849927 VRT0010.1177/1178122X19849927Virology: Research and TreatmentLanguon and Quaye
review-article2019
Filovirus Disease Outbreaks: A Chronological Overview Virology: Research and TreatmentVolume 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 hDttOpsI:: /1/d0o.i1.o1rg7/71/01.1177871/12127X819228X4199982479927
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 
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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. A suspected case of EBOD or MARD is few outbreaks occurring outside Africa—but mostly traced 
defined as any person, alive or dead, suffering or having suf- back to Africa. Table 1 shows the chronological occurrence of 
fered from high fever and having had contact with a suspected, MARD outbreaks, along with the number of infected cases 
probable or confirmed ebolavirus or marburgvirus case; a dead and mortality. The first reported outbreak of MARD was in 
or sick animal (for ebolavirus) or a mine (for marburgvirus) Germany and Yugoslavia simultaneously, when laboratory 
with at least one of the following symptoms: bloody diarrhea, workers experimenting on grivets (Chlorocebus aethiops) 
bleeding from gums, bleeding into skin, or bleeding into eyes imported from Uganda were infected with MARV after han-
and urine. A probable case is any deceased suspected case dling tissues/organs of these wild animals.37 In addition to the 
(where it has not been possible to collect specimens for labora- laboratory personnel who got infected through direct contact 
tory confirmation) having an epidemiological link with a con- with the monkeys, there were more cases reported due to noso-
firmed case. A confirmed case refers to any suspected or comial transmission. A woman whose husband was infected 3 
probable case with a positive laboratory result.35 Laboratory months earlier is reported to have contracted the disease 
Languon and Quaye 3
through her infected husband’s semen.37 After the outbreak, a while 106 were regarded as suspected cases. After a period of 4 
primary case was serologically diagnosed retrospectively.38 The years, in 2004, an outbreak was reported in Angola which 
second outbreak of MARD occurred in South Africa in 1975, turned out to be the largest MARD outbreak on record as of 
and was the first on the African continent. Data gathered dur- today. However, due to a lag in outbreak identification, and 
ing the outbreak suggested that the index patient visited Sinoia coupled with complications in conducting surveillance and 
caves in Rhodesia (now Zimbabwe) with a companion as tour- contact tracing, there was poor epidemiological linkage of the 
ists, and reported to have slept in rooms containing insectivo- cases. As a result, efforts to identify the origin of the infection 
rous bats.39 The circumstances regarding their itinerary suggest or mount an ecological study were unsuccessful.45
that there was likely a direct contact with bats or bat discharge, There was an outbreak of MARD in Uganda in 2007, in 
which led to the infection. which only four cases were confirmed during the outbreak.46,47 
Five years after the first reported outbreak in Africa, the All the patients were working in the Kitaka mine which is 
third incident of MARD occurred in Kenya in 1980, which located in the Ibanda District. The index case shared a tent 
was retrospectively traced. The index case was found to have camp with two other patients—coworkers who were identified 
had frequent visits to small forested areas; carrying along food through contact tracing—in the Kashoya-Kitomi Central 
for mammals and birds. Two weeks before the onset of the ill- Forest Reserve which surrounds the mine. The fourth patient 
ness, the subject was reported to have entered the Kitum cave got infected after entering the mine without personal protec-
at Mount Elgon National Park, where a large population of tive equipment (PPE) during the time of the outbreak. 
bats exists.40 Exposure to wild animals and bats during forest Thousands of bats roosted in tunnels of the mine where the 
visits could have led to a possible contact with a reservoir of the miners are reported to work with only gloves; no masks, respi-
virus. A medical doctor developed symptoms after attempting rators, nor googles.46,47 Exposure to bats or bat discharge in the 
to resuscitate the patient but later recovered. mine have been speculated to be the probable primary source of 
Another MARD outbreak occurred in Kenya in 1987, 7 infection. Ecological sampling of bats from the mine resulted 
years after the first outbreak in that country; when the index in the isolation of MARV from Rousettus aegyptiacus, and the 
case—a 15-year-old Danish boy—visited the Kitum cave just first time a definitive filovirus reservoir was identified.46
like the index case of the 1980 outbreak.41 Although it was In 2008, a case of MARD involving a US tourist was 
speculated that the boy most likely got infected after direct reported. The traveler went for a holiday safari in Uganda, 
contact with bats or exposure to bat discharge, analysis of sam- where her activities included camping, visiting local villages, 
ples collected from several animal species in and around the and viewing wildlife.48 The infection could have been acquired 
cave did not detect filovirus.42 An incident of MARV infection during her camping trips or viewing of wildlife; considering 
occurred in the Union of Soviet Socialist Republics (USSR) in that she could have had contact with wild animals. In the same 
1990, when a research scientist got into contact with archived year, a Dutch tourist was also infected with MARV after she 
serum sample of an animal infected with MARV, and was the went on a vacation to Uganda, where she entered two caves—
only recorded case in this laboratory contamination.43 Python Cave and another cave without bats—and came within 
About a decade after the last MARD outbreak in Africa 5 m to gorillas in the wild.49 From her activities, it was hypoth-
(Kenya), an outbreak occurred in 1998 in the Democratic esized that she most likely got exposed to bats species in the 
Republic of Congo (DRC), among workers of a gold mine Python Cave that have been identified to be reservoirs of 
reported to have come into contact with fauna littered around MARV.49–51 Another MARD outbreak occurred in Uganda 4 
the mine. The mine was found to contain animals such as years later in 201252 and although the index case was not iden-
rodents, bats, frogs, shrews, cockroaches and moth flies; how- tified, contact tracing found the earliest confirmed case to have 
ever, none of the infected persons was found to have direct originated in Ibanda District,53 the same district housing the 
exposure or insect bites in the mine. Nonetheless, miners usu- Kitaka mine where the 2007 MARD outbreak occurred and a 
ally worked in a filthy environment—stained with human and large roost of R. aegyptiacus were found to be infected with 
bat excreta—and were found to usually work with simple hand MARV.47 Ecological studies also suggest that exposure to R. 
tools and no protective gear.44 Some of the mineworkers were aegyptiacus bats could have been the cause of the 2012 out-
reported to have had contact with infected persons (27%), as break.54 The timing of the outbreak had interestingly coincided 
well as family members of miners who were non-miners but with the second of the bi-annual virus circulation in R. aegyp-
got infected. Evidence of multiple introductions of infection tiacus bat populations. In 2014, a fatal case of MARD involving 
into the population was confirmed by the detection of about a health care worker occurred in Uganda. Epidemiological 
nine genetically different lineages of the virus in circulation.44 studies did not identify secondary infections following the out-
The outbreak finally ceased in late 2000, after the gold mine break, and ecologic investigations to identify possible contact 
got flooded, thus suggesting that exposure of miners to the (direct or indirect) of the case with R. aegyptiacus bats yielded 
fauna of the mine might have accounted for the outbreak. Out negative results.55 The most recent incidence of MARD was 
of 154 reported cases, 48 were confirmed by laboratory testing, reported in 2017 in the Kween District, Uganda, and is 
4 Virology: Research and Treatment 
geographically linked to the 1980 outbreak. Epidemiological residents possess antibodies to the virus.63 However, the 
investigations revealed that the outbreak occurred within a sin- authors cautioned that another method should be used to 
gle family; three out of a total of four infected persons died of measure antibody titers before a conclusion could be made—
the disease.56 Due to rapid case detection and the presence of due to the possibility of false-positive reactions at the serum 
trained national and district response teams, the outbreak was dilutions used in their measurement. Evidence of the occur-
contained within a month. The index case was found to be a rence of ebolavirus infections in 1972 was through the detec-
herdsman who hunts game in a sub-county where there are tion of ebolavirus antibodies in a physician, who is reported to 
caves harboring large populations of Egyptian fruit bats.57 have performed an autopsy on a student who died of a hem-
orrhagic illness in 1972. With little confidence in the method 
EBOD Outbreaks used to measure antibody titers at that time, the 1972 out-
Numerous EBOD outbreaks have occurred since ebolaviruses break of EBOD is questionable. Three years after the first 
emerged in 1976 with two near-simultaneous outbreaks caused EBOD outbreak, in 1979, cases of EBOD occurred among 
by two diverse species. A total of 37 EBOD outbreaks have five families in Nzara, the same site as the 1976 Sudan epi-
occurred since 1976, and have been chronologically outlined in demic, with some cases reported in Yambio, a town which is 
Table 2. The first two recorded outbreaks of EBOD were in about 25 km away from Nzara.64 The index case is reported 
Sudan and DRC,22 and in the same year, a case of laboratory to have been employed in the Nzara cotton factory; the sus-
contamination was also reported in England.58 The Sudan out- pected source of the 1976 outbreak. However, there was no 
break occurred in four towns—Nzara, Maridi, Tembura, and evidence to link the factory to the outbreak. Apart from the 
Juba—with Nzara reported as the source of the outbreak. index case, all other infections were traced to human sources. 
Serological data indicated that 37% of workers in the Nzara Although the ecology of the virus was unidentified, antibod-
cotton factory were infected, suggesting that the factory, where ies were found in the sera of 18% of persons unassociated 
bats were hanging from beams, may have been the primary with the outbreak; thus suggesting that the region is an 
source of infection.59,60 In Maridi, the disease was magnified by endemic zone.64
nosocomial transmission in a large hospital. For the outbreak in After a decade of zero cases of EBOD in both animals and 
the DRC, it was focused in the Bumba Zone of the Equateur humans, in 1989 to 1990, there was an outbreak of EBOD in 
Region within a 75 km radius of Yambuku, with few cases in primates housed in quarantine facilities in Virginia and 
Bumba, Abumombazi, and Kinshasa; where there were sec- Pennsylvania, which was due to the importation of cynomolgus 
ondary transmissions due to nosocomial infection. The index monkeys (Macaca fascicularis) from the Philippines. There were 
case is reported to have gone for a 2-week driving excursion seven shipments of cynomolgus monkeys from three suppliers 
from Bumba Zone to northern Zaire, and on his expedition, he in the Philippines to the United States between 1989 and 
bought antelope and smoked monkey meat—the plausible 1990, all of which were infected with RESTV.65,66 This was the 
source of infection. He later visited the outpatient clinic at first time ebolavirus infection had been reported outside Africa. 
Yambuku Mission Hospital (YMH) where he received an Four animal handlers were found to have serologic evidence of 
injection of chloroquine to treat probable malaria—with remis- infection, with the isolation of RESTV from one of the animal 
sion of symptoms. He developed symptoms similar to EBOD handlers who cut his finger during necropsy of an infected 
five days later, and in a period of one week several individuals monkey.67,68 Following the recovery of several isolates of 
who received injections via unsterilized needles at YMH also RESTV, a serological survey was initiated by the Philippine 
developed EBOD. Subsequent cases of the outbreak either vis- Department of Health to assess the risk of transmission of 
ited YMH, or had close contact with infected individuals.22,60 RESTV from animals to humans. Though asymptomatic, 
Although the EBOD outbreak in Sudan and the DRC over- three out of five workers at one of the export facilities were 
lapped, virus isolation attempts revealed that the agents respon- found to have antibody titers comparable to primates with con-
sible for the outbreaks were related but not identical61: the virus firmed RESTV infection.69 An analogous study aimed at iden-
strains were later found to be antigenically distinct.62 The tifying RESTV transmission at export facilities located in the 
EBOD outbreak in England was as a result of accidental inoc- Philippines was conducted. At one of the export facilities, 
ulation of an investigator at the Microbiological Research RESTV was found to be responsible for high mortality among 
Establishment by a contaminated needle; during the transfer of cynomolgus monkeys with the death of about 53% of 161 
homogenized liver sample from a rodent infected with SUDV, monkeys over a period of 2.5 months.70 In 1992, RESTV was 
which was isolated from patients of the Sudan outbreak.58 introduced into quarantine facilities in Sienna by cynomolgus 
In 1977, a single case of EBOD was recorded in Tandala, monkeys imported from the same export facility in the 
northwestern Zaire, when a 9-year-old girl succumbed to an Philippines that was involved in the outbreak outbreaks in the 
ebolavirus infection and later died. Retrospective investiga- United States in 1990. However, all the workers who had con-
tions after the outbreak revealed that two clinical infections tact with the infected monkeys showed no clinical or serologi-
of EBOV had occurred in 1972, and approximately 7% of the cal signs of infection.71
Languon and Quaye 5
Table 2. Outbreaks of Ebola disease.
YEAR (S) COUNTRY VIRUS REPORTED NUMBER REPORTED NUMBER OF 
SUBTYPE OF hUMAN CASES DEAThS AMONG CASES
1976 (June-November) Sudan SUDV 284 151
1976 (September-October) DRC EBOV 318 280
1976 (November) England SUDV 1 0
1977 (June) DRC EBOV 1 1
1979 (July-October) Sudan SUDV 34 22
1989-1990 Philippines and United States RESTV 7 (asymptomatic) 0
1992 Italy RESTV 0 0
1994 Gabon EBOV 52 31
1994 Côte d' Ivoire TAFV 1 0
1995 DRC EBOV 315 250
1996 (January—April) Gabon EBOV 37 21
1996-1997 (July—January) Gabon EBOV 60 45
1996 South Africa EBOV 2 1
1996 United States RESTV 0 0
1996 Philippines RESTV 0 0
1996 Russia EBOV 1 1
2000-2001 Uganda SUDV 425 224
2001-2002 (October-March) Gabon and Republic of Congo EBOV 124 97
2002-2003 (December-April) Republic of the Congo EBOV 143 128
2003 (November-December) Republic of the Congo EBOV 35 29
2004 Sudan SUDV 17 7
2004 Russia EBOV 1 1
2005 Republic of the Congo EBOV 12 10
2007 DRC EBOV 264 186
2007-2008 (December-January) Uganda BDBV 131 42
2008 Philippines RESTV 6 (asymptomatic) 0
2008-2009 (December-February) DRC EBOV 32 15
2011 (May) Uganda SUDV 1 1
2012 (July-August) Uganda SUDV 11 4
2012 (August-October) DRC BDBV 36 13
2012-2013 (November) Uganda SUDV 6 3
2013-2016 (December-March) Multiple countries EBOV 28,616 11,310
2014 (August-November) DRC EBOV 69 49
2015 Philippines RESTV 0 0
2017 (May-July) DRC EBOV 8 4
2018 (May-July) DRC EBOV 54 33
2018-2019 (August-May) DRC EBOV 1,604a 1,074a
EBOV: Ebola virus; RESTV: Reston virus; SUDV: Sudan virus; BDBV: Bundibugyo virus; TAVF: Taï Forest virus.
aSituation as at May 8, 2019.
Table adapted from CDC: https://www.cdc.gov/vhf/ebola/outbreaks/history/chronology.html#thirtyfour.
6 Virology: Research and Treatment 
In about a decade and a half since the last human outbreak RESTV into a quarantine facility in Texas by monkeys 
of EBOD, in 1994, an outbreak occurred in northwestern imported from the Philippines. The infected monkeys were 
Gabon with two groups of patients—the first was from three part of a batch of monkeys from the same Philippine facility 
gold-panning campsites (Me’kouka, Andock, and Minke’be) that shipped animals infected with ebolavirus to the United 
situated at the edge of a rainforest, and the second group of States in 1989 and 1990.76 Consequently, a survey conducted at 
patients (termed secondary cases) who did not originate from monkey export facilities in the Philippines identified the circu-
the gold-panning campsites. A hospitalized patient from the lation of RESTV in the monkeys at one of the facilities. 
first group, against medical advice, left Makokou General However, none of the employees of the facilities showed signs 
Hospital to seek care from a traditional healer, “nganga,’’ which and symptoms similar to EBOD, thus suggesting that RESTV 
probably led to the infection of the first person in the second infection is rare in humans.77 The outbreak of EBOD in Russia 
group of patients—which was composed of individuals in was due to laboratory contamination and led to the death of 
direct contact with sick relatives. Although transmission was one individual—the only infected case.78
through contact with infected persons, the index case in the In the year 2000, 4 years since the last outbreak of EBOD, 
first group of patients was not identified.72 However, disrup- an EBOD epidemic occurred in Uganda, and was one of the 
tion of the forest canopy by gold mining activities is hypothe- largest outbreaks to have occurred. Although the index case 
sized to have caused exposure of humans to some animal responsible for the outbreak was not known, most secondary 
species, and led to the outbreak. In the same year (1994), an infection cases were linked to the attendance of burial ceremo-
outbreak of EBOD occurred in Côte d' Ivoire, where a scientist nies of infected individuals.79 About a year later (2001), there 
fell ill after carrying out an autopsy on a wild chimpanzee in was an outbreak of EVD over the border of Gabon and the 
the Taï Forest, which later led to the isolation of Taï Forest Republic of the Congo, with the index cases recounted to have 
virus.73 Acquisition of an infection after contact with the chim- had contacts with gorillas, chimpanzees, monkeys, forest duik-
panzee suggests the wild animal was the source of infection. ers and porcupines.80 Epidemiological data revealed six sepa-
About a year later (1995), an outbreak of EBOD occurred in rate introductions—four in Gabon and two in Congo—of the 
Kikwit, DRC. The index case was traced to a farmer cum char- virus into human populations, with each introduction con-
coal worker who was hypothesized to have been infected by a nected to a hunting event.80 This was the first EBOD reported 
natural reservoir on his farm, which is about 15 km from in the Republic of the Congo. Within a year after the outbreak 
Kikwit. Three immediate family members who were infected, at the Gabon-Congo border (in 2002), another outbreak of 
and 10 secondary cases among extended family members, all EVD was reported in the Republic of the Congo. 
died of the disease.74 A total of 315 EVD cases were recorded, Epidemiological evidence during the outbreak found that three 
10 of which were excluded due to negative laboratory results. primary cases involving hunters were responsible for the intro-
In 1996, there were a total of six EBOD outbreaks, an out- duction of the virus into the human population, and in all the 
break each in Russia, Philippines, United States and South three primary cases, the onset of disease followed contact with 
Africa, and two outbreaks in Gabon. The first outbreak in a non-human primate and other mammals (e.g. antelope), 
Gabon occurred in Mayibout, which is about 40 km south of which were either hunted for or found dead.81 During the 2001 
the villages where the 1994 epidemic occurred. The outbreak EVD outbreak, a large number of non-human primates were 
started when 18 individuals showed signs and symptoms simi- found dead in the same district where the outbreak occurred.80 
lar to EBOD after they pared and sliced a chimpanzee cadaver, A similar die off of wild animals was observed during the 2002 
and subsequently, infections were recorded in family members EVD outbreak, and thus suggests the occurrence of EVD in 
of persons involved in the butchery of the animal.72 However, wildlife populations prior to the outbreaks in humans.
there were no recorded infections in individuals who partook in The second EVD outbreak in the Republic of Congo 
the eating of the cooked meat. The second epidemic began occurred at the latter part of 2003 in two villages of the Mbomo 
with the death of a hunter in a logging camp close to Booue’, District, but the primary source of introduction of the virus was 
which is about 200 km from Me’kouka and 120 km from not identified.82 Within a year (in 2004), an outbreak of EBOD 
Makokou to the southwest. Even though no clear index case was reported in South Sudan and the index case was found to 
was identified, retrospective investigations suggested that the frequently hunt baboons (Papio Anubis) in a forest in the DRC, 
infection might have originated from hunters in the logging and had been in contact with fresh monkey meat some few days 
camp.72 The outbreak that occurred in South Africa was the before onset of symptoms.83 Thus, it is highly plausible that the 
first case of EBOD diagnosed in the southern African country. index case got infected with SUDV after exposure to baboon 
The source of infection was traced to a nurse who had been meat. In the same year, a fatal case of EBOD due to laboratory 
exposed to the blood of a sick medical professional who traveled contamination was reported in Russia.84 In 2005, there was an 
from Gabon to Johannesburg, after the medical professional outbreak of EVD in Etoumbi, Republic of the Congo, when 
had treated EBOD patients.75 The outbreak of RESTV infec- two hunters (index patients) got infected while poaching, and 
tion in the United States was as a result of the introduction of they both later died at the Etoumbi Medical Center.85
Languon and Quaye 7
In 2007, EBOD outbreaks occurred in the DRC and quickly spread to bordering countries, Liberia and Sierra 
Uganda. Field investigations during the DRC outbreak Leone. Although this was not the first time an EVD outbreak 
revealed that the index case had frequently bought bats at a expanded to densely populated cities (a similar situation 
nearby market every year. As a result, he had direct contact with occurred during the EVD outbreak in Uganda in 2000), trans-
the blood of bats he acquires from the market, which could be mission was effective and swift, which contributed to wide-
the source of the infection.86 Immediate family members of the spread infection. Statistical highlights on the countries that 
index case acquired the disease, and eventually led to an out- were affected during the outbreak in West Africa are provided 
break. The outbreak was later linked to a massive fruit bats in Table 3. Retrospective epidemiological studies identified bat 
migration to the area.87 In the outbreak which occurred in species suspected to be potential carriers of EBOV, close to the 
Bundibugyo, Uganda, the index case of the epidemic was not home of the index case.93 However, RT-PCR and serological 
clearly identified due to a delayed investigation,88 however, a assays showed no evidence of EBOV in specimens obtained 
new species of Ebolavirus was reported and led to the isolation from bats in the area. While the West African epidemic was 
of BDBV.89 A year later (in 2008), swine was discovered as a on-going, a concomitant EVD outbreak was reported in the 
source of RESTV for the first time, with the isolated virus DRC in 2014, in which the index case was reported to have 
strain closely related to known species of Ebolavirus.90 become ill after butchering a dead monkey of unknown arbo-
Although antibodies were detected in some of the workers of real species,95 and suggesting exposure to the virus during the 
the pig farm and slaughterhouse, none of them became sick, butchering. In 2015, there was an outbreak of EBOD in a non-
and once again suggested the mild pathogenicity of RESTV in human facility in the Philippines involving cynomolgus mon-
humans. At the latter part of 2008 and early 2009, there was an keys with no reported human cases.96 RESTV was found to be 
outbreak of EVD at Mweka and Luebo health zones in the the cause of the outbreak, and the virus is reported to be geneti-
Kasai Occidental province of the DRC; however, the index cally identical to one of four RESTVs responsible for the 2008 
case of the outbreak was not identified.91 outbreak among swine in the Philippines. Three years after the 
A fatal case of EBOD involving a 12-year-old girl occurred last EBOD outbreak involving humans (2014), an outbreak of 
in Uganda in 2011, and an epidemiologic link to any suspected EVD was reported in the DRC97 in 2017, but due to the 
EBOD cases before the onset of the patient’s illness was remoteness of the area and limited services, the response team 
unsuccessful; no environmental source of infection was con- could not identify the index case.
clusively acknowledged either.92 SUDV antibodies were, how- In 2018, two EVD outbreaks occurred in the DRC—the 
ever, detected in the patient’s blood and EBOV antibodies 9th and 10th outbreaks in that country alone. The first out-
were also detected in one of the patient’s family members, but break of the 2018 outbreaks started on May 8, in the Bikoro 
the antibodies were found to be from an epidemiologically health zone of Equateur Province, with transmission extending 
unrelated virus infection. These findings thus suggest the pos- to Iboko and Wangata health zones within weeks. After more 
sibility of zoonotic exposures in the index patient’s vicinity. than 2 months of intensive control measures, contact tracing, 
Three EBOD outbreaks occurred in Uganda and the DRC and vaccination using trial vaccines, the outbreak was declared 
between the period of June 2012 and January 2013—two in to be over on July 24 with a total of 54 cases, comprising 38 
Uganda (caused by SUDV) and one in the DRC (caused by confirmed and 16 probable cases, with 33 deaths.98 The index 
BDBV). The first outbreak occurred in the Kibaale District of case of the outbreak has not yet been identified. The second 
Uganda, the second occurred in DRC’s province Orientale, 2018 outbreak (the tenth EBOD outbreak in the DRC) begun 
and the third occurred in Luwero, Jinja, and Nakasongola less than a week after the ninth outbreak was declared to be 
Districts of Uganda. Index cases were not identified for these over. Official reportage of EVD cases by the DRC Health 
outbreaks, although investigations were reported to have been Ministry was on July 28, and on August 1, there was a declara-
carried out.52 tion of a new EVD outbreak (the second of the 2018 out-
From December 2013 to March 2016, a massive outbreak of breaks). The outbreak started in the Mangina health zone in 
EVD occurred in several West African countries, Europe and the Province of North Kivu, northwestern part of the DRC, 
the United States, and the impact, particularly in West Africa, about 780 miles away from the first 2018 (ninth) outbreak.99 
was highly significant. The index case, a 2-year-old boy from a The outbreak later spread to nearby towns and to a neighbor-
small village in Guinea, is alleged to have been infected by ing province, Ituri Province, with cases reported in nine health 
insectivorous bats.93 Following more cases of fatal diarrhea, zones in these two provinces. Currently, there is no evidence 
there was an alert of an unidentified illness, pending confirma- that links the 9th to the 10th EVD outbreak. The National 
tion by the Pasteur Institute in France. By the time the confir- Institute of Biomedical Research (NIRB) reported that the 
mation was obtained, several deaths have already been recorded, strains of EBOV in the two 2018 outbreaks are entirely differ-
and the disease had already spread to Conakry, the capital of ent, even though they are of the same species. As such, vaccines 
Guinea.94 Due to poor surveillance systems and deprived pub- which were instrumental in stopping the spread of disease in 
lic health infrastructure, the outbreak got out of control and the 9th outbreak are currently being used in the 10th outbreak 
8 Virology: Research and Treatment 
Table 3. Summary of cases in the 2013-2016 Ebola virus epidemic in West Africa.
COUNTRY TOTAL NUMBER OF CASES  LABORATORY TOTAL 
(SUSPECTED, PROBABLE, CONFIRMED) CONFIRMED CASES DEAThS
Countries with widespread transmission
 Guinea 3,814 3,358 2,544
 Liberia 10,678 3,163 4,810
 Sierra Leone 14,124 8,706 3,956
Affected countries
 Italy 1 1 0
 Mali 8 7 6
 Nigeria 20 19 8
 Senegal 1 1 0
 Spain 1 1 0
 United Kingdom 1 1 0
 United States 4 4 1
Total 28,652 15,261 11,325
Table adapted from CDC: https://www.cdc.gov/vhf/ebola/history/2014-2016-outbreak/index.html.
in the DRC. At the time of writing this review, a total of 1604 numerous pathogens which cause a plethora of diseases in 
cases which consist of 1538 confirmed and 66 probable cases humans. Activities such as agriculture, mining, forest clearing 
have been recorded, with the occurrence of 1008 deaths among and the hunting of bush-meat have increased the likelihood of 
the confirmed cases.98 The current outbreak is the largest EVD pathogen spillover from wildlife into human populations. 
outbreak in the DRC and doubles as the second largest EVD Slaughtered non-human primates, which are possibly infected 
outbreak in history, after the 2013-2016 EVD epidemic in by fruit bats and are eaten as bush-meat, have been the incep-
West Africa. The unsafe burial of a 65-year-old victim who tion of human infections in most EBOD outbreaks, followed 
had symptoms similar to EBOD is reported to have triggered by subsequent human-to-human transmission in communities 
the 10th EBOD outbreak in the DRC.100 and health facilities.101 Wildlife trade, much of which is con-
ducted informally and/or illegally, can also upsurge the risk of 
Ecological Trends of Filovirus Disease Outbreaks outbreaks, as contact between hunters, middlemen, consumers 
Most filovirus disease outbreaks that have occurred can be epi- on one hand, and wildlife on the other hand increases the pos-
demiologically categorized into two main groups. The first sibility of disease transmission from infected animals.102
group occur in secluded forest areas (relatively few cases) and Filovirus disease is a classic zoonotic disease that is fortui-
are presumptively linked to consumption or interaction with tously transmitted via direct contact with infected live or dead 
bush-meat/wildlife. The second group consists of outbreaks animals. However, there are numerous questions regarding the 
that occur in populated areas with transmission in inhabited ecology of filoviruses and the role wildlife plays in filovirus dis-
communities including nosocomial transmissions, and results ease epidemiology. Apart from being highly pathogenic to 
in a large number of cases. The forest outbreaks are mainly in humans, EBOV has caused outbreaks among chimpanzees and 
Gabon, Uganda, and the DRC, probably due to the rainforest gorillas, resulting in the death of thousands of these animals in 
vegetation which supports animal reservoirs of filoviruses. Gabon and Republic of Congo.103–108 TAFV has been associ-
After the first three EBOD outbreaks between 1976 and ated with the loss of 11 members of a group of 43 chimpanzees 
1979, there was a 15-year hiatus after which subsequent EBOD in the Taï forest of Ivory Coast.109 Outbreaks in chimpanzees 
outbreaks occurred between 2 and 3 years apart in the 1990s and gorillas could thus pose a huge threat to the conservation 
and then yearly intervals in the 2000s. A similar trend can be of great apes in Africa.
observed for MARD outbreaks, and this increase in filovirus Although bats are implicated as principal drivers of filovi-
disease outbreaks in Africa has been attributed to heightened rus transmission,110 other animal species including pigs,90 
interaction between humans and wildlife due to widespread dogs,111 duikers, and non-human primates might be 
deforestation, mining and hunting.4 Wildlife are reservoirs of involved.108 To date, infectious MARVs have been isolated 
Languon and Quaye 9
from only one bat species—R. aegyptiacus,46 with the detec- seropositivity increased with age, it had no association with 
tion of EBOV genomic RNA in Epomops franqueti, exposure to risk factors such as contact with bats or monkeys.
Hypsignathus monstrosus and Myonycteris torquata.54,112 The A seroprevalence study conducted in the Central African 
genomic RNA of MARV has been detected in Miniopterus Republic among pygmy and non-pygmy populations, in an 
inflatus and Rhinolophus eloquens,51 and that of Lloviu virus in area where there has been no filovirus disease outbreak, detected 
Miniopterus schreibersii.113 Unsurprisingly, the distribution of the presence of antibodies against EBOV and MARV. Pygmies 
bat species in which ebolavirus and MARV RNAs have been were found to have a significantly higher level of seropreva-
discovered are within a number of countries where outbreaks lence, with one of the pygmy sample being cross-reactive to 
have occurred.114 Filovirus antibodies have been detected in SUDV.125 Data from convalescent patients suggest the possi-
several other bat species,27,115 which have distribution in areas bility of high levels of cross-reactive ebolavirus antibody 
where there have been no outbreaks. In an effort to determine responses,126 and thus underscores the need to use highly spe-
the role of bats in ebolavirus ecology, a longitudinal study was cific and sensitive serological assays in serosurveys. An identical 
conducted in countries that have experienced filovirus out- survey, conducted in a population with no history of EVD out-
breaks, or at high risk of outbreaks.116 Out of 4,022 samples, breaks in the DRC revealed that forest visits or hunting of 
a seropositivity of 0.05%—0.92% for EBOV and 0%—0.75% rodents and duikers increase the likelihood of EBOV seroposi-
for SUDV was recorded. Ebolavirus antibodies were detected tivity.127 An analogous serosurvey was conducted in healthcare 
in 1 insectivorous bat genus and 6 frugivorous bat species. facilities in Southwestern Uganda,128 and even though viral 
Some researchers have, however, expressed concern about the nucleic acid was not detected, data gathered suggests that men 
labeling of bats as the only reservoir of ebolaviruses,117 and who hunt, especially duikers, have had exposure to filoviruses.
have thus provided possible hypotheses that could be tested A hospital-based surveillance program for viral hemor-
to examine the role of different animal species in the mainte- rhagic fevers is described in a study from Ghana.129 A total of 
nance of ebolaviruses. 18 hospitals in the Northern and Central Regions of the coun-
Climate change has been hypothesized to affect wildlife try participated in the program, and although no cases of viral 
habitats and densities, thus increasing the frequency of disease hemorrhagic fevers were found, the study demonstrated the 
outbreaks through increased risk of exposure of humans to res- feasibility of setting up such a hospital-based surveillance sys-
ervoir host.118 In addition, encroachment of forest areas by tem over a wide area.
humans for the purposes of agriculture and settlement has sig- A growing global population, which has led to increased 
nificantly contributed to the emergence of zoonotic diseases. demand for resources, has forced people to invade previously unat-
Using remote sensing techniques, it has been found that a posi- tended land for agricultural and mining activities, and thus bring-
tive correlation exists between deforestation (both in time and ing humans into close contact with unknown pathogens, as well as 
space) and EVD outbreaks in Central and West Africa,119 sug- reservoir hosts and/or amplifying hosts of known pathogens.130,131 
gesting that a reduction of deforestation could decrease the Due to continuously high numbers of international and intercon-
chance of future EVD outbreaks. Through efforts to map the tinental travels, the world has become a global village, and has 
pandemic potential of viral hemorrhagic fever viruses (includ- therefore significantly increased the risk of exposure of human 
ing filoviruses) using a multistage analysis, regions with previ- populations to infected people and/or animals.130,132 An example 
ous outbreaks and those without outbreaks have both been is the 2013-2016 EVD epidemic in West Africa. The disease 
found to be at risk.120 emerged from southern Guinea forests, spread into surrounding 
districts and to Conakry—the capital city,133 and later imported to 
Filovirus Sero-Surveys and Surveillance Activities Liberia by travelers to Guinea and Sierra Leone.134 The West 
Our presentation of filovirus disease outbreaks implicates African outbreak strongly suggests that international borders are 
wildlife in the transmission of ebolaviruses. As such, surveil- not barriers to filovirus disease outbreaks.
lance studies were implemented in the DRC following previ- The volatile nature of filovirus diseases, coupled with the 
ous sporadic reports of possible EVD cases and the 1995 EVD high case fatality make ebolavirus and marburgvirus infections 
outbreak in Kikwit.121,122 A large serological survey conducted major public health issues for Africa. However, research 
in rural populations of Gabon detected the presence of humoral advances in the biology and pathogenesis of filoviruses are only 
and cellular immunity against EBOV, with high seroprevalence made either during or after the occurrence of an outbreak. For 
among participants in forested areas compared to those in example, unlicensed EBOV vaccines, which were authorized 
grassland, savannah or Lakeland ecosystems.123 However, there for emergency use, were employed to minimize the impact of 
were no significant variations in seroprevalence between group the 2013-2016 EVD epidemic in Guinea and its neighboring 
of individuals that hunted or had contact with animals and countries and the recent 2018 EVD outbreaks in the DRC. In 
those that did not. A similar study conducted in 2002 in north- view of the sudden nature by which filovirus disease outbreaks 
eastern DRC among Efé pygmies found that 18.7% of the par- occur, surveillance is critical in both areas where there have 
ticipants (a total of 300) had anti-EBOV IgG.124 Although been outbreaks, as well as areas where the filovirus outbreaks 
10 Virology: Research and Treatment 
are likely to emerge. Such a proactive measure would aid in subsequent outbreaks. It is worth mentioning that unlike pre-
mitigating outbreaks and control disease transmission. vious EVD outbreaks, the ninth outbreak in the DRC was 
characterized by a swift response—tireless contact tracing, 
The Search for the Reservoir of Ebolaviruses education of affected communities and ring vaccination using 
The occurrence of EVD outbreaks have been associated with trial vaccines—which led to containment of the outbreak. A 
hunting and handling of bush-meat while that of MVD out- similar response can be described for the current (tenth) EVD 
breaks have often been linked to entry into caves or working in outbreak in the DRC, although a long-running conflict in the 
decommissioned mines in which bats roosts44,47,108; as shown in affected provinces have posed challenges to the fight against 
the chronological presentation of the filovirus disease out- disease transmission.145
breaks in this review. However, with the exception of Egyptian 
rousettes (R. aegyptiacus), which have been implicated in the Author Contributions
transmission/occurrence of MVD, there is currently no sub- Concept and design of the review was by SL and OQ; 
stantial scientific evidence to implicate wildlife in the occur- Drafting of Manuscript was done by SL; Critical Review 
rence of ebolavirus disease outbreaks. In an effort to determine of Manuscript was done by OQ; Both authors approved the 
the natural reservoir of EBOV, several surveillance studies have manuscript for publication.
been conducted on diverse taxa including bats, rodents, arthro-
pods and plants,135–139 and a large number of animal species ORCID iD
have been found to be permissible to EBOV infection. The Osbourne Quaye  https://orcid.org/0000-0002-0621-876X
permissibility and differential sensitivity to EVD suggests that 
there could be complex transmission cycles of ebolaviruses in 
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