Effect of Mass Artesunate-Amodiaquine Distribution on Mortality of Patients With Ebola Virus Disease During West African Outbreak

Abstract

Background Experiments in vitro have shown that the drug amodiaquine may inhibit Ebola virus activity. During the Ebola virus disease (EVD) epidemic in West Africa in 2014–2016, 2 mass drug administrations (MDAs) of artesunate-amodiaquine (ASAQ) were implemented to decrease the burden of malaria. The objective of this study was to assess the effect of the ASAQ MDAs on the mortality of patients with EVD. Methods A retrospective cohort design was used to analyze mortality data for patients with EVD admitted to 5 Ebola treatment units in Liberia and Sierra Leone. Patients admitted to the ETUs during the time period of ASAQ’s therapeutic effect from areas where the MDA was implemented were matched to controls not exposed to ASAQ, using a range of covariates, including malaria co-infection status, and a logistic regression analysis was performed. The primary outcome was Ebola treatment unit mortality. Results A total of 424 patients with EVD had sufficient data for analysis. Overall, the mortality of EVD patients was 57.5%. A total of 22 EVD patients were exposed to ASAQ during the MDAs and were found to have decreased risk of death compared with those not exposed in a matched analysis, but this did not reach statistical significance (relative risk, 0.63; 95% confidence interval, 0.37–1.07; P = .086). Conclusions There was a non–statistically significantly decreased risk of mortality in EVD patients exposed to ASAQ during the 2 MDAs as compared with EVD patients not exposed to ASAQ. Further prospective trials are needed to determine the direct effect of ASAQ on EVD mortality.

In Vivo Activity of Amodiaquine against Ebola Virus Infection

“…All patients were admitted into the same treatment center within a 5-month span, had confirmed EVD, and had no other obvious changes in their care during this period. Another retrospective study performed on data from 5 Ebola treatment centers in Liberia and Sierra Leone also showed a trend towards decreased mortality in EVD patients that received ASAQ 3 . As both artemether and AS are derivatives of artemisinin, the potential beneficial anti-EBOV effect observed with ASAQ could possibly be attributed to the change from lumefantrine to AQ.…”

The Use of Antimalarial Drugs against Viral Infection

“…Although the risk of mortality for treated patients compared to that of EBOV infected patients not exposed to AS-AQ was decreased, the effect was not significant. Prospective trials are needed [60].…”

“…Herpesviridae HCMV Artesunate [12,13,[46][47][48] Artesunate-amodiaquine [49] Arthemeter-lumefantrine [64] HHV6 Artesunate [52] Polyomaviridae JCPyV Artesunate [54,55] Mefloquine [72][73][74][75][76][77][78][79][80][81][82][83][84][85][86][87][88][122][123][124][125][126] Mefloquine and mirtazapine [86,87,127,128] Mefloquine, mirtazapine and a third drug [118,119] Mefloquine and risperidone [75] Mefloquine, risperidone and cytarabine [120] Mefloquine and cidofovir [121] Mefloquine and PML standard of care [129] Filoviridae EBOV Artesunate-amodiaquine [58,60] Nevertheless, some drugs have already been used in several clinical trials, as summarized in Table 1. Most of them regard the use of antimalarial drugs against HIV infection, but some of them failed, and...…”

Association between treatment with oral third‐generation cephalosporin antibiotics and mortality outcomes in Ebola virus disease: a multinational retrospective cohort study

“…During the 2014–2015 West African outbreak, the humanitarian response organisation International Medical Corps (IMC) worked with local partners to manage five Ebola Treatment Units (ETUs) in Sierra Leone and Liberia that cumulatively cared for 470 patients with EVD. Demographic, clinical and laboratory data were collected during the course of patient care and combined into a robust multinational database that has been used to evaluate specific types of care provision on patient outcomes in EVD . Given the recommended use of empiric antibiotics in EVD care, and the dearth of data on patient‐centred outcomes with antibiotic use, this study aimed to evaluate the association between early treatment with oral third‐generation cephalosporin antibiotics, in the form of cefixime, and mortality among patients with EVD admitted to IMC ETUs in West Africa.…”