











































Article- 07 [Converted].eps


Abstract

Ebola virus is a filamentous, enveloped, non-segmented, single-stranded, negative-sense RNA 
virus. It belongs to the Filoviridae and was first recognized near the Ebola River valley in Zaire in 
1976. Since then most of the outbreaks have occurred to both human and nonhuman primates in 
sub-Saharan Africa. Ebola virus causes highly fatal hemorrhagic fever in human and nonhuman 
primates. In addition to hemorrhagic fever, it could be used as a bioterrorism agent. Although its 
natural reservoir is yet to be proven, current data suggest that fruit bats are the possibility. 
Infection has also been documented through the handling of infected chimpanzees, gorillas, 
monkeys, forest antelope and porcupines. Human infection is caused through close contact with the 
blood, secretion, organ or other body fluids of infected animal. Human-to-human transmission is 
also possible. Ebola virus infections are characterized by immune suppression and a systemic 
inflammatory response that causes impairment of the vascular, coagulation, and immune systems, 
leading to multiorgan failure and shock. The virus constitutes an important public health threat in 
Africa and also worldwide as no effective treatment or vaccine is available till now.
Key words: Ebola virus; Hemorrhagic fever; Fruit bats

J Enam Med Col 2015; 5(1): 44–51

 

Ebola virus (EV) is the causative agent of the ongoing 
deadly epidemic in West Africa. It is one of the world's 
most dreadful pathogens, causing catastrophic clinical 
disease1 and remains one of the most lethal 
transmissible infections with high fatality rates up to 
90% and substantial morbidity during sporadic 
outbreaks.2,3 High case-fatality rates, as well as known 
aerosol infectivity, make the virus a potential global 
health threat and possible biological warfare agent and 
is classified as category A bioterrorism threats.4-6 
EBOV together with Marburg virus comprise the family 
Filoviridae in the order Mononegavirales.7 The genus 
Ebolavirus is comprised of five genetically distinct 
species: Bundibugyo Ebolavirus (BDBV), Zaire 
Ebolavirus (ZEBOV), Sudan Ebolavirus (SUDV), Tai 
Forest Ebolavirus (TAFV) and Reston Ebolavirus 
(RESTV).8-10 Among the five species Zaire, Sudan and 
Bundibugyo Ebolaviruses are responsible for most of 
the Ebola hemorrhagic fever (EHF) outbreaks.11 Reston 

Ebolavirus has caused disease in nonhuman primates 
but not in humans in the Philippines.12 The recent 
ongoing epidemic is caused by the ZEBOV and has 
been the most severe outbreak since Ebola virus was 
first identified in 1976.13 No previous outbreak has 
been as large or persistent as the current epidemic. To 
date, the number of cases now exceeds the number from 
all previous outbreaks combined. In addition to 
mortality, indirect effects include disruption of standard 
medical care, substantial economic losses, insecurity 
and social disruption in countries that were already 
struggling to recover from decades of war.14 On August 
8, 2014 the World Health Organization (WHO) declared 
the current epidemic as a Public Health Emergency of 
International Concern (PHEIC).15 Though Ebola 
infections are generally confined to Central Africa, 
there is always a risk of spreading to the rest of the 
world. Furthermore, the virus causes highly fatal 
disease in human, could be used as a bioterrorism agent 

Introduction

 

44

Ebola Virus --- A Global Threat

1. Associate Professor, Department of Microbiology, Enam Medical College, Savar, Dhaka
2. Assistant Professor, Department of Microbiology, Enam Medical College, Savar, Dhaka
Correspondence  Mejbah Uddin Ahmed, Email: mejbahua@gmail.com

Review Article

   Mejbah Uddin Ahmed1, Sushmita Roy2
 Received: September 6, 2014     Accepted: October 25, 2014   doi: 10.3329/jemc.v5i1.21497

Journal of Enam Medical College
Vol 5 No 1 January 2015



and at present no effective treatment or vaccine is 
available. Therefore, people should be aware of the 
threats from the Ebola virus in order to avoid infection 
and scientists should try their best to formulate a 
treatment and vaccine. 

History and geographic distribution
Sporadic outbreaks of Marburg virus and Ebola virus 
infection have presumably occurred in central Africa for 
millennia, but the agents were not recognized by the 
scientific community until the late 20th century.16 The 
cases of filovirus hemorrhagic fever were reported first 
in 1967 among workers in German and Yugoslavian 
vaccine plants who were processing tissues from 
monkeys imported from Uganda. The causative agent 
was identified as Marburg virus.17,18 Similar cases of 
hemorrhagic fever were described in 1976 from 
outbreaks in two neighboring locations: first in southern 
Sudan and subsequently in northern Zaire, now 
Democratic Republic of the Congo (DRC). An unknown 
causative agent was isolated from patients in both 
outbreaks and was named Ebolavirus after a small river 
in northwestern DRC.19 These two epidemics were 
caused by two distinct species of Ebolavirus, Sudan 
Ebolavirus and Zaire Ebolavirus. The third African 
Ebola virus species, Tai Forest Ebolavirus (Côte d'Ivoire 
Ebolavirus) was discovered in 1994 from an infected 
ethnologist who had worked in the Tai Forest reserve in 
Côte d'Ivoire and had done a necropsy on a chimpanzee. 
Bundibugyo Ebolavirus is the fourth species of Ebola 
virus found in equatorial Africa.7,20 An additional 
species, the Reston Ebolavirus, was first described in 
1989 and isolated from Cynomolgus monkeys (Macaca 
fascicularis) housed at a quarantine facility in Reston, 
VA, USA.  Subsequently, Reston Ebolavirus has been 
found in the Philippines on several occasions in 
pigs.20,21 Since the time of first recovery, with the 
exception of a few accidental laboratory infections, 
Ebola outbreaks have been mostly concentrated in 
remote areas of sub-Saharan Africa, but evidence of 
Ebola infection of swine in the Philippines, the presence 
of antibodies among orangutans in Indonesia and bats in 
China indicates that Ebola virus may be more 
widespread than previously thought.22-24 The frequency 
of recognized outbreaks has been increasing since 
1990.25 After smaller outbreaks in Zaire and Sudan, 
some 15 years passed before Ebola virus reappeared in 
1994 in Gabon. A large hospital-based epidemic in the 
Democratic Republic of Congo in 1995 brought the 

virus to worldwide attention and re-emergence of Sudan 
Ebolavirus in Uganda in late 2000 resulted in 425 cases 
and 225 deaths. Epidemics of Zaire Ebolavirus have 
increased in frequency in recent years.16 The virus has 
caused more than 20 outbreaks since its identification. 
In most instances, the virus emerged in geographically 
restricted rural regions.26 Outbreak of Ebola virus 
disease in West Africa is so large and severe; there are 
many factors behind it, but poverty is considered as the 
main reason. The hardest-hit countries Guinea, Liberia 
and Sierra Leone are among the poorest nations and 
have recently emerged from years of conflict and civil 
war. Their health systems are destroyed or severely 
disabled and in some areas war left a generation of 
children without education. Health care infrastructure is 
inadequate and health workers and essential supplies 
including personal protective equipments are scarce. 
Population movements across the porous borders are 
constant, so transmission is intense and people continue 
to reinfect each other.27 Traditional practices, such as 
bathing of corpses before burial, are also an important 
factor for disease transmission.26

Current situation
The recent ongoing epidemic caused by the Zaire     
Ebolavirus started in Guinea in December 2013 and 
then spread to Liberia, Sierra Leone and Nigeria; it is 
the largest Ebola virus epidemic in history. It has been 
the most severe outbreak in terms of the number of 
human cases and fatalities since the discovery of the 
virus in 1976.13 The situation is changing rapidly and 
other countries might experience imported cases or 
outbreaks. Instances of civil unrest and violence against 
aid workers have been reported in West Africa as a 
result of the outbreak. The public health systems in the 
affected countries are being severely strained as the 
outbreak grows.28 On 10 December 2014, WHO 
reported a total of 17,942 suspected cases and 6,388 
deaths.29

Ebola virus and Bangladesh situation 
Olival et al19 conducted a study in Bangladesh during 
April 2010 to March 2011. They tested 276 bats of 
several species from Faridpur, Rajbari, Lalmonirhat, 
and Comilla districts. Among them five bats were 
positive for antibodies against Ebola Zaire and Reston 
viruses, but no virus was detected by PCR. There are 
reasons to speculate that bats might be a reservoir for 
Ebola or Ebola-like viruses and extend the range of 

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J Enam Med Col  Vol 5  No 1 January 2015



filoviruses to mainland Asia. Failure to detect filovirus 
nucleic acid might reflect the relatively small sample size, 
low virus prevalence, or use of a PCR that has low 
sensitivity for filoviruses circulating in Bangladesh.19 The 
national disease monitoring arm Institute of Epidemiology, 
Disease Control and Research (IEDCR) is keeping a close 
watch on the current situation. Due to travel restrictions on 
Ebola patients and the absence of direct air links with the 
affected West African countries made the deadly virus 
making its way to Bangladesh “a remote possibility”. 
Director of IEDCR considers Bangladesh a low-risk 
country and urged everyone not to spread panic. 
Bangladesh has also issued an alert against Ebola virus for 
three months, after the WHO declared the epidemic an 
international health emergency.30

Viral structure
Ebola virus is filamentous, enveloped, non-segmented, 
single-stranded, negative-sense RNA virus.31,32 The EBOV 
genome is about 19000 nucleotides long that encodes seven 
structural proteins, nucleoprotein (NP), polymerase 
cofactor (VP35), matrix protein (VP40), glycoprotein (GP), 
replication-transcription protein (VP30), minor matrix 
protein (VP24) and RNA-dependent RNA polymerase 
(L).33,34 The structural proteins VP40 and VP24 represent 
viral matrix proteins connecting the nucleocapsid with the 
viral envelope. VP40 plays an essential role in assembly 
and budding of the virus.35 Ebola virus is susceptible to 3% 
acetic acid, 1% glutaraldehyde, alcohol-based products and 
dilutions of 5.25% sodium hypochlorite and calcium 
hypochlorite. The WHO recommendation for cleaning up 
spills of blood or body fluids is flooding the area with a 
1:10 dilution of 5.25% sodium hypochlorite for 10 minutes. 
The virus is moderately thermolabile and can be 
inactivated by heating for 30 to 60 minutes at 60°C, boiling 
for 5 minutes or gamma irradiation combined with 1% 
glutaraldehyde. It has been reported that the virus is 
capable to survive for weeks in blood particularly at low 
temperatures (4°C). When dried in tissue culture media and 
stored at 4°C, Zaire Ebolavirus survived for over 50 days. 
This information is based on experimental findings and 
intended to be used to support local risk assessments in a 
laboratory setting.36 

Cell tropism and replication
Ebola virus is known to be pantropic in infection of human 
and can infect a wide variety of cell types. Though Ebola 
shows broad tissue tropism, hepatocytes, endothelial cells, 
dendritic cells, monocytes, and macrophages are thought to 

be their preferred target cells.31 Infection begins 
with the attachment of the virion to a receptor or 
lectin on the cell surface. Binding is followed by 
endocytosis, fusion of the viral envelope with the 
cellular endosomal membrane and release of the 
RNA genome and viral proteins into the cytoplasm. 
A replication complex made up of VP30, 
nucleoprotein, VP35 and large protein then 
generates mRNA transcripts. The new genomes 
associate with nucleoprotein and VP30 to form 
nucleocapsids which accumulate in inclusion bodies. 
Meanwhile, newly synthesized viral glycoprotein 
becomes glycosylated during its transit through the 
host-cell Golgi apparatus and is cleaved by a furin-
like enzyme before transfer to the cell surface, 
producing extracellular GP1 and transmembrane 
GP2 segments that remain linked by a disulphide 
bond. The assembly of new virions takes place on 
the inner surface of the plasma membrane, when 
nucleocapsids associate with matrix proteins linked 
to the cytoplasmic tail of membrane-bound GP. The 
nascent virions leave the cell through budding.16

Natural reservoir
The first recorded human outbreak of Ebola virus 
was in 1976, but the wild reservoir of this virus is 
still unknown.37 Since the discovery of filoviruses 
more than 40 years ago, ostensibly random, sporadic 
and fatal outbreaks of disease in primates have 
evoked interest in delineation of host tropisms, 
potential reservoirs for disease transmission and 
persistence in nature.8 However, researchers have 
hypothesized that it is an animal origin virus.38 
Current data suggest that in Africa fruit bats are the 
possible natural reservoir hosts. As a result, the 
geographic distribution of Ebola viruses may 
overlap with the range of the fruit bats.9 Infection 
has also been documented through the handling of 
infected chimpanzees, gorillas, monkeys, forest 
antelope and porcupines.13

Transmission
The exact mode of transmission of the virus from 
the natural reservoir to a human is not known. 
Evidence suggests that human infection is caused 
through close contact with the blood, secretion, 
organ or other body fluids of infected animal. 
Human-to-human transmission is also possible.9 
EBOV is shed in a wide variety of body fluids 

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(saliva, stool, semen, breast milk, tears, nasal blood and 
skin swab of infected person) during the acute period of 
illness. However, the risk of transmission from fomite 
of a patient and during the convalescent period is low.39 
It was found that men who have recovered from the 
disease can still transmit the virus through their semen 
for up to 7 weeks after recovery from illness. Health-
care workers may get infection through close contact 
with patients, when infection control precautions are 
not practiced properly.9 Although Ebola virus has been 
detected in breast milk, it is not known clearly whether 
Ebola virus can be transmitted through breastfeeding. 
Infected mothers may be critically ill and unable to 
breastfeed; but when they are able to breastfeed, 
decisions about whether or not to breastfeed may 
depend on the age of the infant, the availability and 
feasibility of safe nutrition and infant care and overall 
sanitary conditions. The recommendation of CDC is 
when safe alternatives to breastfeeding and infant care 
exist, mothers with probable or confirmed Ebola virus 
disease should not have close contact with their infants 
including breastfeeding.40

Pathogenesis
EBOV is an aggressive pathogen that causes highly 
fatal hemorrhagic fever in human and nonhuman 
primates.41 The virus has the specialized mechanisms to 
evade the immune system and the course of illness 
results from a complex pathogenic mechanism.16 In a 
study it is shown that fatal outcome is associated with 
aberrant innate immune responses and suppression of 
the adaptive immunity. The innate immune responses 
are characterized by the hypersecretion of numerous 
proinflammatory cytokines (IL-1β, IL-1RA, IL-6, IL-8, 
IL-15 and IL-16), chemokines, growth factors (MIP-1α, 
MIP-1β, MCP-1, M-CSF, MIF, IP-10, GRO-α and 
eotaxin) and by the noteworthy absence of antiviral 
IFNα2. Suppression of adaptive immunity is 
characterized by very low levels of circulating 
cytokines produced by T lymphocytes and by massive 
loss of peripheral CD4 and CD8 lymphocytes.37,42 Viral 
replication, in conjunction with immune and vascular 
dysregulation, is thought to play the vital role in the 
disease process. Specific organ involvement includes 
extensive disruption of the parafollicular regions in the 
spleen and lymph nodes and proliferation of the virus in 
mononuclear phagocytic cells has been demonstrated.43 
Studies in nonhuman primate models depicted 
monocytes, macrophages and dendritic cells are the 

major sites of initial viral replication. Virus is then 
distributed by the circulating phagocytic cells to a wide 
variety of organs and cells. Infected dendritic cell 
cultures supported exponential viral growth without 
releasing interferon (IFN-α).44 Two viral proteins 
(EBOV VP35 and EBOV VP24) are responsible for 
suppression of interferon responses. It seems that 
EBOV infection blocks the cellular production of IFN-
α/β and the ability to respond to IFN-α/β or IFN-γ. The 
VP24 is likely to be an important virulence factor that 
allows the virus to evade the antiviral effects of 
IFNs.45,46 In most instances, patients fail to produce 
antibodies against the virus and die with persistent high 
viremia. For initiation of an adaptive immune response 
presentation of viral antigens to lymphocytes is 
required. Phagocytic cells are the major sites of viral 
replication, which block their maturation and cause 
their death through necrosis. The system-wide release 
of proinflammatory cytokines and chemokines by these 
infected cells causes fever, disseminated intravascular 
coagulation, vascular instability, hypotension, shock 
and multi-organ failure. Although lymphocytes remain 
free of infection, they are destroyed in massive numbers 
over the course of illness through apoptosis.47 Massive 
apoptosis of natural killer and T cells further impairs 
immunity.48 Although some studies have shown that 
survival of the patient is associated with the ability of 
production of antigen-specific antibodies, a recent 
report from Sudan suggests that cell-mediated 
responses could also play an important role in 
protection.49,50 Blood samples obtained during several 
outbreaks in Gabon also suggested that survival is 
associated with the earlier appearance of 
proinflammatory cytokines in the blood.51

Clinical features 
Clinical findings are variable in Ebola infection. After 
an incubation period of around 2–21 days,4 disease 
starts nonspecifically with the abrupt onset of fever, 
chills, headache, malaise, anorexia, sore throat, myalgia 
and joint pains.20,46 The initial features of the disease 
may mimic other tropical diseases and  it is difficult to 
distinguish these features from other febrile illnesses. 
Conjunctival infection is seen in up to half of the 
patients.46 Respiratory symptoms include chest pain, 
shortness of breath, dry cough and nasal discharge.20  
Gastrointestinal manifestations including nausea, 
vomiting, abdominal pain and diarrhea develop within 
the first few days of illness. In severe cases, vascular 

 

 

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instability develops, usually 4–5 days after the onset of 
symptoms and may be evidenced by facial flushing, 
edema, proteinuria, bleeding, hypotension and shock.46 
Maculopapular rash associated with varying severity of 
erythema appears which desquamates by day 5–7 of the 
illness; this symptom is a valuable differential 
diagnostic feature and is usually followed by 
desquamation in survivors.20 Hemorrhage is most often 
gastrointestinal but vaginal bleeding, petechie, purpura, 
epistaxis and bleeding from the gums may be seen. 
Central nervous system manifestations including 
disorientation, gait anomalies, convulsions and hiccups 
may also be noted in end-stage disease.46

Laboratory diagnosis
In the absence of effective intervention strategies, 
diagnosis becomes a key element in response to Ebola 
virus infection. Diagnosis of EHF must be sensitive, 
specific and reliable because misdiagnosis may bring 
huge turmoil to society. Therefore, the diagnosis of 
EHF must not rely on any single method. During 
outbreak, patients with EHF must be isolated and a 
false-positive result will put an individual at 
unnecessary risk of cross infection by placing the 
person in an isolation ward. A false-negative result will 
allow infected persons to be released into the 
community and may cause person-to-person 
transmission of the virus in the community.52 
Laboratory diagnosis of Ebola virus is achieved in two 
ways: measurement of host-specific immune responses 
to infection and detection of viral particles or particle 
components in infected individuals.20 Therefore, the 
diagnosis rests largely on molecular techniques utilizing 
multiple reverse-transcriptase–polymerase-chain-
reaction assays that can be used at remote outbreak 
sites. Antigen detection may be performed in parallel or 
serve as a confirmatory test for immediate diagnosis 
whereas assays for detection of antibodies (IgM and 
IgG) using unique virus antigens are secondary tests 
that are primarily important in surveillance.53,54 
Definitive diagnosis  is usually made by PCR and virus 
isolation on Vero cells. As a class-4 pathogen, Ebola 
virus culture requires a maximum containment facility. 
Additional immunological tests include ELISAs for the 
detection of Ebola IgG- and IgM-specific antibodies 
and virus antigens; more specialized molecular testing 
is also available but is not readily available in the usual 
clinical setting.11 Now-a-days, RT-PCR and antigen 
detection ELISA are the primary assays to diagnose an 

acute infection. Viral antigen and nucleic acid can be 
detected in blood from day 3 up to 7–16 days after 
onset of symptoms. For antibody detection the most 
generally used assays are direct IgG and IgM ELISAs 
and IgM capture ELISA. IgM antibodies can appear as 
early as 2 days postonset of symptoms and disappear 
between 30 and 168 days after infection. IgG-specific 
antibodies develop between day 6 and 18 after onset 
and persist for many years. An IgM or rising IgG titer 
constitutes a strong presumptive diagnosis. Decreasing 
IgM or rising IgG titers (four-fold), or both, in 
successive paired serum samples are highly suggestive 
of a recent infection.20 Histopathological techniques 
and antigen detection by immunohistochemical analyses 
are sensitive methods, particularly for postmortem 
diagnosis. Diagnosis by detection of virus antigens is 
suitable for patients in the early stage and detection of 
specific IgM and IgG antibodies is suitable for patients 
in a relatively late stage of illness.48

Treatment
EBOV infections are a public health concern because of 
the high mortality rate and lack of prophylactic and 
therapeutic interventions as no specific antiviral 
treatment is available at present.55 Severely ill patients 
require intensive supportive care which includes 
oxygen, blood pressure medication, blood transfusions, 
rehydration with intravenous fluids containing 
electrolytes and treatment for other infections.9 A study 
done by Qiu et al in 2012 shows that a combination of 
three neutralizing monoclonal antibodies directed 
against the envelope glycoprotein resulted in complete 
survival of four of four cynomolgus macaques with no 
apparent side effects when three doses were 
administered 3 days apart beginning at 24 hours after a 
lethal challenge with EBOV. The same treatment 
initiated 48 hours after resulted in two of four 
cynomolgus macaques fully recovering.56

Prevention
Although safe and effective vaccines or other medicinal 
agents to block Ebola infection are currently 
unavailable, a significant effort has been put forth to 
identify several promising candidates for the treatment 
and prevention.2,57 Some vaccines under trial  have 
been shown to protect NHPs: a replication-incompetent 
adenovirus expressing the EBOV glycoprotein  
(29–31), a replication-competent vesicular stomatitis 
virus (VSV) expressing GP (7, 15), a recombinant 

 

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paramyxovirus expressing GP (4), and virus-like 
particles  (38, 41).5 In the absence of effective treatment 
and vaccine, raising awareness regarding the risk 
factors and personal protective measures is the only 
way to reduce human infection and death.9 There are 
three key preventive interventions which have gained 
attention with encouraging outcome. The first is 
meticulous infection control in health care settings. 
Second is educating and supporting the community to 
avoid contact with body fluids of people who died from 
EVD, at least temporarily until the outbreak is 
controlled. And the third is avoiding handling of bush 
meat and contact with bats.14

Conclusion
The main goal currently being addressed with Ebola 
virus is finding ways of treatment and effective 
vaccines that can be applied to humans. Although Ebola 
virus infection is not a problem right now for most 
populations outside Africa, it has the potential to be 
alarming from the point of view in global health in the 
future. 

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