Journal Article

Efficacy of artesunate–amodiaquine, dihydroartemisinin–piperaquine and artemether–lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in Maradi, Niger

Rigal, Jean, Ouwe Missi Oukem-Boyer, Odile, Dama, Souleymane, Doumbo, Ogobara K., Makarimi, Rockyath, Traore, Aliou, Etard, Jean-François, de Smet, Martin, Laminou, Ibrahim Maman, Woi Messe, Lynda, Grandesso, Francesco, Djimdé, Abdoulaye, Guindo, Ousmane

2018

Overview

Background Malaria endemic countries need to assess efficacy of anti-malarial treatments on a regular basis. Moreover, resistance to artemisinin that is established across mainland South-East Asia represents today a major threat to global health. Monitoring the efficacy of artemisinin-based combination therapies is of paramount importance to detect as early as possible the emergence of resistance in African countries that toll the highest burden of malaria morbidity and mortality. Methods A WHO standard protocol was used to assess efficacy of the combinations artesunate–amodiaquine (AS–AQ Winthrop ® ), dihydroartemisinin–piperaquine (DHA–PPQ, Eurartesim ® ) and artemether–lumefantrine (AM–LM, Coartem ® ) taken under supervision and respecting pharmaceutical recommendations. The study enrolled for each treatment arm 212 children aged 6–59 months living in Maradi (Niger) and suffering with uncomplicated falciparum malaria. The Kaplan–Meier 42-day PCR-adjusted cure rate was the primary outcome. A standardized parasite clearance estimator was used to assess delayed parasite clearance as surrogate maker of suspected artemisinin resistance. Results No early treatment failures were found in any of the study treatment arms. The day-42 PCR-adjusted cure rate estimates were 99.5, 98.4 and 99.0% in the AS–AQ, DHA–PPQ and AM–LM arms, respectively. The reinfection rate (expressed also as Kaplan–Meier estimates) was higher in the AM–LM arm (32.4%) than in the AS–AQ (13.8%) and the DHA–PPQ arm (24.9%). The parasite clearance rate constant was 0.27, 0.26 and 0.25 per hour for AS–AQ, DHA–PPQ and AM–LM, respectively. Conclusions All the three treatments evaluated largely meet WHO criteria (at least 95% efficacy). AS–AQ and AL–LM may continue to be used and DHA–PPQ may be also recommended as first-line treatment for uncomplicated falciparum malaria in Maradi. The parasite clearance rate were consistent with reference values indicating no suspected artemisinin resistance. Nevertheless, the monitoring of anti-malarial drug efficacy should continue. Trial registration details Registry number at ClinicalTrial.gov: NCT01755559

• Publisher: BioMed Central,BioMed Central Ltd,BMC
• Subject: Amodiaquine - administration & dosage / Amodiaquine - adverse effects / Amodiaquine - therapeutic use / Antimalarial / Antimalarials / Antimalarials - administration & dosage / Antimalarials - adverse effects / Antimalarials - therapeutic use / Artemisinin / Artemisinins - administration & dosage / Artemisinins - adverse effects / Artemisinins - therapeutic use / Biomedical and Life Sciences / Biomedicine / Care and treatment / Child, Preschool / Dosage and administration / Drug Combinations / Drug therapy / Drug therapy, Combination / Efficacy / Entomology / Female / Health aspects / Humans / Infant / Infectious Diseases / Kaplan-Meier Estimate / Lumefantrine - administration & dosage / Lumefantrine - adverse effects / Lumefantrine - therapeutic use / Malaria / Malaria, Falciparum - drug therapy / Malaria, Falciparum - mortality / Male / Methods / Microbiology / Niger / Parasite clearance / Parasite Load / Parasitology / Patient outcomes / Plasmodium falciparum / Public Health / Quinolines - administration & dosage / Quinolines - adverse effects / Quinolines - therapeutic use / Resistance / Tropical Medicine