title: In vivo efficacy of artemether-lumefantrine and chloroquine against Plasmodium vivax: a randomized open label trial in central Ethiopia.
abstract: BACKGROUND
  In vivo efficacy assessments of antimalarials are essential for ensuring effective case management. In Ethiopia, chloroquine (CQ) without primaquine is the first-line treatment for Plasmodium vivax in malarious areas, but artemether-lumefantrine (AL) is also commonly used.
  
  
  RESULTS
  In 2009, we conducted a 42-day efficacy study of AL or CQ for P. vivax in Oromia Regional State, Ethiopia. Individuals with P. vivax monoinfection were enrolled. Primary endpoint was day 28 cure rate. In patients with recurrent parasitemia, drug level and genotyping using microsatellite markers were assessed. Using survival analysis, uncorrected patient cure rates at day 28 were 75.7% (95% confidence interval (CI) 66.8-82.5) for AL and 90.8% (95% CI 83.6-94.9) for CQ. During the 42 days of follow-up, 41.6% (47/113) of patients in the AL arm and 31.8% (34/107) in the CQ arm presented with recurrent P. vivax infection, with the median number of days to recurrence of 28 compared to 35 days in the AL and CQ arm, respectively. Using microsatellite markers to reclassify recurrent parasitemias with a different genotype as non-treatment failures, day 28 cure rates were genotype adjusted to 91.1% (95% CI 84.1-95.1) for AL and to 97.2% (91.6-99.1) for CQ. Three patients (2.8%) with recurrent parasitemia by day 28 in the CQ arm were noted to have drug levels above 100 ng/ml.
  
  
  CONCLUSIONS
  In the short term, both AL and CQ were effective and well-tolerated for P. vivax malaria, but high rates of recurrent parasitemia were noted with both drugs. CQ provided longer post-treatment prophylaxis than AL, resulting in delayed recurrence of parasitemia. Although the current policy of species-specific treatment can be maintained for Ethiopia, the co-administration of primaquine for treatment of P. vivax malaria needs to be urgently considered to prevent relapse infections.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01052584.
authors.affiliation: Malaria Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, USA. jhwang@cdc.gov
authors.forename: Jimee
authors.initials: J
authors.lastname: Hwang
authors.forename: Bereket Hailegiorgis
authors.initials: BH
authors.lastname: Alemayehu
authors.forename: Richard
authors.initials: R
authors.lastname: Reithinger
authors.forename: Samuel Girma
authors.initials: SG
authors.lastname: Tekleyohannes
authors.lastname: Takele Teshi
authors.forename: Sintayehu Gebresillasie
authors.initials: SG
authors.lastname: Birhanu
authors.forename: Leykun
authors.initials: L
authors.lastname: Demeke
authors.forename: David
authors.initials: D
authors.lastname: Hoos
authors.forename: Zenebe
authors.initials: Z
authors.lastname: Melaku
authors.forename: Moges
authors.initials: M
authors.lastname: Kassa
authors.forename: Daddi
authors.initials: D
authors.lastname: Jima
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Malone
authors.forename: Henry
authors.initials: H
authors.lastname: Nettey
authors.forename: Michael
authors.initials: M
authors.lastname: Green
authors.forename: Amanda
authors.initials: A
authors.lastname: Poe
authors.forename: Sheila
authors.initials: S
authors.lastname: Akinyi
authors.forename: Venkatachalam
authors.initials: V
authors.lastname: Udhayakumar
authors.forename: S Patrick
authors.initials: SP
authors.lastname: Kachur
authors.forename: Scott
authors.initials: S
authors.lastname: Filler
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000962:Antimalarials / Q000627:therapeutic use*; D000077549:Artemether; D037621:Artemisinins / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D002738:Chloroquine / Q000627:therapeutic use*; D004983:Ethanolamines / Q000627:therapeutic use*; D005002:Ethiopia; D005260:Female; D005449:Fluorenes / Q000627:therapeutic use*; D005838:Genotype; D006801:Humans; D007223:Infant; D000078102:Lumefantrine; D016780:Malaria, Vivax / Q000188:drug therapy / Q000469:parasitology; D008297:Male; D008875:Middle Aged; D018512:Parasitemia / Q000188:drug therapy* / Q000469:parasitology; D010966:Plasmodium vivax / Q000187:drug effects* / Q000235:genetics; D011319:Primaquine / Q000627:therapeutic use; D011446:Prospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D004983:Ethanolamines; D005449:Fluorenes; D002738:Chloroquine; D000077549:Artemether; D000078102:Lumefantrine; D011319:Primaquine