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N Engl J Med. 2016 Jan 7;374(1):23-32. doi: 10.1056/NEJMoa1504605.

Effect of Artesunate-Amodiaquine on Mortality Related to Ebola Virus Disease.

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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.).



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.


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).


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.


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.

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