Ebola warning sign

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Ebola virus disease is a hemorrhagic febrile illness that has case-fatality rates that vary from 32% to 88% across well-studied outbreaks.  Thankfully, the number of known outbreaks has been limited. Since Ebola first emerged in 1976, the CDC has recognized 26 separate human disease outbreaks of natural origin in Africa.[1]  The devastating 2014-16 West African outbreak killed more than 10,000 people and showed the world that the disease could not only spread beyond its perceived zone of endemicity but had a potentially broader footprint than previously understood. But the truth is, the Ebola virus presence is much broader than a collection of points on a map where the disease has surfaced.

The first evidence that showed that Ebola virus had circulated in areas without known cases of disease came in 1977, near the Ebola outbreak in Tandala, DRC, just 200 miles west of the first known cases in 1976.[2]  Blood samples obtained from individuals in areas with no previous symptoms of Ebola were found to contain antibodies for Ebola virus.  The presence of antibodies to any virus indicates a previous or ongoing infection with that virus. Because subclinical illness is always a possibility with viral infections, the presence of these Ebolavirus-specific antibodies could only be explained by exposure to the virus, which is somewhat reasonable in an area that is endemic to the disease.  But how do we know the true endemic zone of a virus such as Ebolavirus?

Endemic zones are primarily based on where disease can most likely be expected, and are determined by historical accounts of disease, as well as supplemental information such as where animals or insects that might transmit the disease are located.  With respect to the Ebola virus, outbreaks that occur in Central Africa, in or near the Congo River Basin, are expected; outbreaks that take place elsewhere are unexpected and can be problematic, as was the case for the West African outbreak.  And yet, scientists have highlighted the presence of Ebola antibodies well outside the endemic zone for disease for decades.

In the early 1980’s, research based at the Pasteur Institute in Bangui, Central African Republic, demonstrated for the first time that the population of central Africa presented natural antibodies against the Ebolavirus strains of Zaire and Sudan.[3] [4] Research also showed for the first time that several mammal species had Ebolavirus reacting antibodies, including rodents, dogs, and others.  Initially, the scientific community was skeptical of the findings, due to the type of antibody tests used, and because the prevalence of these antibodies was unbelievably dispersed and at a high level of prevalence.  However, a 1989 follow-up study confirmed methodology and preliminary observations, and expanded the results to include similar observations in Cameroon, Chad, Gabon, and Republic of Congo (the latter two of these countries would have their first Ebola outbreaks in 1994 and 2001, respectively).[5]  Moreover, such Ebolavirus antibody prevalence was found in West Africa, preceding the catastrophic 2014-2016 Ebolavirus outbreak11.[6] [7] [8]  Subsequent studies have determined that 20-25% of persons living in or near the Congolese rain forest are seropositive for Ebola, despite never exhibiting symptoms.[9]

Today, Ebola antibody prevalence is widely distributed across the African continent in the absence of severe clinical presentation and/or outbreak manifestation.[10] [11]  A 1989 study even found Ebola Zaire antibodies among people living in Madagascar, an island country that has never had a single known case of Ebola, and which has been geographically separated from continental Africa for 100 million years.[12]  Remarkably, Ebola Zaire appears to be the most prevalent viral infection in Madagascar, despite a total lack of Ebola virus disease occurrence.

How is this possible?  Are Ebola virus infections more prevalent than we understand, causing subclinical infections?  Subclinical infection, a silent infection, is common for most of the viruses known to infect humans.  Maybe other strains of Ebolavirus, not yet isolated, do not cause disease and circulate more widely than we know?  Do these initially harmless strains eventually pass through animal (or even human) hosts, where they undergo genetic changes that make them pathogenic to humans?  The Ebola Reston strain, harmless to humans, actively circulates in the rainforests of the Philippines; how did this virus—initially and so uniquely known to Africa—get there?  These are the questions that researchers are pursuing, in the hopes that in the future, Ebola virus disease outbreaks can be better predicted, contained, or even eliminated by understanding the Ebola virus footprint that stretches much further across Africa than previously expected.

This post was coauthored by Tom Vincent and Dr. Jean-Paul Gonzalez.  Dr. Gonzalez is the Deputy Director of the Center of Excellence in Emerging and Zoonotic Infectious Diseases at Kansas State University.

[1] https://www.cdc.gov/vhf/ebola/outbreaks/history/distribution-map.html
[2] Heymann DL, Weisfeld JS, Webb PA, Johnson KM, Cairns T, Berquist H. 1980. Ebola Hemorrhagic Fever: Tandala, Zaire, 1977-1978. J Infect Dis. 142, 372-376.
[3] Saluzzo JF, Gonzalez JP, Georges AJ & Johnson KM. 1980. Note préliminaire sur la présence d’anticorps vis-à-vis du virus Ebola parmi les populations du sud-est de la République Centrafricaine Bulletin de la Société de Pathologie Exotique, 73, (3):238-241
[4] Gonzalez JP, McCormick JB, Saluzzo JF & Georges AJ. 1983. Les fièvres hémorragiques africaines d’origine virale en République Centrafricaine Cah. ORSTOM, Ser.Ent.Méd. et Parasit., XXI, (2): 119-130
[5] Gonzalez, JP, Josse R, Johnson ED, Merlin M, Georges AJ, Abandja J, Danyod M, Delaporte, E, Dupont A, Ghogomu A, Kouka-Bemba D, Madelon MC, Sima A & Meunier DMY. 1989, Antibody prevalence against haemorrhagic fever viruses in randomized representative central african populations. Research in Virology (Annales de l’Institut Pasteur), 140, 319-331
[6] Gonzalez JP. Ebola Virus Circulation in Africa: a balance between clinical expression and epidemiological silence. 2005. Epidemiologie. 98, 210–217.
[7] Gonzalez JP, M Ar Gouilh, JM Reynes & E Leroy. 2008. Bat Borne Viral Zoonoses Emergence PART I Synthetic Analyses Chapter 6 In People, Health and Forests Carol J. Pierce Colfer and Eckhard Kleinau, eds. Press.
[8] Schoepp RJ, Rossi CA, Khan SH, Goba A, Fair JN. Undiagnosed acute viral febrile illnesses, Sierra Leone. Emerg Infect Dis. 2014;20(7):1176–82. doi: 10.3201/eid2007.131265.
[9] Becquart P, Wauquier N, Mahlakõiv T, Nkoghe D, Padilla C, Souris M, Ollomo B, Gonzalez JP, De Lamballerie X, Kazanji M, Leroy E. High Prevalence of both Humoral and Cellular Immunity to Zaire ebolavirus among Rural Populations in Gabon, 2010, PLoS ONE 5 (2): e9126.
[10] Gonzalez JP. Ebola Virus Circulation in Africa: a balance between clinical expression and epidemiological silence. 2005. Epidemiologie. 98, 210–217.
[11] Bower H, Glynn JR. 2017. A systematic review and meta-analysis of seroprevalence surveys of ebolavirus infection. Scientific Data, 4:160133
[12] Mathiot CC, Fontenille D, Georges AJ, Coulanges P. 1989. Antibodies to haemorrhagic fever viruses in Madagascar populations. Trans R Soc Trop Med Hyg. 83(3):407-9.