether-Lumefantrine against Uncomplicated Malaria in Children Less Than 14 Years in Ngaoundere, North Cameroon: Efficacy, Safety, and Baseline Drug Resistant Mutations in pfcrt, pfmdr1, and pfdhfr Genes
Background. In Cameroon, both Artesunate-amodiaquine (AS/AQ) and artemether-lumefantrine (AL) are used as first-line treatment against uncomplicated malaria in line with the WHO recommendations. We compared the efficacy and safety of both therapeutic combinations and determined the prevalence of drug resistance conferring mutations in three parasite genes. Methods. One hundred and fifty acute malaria patients between six months and 14 years of age were randomized to receive standard doses of either AS/AQ (73) or AL (77) and followedup for 28 days. Outcome of treatment was according to the standard WHO classification. DNA samples from pretreatment parasite isolates were used to determine the prevalence of resistant mutations in the pfcrt, pfmdr1, and dhfr genes. Results. Both drug combinations induced rapid clearance of parasites and malaria symptoms. PCR-corrected cure rates were 100% and 96.4% for AL. The combinations were well tolerated. Major haplotypes included CVIET (71%), CVMNT (25%) for the pfcrt; SND (100%) for the pfmdr1; IRN (79, 8%), NCS (8.8%), and mixed haplotype (11, 8%) for the dhfr. Conclusion. Both AS/AQ and AL were highly effective and well tolerated for the treatment of uncomplicated falciparum malaria in Ngaoundere, Cameroon. High prevalence of mutant pfcrt alleles confirms earlier observations. Long-term monitoring of safety and efficacy and molecular markers is highly solicited. 1. Introduction Malaria remains one of the most serious health problems worldwide and a leading cause of childhood morbidity and mortality in Africa [1]. Early diagnosis and prompt effective treatment remains the cornerstone for the reduction of malaria-related morbidity and mortality [2]. The control of malaria has been challenged by increasing resistance of Plasmodium falciparum to antimalarial drugs, particularly chloroquine (CQ) and sulfadoxine-pyrimethamine (SP), leading to sweeping changes in antimalarial treatment recommendations [3]. However, the decision to change antimalarial treatment guidelines is complex. This is limited by the ready availability of alternatives with proven clinical efficacy, procurement and supply costs, and likely durability of the new policy. The latter is largely determined by the rate at which resistance to the first-line drugs develops, itself a function of the mechanisms of resistance to the antimalarial. Across Africa, P. falciparum resistance to the inexpensive and widely used drugs has reached very high levels, and noticeably hampered malaria control efforts in the region [3–5]. As a consequence, the use of
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