Abstract
During the Ebola virus disease (EVD) epidemic in Western Africa (2013‒2016), antimalarial treatment was administered to EVD patients due to the high coexisting malaria burden in accordance with World Health Organization guidelines. In an Ebola treatment center in Liberia, EVD patients receiving the combination antimalarial artesunate-amodiaquine had a lower risk of death compared to those treated with artemether-lumefantrine. As artemether and artesunate are derivatives of artemisinin, the beneficial anti-Ebola virus (EBOV) effect observed could possibly be attributed to the change from lumefantrine to amodiaquine. Amodiaquine is a widely used antimalarial in the countries that experience outbreaks of EVD and, therefore, holds promise as an approved drug that could be repurposed for treating EBOV infections. We investigated the potential anti-EBOV effect of amodiaquine in a well-characterized nonhuman primate model of EVD. Using a similar 3-day antimalarial dosing strategy as for human patients, plasma concentrations of amodiaquine in healthy animals were similar to those found in humans. However, the treatment regimen did not result in a survival benefit or decrease of disease signs in EBOV-infected animals. While amodiaquine on its own failed to demonstrate efficacy, we cannot exclude potential therapeutic value of amodiaquine when used in combination with artesunate or another antiviral.
Highlights
During the Ebola virus disease (EVD) epidemic in Western Africa (2013‒2016), antimalarial treatment was administered to EVD patients due to the high coexisting malaria burden in accordance with World Health Organization guidelines
Www.nature.com/scientificreports 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 showed a trend towards decreased mortality in EVD patients that received ASAQ3
The antimalarial treatment ASAQ that was administered to EVD patients in 2014, is a coformulation of artesunate (AS) and amodiaquine (AQ)
Summary
During the Ebola virus disease (EVD) epidemic in Western Africa (2013‒2016), antimalarial treatment was administered to EVD patients due to the high coexisting malaria burden in accordance with World Health Organization guidelines. In an Ebola treatment center in Liberia, EVD patients receiving the combination antimalarial artesunate-amodiaquine had a lower risk of death compared to those treated with artemether-lumefantrine. The two largest recorded outbreaks of Ebola virus disease (EVD), which include the recent 2013–2016 Ebola virus outbreak in Western Africa and the ongoing outbreak in the Democratic Republic of Congo, illustrate the critical need for the development and approval of medical countermeasures These countermeasures could potentially treat patients with suspected EVD, prevent the development of disease following a known exposure, or protect those at risk for possible exposure, such family members or health care workers and laboratory support staff working to control EVD outbreaks. Another retrospective study performed on data from 5 Ebola treatment centers in Liberia and Sierra Leone showed a trend towards decreased mortality in EVD patients that received ASAQ3 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. Both the cynomolgus and rhesus macaque models have previously been shown to mimic many critical aspects of human filovirus disease[10]
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