title: In vivo efficacy of artemether-lumefantrine against uncomplicated Plasmodium falciparum malaria in Central Ethiopia.
abstract: BACKGROUND
  In vivo efficacy assessments of the first-line treatments for Plasmodium falciparum malaria are essential for ensuring effective case management. In Ethiopia, artemether-lumefantrine (AL) has been the first-line treatment for uncomplicated P. falciparum malaria since 2004.
  
  
  METHODS
  Between October and November 2009, we conducted a 42-day, single arm, open label study of AL for P. falciparum in individuals >6 months of age at two sites in Oromia State, Ethiopia. Eligible patients who had documented P. falciparum mono-infection were enrolled and followed according to the standard 2009 World Health Organization in vivo drug efficacy monitoring protocol. The primary and secondary endpoints were PCR uncorrected and corrected cure rates, as measured by adequate clinical and parasitological response on days 28 and 42, respectively.
  
  
  RESULTS
  Of 4426 patients tested, 120 with confirmed falciparum malaria were enrolled and treated with AL. Follow-up was completed for 112 patients at day 28 and 104 patients at day 42. There was one late parasitological failure, which was classified as undetermined after genotyping. Uncorrected cure rates at both day 28 and 42 for the per protocol analysis were 99.1% (95% CI 95.1-100.0); corrected cure rates at both day 28 and 42 were 100.0%. Uncorrected cure rates at day 28 and 42 for the intention to treat analysis were 93.3% (95% CI 87.2-97.1) and 86.6% (95% CI 79.1-92.1), respectively, while the corrected cure rates at day 28 and 42 were 94.1% (95% CI 88.2-97.6) and 87.3% (95% CI 79.9-92.7), respectively. Using survival analysis, the unadjusted cure rate was 99.1% and 100.0% adjusted by genotyping for day 28 and 42, respectively. Eight P. falciparum patients (6.7%) presented with Plasmodium vivax infection during follow-up and were excluded from the per protocol analysis. Only one patient had persistent parasitaemia at day 3. No serious adverse events were reported, with cough and nausea/vomiting being the most common adverse events.
  
  
  CONCLUSIONS
  AL remains a highly effective and well-tolerated treatment for uncomplicated falciparum malaria in the study setting after several years of universal access to AL. A high rate of parasitaemia with P. vivax possibly from relapse or new infection was observed.
  
  
  BACKGROUND
  NCT01052584.
authors.affiliation: U.S. Centers for Disease Control and Prevention, Atlanta, GA, USA. jhwang@cdc.gov
authors.forename: Jimee
authors.initials: J
authors.lastname: Hwang
authors.forename: Bereket H
authors.initials: BH
authors.lastname: Alemayehu
authors.forename: David
authors.initials: D
authors.lastname: Hoos
authors.forename: Zenebe
authors.initials: Z
authors.lastname: Melaku
authors.forename: Samuel G
authors.initials: SG
authors.lastname: Tekleyohannes
authors.forename: Takele
authors.initials: T
authors.lastname: Teshi
authors.forename: Sintayehu G
authors.initials: SG
authors.lastname: Birhanu
authors.forename: Leykun
authors.initials: L
authors.lastname: Demeke
authors.forename: Kedir
authors.initials: K
authors.lastname: Gobena
authors.forename: Moges
authors.initials: M
authors.lastname: Kassa
authors.forename: Daddi
authors.initials: D
authors.lastname: Jima
authors.forename: Richard
authors.initials: R
authors.lastname: Reithinger
authors.forename: Henry
authors.initials: H
authors.lastname: Nettey
authors.forename: Michael
authors.initials: M
authors.lastname: Green
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Malone
authors.forename: S Patrick
authors.initials: SP
authors.lastname: Kachur
authors.forename: Scott
authors.initials: S
authors.lastname: Filler
mesh_terms: D000293:Adolescent; D000962:Antimalarials / Q000008:administration & dosage*; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D016054:DNA, Protozoan / Q000235:genetics / Q000302:isolation & purification; D004338:Drug Combinations; D004983:Ethanolamines / Q000008:administration & dosage*; D005002:Ethiopia; D005260:Female; D005449:Fluorenes / Q000008:administration & dosage*; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy*; D008297:Male; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000302:isolation & purification; D016133:Polymerase Chain Reaction; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000962:Antimalarials; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins; D016054:DNA, Protozoan; D004338:Drug Combinations; D004983:Ethanolamines; D005449:Fluorenes