Association between oral antimalarial medication administration and mortality among patients with Ebola virus disease: a multisite cohort study

Abstract

Background Empiric antimalarial treatment is a component of protocol-based management of Ebola virus disease (EVD), yet this approach has limited clinical evidence for patient-centered benefits. Methods This retrospective cohort study evaluated the association between antimalarial treatment and mortality among patients with confirmed EVD. The data was collected from five International Medical Corps operated Ebola Treatment Units (ETUs) in Sierra Leone and Liberia from 2014 through 2015. The standardized protocol used for patient care included empiric oral treatment with combination artemether and lumefantrine, twice daily for three days; however, only a subset of patients received treatment due to resource variability. The outcome of interest was mortality, comparing patients treated with oral antimalarials within 48-h of admission to those not treated. Analysis was conducted with logistic regression to generate adjusted odds ratios (aORs). Multivariable analyses controlled for ETU country, malaria rapid diagnostic test result, age, EVD cycle threshold value, symptoms of bleeding, diarrhea, dysphagia and dyspnea, and additional standard clinical treatments. Results Among the 424 cases analyzed, 376 (88.7%) received early oral antimalarials. Across all cases, mortality occurred in 57.5% (244). In comparing unadjusted mortality prevalence, early antimalarial treated cases yielded 55.1% mortality versus 77.1% mortality for those untreated (p = 0.005). Multivariable analysis demonstrated evidence of reduced aOR for mortality with early oral antimalarial treatment versus non-treatment (aOR = 0.34, 95% Confidence Interval: 0.12, 0.92, p = 0.039). Conclusion Early oral antimalarial treatment in an EVD outbreak was associated with reduced mortality. Further study is warranted to investigate this association between early oral antimalarial treatment and mortality in EVD patients.

Factors associated with death in patients admitted with Ebola virus disease to Ebola Treatment Units in Guinea, Sierra Leone, and Liberia – December 2013 to March 2016

“…15 Finally, there are a few studies with small numbers of patients that have found various interventions beneficial in reducing case fatality: multivitamins or vitamin A given within 48 hours of admission, 16,17 antibiotics such as thirdgeneration oral cephalosporins especially cefixime, 17 and use of empirical antimalarial treatment, especially artesunateamodiaquine rather than artemether-lumefantrine. 18,19 While existing published studies have examined risk factors for mortality, several reasons justify the need for additional research in this area. First, there have been conflicting findings between studies, especially with respect to clinical characteristics associated with mortality.…”