title: Supervised versus unsupervised intake of six-dose artemether-lumefantrine for treatment of acute, uncomplicated Plasmodium falciparum malaria in Mbarara, Uganda: a randomised trial.
abstract: BACKGROUND
  The six-dose regimen of artemether-lumefantrine is effective and is among combination therapies prioritised to replace antimalarials that no longer work in Africa. However, its effectiveness has not been assessed in the field, and could be compromised by poor adherence, incorrect timing of doses, and insufficient intake of fatty foods with every dose. Our aim, therefore, was to assess the effectiveness of artemether-lumefantrine prescribed under routine outpatient conditions, compared with its efficacy when given under supervision to inpatients with acute uncomplicated falciparum malaria.
  
  
  METHODS
  We did a randomised trial to compare the efficacy, safety, and pharmacokinetics of artemether-lumefantrine when given in a supervised (all doses observed with fatty-food intake; n=313) or unsupervised (first dose supervised followed by outpatient treatment with nutritional advice; n=644) setting to patients of all ages (weight >10 kg) with acute, uncomplicated falciparum malaria in Mbarara, Uganda. Our primary endpoint was 28 day, PCR-adjusted, parasitological cure rate. Analysis was by intention to treat and evaluability analysis.
  
  
  RESULTS
  38 patients were lost to follow-up and one withdrew consent. Day-28 cure rates were 97.7% (296 of 303) and 98.0% (603 of 615) in the supervised and unsupervised groups, respectively. We recorded 15 non-severe, drug-related adverse events, all of which resolved.
  
  
  CONCLUSIONS
  Artemether-lumefantrine has a high cure rate irrespective of whether given under supervision with food or under conditions of routine clinic practice. If used as first-line treatment, artemether-lumefantrine could make a substantial contribution to malaria control in Africa, though cost is an issue.
authors.affiliation: Epicentre, 8 rue Saint-Sabin, 75011 Paris, France. uganda@epicentre.msf.org
authors.forename: Patrice
authors.initials: P
authors.lastname: Piola
authors.forename: Carole
authors.initials: C
authors.lastname: Fogg
authors.forename: Francis
authors.initials: F
authors.lastname: Bajunirwe
authors.forename: Samuel
authors.initials: S
authors.lastname: Biraro
authors.forename: Francesco
authors.initials: F
authors.lastname: Grandesso
authors.forename: Eugene
authors.initials: E
authors.lastname: Ruzagira
authors.forename: Joseph
authors.initials: J
authors.lastname: Babigumira
authors.forename: Isaac
authors.initials: I
authors.lastname: Kigozi
authors.forename: James
authors.initials: J
authors.lastname: Kiguli
authors.forename: Juliet
authors.initials: J
authors.lastname: Kyomuhendo
authors.forename: Laurent
authors.initials: L
authors.lastname: Ferradini
authors.forename: Walter
authors.initials: W
authors.lastname: Taylor
authors.forename: Francesco
authors.initials: F
authors.lastname: Checchi
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Guthmann
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000962:Antimalarials / Q000008:administration & dosage* / Q000009:adverse effects; D000077549:Artemether; D037621:Artemisinins / Q000008:administration & dosage* / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D023801:Directly Observed Therapy; D004334:Drug Administration Schedule; D004338:Drug Combinations; D004983:Ethanolamines / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D005449:Fluorenes / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007223:Infant; D000078102:Lumefantrine; D016778:Malaria, Falciparum / Q000175:diagnosis / Q000188:drug therapy*; D008297:Male; D012717:Sesquiterpenes / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D004338:Drug Combinations; D004983:Ethanolamines; D005449:Fluorenes; D012717:Sesquiterpenes; D000077549:Artemether; D000078102:Lumefantrine