title: Effect of Artesunate-Amodiaquine on Mortality Related to Ebola Virus Disease.
abstract: BACKGROUND
  Malaria treatment is recommended for patients with suspected Ebola virus disease (EVD) in West Africa, whether systeomatically or based on confirmed malaria diagnosis. At the Ebola treatment center in Foya, Lofa County, Liberia, the supply of artemether-lumefantrine, a first-line antimalarial combination drug, ran out for a 12-day period in August 2014. During this time, patients received the combination drug artesunate-amodiaquine; amodiaquine is a compound with anti-Ebola virus activity in vitro. No other obvious change in the care of patients occurred during this period.
  
  
  METHODS
  We fit unadjusted and adjusted regression models to standardized patient-level data to estimate the risk ratio for death among patients with confirmed EVD who were prescribed artesunate-amodiaquine (artesunate-amodiaquine group), as compared with those who were prescribed artemether-lumefantrine (artemether-lumefantrine group) and those who were not prescribed any antimalarial drug (no-antimalarial group).
  
  
  RESULTS
  Between June 5 and October 24, 2014, a total of 382 patients with confirmed EVD were admitted to the Ebola treatment center in Foya. At admission, 194 patients were prescribed artemether-lumefantrine and 71 were prescribed artesunate-amodiaquine. The characteristics of the patients in the artesunate-amodiaquine group were similar to those in the artemether-lumefantrine group and those in the no-antimalarial group. A total of 125 of the 194 patients in the artemether-lumefantrine group (64.4%) died, as compared with 36 of the 71 patients in the artesunate-amodiaquine group (50.7%). In adjusted analyses, the artesunate-amodiaquine group had a 31% lower risk of death than the artemether-lumefantrine group (risk ratio, 0.69; 95% confidence interval, 0.54 to 0.89), with a stronger effect observed among patients without malaria.
  
  
  CONCLUSIONS
  Patients who were prescribed artesunate-amodiaquine had a lower risk of death from EVD than did patients who were prescribed artemether-lumefantrine. However, our analyses cannot exclude the possibility that artemether-lumefantrine is associated with an increased risk of death or that the use of artesunate-amodiaquine was associated with unmeasured patient characteristics that directly altered the risk of death.
authors.affiliation: From the Epicentre (E.G., A.T.) and Médecins sans Frontières Access Campaign (J.P.), Paris, and Laboratoire P4 Jean Merieux, INSERM, Lyon (A.B.) - all in France; Médecins sans Frontières, Geneva (E.G., A.S.A., D.J., A.T., R.P., E.S., M. Suzuki, J.-C.C., M. Serafini, I.C.); the Department of Epidemiology, Johns Hopkins University, Baltimore (A.S.A.); Médecins sans Frontières, Brussels (M. de Smet); Ministry of Health and Social Welfare, Monrovia, Liberia (P.A., M.M.); the Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan (M. Suzuki); European Mobile Laboratory Consortium, Hamburg (A.K., A.C., A.B., T.S., C.L., T.P., C.Y.), Robert Koch Institute, Berlin (A.K., C.Y.), and the Institute of Virology, Philipps-University Marburg, Marburg (T.S.) - all in Germany; Istituto Nazionale per le Malattie Infettive L. Spallanzani, Rome (A.C.); and Public Health England, Porton Down, United Kingdom (C.L., T.P.).
authors.forename: Etienne
authors.initials: E
authors.lastname: Gignoux
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Azman
authors.forename: Martin
authors.initials: M
authors.lastname: de Smet
authors.forename: Philippe
authors.initials: P
authors.lastname: Azuma
authors.forename: Moses
authors.initials: M
authors.lastname: Massaquoi
authors.forename: Dorian
authors.initials: D
authors.lastname: Job
authors.forename: Amanda
authors.initials: A
authors.lastname: Tiffany
authors.forename: Roberta
authors.initials: R
authors.lastname: Petrucci
authors.forename: Esther
authors.initials: E
authors.lastname: Sterk
authors.forename: Julien
authors.initials: J
authors.lastname: Potet
authors.forename: Motoi
authors.initials: M
authors.lastname: Suzuki
authors.forename: Andreas
authors.initials: A
authors.lastname: Kurth
authors.forename: Angela
authors.initials: A
authors.lastname: Cannas
authors.forename: Anne
authors.initials: A
authors.lastname: Bocquin
authors.forename: Thomas
authors.initials: T
authors.lastname: Strecker
authors.forename: Christopher
authors.initials: C
authors.lastname: Logue
authors.forename: Thomas
authors.initials: T
authors.lastname: Pottage
authors.forename: Constanze
authors.initials: C
authors.lastname: Yue
authors.forename: Jean-Clement
authors.initials: JC
authors.lastname: Cabrol
authors.forename: Micaela
authors.initials: M
authors.lastname: Serafini
authors.forename: Iza
authors.initials: I
authors.lastname: Ciglenecki
mesh_terms: D000293:Adolescent; D000328:Adult; D000655:Amodiaquine / Q000627:therapeutic use*; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D000962:Antimalarials / Q000009:adverse effects / Q000627:therapeutic use*; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004338:Drug Combinations; D004983:Ethanolamines / Q000627:therapeutic use*; D005260:Female; D005449:Fluorenes / Q000627:therapeutic use*; D019142:Hemorrhagic Fever, Ebola / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D007223:Infant; D007988:Liberia; D008288:Malaria / Q000150:complications* / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D012044:Regression Analysis; D012306:Risk; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D000962:Antimalarials; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins; D004338:Drug Combinations; D004983:Ethanolamines; D005449:Fluorenes; C515299:amodiaquine, artesunate drug combination; D000655:Amodiaquine