This document summarizes information about the Ebola virus, including its characterization, life cycle, transmission, symptoms, outbreaks, treatment and prevention. It describes Ebola virus as a filamentous, enveloped RNA virus that infects monocytes, macrophages and other immune cells. It evades the host immune system and causes hemorrhagic fever through mechanisms such as blocking interferon response. The largest Ebola outbreak occurred in West Africa from 2013-2016. Treatment involves general medical support and isolation, while prevention focuses on avoiding contact with patients, proper PPE and animal surveillance.

2. Characterization of the virus
 Order: Mononegavirales
 Family: Filoviridae
 Genus: Ebolavirus
 Species: Ebola-Zaire, Ebola-Sudan, Ebola-Cote d-Ivoire,
Ebola-Reston

3.  filamentous, enveloped RNA virus
 approx. 19 kb in length (1 kb = 1000 RNA
 bases/nucleotides) or 60-80 nm in diameter
 single-stranded, linear, non-segmented
 negative-sense RNA (encoded in a 3’ to 5’ direction)
 appears to have “spikes” due to glycoprotein on outside
membrane

4.  Transcribed into 8 sub-genomic mRNA proteins: 7
structural and 1 nonstructural

6. Life cycle of ebola virus

7.  The early targets of the virus are the monocytes and the
macrophages of the host immune system. Other target cells
include dendritic cells, liver cells, and endothelial cells.
 Ebola virus employs different mechanisms to interfere with
or even ignore the host immune system completely.
 antibody-dependent enhancement (ADE) wherein the host
antibodies (Abs), facilitate or enhance the virus’s attachment
to the host cells increasing infection in these cells.

8.  the virus’ protein VP35, blocks the immune system’s
interferon (IFN) pathways comprising of various cytokines
that exert anti-viral responses. VP24 blocks transcription
factors like STAT1 that regulate transcription of the immune
system genes
 the primary mRNA transcript of the GP gene encodes the
soluble sGP which is speculated to have an anti-
inflammatory role during infection which further enhances
the virus’ escape from host immune system response.
Moreover, sGP has many similar epitopes with GP, so it
could potentially sequester or absorb host Abs to block
their downstream action

9. The exact mechanism by which the Ebola virus enters host
cells remains poorly understood.
Macropinocytosis is the most likely mechanism employed
by the Ebola virus. This process involves outward
extensions of the plasma membrane formed by actin
polymerization, which can fold back upon themselves.

10.  Once inside the host cell, the virus initiates
transcription at the leader end of the genome
with the binding of the polymerase complex5.
VP30 is an important transcription activation
factor for viral genome transcription, while
VP24 is an inhibitor to this process.

11.  Following replication, the cell loses its
connection with other cells as well as
attachment to its substrate. Meanwhile, the
newly synthesized genomes are packaged into
new buds or virions and egresses from the
host cell surface with the help of the matrix
protein VP40.

13.  The white blood cells respond by releasing large amounts
of proinflammatory cytokines that increase permeability of
the vascular endothelium, which facilitates easier entry into
the virus's secondary targets, endothelial cells .
 These cytokines also recruit more macrophages to the area,
maximizing the number of cells that Ebola can use to spread
throughout the body. In the meantime, hepatocytes are being
destroyed by the virus, ensuring that these cell signals
cannot be cleared from the bloodstream

14.  During this process, the cell detaches from its neighbors
and loses contact with its basement membrane due to a
mechanism of glycan mediated steric occlusion by GP .
The newly created particles then leave via lipid rafts,
leaving a destabilized vascular system responsible for the
massive blood loss characteristic of Ebola patients
 Meanwhile, the immune system is going haywire .
Interferons are not being made because VP35 interferes
with nearly every step in the process .
 White blood cells are trapped inside the circulatory
system because sGP limits their movement .
Macrophages and monocytes are releasing a cocktail of
proinflammatory cytokines that destroy the vascular
endothelium, but also activate the coagulation cascade.

15.  This puts your body in a paradoxical state
in which you can die of hypovolemic
shock from massive hemorrhage, or from
catastrophic thrombosis, the formation of
blood clots around the body

18.  Burial ceremonies in which mourners have direct contact with
the body of the deceased person can also play a role in the
transmission of Ebola
 Ebola then spreads in the community through human-to-
human transmission, with infection resulting from direct
contact (through broken skin or mucous membranes) with the
blood, secretions, organs or other bodily fluids of infected
people, and indirect contact with environments contaminated
with such fluids

19. Incubation period: 2-21 days
Stage I (unspecific):
 -Extreme asthenia (body weakness)
 -diarrhea, nausea and vomiting, anorexia
 abdominal pain
 - headaches
 - arthralgia (neuralgic pain in joints)
 - myalgia (muscular pain or tenderness), back pain
 - mucosal redness of the oral cavity, dysphagia (difficulty in
swallowing)
 - conjunctivitis.
 - rash all over body except in face
If the patients don’t recover gradually at this point, there is a high
probability that the disease will progress to the second phase, resulting in
complications which eventually lead to death .

20. Stage II (Specific):
 - Hemorrhage
 - neuropsychiatric abnormalities
 - anuria (the absence of urine formation)
 - hiccups
 - tachypnea (rapid breathing).
** Patients who progressed to phase two EHF almost always
die.
Late Complications:
 -Arthralgia
 - ocular diseases (ocular pain, photophobia and
hyperlacrimation)
 - hearing loss
 - unilateral orchitis( inflammation of one or both of the
testes)


23. 
 The other genus, Ebola virus, was first recognized when two outbreaks
occurred in Zaire and in Sudan in 1976 . Outbreaks of Ebola virus disease
have been confined to Sub-Saharan Africa. An epidemic caused by the
Zaire species caused several hundred cases in 1995 in Kikwit, Democratic
Republic of the Congo, and the Sudan virus infected more than 400 people
in Gulu, Uganda in 2000. The 2014 Ebola epidemic, caused by the Zaire
species of virus, is not only the first to occur in West Africa, but is far
larger than all previous outbreaks combined .
 In addition to causing human infections, Ebola virus has also spread to
wild nonhuman primates, apparently as a result of their contact with an
unidentified reservoir host (possibly bats).

24.  2014 outbreak in West Africa — Although all previous Ebola outbreaks
occurred in Central Africa, an epidemic began in the West African
nation of Guinea in late 2013 and was confirmed by the World Health
Organization (WHO) in March 2014 .
 The initial case was a two-year-old child who developed fever,
vomiting, and black stools, without other evidence of hemorrhage . The
outbreak subsequently spread to Liberia, Sierra Leone, Nigeria,
Senegal, and Mali . The case-fatality rate has been reported to be as
high as 70 percent .
 The magnitude of the outbreak, especially in Liberia and Sierra Leone,
has probably been underestimated; this is due in part to individuals
with Ebola virus disease being cared for outside the hospital setting .
As of November 23, 2014, the cumulative number of probable,
suspected, and laboratory-confirmed cases attributed to Ebola virus is
15,935, including 5689 deaths . These cases include 592 infected
healthcare workers, of whom approximately 60 percent have died .
Senegal and Nigeria have not reported any new cases since August 29
and September 5, respectively, and the WHO has declared that the
outbreaks are over in these countries .

25.  On September 30, 2014, the first travel-associated case of Ebola was
reported in the United States . An individual who traveled from Liberia
to Dallas, Texas first developed clinical findings consistent with Ebola
virus disease approximately five days after arriving in the United
States. The patient was asymptomatic prior to and during the flight.
Two healthcare workers involved in his care subsequently developed
Ebola virus disease .
 2014 outbreak in the Democratic Republic of the Congo — In August of
2014, an outbreak of Ebola virus disease was reported in the
Democratic Republic of the Congo . The index case was a pregnant
woman who butchered an animal that had been killed by her husband.
As of November 11, 2014, a total of 66 cases of Ebola virus disease
(confirmed and probable), including 49 deaths, had been connected to
this outbreak . Sequence analysis has shown that the Zaire strain of
Ebola virus causing this outbreak is most closely related to one that
caused the 1995 outbreak in Kikwit; there is no connection with the
current epidemic in West Africa

27.  If an outbreak is suspected, the premises should be quarantined
immediately. Culling of infected animals, with close supervision
of burial or incineration of carcasses, may be necessary to
reduce the risk of animal-to-human transmission
 Restricting or banning the movement of animals from infected
farms to other areas can reduce the spread of the disease.
 outbreaks in pigs and monkeys have preceded human infections,
the establishment of an active animal health surveillance system
to detect new cases is essential in providing early warning for
veterinary and human public health authorities.

28.  In the absence of effective treatment and a human
vaccine, raising awareness of the risk factors for Ebola
infection and the protective measures individuals can
take is the only way to reduce human infection and death.
In Africa, during EVD outbreaks, educational public health
messages for risk reduction should focus on several factors:

29.  Close physical contact with Ebola patients should be
avoided
 Gloves and appropriate personal protective
equipment should be worn when taking care of ill
patients at home.

30. Within a few days after symptoms begin :
 Antigen-capture enzyme-linked immunosorbent assay (ELISA) testing
 IgM ELISA
 Polymerase chain reaction (PCR)
 Virus isolation
 Later in disease course or after recovery:
• IgM and IgG antibodies
 Retrospectively in deceased patients:
• Immunohistochemistry testing
• PCR
• Virus isolation

31.  General medical support is critical and should include
replacement of coagulation factors and heparin if disseminated
intravascular coagulation develops. Such care must be
administered with strict attention to barrier isolation. All body
fluids (blood, saliva, urine, and stool) contain infectious virions
and should be handled with great care.
 Currently, no specific therapy is available that has
demonstrated efficacy in the treatment of Ebola hemorrhagic
fever. Surgical intervention generally follows a mistaken
diagnosis in which Ebola-associated abdominal signs are
mistaken for a surgical abdominal emergency. Such a mistake
may be fatal for the patient and for any surgical team members
who become contaminated with the patient’s blood.

32.  An experiment vaccine against Ebola has produced promising results in its
first safety trial in humans. The researchers are now hoping to run Phase II/III
trials in west Africa to test the vaccine's effectiveness.
 The candidate vaccine contains segments of Ebola genetic material from two
strains of the virus – Sudan and Zaire – delivered by an adenovirus vector
that causes the common cold in chimpanzees.
 The investigators also found the vaccine increased production of T cells,
including CD8 T cells, which they think may be an important part of
protection from Ebola. Four weeks after vaccination, CD8 T cells were
detected in two volunteers who had received the lower dose vaccine and in
seven of those who had received the higher dose.

34.  http://www.medicinenet.com/ebola_vaccine_is_it_safe/views.
htm
 http://emedicine.medscape.com/article/216288-treatment
 https://microbewiki.kenyon.edu/index.php/Infection_Mechanis
m_of_Genus_Ebolavirus