Efficacy of Artemisinin-Based Combination Treatments of Uncomplicated Falciparum Malaria in Under-Five-Year-Old Nigerian Children Ten Years Following Adoption as First-Line Antimalarials

• Published in: The American journal of tropical medicine and hygiene Vol. 99; no. 3; pp. 649 - 664
• Main Authors: Ebenebe, Joy C, Ntadom, Godwin, Ambe, Jose, Wammanda, Robinson, Jiya, Nma, Finomo, Finomo, Emechebe, George, Mokuolu, Olugbenga, Akano, Kazeem, Agomo, Chimere, Folarin, Onikepe A, Oguche, Stephen, Useh, Francis, Oyibo, Wellington, Aderoyeje, Temitope, Abdulkadir, Mohammed, Ezeigwe, Nnenna M, Happi, Christian, Sowunmi, Akintunde
• Format: Journal Article
• Language: English
• Published: United States Institute of Tropical Medicine 01-01-2018; The American Society of Tropical Medicine and Hygiene
• Subjects: Amodiaquine - therapeutic use; Antimalarials - therapeutic use; Artemether, Lumefantrine Drug Combination - therapeutic use; Artemisinins - therapeutic use; Child, Preschool; Combined Modality Therapy - statistics & numerical data; Drug Combinations; Drug Therapy, Combination; Female; Humans; Infant; Malaria; Malaria, Falciparum - drug therapy; Malaria, Falciparum - epidemiology; Male; Nigeria - epidemiology; Parasitemia - drug therapy; Parasitemia - epidemiology; Parasites; Plasmodium falciparum - drug effects; Plasmodium falciparum - genetics; Quinolines - therapeutic use; Treatment Outcome; Nigeria
• ISSN: 0002-9637; 1476-1645
• DOI: 10.4269/ajtmh.18-0115

The efficacies of 3-day regimens of artemether-lumefantrine (AL), artesunate-amodiaquine (AA), and dihydroartemisinin-piperaquine (DHP) were evaluated in 910 children < 5 years old with uncomplicated malaria from six geographical areas of Nigeria. Parasite positivity 1 day and Kaplan-Meier estimated risk of persistent parasitemia 3 days after therapy initiation were both significantly higher, and geometric mean parasite reduction ratio 1 day after treatment initiation (PRRD1) was significantly lower in AL-treated children than in AA- and DHP-treated children. No history of fever, temperature > 38°C, enrollment parasitemia > 75,000 μL
, and PRRD1 < 5,000 independently predicted persistent parasitemia 1 day after treatment initiation. Parasite clearance was significantly faster and risk of reappearance of asexual parasitemia after initial clearance was significantly lower in DHP-treated children. Overall, day 42 polymerase chain reaction-corrected efficacy was 98.3% (95% confidence interval [CI]: 96.1-100) and was similar for all treatments. In a non-compartment model, declines of parasitemias were monoexponential with mean terminal elimination half-life of 1.3 hours and unimodal frequency distribution of half-lives. All treatments were well tolerated. In summary, all three treatments evaluated remain efficacious treatments of uncomplicated malaria in young Nigerian children, but DHP appears more efficacious than AL or AA.