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IDCM CME Issue 1-6: Ebola Virus Disease: A Brief History, the 2014 Epidemic, and the Aftermath
Author: Chris Lippincott, MD, MPH
Ebola Virus Disease: A Brief History, the 2014 Epidemic, and the Aftermath
The largest outbreak of Ebola virus disease in history was the West African epidemic between 2014-2016. With new cases reported in the Democratic Republic of Congo earlier this year, we will explore the history of Ebola virus disease, revisit the 2014 epidemic, and explore how our understanding of this virus has since evolved.
Ebola Prior to 2014
Ebola is a member of the filovirus family first and was described in 1976 in the Ebola River region of the Democratic Republic of Congo (DRC, formerly Zaire). That outbreak occurred in the Équateur Province, and resulted in 318 cases of disease. There were only 38 confirmed survivors of that outbreak, yielding an alarming 88% case fatality rate .1
Since that time, cases of Ebola virus disease have been documented every few years, and they are typically small and fairly contained. The largest outbreaks have seen fewer than 500 cases, and most are fewer than 100 cases.
Nearly all Ebola cases have occurred in the sub-Saharan African countries of Democratic Republic of Congo, Gabon, Republic of Congo, and Uganda, and in Sudan.2 Outbreaks are associated with three species of virus: Zaire ebolavirus (first described in 1976), Sudan ebolavirus (first described in 1976), and Bundibugyo ebolavirus (first described in 2007).2 Case fatality rates are high, and range from 30-90%.2 Two other species of Ebola virus are known. Taï Forest ebolavirus was first described in Ivory Coast in 1994 with the only known case occurring in a scientist, who survived, after conducting an autopsy on a wild chimpanzee. Reston ebolavirus, which causes disease in macaque monkeys and was popularized in the 1995 book The Hot Zone, was imported to the United States from the Philippines in 1989.1 Reston ebolavirus does not cause disease in humans.
Ebola virus is a zoonotic infection that is transmitted to humans from other mammals.3 Non-human primates (e.g., gorillas, monkeys, chimpanzees) are known to develop infection and may play a role in transmission to humans. However, the African fruit bat is hypothesized to be a reservoir of the virus and may play a major role in transmission of Ebola virus to other animals.3,4 Pigs are the only livestock known to be susceptible to infection.4 Mosquitos are not known to transmit Ebola virus.
Initial transmission of Ebola virus at the onset of an outbreak typically occurs when humans come into contact with blood, fluids, or tissue of infected animals (such as fruit bats or non-human primates). Human transmission occurs through contact between a broken skin barrier (i.e., a cut or scrape) or a mucous membrane (i.e., eyes, nose, or mouth) and body fluid or blood from an individual with symptoms of, or who has died from, Ebola virus disease. This includes transmission from needles or syringes contaminated with blood or body fluids.3,4 Blood, feces, and vomit carry the highest risk of bodily fluid transmission while saliva and tears carry the lowest risk.5 Ebola virus has never been isolated, or known to be transmitted from, sweat.5 More recently, there was confirmed transmission via the semen from a man who had fully recovered from Ebola virus disease.3,4 There is no evidence of airborne transmission of Ebola.
Symptoms, Diagnosis, & Treatment
Ebola virus disease leads to non-specific symptoms similar to malaria or influenza from 2 to 21 days (typically 8-10 days) after exposure.7 These symptoms include fever, headache, myalgia, fatigue, abdominal pain, vomiting, diarrhea, and easy bruising/bleeding.3,4 Suspected cases of disease include individuals with fever (which is most common and present in nearly all cases) in addition to any of the aforementioned symptoms as well as an epidemiological risk factor within 21 days of the onset of symptoms. Cases can be confirmed through a variety of diagnostic tests; however, the World Health Organization (WHO) currently recommends nucleic acid tests (NAT) or rapid antigen detection performed on blood.4 Treatment of Ebola virus disease remains supportive, and includes providing hydration, electrolyte monitoring/replacement, respiratory support including supplemental oxygen, blood pressure monitoring/support, and monitoring/treatment of secondary bacterial infections (e.g., pneumonia).
2014-2016 Guinea, Liberia, & Sierra Leone: The Epidemic & Aftermath
In March 2014, WHO was informed of an outbreak of a febrile illness in Guinea with a high case fatality rate.6 The causative pathogen was determined to be Zaire ebolavirus.2,6 A subsequent investigation of confirmed cases led epidemiologists to conclude that the outbreak likely began in December 2013. Within weeks, cases were identified in neighboring Liberia and Sierra Leone. Lack of surveillance systems and poor public health infrastructure caused unrecognized chains of transmission, and the outbreak expanded to epidemic proportions.7 This prompted a massive collaboration among national and international partners including local ministries of health, WHO, the Centers for Disease Control (CDC), and Médecins sans Frontières among others. By the end of the epidemic in June 2016, 28,610 cases in total were identified—there were 11,308 deaths, for a case fatality rate of 39%.3
The 2014 epidemic exposed complications of Ebola virus disease that were not reported during previous smaller outbreaks, and it opened the door for novel therapies. For example:
- Ebola can cause a range of convalescent syndromes. Specific immune-privileged locations in the body can harbor virus. Small numbers of Ebola virus disease survivors subsequently developed ophthalmic complications, including predominantly uveitis and rarely optic neuropathy.8
- The virus can be sexually transmitted. Prior to the 2014 epidemic, sexual transmission of Ebola virus was theoretical. In March 2015, a Liberian woman was diagnosed with Ebola virus disease after unprotected sexual contact with a male epidemic survivor whose PCR blood tests were repeatedly negative more than 5 months earlier.9 Subsequent testing strongly suggested this was due to sexual transmission of Ebola virus.9
- Monoclonal antibody and antiviral therapy show promise for neonates. It had been known that Ebola virus can infect the amniotic fluid, placenta, and fetus. Neonates have previously been born to Ebola-infected mothers, however previously all neonates died within 3 weeks of birth.10 In 2017, it was reported that the first Ebola infected neonate survived after treatment with Ebola survivor monoclonal antibodies and an experimental antiviral medication.10
Between 2014 and 2016, one of the multifaceted efforts to contain the rapidly expanding epidemic was to scale up existing Ebola vaccine trials. One candidate, rVSV-ZEBOV, is a recombinant, virus-based vaccine that expressed a protein of Zaire ebolavirus.11 In a study of Ebola virus disease contacts and contacts of contacts, participants were given either immediate vaccination or delayed vaccination. Among subjects with immediate vaccination, there were no cases of Ebola virus disease 10 days or more after vaccination, in comparison with 23 cases of Ebola virus disease among those with delayed vaccination (P=0.003%).11
2018 Democratic Republic of Congo Outbreaks
On May 8, 2018, the DRC government declared an Ebola virus disease outbreak in Bikoro (Équateur Province) after 2 cases were confirmed. Local and international partners, including WHO and CDC, were rapidly mobilized and WHO declared the outbreak ended on July 25, 2018. Of the 54 confirmed or probable cases, there were 33 deaths.3 The rVSV-ZEBOV Ebola vaccine was administered during this outbreak.12 On August 1, 2018, a second, seemingly unrelated, outbreak in the DRC was declared in North Kivu Province, approximately 1,500 miles from the Bikoro outbreak. Within 1 week of the outbreak being declared, vaccination with rVSV-ZEBOV was underway.13 As of August 15, 2018, there have been 78 cases (51 confirmed) and 44 deaths associated with this outbreak.14
Bottom Line: Although Ebola has been studied for more than 40 years, the 2014 West African Ebola epidemic exposed the consequences of a large outbreak in a setting with poor public health infrastructure resulting in a loss of life on a scale unseen in prior Ebola outbreaks. The aftermath of this epidemic led to a better understanding of convalescent complications of Ebola virus disease, and to a promising vaccine that has been utilized in the Bikoro and North Kivu Province outbreaks in the Democratic Republic of Congo in 2018.
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- Ebola (Ebola Virus Disease) Years of Ebola Virus Disease, 40 Years of Ebola Virus Disease around the World, Cases and Outbreaks of EVD by Year. US Centers for Disease Control and Prevention Web site. https://www.cdc.gov/vhf/ebola/history/chronology.html Accessed 8/19/2018.
- Baize S, Pannetier D, Oestereich L, Rieger T, Koivogui L, Magassouba N, Soropogui B, Sow MS, Keïta S, De Clerck H, Tiffany A, Dominguez G, Loua M, Traoré A, Kolié M, Malano ER, Heleze E, Bocquin A, Mély S, Raoul H, Caro V, Cadar D, Gabriel M, Pahlmann M, Tappe D, Schmidt-Chanasit J, Impouma B, Diallo AK, Formenty P, Van Herp M, Günther S. Emergence of Zaire Ebola virus disease in Guinea. N Engl J Med. 2014 Oct 9;371(15):1418-25. doi: 10.1056/NEJMoa1404505. Epub 2014 Apr 16. PMID: 24738640.
- US Centers for Disease Control and Prevention. Ebola (Ebola Virus Disease) Web page. https://www.cdc.gov/vhf/ebola/index.html. Accessed 8/19/2018.
- World Health Organization. Ebola Virus Disease Fact Sheet. https://www.who.int/news-room/fact-sheets/detail/ebola-virus-disease. Accessed 8/19/2018.
- World Health Organization. What we know about transmission of the Ebola virus among humans. https://www.who.int/mediacentre/news/ebola/06-october-2014/en/. Accessed 8/19/2018.
- WHO Ebola Response Team, Aylward B, Barboza P, Bawo L, Bertherat E, Bilivogui P, Blake I, Brennan R, Briand S, Chakauya JM, Chitala K, Conteh RM, Cori A, Croisier A, Dangou JM, Diallo B, Donnelly CA, Dye C, Eckmanns T, Ferguson NM, Formenty P, Fuhrer C, Fukuda K, Garske T, Gasasira A, Gbanyan S, Graaff P, Heleze E, Jambai A, Jombart T, Kasolo F, Kadiobo AM, Keita S, Kertesz D, Koné M, Lane C, Markoff J, Massaquoi M, Mills H, Mulba JM, Musa E, Myhre J, Nasidi A, Nilles E, Nouvellet P, Nshimirimana D, Nuttall I, Nyenswah T, Olu O, Pendergast S, Perea W, Polonsky J, Riley S, Ronveaux O, Sakoba K, Santhana Gopala Krishnan R, Senga M, Shuaib F, Van Kerkhove MD, Vaz R, Wijekoon Kannangarage N, Yoti Z.. Ebola virus disease in West Africa--the first 9 months of the epidemic and forward projections. N Engl J Med. 2014 Oct 16;371(16):1481-95. doi: 10.1056/NEJMoa1411100. Epub 2014 Sep 22. PMCID: PMC4235004
- US Centers for Disease Control and Prevention. CDC’s Response to the 2014–2016 Ebola Epidemic — West Africa and United States. MMWR Suppl. 2016 Jul 8;65(3):4-11. https://www.cdc.gov/mmwr/volumes/65/su/pdfs/su6503.pdf. Accessed 8/19/2018.
- Shantha JG, Crozier I, Hayek BR, Bruce BB, Gargu C, Brown J, Fankhauser J, Yeh S. Ophthalmic manifestations and causes of vision impairment in Ebola virus disease survivors in Monrovia, Liberia. Ophthalmology. 2017 Feb;124(2):170-177. doi: 10.1016/j.ophtha.2016.10.011. Epub 2016 Nov 30. PMCID: PMC5272811.
- Fischer WA 2nd, Wohl DA. Confronting Ebola as a sexually transmitted infection. Clin Infect Dis. 2016 May 15;62(10):1272-6. doi: 10.1093/cid/ciw123. Epub 2016 Mar 1. PMCID: PMC4845792.
- Henao-Restrepo AM, Camacho A, Longini IM, Watson CH, Edmunds WJ, Egger M, Carroll MW, Dean NE, Diatta I, Doumbia M, Draguez B, Duraffour S, Enwere G, Grais R, Gunther S, Gsell PS, Hossmann S, Watle SV, Kondé MK, Kéïta S, Kone S, Kuisma E, Levine MM, Mandal S, Mauget T, Norheim G, Riveros X, Soumah A, Trelle S, Vicari AS, Røttingen JA, Kieny MP. Efficacy and effectiveness of an rVSV-vectored vaccine in preventing Ebola virus disease: final results from the Guinea ring vaccination, open-label, cluster-randomised trial (Ebola Ça Suffit!). Lancet. 2017 Feb 4;389(10068):505-518. doi: 10.1016/S0140-6736(16)32621-6. Epub 2016 Dec 23. PMCID: PMC5364328.
- Ebola vaccine provides protection and hope for high-risk communities in the Democratic Republic of the Congo [news release]. Geneva, Switzerland: World Health Organization; May 30, 2018. https://www.who.int/news-room/feature-stories/detail/ebola-vaccine-provides-protection-and-hope-for-high-risk-communities-in-the-democratic-republic-of-the-congo. Accessed 8/19/2018.
- Ebola vaccination begins in North Kivu [news release]. Geneva, Switzerland: World Health Organization; August 8, 2018. https://www.who.int/news-room/detail/08-08-2018-ebola-vaccination-begins-in-north-kivu. Accessed 8/19/2018.
- Ebola virus disease – Democratic Republic of the Congo World Health Organization [news release]. Geneva, Switzerland: World Health Organization; August 17, 2018. https://www.who.int/csr/don/17-august-2018-ebola-drc/en/. Accessed 8/19/2018.