Int. J. Life. Sci. Scienti. Res.

, 3(6):1500-1505 November 2017

REVIEW ARTICLE

Ebola Hemorrhagic Fever: Re-Emerging

Infectious Disease
Anurag Rai1, Areena Hoda Siddiqui2*, Sunita Singh3, Chandranandani Negi4, Shabnam Parveen5
1
Tutor, Department of Microbiology, Prasad Institute of Medical Sciences, Lucknow, India
2
Consultant Microbiologist, Department of Lab Medicine, Sahara Hospital, Lucknow, India
3
Research Officer, Department of Microbiology, King George Medical University, Lucknow, India
4
Lecturer, Department of Biotechnology, Dr. P. D. B. H Govt. P.G. College, Kotdwara, Uttarakhand, India
5
Regional Coordinator, International Journal of Life Sciences Scientific Research, India
*
Address for Correspondence: Dr. Areena Hoda Siddiqui, Consultant Microbiologist, Department of Lab Medicine,
Sahara Hospital, Lucknow, India
Received: 21 June 2017/Revised: 23 August 2017/Accepted: 26 October 2017

ABSTRACT- Ebola can cause disease in humans and non-human primates like chimpanzees, gorillas, and monkeys).
The spring of 2014 has brought a new calamity, the exotic infectious disease: Ebola Hemorrhagic Fever, which is
caused by the highly contagious and pathogenic virus, transmitted directly by interpersonal contact or indirectly by
common usage of the objects. The epidemic which occurred in Guinea tended to expand to neighboring countries; 83
deaths have been reported on April 1st 2014. Genetic analysis have revealed that the virus that causes this epidemic is
similar in a proportion of 98% to Ebolavirus Zaire (EBOV) species that were responsible for the epidemic in
Democratic Republic of Congo, in 2008. The Ebola virus belongs to the Filoviridae family and genus Ebolavirus. Each
species of the genus Ebola virus has one member virus, and four of these cause Ebola virus disease (EVD) in humans, a
type of hemorrhagic fever having a very high case fatality rate up to 90% in humans. There are five identified Ebola
virus species Bundibugyo Ebolavirus (BDBV), Ebolavirus Zaire (EBOV), Reston Ebolavirus (RESTV), Sudan
Ebolavirus (SUDV), and Tai Forest Ebolavirus (TAFV). Ebola viruses are present in numerous African countries. The
four of the five virus strains occur in an animal host native to Africa.
Key-words- Ebola Virus (EBOV), Ebola Virus Disease (EVD), Viral Hemorrhagic Fevers (VHFs), Emerging
Infectious Disease (EID)

INTRODUCTION
Ebola, previously known as Ebola hemorrhagic fever, is Ebola in India: Ebola is the new threat the world is
a rare and deadly disease caused by infection with one of currently fighting with no defense mechanisms. With the
the Ebola virus species. Ebola can cause disease in disease taking lives and the danger of it in India has been
humans and nonhuman primates (monkeys, gorillas, and giving many sleepless nights. On 18th November 2014,
chimpanzees). Outbreak of Ebola virus in West Africa one of the headlines of The Times of India
could be described as most severe public health was India's first ebola patient has been quarantined. The
emergency in modern times. Before the current situation, 26-year-old man, travelling from Liberia to India is being
outbreaks have appeared sporadically in Africa. EVD isolated in a facility at Delhi's Indira Gandhi International
(Ebola hemorrhagic fever) first appeared in 1976 with airport. The infected male arrived at New Delhi airport
two concurrent outbreaks of acute viral hemorrhagic fever from Liberia on November 10. He was admitted in a
involving 284 cases (151 deaths [53%]) centered in health facility in Liberia on September 11 and was
Nzara, Sudan [1], and 318 cases (280 deaths [88%]) in discharged on September 30. Three blood samples from
Yambuku (near the Ebola River), Democratic Republic of him were tested at National Centre for Disease Control
Congo (DRC) [2]. Since these original cases, there have (NDC), Delhi since November 10 to 13. Even as the
been approximately 20 other outbreaks occurring through blood tests were found to be negative for EVD, as has
to 2013, involving nearly 2500 cases in the Democratic been reported in the past, the virus may continue to be
Republic of Congo, Sudan, Gabon, Cote dIvoire, Uganda positive in secretions like urine and semen for a longer
and the Republic of the Congo [3]. time. His semen and urine samples were sent to NDC for
reconfirmation tests. His semen sample tested positive for
Access this article online EBOV. The tests for semen samples were repeated at
Quick Response Code Website:
National Institute of Virology, Pune, on Nov 17, 2014,
which was also tested positive.
www.ijlssr.com
Ebola Virus (EBOV)- EBOV is zoonotic filovirus and
belongs to the Filoviridae family, along with the genus
Marburg virus comprised of envelope, non-segmented
DOI: 10.21276/ijlssr.2017.3.6.12 negative-stranded RNA. Up to now five species have

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Int. J. Life. Sci. Scienti. Res., 3(6):1500-1505 November 2017
been identified: Zaire ebolavirus, Bundibugyo ebolavirus,
Tai Forest ebolavirus (formerly known as Cote dIvore),
Sudan ebolavirus, and Reston ebolavirus (found in
Western Pacific, highly pathogenic in nonhuman
primates) [4-5]. The former three have been responsible for
the large outbreaks that have occurred in Africa, whereas
the Reston ebolavirus has been observed in animals in
Asia but not as a cause of human disease [6]. The natural
reservoir host of Ebola virus still remains unknown.
However, on the basis of verification and the environment
of similar viruses, researchers believe, the virus is animal-
borne and that fruit bat bats are the most likely reservoir.
Four of the five virus strains occur in an animal host
native to Africa. Fruit bats of the Pteropodidae family,
including the species Hypsignathus monstrosus, Epomops
franqueti, and Myonycteris torquata, are believed to be
the natural hosts of Ebola viruses, with humans and other
mammals serving as accidental hosts [7].
Table 1: Pathological Features of Hemorrhagic Fever
Ebola virus

Agent Major Pathologic Features

Fig 2: Structure of a virion belonging to the genus
Ebolvairus (An Ebola virus)
Ebola Wide hepatocellular necrosis with Source: https://www.nap.edu/read/18975/chapter/2
virus
intracytoplasmic viral inclusions
Viral Hemorrhagic Fevers (VHFs)- Viral
Necrosis linking macrophages, parenchymal hemorrhagic fevers (VHFs) are caused by four families of
cells, and endothelial cells in main organs viruses (Bunyaviridae, Arenaviridae, Flaviviridae, and
Filoviridae) with several genera and species causing
Follicular necrosis with necrotic debris in illness (Table 2). All four viral families are
spleen as well as lymph nodes single-stranded RNA viruses that have a lipid envelope,
which makes them susceptible to detergents and
Apoptosis of lymphocytes along with
environments with low pH; however, they are stable in
lymphoid depletion blood and cold storage [8]. The four families of viruses are
Myocardial edema zoonoses, with reservoirs recognized for all species
except for Ebola virus (EBOV). Fruit bats are assumed to
Microvascular infection as well as wound be the reservoir, but only serological evidence and viral
sequences of EBOV have been detected [9]. Are
naviruses, Crimean-Congo hemorrhagic fever virus
(CCHFV), and filoviruses can be transmitted from human
to human by contact with blood and other body fluids,
potentially expanding exposed individual cases into
epidemic outbreaks, including the current EBOV disease
outbreak in western Africa [10].
Special Pathogens Branch (SBP) divides viral
hemorrhagic fever into following:
BSL-4 (Biosafety level 4) pathogen: Arenaviruses,
Filoviruses, Buniaviruses
Non BSL-4 pathogen: Dengue hemorrhagic fever,
Yellow fever

Fig 1: Ebola Virus (Microscopic observation)

Source: https://vision-life-sl.de/en/facts-about-sierra-
leone/

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Int. J. Life. Sci. Scienti. Res., 3(6):1500-1505 November 2017
Table 2: Viral Families causing Viral Hemorrhagic Fever [11]
Usual Source of
Virus Family Disease (Virus) Natural Distribution Incubation (Days)
Human Infection

Arenaviridae

Arenavirus Lassa fever Africa Rodent 5-16

Argentine HF (Junin) South America Rodent 7-14

Bolivian HF (Machupo) South America Rodent 9-15

Brazilian HF (Sabia) South America Rodent 7-14

Venezuelan HF South America Rodent 7-14

(Guanarito)
Bunyaviridae

Phlebovirus Rift Valley fever Africa Mosquito 2-5

Nairovirus Crimean-Congo HF Europe, Asia, Africa Tick 3-12

Hemorrhagic fever
with renal syndrome, Asia, Europe,
Hantavirus Rodent 9-35
Hantavirus pulmonary worldwide
syndrome
Filoviridae

Filovirus Marburg and Ebola Africa Fruit bat 2-216

Flaviviridae

Flavivirus Yellow fever Tropical Africa, South Mosquito 3-6

America
Unknown for
Dengue HF Asia, Americas, Africa Mosquito dengue HF, 5-7 for
dengue

Epidemiology- On March 23, 2014, the World and confirmed cases, including 11,313 deaths had been
Health Organization (WHO) notified of an outbreak of reported [14].
EVD in Guinea [12]. The initial source of the recent WHO Ebola response roadmap situation report reported
outbreak appears to be a tiny village called Meliandou in the progression of epidemic of EBOV after outbreak
southern Guinea where an index-case, a two-year old boy occurred in Nigeria. There were 20 cases found and
name Emille developed a hemorrhagic fever and died on 7 cases found in Mali. Four other countries (Senegal,
6th December 2013 [13]. Soon after that, the infection Spain, the United Kingdom and the United States of
spread to Liberia and Sierra Leone. Outbreak of Ebola America) also reported cases imported from West Africa
[15-17]
virus in West Africa could be described as most severe . WHO presented the data on 31st March 2015, after
public health emergency in modern times. The number of one year of outbreak, the total number of cases were in
potential cases ranges from thousands to millions with excess of 25,000 with over 10,000 deaths [18]. After all, on
high mortality rate. 14th Jan 2016, the previously infected countries had been
According to Ebola situation report by WHO as of declared Ebola-free.
October 28, 2015 - The Ebola virus disease (EVD)
epidemic occurring in West Africa is unprecedented in its Transmission- Transmission to humans required the
duration and scale, a total of 28,575 suspected, probable contact with animal tissues or body fluids, including
handling and ingestion of animal tissues, or ingestion of

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Int. J. Life. Sci. Scienti. Res., 3(6):1500-1505 November 2017
plants or water contaminated with bats faces or bodily bystander effect of which lymphocytes undergo massive
fluids [18]. A range of animal accidental hosts have been apoptosis due to the apoptotic induction of inflammatory
documented, and Ebola virus has been implicated as one mediators or loss of support signals from dendritic cells
[18,25-26]
of the major causes of decline of African chimpanzee and . After the infection virus is disseminated within
gorilla populations in recent decades [19-20]. Ebola virus is the monocytes, macrophages, dendritic cells to the lymph
transmitted to humans through close contact with blood nodes, and then by blood to the spleen and liver [18,27].
and bodily fluids from another infected human or animal, EBOV entry, which includes attachment and penetration
either by direct contact or indirectly from a contaminated into the cytoplasm, is mediated by the surface
environment. glycoprotein (GP) [5].
It was proved that patients who are able to develop
antibodies within the second week of infection have
cleared viremia and improved clinical symptoms.
Progression of the disease is leading to the vasodilatation
and increased vascular permeability, induction of
extrinsic coagulation cascade and lymphocytes apoptosis
[4,18,28]
.

Viral Diagnosis- For confirmation of a clinically

suspected case of Ebola virus disease, we should perform
NGS (new generation sequencing). However, because of
the extreme biohazard risk, testing using antigen or
antibody-based assays or reverse transcriptase polymerase
chain reaction testing in a biosafety level 4 laboratories is
required. To establish diagnosis viral RNA by PCR or
viral antigen (i.e. NP, VP40 and GP) by
immunoenzymatic methods (ELISA) should be detected
in the blood or other body fluids. Rapid tests are
available. Cell culture can be done in vero cell lines. It
Fig 3: Ebola virus replication cycle must be stressed that EBOV RNA can be detected 3 days
Source: http://slideplayer.com/slide/8088359/ after the infection. Laboratory findings include
leukopenia, followed by leukocytosis and atypical
Clinical presentation- The incubation period for Ebola
lymphocytosis. Thrombocytopenia, as well as elevation
virus disease ranges from two to 21 days and is
of aminotransferases (AST & ALT) is a characteristic
characterized by fever, headache, myalgias and
feature. Prolongation of the partial thromboplastin time
gastrointestinal symptoms [3]. Multisystem involvement
and the international normalized ratio (INR) are common
with hypotension and respiratory, kidney and liver failure
abnormality [4,18,24,27-28].
may ensue, as well as internal and external bleeding [21].
In one detailed prospective assessment of 26 of 30 Treatment and Prophylaxis- Still Ebola has no
hospitalized patients with Ebola virus disease during the specific treatment. There is also no therapeutics for
2007-2008 Bundibugyo outbreaks, the median duration of prevention or post exposure. Several experimental
symptoms was nine days from onset to death and 10 days therapies are under development, but not fully tested in
from onset to discharge for survivors [22]. The most human. About 15 different vaccines were in preclinical
common symptoms will fever, nausea/vomiting and stages of development, including DNA vaccines,
diarrhea, abdominal pain and conjunctivitis. The most virus-like particles and viral vectors [29]. However, FDA
common clinical features will severe headache, asthenia, has approved some experimental treatments for
myalgia, dysphagia, anorexia and diarrhea. Among the emergency use in patients with Ebola infection [30]. One
cohort of 26 cases, seven exhibited hemorrhagic features, of them is brincidofovir oral nucleotide analog, which is
which included melena, prolonged bleeding at injection modified version of cidofovir. In vitro data suggest its
sites, hematemesis, bleeding gums, hemoptysis, activity against Ebola and recently FDA approved it for
hematuria and postpartum vaginal bleeding [22]. In severe Phase 2 study [30].
cases patients are developing hypovolemic shock and Another antiviral drug favipiravir [30]. TKM Ebola and
multi organ failure, including hepatic damage, kidney and AVI 6002 are molecules used for blocking of viral
respiratory failure. Seizures and coma can occur as well replication genes via gene silencing. These drugs have
[4,23-24]
. shown effects against EVD in animal model [29]. Z Map is
another experimental treatment for EVD. It contains three
Pathogenesis- EBOV tropism toward antigen presenting
monoclonal antibodies. Oral fluid replacement with
cells (APCs) seems play also an important role in viral
rehydration solutions is preferred [31]. Giving that Ebola is
pathogenesis [25]. The infected APCs fail to undergo
highly contagious through direct contact with bodily
maturation; as such they are unable to present viral
fluids, contaminated objects and possibility of its aerosol
antigens to naive lymphocytes. This is followed by
route of infection isnt definitely excluded it is crucial to
massive loss of uninfected lymphocytes due to the

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Int. J. Life. Sci. Scienti. Res., 3(6):1500-1505 November 2017
reduce the risk of human-to-human transmission. repurposing in the treatment of viral hemorrhagic fevers,
Isolation of the infected patients, protective cloths and and screening programs leading to discovery of potential
equipment, control protocols, proper waste and samples drugs have emerged, however, a systematic assessment of
management are essential to protect medical personnel current evidence is warranted to justify their use in
and prevent spreading of the infection. specific treatment. The public healthcare system in
developing countries must prepare strategies, holding the
Preventive measurement to be taken Ebola in available resources in mind, to deal with the outbreak
Healthcare providers- During an outbreak, healthcare before it occurs.
providers take specific preventive measures to protect
themselves and others in the affected areas, called FUTURE PROSPECT
standard and other addition precautions. Risks for Rapid and wide geographic spread of the EBOV
Healthcare providers involved in health care and outbreak, the initial non-specific presentation of EVD,
epidemic response to EVD include psychological distress, high-risk exposure and lack of an effective treatment,
stigma, violence, long working hours, heat stress and WHO declared the EBOV epidemic an international
dehydration from using heavy PPE and ergonomic crisis. Recent advances in field testing have made assays
problems from handling bodies and loads. These require for VHF available to those in endemic areas but still
specific measures for psychosocial support, security and require capital investment, highly trained personnel, and
work organization. advanced technology from outside nations. Future
Healthcare providers at all levels of the health advancements in diagnostic testing may occur as a result
system- hospitals, clinics, laboratories, health posts, of biomarkers or other host signatures that can predict
laundries, transport should be briefed and must be trained active disease. These approaches will ultimately lead to
in infection control and adhere to the universal infection faster contact tracing and containment of disease
control standard guidelines to facilitate prevention and outbreaks.
precaution. All staff handling suspected or confirmed In India, there is lot of scientific and technical
cases of EVD or contaminated specimens and materials capabilities. Infrastructure in the areas of technology,
should use special personal protective equipment for computational biology, bio-informatics, molecular
working with biohazards, and apply hand hygiene biology, genomics are excellent for research. According
measures according to WHO recommendations. If the to WHO, India has done very well in terms of polio
recommended level of precaution is implemented, eradication. In the last few years or decades global
transmission of disease should be prevented. pandemics like MERS, SARS, avian influenza, swine flu,
Zika and Ebola diseases are becoming global. We can't
Following these evidence-based guidelines is imperative guess what's going to emerge and from where? We should
for the stoppage of an outbreak: take the necessary steps now to better prepare and educate
Identify, Isolate, Inform- According to CDC, if ourselves and families from the sequela of such events
someone is suspected of Ebola, the healthcare provider and provide effective treatment for those to whom we will
should place the patient in a room with the door closed provide care during this and subsequent epidemics
and call the local health department and does not
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haemorrhagic fever caused by a newly identified virus references, and ethical issues.
strain, Bundibugyo, Uganda. PloS One, 2012; 7:e52986. IJLSSR publishes all articles under Creative Commons
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How to cite this article:

Rai A, Siddiqui AH, Singh S, Negi C, Parveen S: Ebola Hemorrhagic Fever: Re-Emerging Infectious Disease. Int. J. Life. Sci.
Scienti. Res., 2017; 3(6):1500-1505. DOI:10.21276/ijlssr.2017.3.6.12
Source of Financial Support: Nil, Conflict of interest: Nil

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