Ebola virus disease (
EVD) or
Ebola hemorrhagic fever (
EHF) is the human disease caused by
ebola viruses. Symptoms start two days to three weeks after contracting the virus with a
fever, throat and muscle pains, and
headaches. There is then
nausea, vomiting and
diarrhea along with decreased functioning of the
liver and
kidneys. At this point some people begin to have problems with
bleeding.
[1]
The disease is first acquired by a population when a person comes into contact with the
blood or
bodily fluids of an infected animal such as a monkey or
fruit bat.
Fruit bats are believed to carry and spread the disease without being
affected by it. Once infected the disease may be spread from one person
to another. Men who survive may be able to transmit the disease sexually
for nearly two months. To make the diagnosis, typically other diseases
with similar symptoms such as
malaria,
cholera and other
viral hemorrhagic fever are excluded. The blood may then be tested for either
antibodies to the virus, the viral
DNA, or the virus itself to confirm the diagnosis.
[1]
Prevention involves decreasing the spread of the disease from
infected monkeys and pigs to humans. This may be done by checking these
animals for infection and killing and properly disposing of the bodies
if the disease is discovered. Properly cooking meat and wearing
protective clothing when handling meat may be helpful, as may wearing
protective clothing and
washing hands
when around someone sick with the disease. Samples from people with the
disease should be handled with an extra degree of caution.
[1]
There is no specific treatment for the virus with efforts to help people including giving the person either
oral rehydration therapy or
intravenous fluids. The disease has a high death rate: possibly up to 90%. It typically occurs in outbreaks in tropical regions of
Sub-Saharan Africa.
Between 1976, when it was first identified, and 2012, fewer than 1,000
people a year have been infected. The disease was first identified in
the
Sudan and the
Democratic Republic of the Congo. Efforts are ongoing to develop a
vaccine; however, none exists as of 2014.
[1]
Signs and symptoms
Manifestation of Ebola begins abruptly with a sudden onset of an
influenza-like stage characterized by general
malaise, fever with chills, sore throat, severe headache, weakness, joint pain, muscle pain, and chest pain.
[2] Respiratory tract involvement is characterized by
pharyngitis with sore throat, cough,
dyspnea, and hiccups. The
central nervous system is affected as judged by the development of severe headaches,
agitation, confusion,
fatigue,
depression,
seizures, and sometimes
coma.
Cutaneous presentation may include:
maculopapular rash,
petechiae,
purpura,
ecchymoses, and
hematomas
(especially around needle injection sites). In general, development of
hemorrhagic symptoms is indicative of a negative prognosis. However,
contrary to popular belief, hemorrhage does not lead to
hypovolemia and is not the cause of
death (total blood loss is low except during
labor). Instead, death occurs due to
multiple organ dysfunction syndrome (MODS) due to fluid redistribution,
hypotension,
disseminated intravascular coagulation, and focal
tissue necroses.
The average time between contracting the infection and the onset of symptoms is 13 days, but can be as long as 25 days.
[3]
Hemorrhage
All people infected show some extent of
coagulopathy and impaired circulatory system symptomology.
[4] Bleeding from mucous membranes and puncture sites is reported in 40–50% of cases,
[5] while maculopapular rashes are evident in approximately 50% of cases.
[4] Sources of bleeds include
hematemesis,
hemoptysis,
melena, and aforementioned bleeding from
mucous membranes (
gastrointestinal tract,
nose,
vagina and
gingiva). However diffuse bleeding (i.e. heavy) is rare; occurrence is usually exclusive to the gastrointestinal tract.
[4][6]
Causes
EVD is caused by five of six viruses classified in the genus
Ebolavirus, family
Filoviridae, order
Mononegavirales:
Bundibugyo virus (BDBV),
Ebola virus (EBOV),
Sudan virus (SUDV),
Taï Forest virus (TAFV) and an as-yet unnamed Ebolavirus responsible for the
2014 West Africa Ebola outbreak.
[7] The sixth virus,
Reston virus (RESTV), is thought to be not disease causing for humans and therefore not discussed here.
Transmission
EVD is believed to occur after an ebolavirus is transmitted to a human index case via contact with an infected animal
host[citation needed].
Human-to-human transmission occurs via direct contact with blood or
bodily fluids from an infected person (including embalming of an
infected dead person) or by contact with contaminated medical equipment
such as needles
[citation needed]. In the past, explosive
nosocomial transmission has occurred in under-equipped African hospitals due to the reuse of needles and lack of implementation of
universal precautions[citation needed]. Aerosol transmission has not been observed during natural EVD outbreaks
[citation needed]. The potential for widespread EVD
epidemics
is considered low due to the high case-fatality rate, the rapidity of
demise of patients, and the often remote areas where infections occur.
[citation needed]
Risk factors
Bushmeat being prepared for cooking in
Ghana, 2013. Human consumption of equatorial animals in Africa in the form of
bushmeat has been linked to the transmission of diseases to people, including ebola.
[8]
Between 1976 and 1998, in 30,000 mammals, birds, reptiles, amphibians, and
arthropods sampled from outbreak regions, no
ebolavirus was detected apart from some genetic traces found in six rodents (
Mus setulosus and
Praomys) and one
shrew (
Sylvisorex ollula) collected from the
Central African Republic.
[9][10] Traces of EBOV were detected in the carcasses of
gorillas
and chimpanzees during outbreaks in 2001 and 2003, which later became
the source of human infections. However, the high lethality from
infection in these species makes them unlikely as a
natural reservoir.
[9]
Plants,
arthropods, and birds have also been considered as possible reservoirs; however,
bats are considered the most likely candidate.
[11] Bats were known to reside in the cotton factory in which the
index cases for the 1976 and 1979 outbreaks were employed, and they have also been implicated in Marburg virus infections in 1975 and 1980.
[9] Of 24 plant species and 19 vertebrate species experimentally inoculated with EBOV, only bats became infected.
[12]
The absence of clinical signs in these bats is characteristic of a
reservoir species. In a 2002–2003 survey of 1,030 animals including 679
bats from
Gabon and the
Republic of the Congo, 13 fruit bats were found to contain EBOV RNA fragments.
[13] As of 2005, three types of
fruit bats (
Hypsignathus monstrosus,
Epomops franqueti, and
Myonycteris torquata) have been identified as being in contact with EBOV. They are now suspected to represent the EBOV reservoir hosts.
[14][15]
The existence of integrated genes of filoviruses in some genomes of
small rodents, insectivorous bats, shrews, tenrecs, and marsupials
indicates a history of infection with filoviruses in these groups as
well.
[16] However, it has to be stressed that infectious ebolaviruses have not yet been isolated from any nonhuman animal.
Bats drop partially eaten fruits and pulp, then terrestrial mammals such as gorillas and
duikers
feed on these fallen fruits. This chain of events forms a possible
indirect means of transmission from the natural host to animal
populations, which have led to research towards viral shedding in the
saliva of bats. Fruit production, animal behavior, and other factors
vary at different times and places that may trigger outbreaks among
animal populations.
[17]
Transmission between natural reservoirs and humans are rare, and
outbreaks are usually traceable to a single index case where an
individual has handled the carcass of gorilla, chimpanzee, or duiker.
[18]
Fruit bats are also reported to be a treat eaten by people in parts of
West Africa where they are smoked, grilled or made into a spicy soup.
[15] The virus then spreads person-to-person, especially within families, hospitals, and during some
mortuary rituals where contact among individuals becomes more likely.
[19]
The virus has been confirmed to be transmitted through
body fluids. Transmission through oral exposure and through
conjunctiva exposure is likely
[20] and has been confirmed in non-human primates.
[21]
Filoviruses are not naturally transmitted by aerosol. They are,
however, highly infectious as breathable 0.8–1.2 micrometre droplets in
laboratory conditions;
[22] because of this potential route of infection, these viruses have been classified as Category A biological weapons.
[23]
All epidemics of Ebola have occurred in sub-optimal hospital
conditions, where practices of basic hygiene and sanitation are often
either luxuries or unknown to caretakers and where disposable needles
and
autoclaves
are unavailable or too expensive. In modern hospitals with disposable
needles and knowledge of basic hygiene and barrier nursing techniques,
Ebola has never spread on a large scale. In isolated settings such as a
quarantined hospital or a remote village, most victims are infected
shortly after the first case of infection is present. The quick onset of
symptoms from the time the disease becomes contagious in an individual
makes it easy to identify sick individuals and limits an individual's
ability to spread the disease by traveling. Because bodies of the
deceased are still infectious, some doctors had to take measures to
properly dispose of dead bodies in a safe manner despite local
traditional burial rituals.
[24]
Virology
Main article:
Ebola virus
Table legend: "*" denotes the type species and "accepted" refers to a
taxon that has been accepted by the Executive Committee of the ICTV but
that has yet to be ratified.
Genome
Like all
mononegaviruses, ebolavirions contain linear nonsegmented, single-strand, non-infectious
RNA genomes of negative polarity that possesses inverse-complementary 3' and 5' termini, do not possess a
5' cap, are not
polyadenylated, and are not
covalently linked to a
protein.
[26] Ebolavirus genomes are approximately 19 kilobase pairs long and contain seven
genes in the order
3'-UTR-
NP-
VP35-
VP40-
GP-
VP30-
VP24-
L-
5'-UTR.
[27] The genomes of the five different ebolaviruses (BDBV, EBOV, RESTV, SUDV, and TAFV) differ in
sequence and the number and location of gene overlaps.
Structure
Like all
filoviruses,
ebolavirions are filamentous particles that may appear in the shape of a
shepherd's crook or in the shape of a "U" or a "6", and they may be
coiled, toroid, or branched.
[27] In general, Ebolavirions are 80 nm in
width,
but vary somewhat in length. In general, the median particle length of
ebolaviruses ranges from 974 to 1,086 nm (in contrast to marburgvirions,
whose median particle length was measured to be 795–828 nm), but
particles as long as 14,000 nm have been detected in tissue culture.
[28] Ebolavirions consist of seven structural proteins. At the center is the
helical ribonucleocapsid, which consists of the genomic RNA wrapped around a
polymer of
nucleoproteins (NP). Associated with the ribonucleoprotein is the
RNA-dependent RNA polymerase
(L) with the polymerase cofactor (VP35) and a transcription activator
(VP30). The ribonucleoprotein is embedded in a matrix, formed by the
major (VP40) and minor (VP24) matrix proteins. These particles are
surrounded by a
lipid membrane derived from the host cell membrane. The membrane anchors a glycoprotein (GP
1,2)
that projects 7 to 10 nm spikes away from its surface. While nearly
identical to marburgvirions in structure, ebolavirions are
antigenically distinct.
Entry
Niemann–Pick C1 (
NPC1) appears to be essential for Ebola infection. Two independent studies reported in the same issue of
Nature showed that Ebola virus cell entry and replication requires the cholesterol transporter protein NPC1.
[29][30] When cells from
Niemann-Pick disease, type C1
patients (who have a mutated form of NPC1) were exposed to Ebola virus
in the laboratory, the cells survived and appeared immune to the
virus,
further indicating that Ebola relies on NPC1 to enter cells. This might
imply that genetic mutations in the NPC1 gene in humans could make some
people resistant to one of the deadliest known viruses affecting
humans. The same studies described similar results with Ebola's cousin
in the
filovirus group,
Marburg virus, showing that it too needs NPC1 to enter cells.
[29][30] Furthermore, NPC1 was shown to be critical to
filovirus entry because it mediates infection by binding directly to the
viral envelope glycoprotein.
[30] A later study confirmed the findings that NPC1 is a critical
filovirus receptor that mediates infection by binding directly to the
viral envelope glycoprotein and that the second lysosomal domain of NPC1 mediates this binding.
[31]
In one of the original studies, a
small molecule was shown to inhibit Ebola virus infection by preventing the virus glycoprotein from binding to NPC1.
[30][32]
In the other study, mice that were heterozygous for NPC1 were shown to
be protected from lethal challenge with mouse adapted Ebola virus.
[29] Together, these studies suggest NPC1 may be potential therapeutic target for an Ebola anti-viral drug.
Replication
The ebolavirus
life cycle begins with virion attachment to specific cell-surface
receptors, followed by
fusion of the virion envelope with cellular membranes and the concomitant release of the virus
nucleocapsid into the
cytosol. The viral
RNA polymerase, encoded by the L gene, partially uncoats the nucleocapsid and
transcribes the
genes into positive-strand
mRNAs, which are then
translated into structural and nonstructural
proteins. Ebolavirus RNA polymerase (L) binds to a single
promoter
located at the 3' end of the genome. Transcription either terminates
after a gene or continues to the next gene downstream. This means that
genes close to the 3' end of the genome are transcribed in the greatest
abundance, whereas those toward the 5' end are least likely to be
transcribed. The gene order is, therefore, a simple but effective form
of transcriptional regulation. The most abundant protein produced is the
nucleoprotein, whose
concentration
in the cell determines when L switches from gene transcription to
genome replication. Replication results in full-length, positive-strand
antigenomes that are, in turn, transcribed into negative-strand virus
progeny genome copy. Newly synthesized structural proteins and genomes
self-assemble and accumulate near the inside of the
cell membrane. Virions
bud
off from the cell, gaining their envelopes from the cellular membrane
they bud from. The mature progeny particles then infect other cells to
repeat the cycle.
[33]
Pathophysiology
Endothelial cells, mononuclear
phagocytes, and
hepatocytes
are the main targets of infection. After infection, a secreted
glycoprotein (sGP) known as the Ebola virus glycoprotein (GP) is
synthesized. Ebola replication overwhelms protein synthesis of infected
cells and host immune defenses. The GP forms a
trimeric complex, which binds the virus to the endothelial cells lining the interior surface of blood vessels. The sGP forms a
dimeric protein that interferes with the signaling of
neutrophils, a type of
white blood cell,
which allows the virus to evade the immune system by inhibiting early
steps of neutrophil activation. These white blood cells also serve as
carriers to transport the virus throughout the entire body to places
such as the lymph nodes, liver, lungs, and spleen.
[34] The presence of viral particles and cell damage resulting from budding causes the release of
cytokines (to be specific,
TNF-α,
IL-6,
IL-8, etc.), which are the signaling molecules for fever and inflammation. The
cytopathic effect,
from infection in the endothelial cells, results in a loss of vascular
integrity. This loss in vascular integrity is furthered with synthesis
of GP, which reduces specific integrins responsible for cell adhesion to
the inter-cellular structure, and damage to the liver, which leads to
coagulopathy.
[35]
Diagnosis
EVD cannot be separated from
Marburg virus disease based on symptoms. It can also easily be confused with many other diseases common in
Equatorial Africa such as other
viral hemorrhagic fevers,
falciparum malaria,
typhoid fever,
shigellosis,
rickettsial diseases such as
typhus,
cholera,
gram-negative septicemia,
borreliosis such as
relapsing fever or
EHEC enteritis. Other infectious diseases that should be included in the
differential diagnosis include the following:
leptospirosis,
scrub typhus,
plague,
Q fever,
candidiasis,
histoplasmosis,
trypanosomiasis,
visceral leishmaniasis, hemorrhagic
smallpox,
measles, and fulminant
viral hepatitis.
[citation needed] Non-infectious diseases that can be confused with EVD are
acute promyelocytic leukemia,
hemolytic uremic syndrome,
snake envenomation,
clotting factor deficiencies/platelet disorders,
thrombotic thrombocytopenic purpura,
hereditary hemorrhagic telangiectasia,
Kawasaki disease, and even
warfarin intoxication.
[36][37][38][39]
EVD's most important clinical indicator is the persons
medical history,
especially travel and occupational history and the patient's exposure
to wildlife. EVD can be confirmed by isolating ebolaviruses from or by
detection of ebolavirus antigen or genomic or subgenomic RNAs in patient
blood or
serum samples during the acute phase of EVD. Ebolavirus isolation is usually performed by
inoculation of
grivet kidney epithelial
Vero E6 or MA-104
cell cultures or by inoculation of human adrenal carcinoma SW-13 cells, all of which reacting to infection with characteristic
cytopathic effects.
[40][41] Filovirions can easily be visualized and identified in cell culture by
electron microscopy
due to their unique filamentous shapes, but electron microscopy cannot
differentiate the various filoviruses alone despite some overall length
differences.
[28] Immunofluorescence assays
are used to confirm ebolavirus presence in cell cultures. During an
outbreak, virus isolation and electron microscopy are most often not
feasible options. The most common diagnostic methods are therefore
RT-PCR[42][43][44][45][46][47][48] in conjunction with
antigen-capture ELISA[49][50][51][52][53] which can be performed in field or mobile hospitals and laboratories.
Indirect immunofluorescence assays (IFAs) are not used for diagnosis of EVD in the field anymore.
Classification
The genera
Ebolavirus and
Marburgvirus were originally classified as the species of the now-obsolete
Filovirus genus. In March 1998, the Vertebrate Virus Subcommittee proposed in the
International Committee on Taxonomy of Viruses (ICTV) to change the
Filovirus genus to the
Filoviridae family with two specific genera:
Ebola-like viruses and
Marburg-like viruses.
This proposal was implemented in Washington, DC on April 2001 and in
Paris on July 2002. In 2000, another proposal was made in Washington,
D.C., to change the "-like viruses" to "-virus" resulting in today's
Ebolavirus and
Marburgvirus.
[54]
Phylogenetic tree comparing the Ebolavirus and Marburgvirus. Numbers indicate percent confidence of branches.
Rates of genetic change are 100 times slower than
influenza A in humans, but on the same magnitude as those of
hepatitis B.
Extrapolating backwards using these rates indicates that Ebolavirus and Marburgvirus diverged several thousand years ago.
[55] However,
paleoviruses (genomic fossils) of
filoviruses (Filoviridae) found in mammals indicate that the family itself is at least tens of millions of years old.
[16] Fossilized viruses that are closely related to ebolaviruses have been found in the genome of the
Chinese hamster.
[56]
The five characterised Ebola species are:
- Zaire ebolavirus (EBOV; previously ZEBOV)
- Also known simply as the Zaire virus, ZEBOV has the highest case-fatality rate
of the ebolaviruses, up to 90% in some epidemics, with an average case
fatality rate of approximately 83% over 27 years. There have been more
outbreaks of Zaire ebolavirus than of any other species. The first outbreak occurred on 26 August 1976 in Yambuku.[57] The first recorded case was Mabalo Lokela, a 44‑year-old schoolteacher. The symptoms resembled malaria, and subsequent patients received quinine. Transmission has been attributed to reuse of unsterilized needles and close personal contact.
- Sudan ebolavirus (SUDV; previously SEBOV)
- Like the Zaire virus, SEBOV emerged in 1976; it was at first assumed to be identical with the Zaire species.[58] SEBOV is believed to have broken out first among cotton factory workers in Nzara, Sudan (now South Sudan), with the first case reported as a worker exposed to a potential natural reservoir.
The virus was not found in any of the local animals and insects that
were tested in response. The carrier is still unknown. The lack of barrier nursing
(or "bedside isolation") facilitated the spread of the disease. The
most recent outbreak occurred in May, 2004. Twenty confirmed cases were
reported in Yambio County, Sudan (now South Sudan), with five deaths resulting. The average fatality rates for SEBOV were 54% in 1976, 68% in 1979, and 53% in 2000 and 2001.
- Reston ebolavirus (RESTV; previously REBOV)
- Discovered during an outbreak of simian hemorrhagic fever virus (SHFV) in crab-eating macaques from Hazleton Laboratories (now Covance) in 1989. Since the initial outbreak in Reston, Virginia, it has since been found in non-human primates in Pennsylvania, Texas and Siena, Italy. In each case, the affected animals had been imported from a facility in the Philippines,[59] where the virus has also infected pigs.[60] Despite having a Biosafety status of Level‑4 and its apparent pathogenicity in monkeys, REBOV did not cause disease in exposed human laboratory workers.[61]
- Côte d'Ivoire ebolavirus (TAFV; previously CIEBOV)
- Also referred to as Taï Forest ebolavirus and by the English place name, "Ivory Coast", it was first discovered among chimpanzees from the Taï Forest in Côte d'Ivoire, Africa, in 1994. Necropsies
showed blood within the heart to be brown; no obvious marks were seen
on the organs; and one necropsy showed lungs filled with blood. Studies
of tissues taken from the chimpanzees showed results similar to human
cases during the 1976 Ebola outbreaks in Zaire and Sudan. As more dead
chimpanzees were discovered, many tested positive for Ebola using
molecular techniques. The source of the virus was believed to be the
meat of infected Western Red Colobus
monkeys, upon which the chimpanzees preyed. One of the scientists
performing the necropsies on the infected chimpanzees contracted Ebola.
She developed symptoms similar to those of dengue fever
approximately a week after the necropsy, and was transported to
Switzerland for treatment. She was discharged from the hospital after
two weeks and had fully recovered six weeks after the infection.[62]
- Bundibugyo ebolavirus (BDBV; previously BEBOV)
- On 24 November 2007, the Uganda Ministry of Health confirmed an outbreak of Ebolavirus in the Bundibugyo District. After confirmation of samples tested by the United States National Reference Laboratories and the CDC, the World Health Organization
confirmed the presence of the new species. On 20 February 2008, the
Uganda Ministry officially announced the end of the epidemic in
Bundibugyo, with the last infected person discharged on 8 January 2008.[63]
An epidemiological study conducted by WHO and Uganda Ministry of Health
scientists determined there were 116 confirmed and probable cases of
the new Ebola species, and that the outbreak had a mortality rate of 34%
(39 deaths). In 2012, there was an outbreak of Bundibugyo ebolavirus in
a northeastern province of the Democratic Republic of the Congo. There
were 15 confirmed cases and 10 fatalities.[64]
Prevention
Ebola viruses are highly
infectious as well as
contagious. Governments and individuals often quickly respond to
quarantine the area while the lack of roads and transportation in many parts of Africa helps to contain the outbreak.
[59]
Airline crews are trained to spot the symptoms of Ebola in passengers
flying from places where the virus is found. Crews are told to
quarantine anyone who looks infected.
[65]
As an outbreak of ebola progresses, bodily fluids from diarrhea,
vomiting, and bleeding represent a hazard. Due to lack of proper
equipment and hygienic practices, large-scale epidemics occur mostly in
poor, isolated areas without modern hospitals or well-educated medical
staff. Many areas where the infectious reservoir exists have just these
characteristics. In such environments, all that can be done is to
immediately cease all needle-sharing or use without adequate
sterilization
procedures, isolate patients, and observe strict barrier nursing
procedures with the use of a medical-rated disposable face mask, gloves,
goggles, and a gown at all times, strictly enforced for all medical
personnel and visitors.
[66]
The aim of all of these techniques is to avoid any person’s contact
with the blood or secretions of any patient, including those who are
deceased.
[67]
Vaccines have protected nonhuman primates. The six months needed for
immunization impede counter-epidemic uses. In 2003, a vaccine using an
adenoviral
(ADV) vector carrying the Ebola spike protein therefore was tested on
crab-eating macaques. The monkeys twenty-eight days later were
challenged with the virus and remained resistant.
[68] A vaccine based on attenuated recombinant
vesicular stomatitis virus (VSV) vector carrying either the Ebola glycoprotein or the Marburg glycoprotein in 2005 protected nonhuman primates,
[69] opening clinical trials in humans.
[70]
The study by October completed the first human trial, over three months
giving three vaccinations safely inducing an immune response.
Individuals for a year were followed, and, in 2006, a study testing a
faster-acting, single-shot vaccine began; this new study was completed
in 2008.
[71] Trying the vaccine on a strain of Ebola that more resembles the one that infects humans is the next step.
[citation needed]
The
Food and Drug Administration has approved no candidate
vaccines,
[72][73][74] the most promising whereof are
DNA vaccines[75] or derive from
adenoviruses,
[68] vesicular stomatitis Indiana virus (VSIV)[76][77][78] or
filovirus-like particles (VLPs)[79]
because these candidates could protect nonhuman primates from
ebolavirus-induced disease. DNA vaccines, adenovirus-based vaccines, and
VSIV-based vaccines have entered clinical trials.
[70][71][80][81]
Ebolaviruses are not transmitted by
aerosol during natural EVD outbreaks. Without an approved vaccine, EVD prevention predominantly involves behavior modification, proper
personal protective equipment, and
sterilization/
disinfection.
On 6 December 2011, the development of a successful
vaccine against Ebola for mice was reported. Unlike the predecessors, it can be
freeze-dried and thus stored for long periods in wait for an outbreak. The research is reported in
Proceedings of National Academy of Sciences.
[82]
Endemic zones
The natural maintenance hosts of ebolaviruses are unidentified:
primary infection cannot necessarily be prevented in nature. Avoiding
EVD such risk factors as contact with
bats or nonhuman
primates
therefore is highly recommended and may be impossible for inhabitants
of tropical forests or people dependent on nonhuman primates as a
food source.
During outbreaks
The most straightforward prevention method during EVD outbreaks is not touching patients, their
excretions, and
body fluids, or possibly
contaminated
materials and utensils. Patients should be isolated, and medical staff
should be trained and apply strict barrier nursing techniques
(disposable face mask, gloves, goggles, and a gown at all times).
Traditional
burial rituals, especially those requiring
embalming of bodies, should be discouraged or modified.
[66]
In the laboratory
Ebola viruses are
World Health Organization Risk Group 4 Pathogens, requiring
Biosafety Level 4-equivalent containment. Laboratory researchers have to be properly trained in BSL-4 practices and wear proper personal protective equipment.
Treatment
A hospital isolation ward in
Gulu,
Uganda, during the October 2000 outbreak
No ebolavirus-specific treatment exists. Treatment is primarily
supportive in nature and includes minimizing invasive procedures,
balancing fluids and
electrolytes to counter
dehydration, administration of
anticoagulants early in infection to prevent or control
disseminated intravascular coagulation, administration of
procoagulants late in infection to control
hemorrhaging, maintaining
oxygen levels,
pain management, and administration of
antibiotics or
antimycotics to treat secondary infections.
[83][84][85]
Experimental therapies
Hyperimmune equine immunoglobulin
raised against EBOV has been used in Russia to treat a laboratory
worker who accidentally infected herself with EBOV—but the patient died
anyway.
[86] Experimentally, recombinant
vesicular stomatitis Indiana virus
(VSIV) expressing the glycoprotein of EBOV or SUDV has been used
successfully in nonhuman primate models as post-exposure prophylaxis.
[87][88]
Such a recombinant post-exposure vaccine was also used to treat a
German researcher who accidentally pricked herself with a possibly
EBOV-contaminated needle. Treatment might have been successful as she
survived. However, actual EBOV infection could never be demonstrated
without a doubt.
[89] Novel, very promising, experimental therapeutic regimens rely on
antisense technology. Both
small interfering RNAs (siRNAs) and
phosphorodiamidate morpholino oligomers (PMOs) targeting the EBOV genome could prevent disease in nonhuman primates.
[90][91]
Researchers from the U.S. Army Medical Research Institute of
Infectious Diseases also found that FDA-Approved estrogen receptor drugs
used to treat infertility and breast cancer (
clomiphene and
toremifene) inhibit the progress of Ebola virus in infected mice.
[92] Ninety percent of the mice treated with clomiphene and 50 percent of those treated with toremifene survived the tests.
[93]
The authors of the study concluded that given their oral availability
and history of human use, these drugs would be excellent candidates for
repurposing efforts to treat Ebola virus infection in remote
geographical locations, either on their own or together with other
antiviral drugs.
During an outbreak in the Democratic Republic of the Congo in 1995,
seven of eight patients having received blood transfusions from
convalescent individuals survived.
[94] However, this potential treatment is considered controversial.
[58]
Prognosis
In general, outcomes are poor with 68% of all cases resulting in death
[citation needed]. If an infected person survives, recovery may be quick and complete, or prolonged with long term problems, such as
inflammation of the testicles,
joint pains,
muscle pains,
skin peeling, or
hair loss. Eye symptoms, such as
light sensitivity,
excess tearing,
iritis,
iridocyclitis,
choroiditis and
blindness have also been described. EBOV and SUDV may be able to persist in the
sperm of some survivors, which could give rise to secondary infections and disease via
sexual intercourse.
[1]
Epidemiology
Outbreaks of EVD have occurred mainly in Africa.
Ebola virus disease (EVD) outbreaks
| 1976 |
SUDV |
Juba, Maridi, Nzara, and Tembura, Sudan |
151 |
284 |
53% |
| 1976 |
EBOV |
Yambuku, Zaire |
280 |
318 |
88% |
| 1977 |
EBOV |
Bonduni, Zaire |
1 |
1 |
100% |
| 1979 |
SUDV |
Nzara, Sudan |
22 |
34 |
65% |
| 1988 |
EBOV |
Porton Down, United Kingdom [laboratory accident] |
0 |
1 |
0% |
| 1994 |
TAFV |
Taï National Park, Côte d'Ivoire |
0 |
1 |
0% |
| 1994–1995 |
EBOV |
Woleu-Ntem and Ogooué-Ivindo Provinces, Gabon |
32 |
52 |
62% |
| 1995 |
EBOV |
Kikwit, Zaire |
245 |
317 |
77% |
| 1996 |
EBOV |
Mayibout 2, Gabon |
21 |
31 |
68% |
| 1996 |
EBOV |
Sergiyev Posad, Russia [laboratory accident] |
1 |
1 |
100% |
| 1996–1997 |
EBOV |
Ogooué-Ivindo Province, Gabon; Cuvette-Ouest Department, Republic of the Congo |
46 |
62 |
74% |
| 2000–2001 |
SUDV |
Gulu, Mbarara, and Masindi Districts, Uganda |
224 |
425 |
53% |
| 2001–2002 |
EBOV |
Ogooué-Ivindo Province, Gabon; Cuvette-Ouest Department, Republic of the Congo |
97 |
124 |
78% |
| 2002 |
EBOV |
Ogooué-Ivindo Province, Gabon; Cuvette-Ouest Department, Republic of the Congo |
10 |
11 |
91% |
| 2002–2003 |
EBOV |
Cuvette-Ouest Department, Republic of the Congo; Ogooué-Ivindo Province, Gabon |
128 |
143 |
90% |
| 2003–2004 |
EBOV |
Cuvette-Ouest Department, Republic of the Congo |
29 |
35 |
83% |
| 2004 |
EBOV |
Koltsovo, Russia [laboratory accident] |
1 |
1 |
100% |
| 2004 |
SUDV |
Yambio County, Sudan |
7 |
17 |
41% |
| 2005 |
EBOV |
Cuvette-Ouest Department, Republic of the Congo |
9 |
11 |
82% |
| 2007 |
EBOV |
Kasai Occidental Province, Democratic Republic of the Congo |
186 |
264 |
71% |
| 2007–2008 |
BDBV |
Bundibugyo District, Uganda |
39 |
116 |
34% |
| 2008–2009 |
EBOV |
Kasai Occidental Province, Democratic Republic of the Congo |
15 |
32 |
47% |
| 2011 |
SUDV |
Luweero District, Uganda |
1 |
1 |
100% |
| 2012 |
SUDV |
Kibaale District, Western Uganda |
17 |
24 |
71% |
| 2012 |
BDBV |
Orientale Province, Democratic Republic of the Congo |
34 |
62 |
54% |
| 2014 |
EBOV |
Guinea, Sierra Leone, Liberia [95] |
337 |
528 (364 laboratory confirmed) |
64% |
CDC worker incinerates med-waste from Ebola patients in Zaire in 1976
While investigating an outbreak of
Simian hemorrhagic fever virus (SHFV) in November 1989, an electron microscopist from
USAMRIID discovered filoviruses similar in appearance to Ebola in tissue samples taken from
crab-eating macaque imported from the Philippines to Hazleton Laboratories Reston, Virginia.
[96]
Blood samples were taken from 178 animal handlers during the incident.
[97] Of those, six animal handlers eventually
seroconverted. When the handlers failed to become ill, the CDC concluded that the virus had a very low pathogenicity to humans.
[98]
Because of the virus's high mortality, it is a potential agent for biological warfare.
[99]
Given the lethal nature of Ebola, and since no approved
vaccine or treatment is available, it is classified as a
biosafety level 4 agent, as well as a
Category A bioterrorism agent by the Centers for Disease Control and Prevention. It has the potential to be weaponized for use in
biological warfare.
[100] The BBC reports in a study that frequent outbreaks of Ebola may have resulted in the deaths of 5,000 gorillas.
[101]
2007 to 2011
As of 30 August 2007, 103 people (100 adults and three children) were
infected by a suspected hemorrhagic fever outbreak in the village of
Kampungu,
Democratic Republic of the Congo. The outbreak started after the
funerals of two village chiefs, and 217 people in four villages fell
ill. The World Health Organization sent a team to take blood samples for
analysis and confirmed that many of the cases are the result of
Ebolavirus.
[102][103] The Congo's last major Ebola epidemic killed 245 people in 1995 in
Kikwit, about 200 miles (320 km) from the source of the August 2007 outbreak.
[104]
On 30 November 2007, the Uganda Ministry of Health confirmed an
outbreak of Ebola in the Bundibugyo District. After confirmation of
samples tested by the United States National Reference Laboratories and
the Centers for Disease Control, the World Health Organization confirmed
the presence of a new species of
Ebolavirus, which is now tentatively named Bundibugyo.
[105]
The epidemic came to an official end on 20 February 2008. While it
lasted, 149 cases of this new strain were reported, and 37 of those led
to deaths.
An International Symposium to explore the environment and filovirus,
cell system and filovirus interaction, and filovirus treatment and
prevention was held at Centre Culturel Français,
Libreville, Gabon, during March 2008.
[106] The virus appeared in southern
Kasai Occidental on 27 November 2008,
[107] and blood and stool samples were sent to laboratories in Gabon and South Africa for identification.
On 25 December 2008, a mysterious disease that had killed 11 and
infected 21 people in southern Democratic Republic of Congo was
identified as the Ebola virus.
[108]
Doctors Without Borders reported 11 deaths as of 29 December 2008 in
the Western Kasai province of the Democratic Republic of Congo, stating
that a further 24 cases were being treated. In January 2009, Angola
closed down part of its border with DRC to prevent the spread of the
outbreak.
[109]
On 12 March 2009, an unidentified 45-year-old scientist from Germany
accidentally pricked her finger with a needle used to inject Ebola into
lab mice. She was given an experimental vaccine never before used on
humans. Since the peak period for an outbreak during the 21-day Ebola
incubation period has passed as of 2 April 2009, she has been declared
healthy and safe. It remains unclear whether or not she was ever
actually infected with the virus.
[110]
In May 2011, a 12-year-old girl in Uganda died from Ebola (Sudan subspecies). No further cases were recorded.
[111]
2012 outbreaks
In July 2012, the Ugandan Health Ministry confirmed 13 deaths due to an outbreak of the Ebola-Sudan variant
[112] in the
Kibaale District.
[113] As of 28 July 2012, 14 out of 20 (70% mortality rate) had died in Kibaale.
[114] On July 30,
Stephen Byaruhanga, a health official in Kibaale District, said the Ebola outbreak has spread from one remote village to several villages.
[115]
The
World Health Organization's
global and alert response network reported on August 3 that the
suspected case count had risen to 53, including 16 deaths. Of these
cases, five were confirmed by
UVRI as Ebola cases. There have been no confirmed cases outside of
Kibaale District except for a patient who was medically evacuated to
Kampala District and has since died.
WHO and
CDC support is on the ground in Uganda supporting the government response. There have been no confirmed cases outside of
Uganda.
[116]
Included among the populations confirmed to be affected are prisoners
in Kabbale prison. One of the inmates suspected of infection escaped
from medical isolation on the same day.
[117] Dr. Joaquim Saweka, the
WHO
representative to Uganda, also reported that the outbreak was then
under control and that everyone known to have had contact with a known
Ebola patient is now in isolation.
[118]
On 8 August 2012, the Ugandan Ministry of Health has recorded 23
probable and confirmed cases, including 16 deaths. Ten cases were
confirmed by the
Uganda Virus Research Institute
as Ebola. 185 people who came into contact with probable and confirmed
Ebola cases are being followed up during the incubation period of 21
days.
[119]
On 17 August 2012, the Ministry of Health of the
Democratic Republic of the Congo reported an outbreak of the Ebola-Bundibugyo variant
[120] in the eastern region.
[121] By August 21, the
WHO reported a total of 15 cases and 10 fatalities.
[122] No evidence suggests that this outbreak connects to the Ugandan outbreak.
[123]
By 13 September 2012, the World Health Organisation revealed that the
virus had claimed 32 lives and that the probable cause of the outbreak
was tainted bush-meat hunted by local villagers around the towns of
Isiro and Viadana.
[124]
2014 outbreak
In February 2014, a strain of the Ebola Virus appeared in
Guinea.
This is the first Ebola virus outbreak registered in the region. As of
April 10, 157 suspected and confirmed cases and 101 deaths have been
reported in Guinea, 22 suspected cases in
Liberia including 14 deaths, 8 suspected cases in
Sierra Leone including 6 deaths, and 1 suspected case in
Mali.
[125][126] Investigations on these are under way.
[127][128][129]
History
Cases of ebola fever in Africa from 1979 to 2008.
Ebola virus first emerged in 1976 in outbreaks of Ebola hemorrhagic fever in Zaire and Sudan.
[130] The strain of Ebola that broke out in Zaire has one of the highest
case fatality rates of any human virus, roughly 90%.
[131]
The name of the disease originated from one of those first recorded outbreaks in 1976 in
Yambuku, Democratic Republic of the Congo (then Zaire) which lies on the
Ebola River.
The Philippines and the United States had no previous cases of
infection, and upon further isolation it was concluded to be another
strain of Ebola or a new filovirus of Asian origin, and named
Reston ebolavirus (REBOV) after the location of the incident.
Some scientists also believe that the Plague of Athens, which wiped out about a third of its inhabitants during the
Peloponnesian War, may have been caused by Ebola. However, these studies are conflicting, and point to other possible diseases such as typhoid.
[132]
Other animals
In general, outbreaks of EVD among human populations result from
handling infected wild animal carcasses. In general, declines in animal
populations precede outbreaks among human populations. Since 2003, such
declines have been monitored through surveillance of animal populations
with the aim of predicting and preventing EVD outbreaks in humans.
[133]
Recovered carcasses from gorillas contain multiple Ebola virus strains,
which suggest multiple introductions of the virus. Bodies decompose
quickly and carcasses are not infectious after three to four days.
Contact between gorilla groups is rare, suggesting transmission among
gorilla groups is unlikely, and that outbreaks result from transmission
between viral reservoir and animal populations.
[134]
Outbreaks of EVD may have been responsible for an 88% decline in
tracking indices of observed chimpanzee populations in 420 square
kilometer Lossi Sanctuary between 2002 and 2003.
[134] Transmission among chimpanzees through meat consumption constitutes a significant 5.2 (1.3–21.1 with 95%
confidence)
relative risk factor, while contact between individuals, such as touching dead bodies and grooming, do not.
[135]
Domestic animals
Ebola virus can be transmitted to
dogs and
pigs.
[136] While dogs may be asymptomatic, pigs tend to develop clinical disease.
Recent research
In late 2012, Canadian scientists discovered that the deadliest form of the virus could be transmitted by air between species.
[137]
They managed to prove that the virus was transmitted from pigs to
monkeys without any direct contact between them, leading to fears that
airborne transmission could be contributing to the wider spread of the
disease in parts of Africa. Evidence was also found that pigs might be
one of the
reservoir hosts for the virus; the fruit bat has long been considered as the reservoir.
[137]
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External links
Guinea – 390 cases, 270 deaths
Liberia – 51 cases, 34 deaths
Sierra Leone — 158 cases, 58 deaths[1]
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