VRT0010.1177/1178122X19849927Virology: Research and TreatmentLanguon and Quaye 849927review-article2019 Virology: Research and Treatment Filovirus Disease Outbreaks: A Chronological Overview Volume 10: 1–12 © The Author(s) 2019 Sylvester Languon1 and Osbourne Quaye1,2 Article reuse guidelines: sagepub.com/journals-permissions 1West African Centre for Cell Biology of Infectious Pathogens (WACCBIP), Department of DOI:https://doi.org/10.1177/1178122X19849927 10.1177/1178122X19849927 Biochemistry, Cell and Molecular Biology, University of Ghana, Accra, Ghana. 2Stellenbosch Institute for Advance Study (STIAS), Stellenbosch, South Africa. ABSTRACT: Filoviruses cause outbreaks which lead to high fatality in humans and non-human primates, thus tagging them as major threats to public health and species conservation. In this review, we give account of index cases responsible for filovirus disease outbreaks that have occurred over the past 52 years in a chronological fashion, by describing the circumstances that led to the outbreaks, and how each of the outbreaks broke out. Since the discovery of Marburg virus and Ebola virus in 1967 and 1976, respectively, more than 40 filovirus disease outbreaks have been reported; majority of which have occurred in Africa. The chronological presentation of this review is to provide a concise overview of filovirus disease outbreaks since the discovery of the viruses, and highlight the patterns in the occurrence of the outbreaks. This review will help researchers to better appreciate the need for surveillance, especially in areas where there have been no filovirus disease outbreaks. We conclude by summarizing some recommendations that have been proposed by health and policy decision makers over the years. KEYWords: filoviruses, ebolaviruses, Marburg virus, outbreak, index case RECEIVED: February 14, 2019. ACCEPTED: April 18, 2019. Agency (NEPAD Agency). The views expressed in this publication are those of the author(s) and not necessarily those of the funders. TYPE: Review DECLaratioN of coNFLictiNG INTEREsts: The author(s) declared no potential FUNdiNG: The author(s) disclosed receipt of the following financial support for the research, conflicts of interest with respect to the research, authorship, and/or publication of this article. authorship, and/or publication of this article: This study was supported by WACCBIP-World Bank ACE Grant (ACE02-WACCBIP: Awandare) and DELTAS Africa grant (DEL-15-007: CORRESPONDING AUTHOR: Osbourne Quaye, West African Centre for Cell Biology of Awandare). The DELTAS Africa Initiative is an independent funding scheme of the African Infectious Pathogens (WACCBIP), Department of Biochemistry, Cell and Molecular Academy of Sciences (AAS)’s Alliance for Accelerating Excellence in Science in Africa (AESA) Biology, University of Ghana, P.O. Box LG 54, Legon, Accra, Ghana. Email: oquaye@ and supported by the New Partnership for Africa’s Development Planning and Coordinating ug.edu.gh Introduction Marburgvirus, Cuevavirus, Striavirus, and Thamnovirus, with In the history of the world, infectious diseases have posed a the proposal of a sixth genus, Dianlovirus.15,16 The species burden to the survival and development of the human race. under the Cuevavirus, Striavirus and Thamnovirus genus are Infectious diseases comprise a significant fraction of all human Lloviu cuevavirus, Xīlǎng striavirus, and Huángjiāo thamnovi- diseases, with their importance derived from the nature of the rus, respectively, with Lloviu virus, Xīlǎng virus and Huángjiāo causal agent, and the extent of damage inflicted on organs and virus being the respective members. The Marburgvirus genus tissues upon entry into a host.1 Out of an approximately 60 comprise of a single species: Marburg marburgvirus, with million deaths recorded worldwide each year, 25% are esti- Marburg virus (MARV) and Ravn virus (RAVV) as members. mated to be due to infectious diseases.2 Early detection of The Ebolavirus genus, however, consists of six species: Zaire infectious diseases aids in mitigating potential outbreaks, and ebolavirus, Sudan ebolavirus, Tai Forest ebolavirus, Reston ebola- thus helps to reduce adverse impacts.3–7 Even though early rec- virus, Bundibugyo ebolavirus, and Bombali ebolavirus, with ognition plays a crucial role in infectious disease surveillance, Ebola virus (EBOV), Sudan virus (SUDV), Taï Forest virus the explicit detection of some infections is difficult due to over- (TAFV), Reston virus (RESTV), Bundibugyo virus (BDBV), lapping signs and symptoms with other diseases. Infectious and Bombali virus (BOMV) as the respective members, of diseases can spread precipitously over a wide geographical area, which EBOV is considered to be the most virulent.15,17–19 leading to outbreaks which significantly affect the health of BOMV was first discovered in insectivorous bats in Sierra individuals, huge losses to national economies, and have a neg- Leone20 and have been identified in a bat in Kenya as well.21 ative influence on the well-being of societies.8–11 Filovirus dis- The Dianlovirus genus has been proposed following the recent ease outbreaks have been of public health concern over the past discovery of Měnglà virus (MLAV); a new filovirus character- 52 years, due to their spontaneity and unpredictability. ized from a fruit bat in China, which has been found to be Filoviruses are non-segmented negative-stranded RNA phylogenetically distinct from EBOV and MARV.16 Six out of viruses belonging to the family Filoviridae in the order the 12 filoviruses are known to cause disease in humans. Mononegavirales, and are genetically, morphologically, physio- Further studies are, however, needed to determine the patho- chemically and biologically distinct from other members of the genicity of the newly discovered member of the Ebolavirus order Mononegavirales.12–14 The accumulation of data follow- genus, BOMV, and the only member of the Dianlovirus genus, ing the 2013-2016 West African Ebola virus disease (EVD) MLAV. Ebola disease (EBOD) is caused by virus species in the epidemic, and the discovery of new viruses belonging to the Ebolavirus genus (ebolaviruses), while Marburg disease family Filoviridae have led to a revision of filoviruses classifica- (MARD) is caused by virus species in the Marburgvirus genus tion and disease names,15 which is used in this review. There (marburgviruses).15 Among the ebolaviruses, EBOV, SUDV are currently five genera in the filovirus family: Ebolavirus, and BDBV cause fatality ranging from 25% to 90% in Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage). 2 Virology: Research and Treatment Table 1. Outbreaks of Marburg disease. YEAR (S) Country Virus SUBTYPE Reported NUMBER Reported NUMBER OF OF HUMAN cases deatHS AMONG cases 1967 Germany and Yugoslavia MARV 31 7 1975 South Africa MARV 3 1 1980 Kenya MARV 2 1 1987 Kenya RAVV 1 1 1990 Russia MARV 1 1 1998-2000 DRC MARV (& RAVV) 153 (1) 128 2004-2005 Angola MARV 252 227 2007 Uganda RAVV (& MARV) 3 (1) 1 2008 United States ex Uganda MARV 1 0 2008 Netherlands ex Uganda MARV 1 1 2012 Uganda MARV 15 4 2014 Uganda MARV 1 1 2017 Uganda MARV 3 3 RAVV: Ravn virus; MARV: Marburg virus. Table adapted from CDC: https://www.cdc.gov/vhf/marburg/outbreaks/chronology.html#eleven. humans.22–24 TAFV and RESTV cause disease in non-human confirmation is usually by the detection of virus RNA by primates, with a single case of TAFV infection in humans and reverse transcriptase-polymerase chain reaction (RT-PCR), or asymptomatic infections with RESTV.25,26 by detection of IgM antibodies directed against marburgvi- Although the importance of filoviruses as deadly pathogens ruses or ebolaviruses. A non-case is defined as any suspected or have been appreciated since the first filovirus (MARV) was probable case with a negative laboratory result. discovered in 1967, the origins, natural history, and ecology of In this review, we give accounts of spillover events that have these viruses have remained mysterious for decades.27 Filovirus led to filovirus disease outbreaks over the past 52 years. In addi- disease outbreaks are of zoonotic origin, and occur when there tion, we attempt to collate recommendations that have been are spillovers from wildlife reservoirs to humans, followed by suggested over the years, with the hope of painting a clear pic- human-to-human transmissions. Therefore, the key to reduc- ture about ways through which the occurrence of filovirus dis- ing filovirus disease outbreaks is to reduce spillover events and ease outbreaks could be mitigated. identify risk factors that lead to their occurrence. A number of reviews have explored the history of filoviruses, their virology, MARD Outbreaks molecular biology and their interaction with the human The first outbreak of MARD occurred in Germany and immune system28–31 and other reviews have also looked at Yugoslavia simultaneously, and led to the discovery of MARV MARD and EBOD outbreaks.4,32–34 In the classification of in 1967.36 After the discovery, there have been a total of 13 cases during EBOD and MARD outbreaks, several criteria are MARD outbreaks, most of which occurred in Africa, with a taken into account.