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Ebola virus (EBOV), the etiologic agent of Ebola virus disease (EVD), is among the deadliest and accounts for the majority of known human infections and deaths within the family Filoviridae. EBOV was responsible for the 2013\u20132016 West Africa epidemic and the 2018\u20132020 Democratic Republic of the Congo epidemic, both of which were declared public health emergencies of international concern by the World Health Organization. The ecology of Ebola virus is poorly characterized, with its animal reservoir and drivers of zoonotic spillover unknown. Once spillover has occurred, EBOV's human-to-human transmission makes containment challenging and poses significant nosocomial risk. Vaccines and targeted therapeutics have been developed, tested, and approved by regulatory agencies over the past decade, but some uncertainty remains regarding efficacy. Infrastructure is often insufficient to effectively provide efficient public health responses and advanced supportive clinical care in EVD outbreak areas. Further research of EBOV in closer proximity to areas most affected by EVD is needed, but the containment facilities required for such work require nontrivial investment and personnel. These factors combine to make EBOV a uniquely challenging virus and cannot be easily overcome. The escalation of impacts from EVD over the past decade serves as a warning, however, that approaching these challenges should not wait until the next major outbreak.<\/jats:p>","DOI":"10.1093\/ofid\/ofaf464","type":"journal-article","created":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T11:39:54Z","timestamp":1753961994000},"source":"Crossref","is-referenced-by-count":9,"title":["Ebola Virus Disease: Uniquely Challenging Among the Viral Hemorrhagic Fevers"],"prefix":"10.1093","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3404-1380","authenticated-orcid":false,"given":"M Jeremiah","family":"Matson","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, Department of Internal Medicine, University of Utah , Salt Lake City, Utah ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel S","family":"Chertow","sequence":"additional","affiliation":[{"name":"Laboratory of Virology, Rocky Mountain Laboratories, 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