Understanding Ebola: the 2014 Epidemic Jolie Kaner1,2 and Sarah Schaack2*
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Kaner and Schaack Globalization and Health (2016) 12:53 DOI 10.1186/s12992-016-0194-4 REVIEW Open Access Understanding Ebola: the 2014 epidemic Jolie Kaner1,2 and Sarah Schaack2* Abstract Near the end of 2013, an outbreak of Zaire ebolavirus (EBOV) began in Guinea, subsequently spreading to neighboring Liberia and Sierra Leone. As this epidemic grew, important public health questions emerged about how and why this outbreak was so different from previous episodes. This review provides a synthetic synopsis of the 2014–15 outbreak, with the aim of understanding its unprecedented spread. We present a summary of the history of previous epidemics, describe the structure and genetics of the ebolavirus, and review our current understanding of viral vectors and the latest treatment practices. We conclude with an analysis of the public health challenges epidemic responders faced and some of the lessons that could be applied to future outbreaks of Ebola or other viruses. Keywords: Ebola, Ebolavirus, 2014 outbreak, Epidemic, Review Abbreviations: BEBOV, Bundibugyo ebolavirus;CIEBOV,Côte d’Ivoire ebolavirus;EBOV,Ebolavirus; EVD, Ebola virus disease or Ebola; Kb, Kilobase; MSF, Médecins Sans Frontières; REBOV, Reston ebolavirus; SEBOV, Sudan ebolavirus;WHO,World Health Organization; ZEBOV, Zaire ebolavirus Background NP (nucleoprotein), VP35 (polymerase cofactor), VP40 As of April 13th, 2016 there have been 28,652 total cases (matrix protein), GP (glycoprotein), VP30 (transcrip- of Ebola virus disease (EVD; or more generally Ebola) in tion activator), VP24 (secondary matrix protein), and the 2014–2015 West African epidemic [1]. Of these, RNA-dependent RNA polymerase [6]. There are currently 11,325 cases (40 %) were fatal [1]. During this epidemic, five recognized species of ebolavirus: Zaire ebolavirus the vast majority of cases were concentrated in Guinea, (ZEBOV), Sudan ebolavirus (SEBOV), Reston ebolavirus Liberia, and Sierra Leone, with a handful of cases (REBOV) (non-pathogenic to humans), Côte d’Ivoire ebo- imported to countries around the world [1]. This was lavirus (CIEBOV) also known as Tai Forest ebolavirus and the first outbreak of Ebola in West Africa, and the most Bundibugyo ebolavirus (BEBOV) [5, 7]. significant Ebola epidemic that has occurred worldwide Estimates of the rate of nucleotide substitution for since the virus was first described [2]. Here, we review filoviruses suggest that these viruses have substitution the current understanding of biology and genetics of rates approximately 100× times lower than other RNA the virus, the past and current epidemiology, and the viruses (e. g. retroviruses and influenza A) [8]. Based on public health response to the 2014–15 Ebola outbreak. these substitution rates, studies have concluded that ebolavirus and marburgvirus, a closely related filovirus that is also pathogenic in humans, likely diverged from Ebolavirus genetics each other several thousand years ago and that the The ebolavirus is a member of the family filoviridae, different species of ebolavirus diverged from each other which is composed of single-stranded negative-sense within the last ~1000 years ago [8, 9]. Genetic analysis enveloped RNA viruses [3]. These filamentous viruses of strains from the 2014–2015 West African Ebola are ~19 kilobases (kb) in length (800–1100 nanometers epidemic have been hindered, in part, due to the limited [nm] long and 80 nm in diameter) [4]. The ebolavirus understanding of the biology of this virus and further genome contains seven genes (3′ NP VP35 VP40 GP exacerbated by delays in sample export, bad record VP30 VP24 L 5′ [5]) encoding a number of proteins: keeping, and a small number of trained specialists * Correspondence: [email protected] [10, 11]. Gire et al. [12] analyzed 81 EBOV sequences, 2Department of Biology, Reed College, 3203 SE Woodstock Blvd, Portland, OR 78 newly derived from patients in Sierra Leone and 3 97202, USA previously published Guinean sequences, and found Full list of author information is available at the end of the article © 2016 The Author(s). Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Kaner and Schaack Globalization and Health (2016) 12:53 Page 2 of 7 341 fixed substitutions and 55 single-nucleotide poly- many locations, suggesting that infection (and survival) morphisms. They concluded that the substitution rate is frequent [4]. Retrospective analysis shows that wildlife during this outbreak is roughly twice as high as those deaths (non-human primates and antelope) tend to pre- previously reported. Other studies show contrasting cede human infections, which this could have important results, however; e.g. Spielman et al. [13] and Hoenen surveillance implications in terms of preventing future et al. [14] analyzed sequences from the recent epidemic outbreaks [20]. In addition, population declines in − − and reported a mutation rates of 9.6 × 10 4 and 1.3 × 10 3 apes have also been chronologically linked to human substitutions per site per year, respectively, which are Ebola outbreaks and a number of molecular studies similar to those reported during past outbreaks. have linked primate ebolavirus cases to human Ebola A more recent study by Carroll et al. [15] used 197 outbreaks [4]. new viral sequences in addition to publicly-available Although two types of transmission (animal-to-human sequences to trace the evolution of the viral genome and human-to-human) have been observed, nosocomial throughout the epidemic. They estimated the date of the transmission has played a key role in the spread of most recent common ancestor of the sampled viruses to Ebola. Transmission from animals has taken place via be between December 12th, 2013 and February 18th, the handling and butchering of infected animals, inc- 2014, which is supported by epidemiological evidence luding bats, non-human primates and duikers (a small that places the index case in late December 2013 [15]. forest antelope) [21]. Healthcare workers are especially Another recent study by Simon-Loriere et al. [16] ana- at risk for exposure to Ebola because they are more lyzed 85 new sequences from Guinean patients along likely to come into contact with contaminated bodily with 110 publicly-available EBOV sequences from this fluids [22]. The traditional funeral and burial practices in − outbreak and reported a mutation rate of 0.87 × 10 3 to West Africa involve washing the body by hand before − 0.91 × 10 3 substitutions per site per year. They point burial and paying respect to the dead through physical out that evolutionary rates in RNA viruses can be strongly contact which are both exceptionally high-risk activities time-dependent, with higher rates observed over short with regard to the spread of Ebola [23]. The incubation time spans than long ones [16]. This may explain why period for Ebola can range from two to 21 days, but is certain estimates of mutation rates during this recent usually one to two weeks [24]. There is no evidence that epidemic have been higher than expected. Ebola is contagious during the incubation period, while infected individuals are still asymptomatic [25]. The Past Ebola outbreaks World Health Organization (WHO) will only declare an Since the first outbreak 40 years ago, EVD outbreaks Ebola outbreak over once 42 days (two incubation pe- have been rare, small and localized. The first recorded riods) have passed with no new infections reported [26]. outbreak of EVD took place in Zaire (now the De- Interrupting Ebola transmission requires rapid identifi- mocratic Republic of the Congo) in 1976, close to the cation of cases, contact tracing, and monitoring of Yambuku Catholic Mission Hospital located near the people identified as high risk [22, 27]. Based on a retro- Ebola River Valley [7]. At the same time, a separate out- spective study of the 1995 outbreak in Kikwit DRC, the break of EVD occurred near Maridi in West Equatoria greatest risk factor for secondary household transmission Region in Sudan [7]. Prior to 2014, the largest recorded of Ebola is direct contact with someone who has clinic- outbreak of Ebola (SEBOV in this case) took place in ally apparent illness [28]. This risk increases if there is Uganda from October 2000 to January 2001, with 425 contact with bodily fluids or the infected person is in the cases and 225 deaths [17, 18]. late stages of the disease. Direct contact was determined After the discovery of the virus, a large variety of to be necessary, but not sufficient, for transmission [28]. organisms were screened as possible Ebola reservoirs. To date, the only comprehensive analysis of viral excre- Bats both efficiently replicate the virus and survive infec- tion and environmental contamination from Ebola found tion, which made them standout as candidate reservoirs viral particles are present in blood, breast milk, saliva, [4]. Despite this initial evidence, the first direct evidence semen, feces, and tears [29]. A review of relevant lite- that bats are reservoir hosts of ebolavirus was reported rature by Thorsen et al. [30] found that the longest re- in a field study in 2005, almost 30 years after the discov- corded persistence of EBOV in semen is 284 days. While ery of the virus [19]. Immunoglobulin G (IgG) specific viral RNA was isolated from this sample, it is not known for ebolavirus was found in serum from bats of three if the viral particles were still infectious. Viable Ebola different species of fruit bat (Hypsignathus monstrosus, virus has been found in semen 82 days post-infection Epomps franqueti, and Myonycteris torquata) and phylo- and may be present much longer than this [30].