title: Artesunate/Amodiaquine Versus Artemether/Lumefantrine for the Treatment of Uncomplicated Malaria in Uganda: A Randomized Trial.
abstract: BACKGROUND
  In treating malaria in Uganda, artemether-lumefantrine (AL) has been associated with a lower risk of recurrent parasitemia, compared with artesunate-amodiaquine (AS/AQ), but changing treatment practices may have altered parasite susceptibility.
  
  
  METHODS
  We enrolled 602 children aged 6-59 months with uncomplicated falciparum malaria from 3 health centers in 2013-2014 and randomly assigned them to receive treatment with AS/AQ or AL. Primary outcomes were risks of recurrent parasitemia within 28 days, with or without adjustment to distinguish recrudescence from new infection. Drug safety and tolerability and Plasmodium falciparum resistance-mediating polymorphisms were assessed.
  
  
  RESULTS
  Of enrolled patients, 594 (98.7%) completed the 28-day study. Risks of recurrent parasitemia were lower with AS/AQ at all 3 sites (overall, 28.6% vs 44.6%; P < .001). Recrudescences were uncommon, and all occurred after AL treatment (0% vs 2.5%; P = .006). Recovery of the hemoglobin level was greater with AS/AQ (1.73 vs 1.39 g/dL; P = .04). Both regimens were well tolerated; serious adverse events were uncommon (1.7% in the AS/AQ group and 1.0% in the AL group). AS/AQ selected for mutant pfcrt/pfmdr1 polymorphisms and AL for wild-type pfcrt/pfmdr1 polymorphisms associated with altered drug susceptibility.
  
  
  CONCLUSIONS
  AS/AQ treatment was followed by fewer recurrences than AL treatment, contrasting with older data. Each regimen selected for polymorphisms associated with decreased treatment response. Research should consider multiple or rotating regimens to maintain treatment efficacies.
authors.affiliation: School of Public Health, Makerere University College of Health Sciences Infectious Diseases Research Collaboration, President's Malaria Initiative, Kampala, Uganda.
authors.forename: Adoke
authors.initials: A
authors.lastname: Yeka
authors.affiliation: Infectious Diseases Research Collaboration, President's Malaria Initiative, Kampala, Uganda.
authors.forename: Ruth
authors.initials: R
authors.lastname: Kigozi
authors.affiliation: Department of Medicine, University of California, San Francisco.
authors.forename: Melissa D
authors.initials: MD
authors.lastname: Conrad
authors.affiliation: National Malaria Control Program, Ministry of Health, President's Malaria Initiative, Kampala, Uganda.
authors.forename: Myers
authors.initials: M
authors.lastname: Lugemwa
authors.affiliation: National Malaria Control Program, Ministry of Health, President's Malaria Initiative, Kampala, Uganda.
authors.forename: Peter
authors.initials: P
authors.lastname: Okui
authors.affiliation: World Health Organization, President's Malaria Initiative, Kampala, Uganda.
authors.forename: Charles
authors.initials: C
authors.lastname: Katureebe
authors.affiliation: US Agency for International Development, President's Malaria Initiative, Kampala, Uganda.
authors.forename: Kassahun
authors.initials: K
authors.lastname: Belay
authors.affiliation: Centers for Disease Control and Prevention (CDC), President's Malaria Initiative, Kampala, Uganda.
authors.forename: Bryan K
authors.initials: BK
authors.lastname: Kapella
authors.affiliation: Malaria Branch, Division of Parasitic Diseases and Malaria, CDC, Atlanta, Georgia.
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Chang
authors.affiliation: Department of Medicine, Makerere University College of Health Sciences Infectious Diseases Research Collaboration, President's Malaria Initiative, Kampala, Uganda.
authors.forename: Moses R
authors.initials: MR
authors.lastname: Kamya
authors.affiliation: Infectious Diseases Research Collaboration, President's Malaria Initiative, Kampala, Uganda London School of Hygiene and Tropical Medicine, United Kingdom.
authors.forename: Sarah G
authors.initials: SG
authors.lastname: Staedke
authors.affiliation: Department of Medicine, University of California, San Francisco.
authors.forename: Grant
authors.initials: G
authors.lastname: Dorsey
authors.affiliation: Department of Medicine, University of California, San Francisco.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Rosenthal
mesh_terms: D000655:Amodiaquine / Q000627:therapeutic use*; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins / Q000627:therapeutic use*; D002675:Child, Preschool; D004338:Drug Combinations; D004983:Ethanolamines / Q000627:therapeutic use*; D005260:Female; D005449:Fluorenes / Q000627:therapeutic use*; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000453:epidemiology; D008297:Male; D014454:Uganda / Q000453:epidemiology
chemical_list: D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins; D004338:Drug Combinations; D004983:Ethanolamines; D005449:Fluorenes; C515299:amodiaquine, artesunate drug combination; D000655:Amodiaquine
keywords: Uganda; amodiaquine-artesunate; artemether-lumefantrine; drug resistance; malaria