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BackgroundThe Ebola virus has been responsible for numerous outbreaks since the 1970s, with the most recent outbreak taking place between 2014 and 2016 and causing an international public health emergency. Ebola virus disease (EVD) has a high mortality rate and no approved targeted treatment exists to date. A number of established drugs are being considered as potential therapeutic agents for the treatment of EVD.ObjectiveWe aimed to identify potential drug repositioning candidates and to assess the scientific evidence available on their efficacy.MethodsWe conducted a systematic literature search in MEDLINE, Embase, and other relevant trial registry platforms for studies published between January 1976 and January 2017. We included drug screening, preclinical studies, and clinical studies on repurposed drugs for the treatment of EVD. The risk of bias for animal studies and nonrandomized clinical studies was assessed. The quality of reporting for case series and case reports was evaluated. Finally, we selected drugs approved by established regulatory authorities, which have positive in vitro study outcomes and at least one additional animal or clinical trial.ResultsWe identified 3301 publications, of which 37 studies fulfilled our inclusion criteria. Studies were highly heterogeneous in terms of study type, methodology, and intervention. The risk of bias was high for 13 out of 14 animal studies. We selected 11 drugs with potential anti-EVD therapeutic effects and summarized their evidence.ConclusionsSeveral established drugs may have therapeutic effects on EVD, but the quality and quantity of current scientific evidence is lacking. This review highlights the need for well-designed and conducted preclinical and clinical research to establish the efficacy of potential repurposed drugs against EVD.
BackgroundThe Ebola virus has been responsible for numerous outbreaks since the 1970s, with the most recent outbreak taking place between 2014 and 2016 and causing an international public health emergency. Ebola virus disease (EVD) has a high mortality rate and no approved targeted treatment exists to date. A number of established drugs are being considered as potential therapeutic agents for the treatment of EVD.ObjectiveWe aimed to identify potential drug repositioning candidates and to assess the scientific evidence available on their efficacy.MethodsWe conducted a systematic literature search in MEDLINE, Embase, and other relevant trial registry platforms for studies published between January 1976 and January 2017. We included drug screening, preclinical studies, and clinical studies on repurposed drugs for the treatment of EVD. The risk of bias for animal studies and nonrandomized clinical studies was assessed. The quality of reporting for case series and case reports was evaluated. Finally, we selected drugs approved by established regulatory authorities, which have positive in vitro study outcomes and at least one additional animal or clinical trial.ResultsWe identified 3301 publications, of which 37 studies fulfilled our inclusion criteria. Studies were highly heterogeneous in terms of study type, methodology, and intervention. The risk of bias was high for 13 out of 14 animal studies. We selected 11 drugs with potential anti-EVD therapeutic effects and summarized their evidence.ConclusionsSeveral established drugs may have therapeutic effects on EVD, but the quality and quantity of current scientific evidence is lacking. This review highlights the need for well-designed and conducted preclinical and clinical research to establish the efficacy of potential repurposed drugs against EVD.
The clinical management of Ebola created a significant challenge during the outbreak in West Africa, due to the paucity of previous research conducted into the optimum treatment regimen. That left many centres, to some extent, having to ‘work out’ best practice as they went along, and attempting to conduct real time prospective research. Médecins Sans Frontières (MSF) [1] were the only organization to have provided relatively in depth practical guidance prior to the outbreak and this manual was the basis of further planning between the WHO, national Ministry of Health and Sanitation in Sierra Leone, and other relevant stakeholders. Additionally, guidance changed over the epidemic as experience grew. This chapter will describe four key areas in the management of Ebola in West Africa. Firstly, it outlines the most recent WHO guidance; secondly, it looks back at how Ebola was managed in differing low and high resource settings; thirdly it outlines possible and optimal options for managing complications, paying particular attention to some of the controversies faced; fourthly it describes recent and ongoing studies into potential novel therapies that may shape future practice.
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