This document provides an overview of Ebola virus, including its taxonomy, history, molecular biology, symptoms, diagnosis, treatment, and management. Ebola virus is a negative-sense RNA virus that causes severe hemorrhagic fever in humans and non-human primates. It is transmitted through contact with infected body fluids and has a high fatality rate. The current 2014 outbreak in West Africa involving the Zaire species is the largest on record. There is no approved treatment but supportive care and experimental therapies are being used. Strict isolation protocols are necessary to prevent spread in healthcare settings.

1. Ebola Virus A to Z
Dr. Y. Ashok Babu

2. Contents of the topic:
• About the virus (taxonomy)
• History of Ebola of Viral Disease
• Geographical Distribution and Epidemiological preamble
• Molecular Biology of the Virus
• Host pathogen interaction (Entry, Replication and Host immunity
evasion)
• Patho-physiology and clinical manifestations
• Diagnosis
• Treatment and complications
• Disease out brake dynamics
• Management of Ebola outbreak at Health care facilities and
handling of the virus
•Threat perception for India
• Conclusion

3. • Ebola Virus is a ss(-)RNA Virus
• Belongs to order Mononegi virales, Family filovoviridae
• Current species in circulation causing major out breaks is Zaire
ebola virus
• The other virus species which cause Ebola virus disease
include
 Bundibugyo ebolavirus (BDBV)
 Reston ebolavirus (RESTV) –(Live Stock Infection)
 Sudan ebolavirus (SUDV)
 Taï Forest ebolavirus (TAFV) – Asia (Live stock Infection)
Marburg Virus is another genus of Filoviridae causing similar
hemaregic fever with comparative less fatality (30%)

4. History of Ebola Virus Disease
 Initially it was suspected as a species of Marburg Virus with
high virulence recent genetic analysis confirmed as new genus
with 70% homology to Marburg virus
 Since no treatment exists and symptoms are similar to
marburg virus the management of the disease followed same
procedure
 The first case of the infection reported in Zaire (1977) now
called DRC with case fatality of 88%.
 The spread of the disease attributed a single incidence of
handling carcasses dead baboons by a single human which
triggered human to human in close contacts.

5. Date Country Species
Reported
cases
Reported
deaths
Fatality
1976 Zaire ZEBOV 318 280 88%
1976 Sudan SEBOV 284 151 53%
1979 Sudan SEBOV 34 22 65%
1994 Gabon ZEBOV 52 31 60%
1995 Zaire ZEBOV 315 250 79%
1996 Jan–Apr Gabon ZEBOV 37 21 57%
1996–1997Jul–Jan Gabon ZEBOV 60 45 75%
2000–2001 Uganda SEBOV 425 224 53%
2001–2002 Oct–Jul
Gabon
Congo
ZEBOV 122 96 79%
2002–2003 Dec–Apr Congo ZEBOV 143 128 90%
2003 Nov–Dec Congo ZEBOV 35 29 83%
2007 DR Congo ZEBOV 264 187 71%
2007–2008 Dec–Jan Uganda BDBV 149 37 25%
2008–2009 Dec–Feb DR Congo ZEBOV 32 14 45%
2012 Jun–Aug Uganda SEBOV 24 17 71%
2012 Jun–Nov DR Congo BDBV 77 36 47%
2013–2014
Dec–present
Guinea, Liberia
Sierra Leone
Nigeria
ZEBOV 1848 1013 64%

7. Molecular Biology of the Virus
 The virus is a filamentus negative sense SS RNA virus with genome
size of 19kb
 The genome of Ebola virus is continues and codes for 7 structural
genes
 NP: Nucleoprotein…………….Nuclear capsid protein
 VP35: Virion Protein 35……. Polymerase complex
 VP 40: Virion Protein 40…… Matrix Protein
 Gp/sGP: Glyco Protein……….Trans membrane/secretory protein
 VP30: Virion Protein 30……..Transcription regulatory protein
 VP 24: Virion 24…………………. Matrix associated ??? .
 L: RNA dependent RNA polymerase

8. Schematic diagram showing a typical Ebola Virion

10. Host pathogen Interaction
The primary targets of Ebola virus is cell of lymphoid tissues including Dendritic
cells, Monocytes, and Epithelial cells.
However, after initiation of infection in the host the virus can infect all type cells
expressing NPC C1 protein.
The virus enters into the cytoplasm of host cell through Macropinocytosis.
Entry of the virus occurs in two phases, at both the phases involving interaction
of GP protein of the virus with host receptors.
Multiple targets for binding of GP protein on cell surfaced was found such as
Intigrins, Lectins, TAM
Virus internalizes into Macro Pinosome

11. GP1,2 protein cleaved by cathepsin B and L at the glycosylation
rich region GP1 exposing Receptor binding domine.
Receptor Binding site interact with NPC C1 on Macropinosome
leading to release of viral content into the cytoplasm
Being –ssRNA the virus carries along with it the RdRP (L-protein)
to initiate transcription.
The whole genome of the virus is under control of a single
promoter and ORF site at -1 of NP protein.
The peculiar feature of -ssRNA viruses is they have start and stop
regions at the beginning and end of each gene, leading to high
expression of proteins near to promoter than the gene located
away.

12. Entry of Ebola Virus into the cell

13. Over view of life cycle of Ebola virus

14. Host Immunity evasion
 The Ebola infection is fast acting, and highly replicating coupled
with disturbing host protein synthesis
 The virus rapid multiplication outperforms the cellular protection
mechanism leading initial failure of humeral immunity to contain
infection
 The virus releases a secretory form of GP out of the infected cell
in abundance which due to epitope cross reactivity to full GP
competes to bind with neutralizing anti bodies leading to failed
immune response.
 The same reason is the leading concern in developing vaccine
against Ebola infection.

16. Symptoms of Ebola Virus
Initial Signs
• Fever (at least 102°F)
• Weakness & exhaustion
• Pain
– Severe headache
– Muscles & joints
– Abdominal pain
• Sore throat
• Nausea
• Dizziness
Progressed Symptoms
• Vomiting
• Diarrhea
• Extensive bleeding
– Red eyes
• hemorrhage of sclerotic arterioles
– From mouth, nose, eyes, rectum &
mucouse membranes
• Maculopapular rash
– Spreads over the body (often
hemorrhagic)
• Other secondary symptoms
– Hypotension , Hypovolemia , Tachycardia
– Organ damage
– Internal and external bleeding

18. Diagnosis: Tool and Techniques
The clinical samples of Ebola virus infection pose serious Bio Hazard to laboratory
workers at par with the care givers.
Use of protocols involving possible generation of Aerosol such as pippetting,
Centrifugation, overtaxing completely banned outside BSL4 facility

20. Treatment and complications
There is no treatment for the infection of Ebola Virus.
Symptomatic supportive care can be given to the Individuals
including re hydration, supplementing with coagulation factors.
The virus pose high risk of Nosocomial transmission and hence
bio hazardous to health care workers and doctors.
Various studies on protection against EBOV infection in non
human primates with monoclonal antibodies, and si RNA
against NP and VP40 protein shown encouraging results.
There is no FDA approved therapy available for either Pre- or
Post exposure to the virus

21. However, very recently an American doctor and his assistant
who acquired the Infection was given the experimental drug
containing monoclonal antibodies against three EBOV.
Both of them recovered from the infection
On 6th August in the meeting of WHO it has recommended that
a controlled treatment with experimental drug may be
permitted in humans with learned consent as humanitarian
crisis over looming over ethics of experimental drug use.
However, the WHO recommendations limited to 2014 Ebola
outbreak only

22. Management of Ebola outbreak at Health care facilities
 Ebola vial infection is highly contagious with rapid health
deterioration in the infected patients
 The virus get secreted in abundance in all body fluids including
tears, saliva, blood, vomit, urine.
 Extreme personal protection is required while handling the
infected patients, and contaminated material.
 WHO, CDC recommended personal protection protocol after the
recent outbreak include full impermeable suite (Single use), N95
particulate filter max, impermeable boots, and gloves, protective
goggles.
 Minimum handling of the infected patient is recommended and
patient care by the relatives may be totally avoided except in case of
children with full protection

23.  Frequent hand hygiene with detergent or alcohol based solutions is
paramount to protect against infection in health care workers
 The virus can be easily get destroyed by 70% alcohol , 0.05% Sodium
Hypochlorite solution, bleaching powder or solution containing 500ppm
chlorine.
 Contaminated materials need to be treated with above solution before
disposal , if available incineration of contaminated materials such as
clothes, cotton swabs soiled with body fluids.
 Funeral of dead people with confirmed or suspected Ebola infection
should be strictly adhered to personal protection protocol, Un-protected
handling of dead body should be fully avoided

24. Threat perception for India
Ebola is a zoonotic infection transmitted through a direct or indirect
contact with the reservoir
Initial contact with natural reservoir fruit bat or in contact with infected
monkeys, other non human primates is the actual trigger for initiation of
spread of disease
Persistence of the disease in the wild depends on abundance of the
carrier in the area, and its initial spread largely depends on human and
wild animal contact
In Sub-Saharan region predominantly of worlds poorest countries,
majority of the population depend on forest, and consumption of wild
animals which make these population vulnerable to repeated epidemic
of the infection.
This single point shows how this virus remained an exotic pathogen to
India.

25. However, In the recent decades with increased economic interaction with
African countries, and presence of Indian UN peace keeping forces made
transmission of the disease to India become a possible threat
Heightened monitoring public transiting from these countries at entry points is
the most important to prevent entry of the virus.
With proper health care management in the event of out break the disease may
be contained. The extent of causality is inversely proportional to the availability
quality health care facilities.
Since the infection pose a serious Nosocomial bio-hazard, proper equipping
with PPE, training of health care workers and doctors should be initiated.
Mass awareness about the disease and spread of disease may be issued to
general public, which is sufficient at the moment.

26. With the reports of 4 Indian doctors want to return to India in fear of
Ebola infection where doctors health workers of WHO, MSF, Samaritan
Purse combating to contain the disease spread, there will requirement
of sensitization of Indian health care workers, and doctors for their
cooperation as the disease is a serious threat to health care givers.
Since entry point for the pathogen is major cities with international air
ports, Establishing quarantine facility is easier than other places as
such cities have better health care infra structure.

27. Conclusion
The ebola virus infection causes severe hemorrhagic disease with case
fatality ranging from 30% to 90% among different species.
The species causing the current out break is Zaire Ebola virus with high
case fatality rate of above 70%
Morphologically Ebola virus resembles with that of other filoviride
virus Marburg virus with a difference of filament size
With small molecule inhibitors NPC 1 (Cholesterol carrier) indentified
to be the required for entry of virus into cytoplasm
The viral protein GP shown to be cytotoxic to epithelial cells causing
inhibition of expression of cell adhesion molecules leading to vesicular
leakage.
Ebola virus evade host immunity by antibody subversion, by
producing antigen decoys, which render neutralizing antibodies
useless.

28. Early diagnosis of the infection involves Antigen Capture ELISA, PCR, RT-PCR,
IgM detection and electron microscopy, In the later stage of disease the
infection may be detected by IgG ELISA apart from above methods.
Treatment with monoclonal antibodies against the virus may be possible as
researchers shown their positive effect in mouse and no human primates.
Aseptic management and handling of infected persons and contaminated
materials is the key to containment of the disease.
Repeated outbreak of the Ebola virus is associated with regular human and
wild animal contact which is prevalent in African countries. Poor Health
care infrastructure fans the spread of disease from human to human.
Prevention of entry of the pathogen is paramount for India.

29. Thanks