title: Efficacy and safety of fixed-dose artesunate-amodiaquine vs. artemether-lumefantrine for repeated treatment of uncomplicated malaria in Ugandan children.
abstract: The safety and efficacy of the two most widely used fixed-dose artemisinin-based combination therapies (ACT), artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) are well established for single episodes of uncomplicated Plasmodium falciparum malaria, but the effects of repeated, long-term use are not well documented. We conducted a 2-year randomized, open-label, longitudinal, phase IV clinical trial comparing the efficacy and safety of fixed-dose ASAQ and AL for repeated treatment of uncomplicated malaria in children under 5 years at Nagongera Health Centre, Uganda. Participants were randomized to ASAQ or AL and all subsequent malaria episodes were treated with the same regimen. 413 children were enrolled and experienced a total of 6027 malaria episodes (mean 15; range, 1-26). For the first malaria episode, the PCR-corrected-cure rate for ASAQ (97.5%) was non-inferior to that for AL (97.0%; 95% CI [-0.028; 0.037]). PCR-corrected cure rates for subsequent malaria episodes that had over 100 cases (episodes 2-18), ranged from 88.1% to 98.9% per episode, with no clear difference between the treatment arms. Parasites were completely cleared by day 3 for all malaria episodes and gametocyte carriage was less than 1% by day 21. Fever clearance was faster in the ASAQ group for the first episode. Treatment compliance for subsequent episodes (only first dose administration observed) was close to 100%. Adverse events though common were similar between treatment arms and mostly related to the disease. Serious adverse events were uncommon, comparable between treatment arms and resolved spontaneously. Anemia and neutropenia occurred in <0.5% of cases per episode, abnormal liver function tests occurred in 0.3% to 1.4% of cases. Both regimens were safe and effective for repeated treatment of malaria.
  
  
  BACKGROUND
  Current Controlled Trials NCT00699920.
authors.affiliation: School of Public Health, College of Health Sciences, Makerere University, Kampala, Uganda; Uganda Malaria Surveillance Program, Kampala, Uganda.
authors.forename: Adoke
authors.initials: A
authors.lastname: Yeka
authors.affiliation: Sanofi Access to Medicines, Gentilly, France.
authors.forename: Valerie
authors.initials: V
authors.lastname: Lameyre
authors.affiliation: Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda.
authors.forename: Kibuuka
authors.initials: K
authors.lastname: Afizi
authors.affiliation: Uganda Malaria Surveillance Program, Kampala, Uganda.
authors.forename: Mudangha
authors.initials: M
authors.lastname: Fredrick
authors.affiliation: Uganda Malaria Surveillance Program, Kampala, Uganda.
authors.forename: Robinson
authors.initials: R
authors.lastname: Lukwago
authors.affiliation: Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda; Uganda Malaria Surveillance Program, Kampala, Uganda.
authors.forename: Moses R
authors.initials: MR
authors.lastname: Kamya
authors.affiliation: Uganda Malaria Surveillance Program, Kampala, Uganda; Malaria Public Health Department, University of Oxford-KEMRI-Wellcome Trust Programme, Nairobi, Kenya.
authors.forename: Ambrose O
authors.initials: AO
authors.lastname: Talisuna
mesh_terms: D000655:Amodiaquine / Q000009:adverse effects / Q000627:therapeutic use; D000962:Antimalarials / Q000009:adverse effects* / Q000627:therapeutic use*; D000077549:Artemether; D037621:Artemisinins / Q000009:adverse effects / Q000627:therapeutic use; D002675:Child, Preschool; D003625:Data Collection; D004338:Drug Combinations; D004983:Ethanolamines / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D005334:Fever / Q000150:complications; D005449:Fluorenes / Q000009:adverse effects / Q000627:therapeutic use; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007223:Infant; D057148:Insecticide-Treated Bednets / Q000706:statistics & numerical data; D000078102:Lumefantrine; D016778:Malaria, Falciparum / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000517:prevention & control; D008297:Male; D059208:Parasite Load; D010349:Patient Compliance / Q000706:statistics & numerical data; D012449:Safety; D013163:Splenomegaly / Q000150:complications; D016896:Treatment Outcome; D014454:Uganda
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D004338:Drug Combinations; D004983:Ethanolamines; D005449:Fluorenes; D006454:Hemoglobins; C515299:amodiaquine, artesunate drug combination; D000655:Amodiaquine; D000077549:Artemether; D000078102:Lumefantrine