Ebola, also known as Ebola virus disease (EVD) and Ebola hemorrhagic fever (EHF),
is a viral hemorrhagic fever in humans and other primates, caused by ebolaviruses.
[1] Symptoms typically start anywhere between two days and three weeks after
infection.[3] The first symptoms are usually fever, sore throat, muscle pain, and
headaches.[1] These are usually followed by vomiting, diarrhoea, rash and decreased
liver and kidney function,[1] at which point some people begin to bleed both
internally and externally.[1] It kills between 25% and 90% of those infected –
about 50% on average.[1] Death is often due to shock from fluid loss, and typically
occurs between six and 16 days after the first symptoms appear.[2] Early treatment
of symptoms increases the survival rate considerably compared to late start.[4] An
Ebola vaccine was approved by the US FDA in December 2019.
The virus spreads through direct contact with body fluids, such as blood from
infected humans or other animals,[1] or from contact with items that have recently
been contaminated with infected body fluids.[1] There have been no documented
cases, either in nature or under laboratory conditions, of spread through the air
between humans or other primates.[5] After recovering from Ebola, semen or breast
milk may continue to carry the virus for anywhere between several weeks to several
months.[1][6][7] Fruit bats are believed to be the normal carrier in nature; they
are able to spread the virus without being affected by it.[1] The symptoms of Ebola
may resemble those of several other diseases, including malaria, cholera, typhoid
fever, meningitis and other viral hemorrhagic fevers.[1] Diagnosis is confirmed by
testing blood samples for the presence of viral RNA, viral antibodies or the virus
itself.[1][8]
Control of outbreaks requires coordinated medical services and community
engagement,[1] including rapid detection, contact tracing of those exposed, quick
access to laboratory services, care for those infected, and proper disposal of the
dead through cremation or burial.[1][9] Prevention measures involve wearing proper
protective clothing and washing hands when in close proximity to patients and while
handling potentially infected bushmeat, as well as thoroughly cooking bushmeat.[1]
An Ebola vaccine was approved by the US FDA in December 2019.[10] While there is no
approved treatment for Ebola as of 2019,[11] two treatments
(atoltivimab/maftivimab/odesivimab and ansuvimab) are associated with improved
outcomes.[12] Supportive efforts also improve outcomes.[1] These include oral
rehydration therapy (drinking slightly sweetened and salty water) or giving
intravenous fluids, and treating symptoms.[1] In October 2020,
atoltivimab/maftivimab/odesivimab (Inmazeb) was approved for medical use in the
United States to treat the disease caused by Zaire ebolavirus.[13]
History and name
Ebola was first identified in 1976, in two simultaneous outbreaks, one in Nzara (a
town in South Sudan) and the other in Yambuku (the Democratic Republic of the
Congo), a village near the Ebola River, for which the disease was named.[1] Ebola
outbreaks occur intermittently in tropical regions of sub-Saharan Africa.[1]
Between 1976 and 2012, according to the World Health Organization, there were 24
outbreaks of Ebola resulting in a total of 2,387 cases, and 1,590 deaths.[1][14]
The largest Ebola outbreak to date was an epidemic in West Africa from December
2013 to January 2016, with 28,646 cases and 11,323 deaths.[15][16][17] On 29 March
2016, it was declared to no longer be an emergency.[18] Other outbreaks in Africa
began in the Democratic Republic of the Congo in May 2017,[19][20] and 2018.[21]
[22] In July 2019, the World Health Organization declared the Congo Ebola outbreak
a world health emergency.[23]
Signs and symptoms
Signs and symptoms of Ebola[24]
Onset
The length of time between exposure to the virus and the development of symptoms
(incubation period) is between 2 and 21 days,[1][24] and usually between 4 and 10
days.[25] However, recent estimates based on mathematical models predict that
around 5% of cases may take longer than 21 days to develop.[26]
Symptoms usually begin with a sudden influenza-like stage characterised by fatigue,
fever, weakness, decreased appetite, muscular pain, joint pain, headache, and sore
throat.[1][25][27][28] The fever is usually higher than 38.3 °C (101 °F).[29] This
is often followed by nausea, vomiting, diarrhoea, abdominal pain, and sometimes
hiccups.[28][30] The combination of severe vomiting and diarrhoea often leads to
severe dehydration.[31] Next, shortness of breath and chest pain may occur, along
with swelling, headaches, and confusion.[28] In about half of the cases, the skin
may develop a maculopapular rash, a flat red area covered with small bumps, five to
seven days after symptoms begin.[25][29]
Bleeding
In some cases, internal and external bleeding may occur.[1] This typically begins
five to seven days after the first symptoms.[32] All infected people show some
decreased blood clotting.[29] Bleeding from mucous membranes or from sites of
needle punctures has been reported in 40–50% of cases.[33] This may cause vomiting
blood, coughing up of blood, or blood in stool.[34] Bleeding into the skin may
create petechiae, purpura, ecchymoses or haematomas (especially around needle
injection sites).[35] Bleeding into the whites of the eyes may also occur.[36]
Heavy bleeding is uncommon; if it occurs, it is usually in the gastrointestinal
tract.[37] The incidence of bleeding into the gastrointestinal tract was reported
to be ~58% in the 2001 outbreak in Gabon,[38] but in the 2014–15 outbreak in the US
it was ~18%,[39] possibly due to improved prevention of disseminated intravascular
coagulation.[31]
Recovery or death
Recovery may begin between seven and 14 days after first symptoms.[28] Death, if it
occurs, follows typically six to sixteen days from first symptoms and is often due
to shock from fluid loss.[2] In general, bleeding often indicates a worse outcome,
and blood loss may result in death.[27] People are often in a coma near the end of
life.[28]
Those who survive often have ongoing muscular and joint pain, liver inflammation,
and decreased hearing, and may have continued tiredness, continued weakness,
decreased appetite, and difficulty returning to pre-illness weight.[28][40]
Problems with vision may develop.[41] It is recommended that survivors of EVD wear
condoms for at least twelve months after initial infection or until the semen of a
male survivor tests negative for Ebola virus on two separate occasions.[42]
Survivors develop antibodies against Ebola that last at least 10 years, but it is
unclear whether they are immune to additional infections.[43]
Cause
EVD in humans is caused by four of six viruses of the genus Ebolavirus. The four
are Bundibugyo virus (BDBV), Sudan virus (SUDV), Taï Forest virus (TAFV) and one
simply called Ebola virus (EBOV, formerly Zaire Ebola virus).[44] EBOV, species
Zaire ebolavirus, is the most dangerous of the known EVD-causing viruses, and is
responsible for the largest number of outbreaks.[45] The fifth and sixth viruses,
Reston virus (RESTV) and Bombali virus (BOMV),[46] are not thought to cause disease
in humans, but have caused disease in other primates.[47][48] All
five[clarification needed] viruses are closely related to marburgviruses.[44]
Virology
Main articles: Ebolavirus (taxonomic group) and Ebola virus (specific virus)
Electron micrograph of an Ebola virus virion
Ebolaviruses contain single-stranded, non-infectious RNA genomes.[49] Ebolavirus
genomes contain seven genes including 3'-UTR-NP-VP35-VP40-GP-VP30-VP24-L-5'-UTR.
[35][50] The genomes of the five different ebolaviruses (BDBV, EBOV, RESTV, SUDV
and TAFV) differ in sequence and the number and location of gene overlaps. As with
all filoviruses, ebolavirus virions are filamentous particles that may appear in
the shape of a shepherd's crook, of a "U" or of a "6," and they may be coiled,
toroid or branched.[50][51] In general, ebolavirions are 80 nanometers (nm) in
width and may be as long as 14,000 nm.[52]
Their life cycle is thought to begin with a virion attaching to specific cell-
surface receptors such as C-type lectins, DC-SIGN, or integrins, which is followed
by fusion of the viral envelope with cellular membranes.[53] The virions taken up
by the cell then travel to acidic endosomes and lysosomes where the viral envelope
glycoprotein GP is cleaved.[53] This processing appears to allow the virus to bind
to cellular proteins enabling it to fuse with internal cellular membranes and
release the viral nucleocapsid.[53] The Ebolavirus structural glycoprotein (known
as GP1,2) is responsible for the virus' ability to bind to and infect targeted
cells.[54] 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. The most abundant protein
produced is the nucleoprotein, whose concentration in the host cell determines when
L switches from gene transcription to genome replication. Replication of the viral
genome results in full-length, positive-strand antigenomes that are, in turn,
transcribed into genome copies of negative-strand virus progeny.[55] Newly
synthesised 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 from which they bud. The mature progeny particles then
infect other cells to repeat the cycle. The genetics of the Ebola virus are
difficult to study because of EBOV's virulent characteristics.[56]
Transmission
Life cycles of the Ebolavirus
An illustration of safe burial practices
It is believed that between people, Ebola disease spreads only by direct contact
with the blood or other body fluids of a person who has developed symptoms of the
disease.[57][58][59] Body fluids that may contain Ebola viruses include saliva,
mucus, vomit, feces, sweat, tears, breast milk, urine and semen.[6][43] The WHO
states that only people who are very sick are able to spread Ebola disease in
saliva, and the virus has not been reported to be transmitted through sweat. Most
people spread the virus through blood, feces and vomit.[60] Entry points for the
virus include the nose, mouth, eyes, open wounds, cuts and abrasions.[43] Ebola may
be spread through large droplets; however, this is believed to occur only when a
person is very sick.[61] This contamination can happen if a person is splashed with
droplets.[61] Contact with surfaces or objects contaminated by the virus,
particularly needles and syringes, may also transmit the infection.[62][63] The
virus is able to survive on objects for a few hours in a dried state, and can
survive for a few days within body fluids outside of a person.[43][64]
The Ebola virus may be able to persist for more than three months in the semen
after recovery, which could lead to infections via sexual intercourse.[6][65][66]
Virus persistence in semen for over a year has been recorded in a national
screening programme.[67] Ebola may also occur in the breast milk of women after
recovery, and it is not known when it is safe to breastfeed again.[7] The virus was
also found in the eye of one patient in 2014, two months after it was cleared from
his blood.[68] Otherwise, people who have recovered are not infectious.[62]
The potential for widespread infections in countries with medical systems capable
of observing correct medical isolation procedures is considered low.[69] Usually
when someone has symptoms of the disease, they are unable to travel without
assistance.[70]
Dead bodies remain infectious; thus, people handling human remains in practices
such as traditional burial rituals or more modern processes such as embalming are
at risk.[69] Of the cases of Ebola infections in Guinea during the 2014 outbreak,
69% are believed to have been contracted via unprotected (or unsuitably protected)
contact with infected corpses during certain Guinean burial rituals.[71][72]
Health-care workers treating people with Ebola are at greatest risk of infection.
[62] The risk increases when they do not have appropriate protective clothing such
as masks, gowns, gloves and eye protection; do not wear it properly; or handle
contaminated clothing incorrectly.[62] This risk is particularly common in parts of
Africa where the disease mostly occurs and health systems function poorly.[73]
There has been transmission in hospitals in some African countries that reuse
hypodermic needles.[74][75] Some health-care centres caring for people with the
disease do not have running water.[76] In the United States the spread to two
medical workers treating infected patients prompted criticism of inadequate
training and procedures.[77]
Human-to-human transmission of EBOV through the air has not been reported to occur
during EVD outbreaks,[5] and airborne transmission has only been demonstrated in
very strict laboratory conditions, and then only from pigs to primates, but not
from primates to primates.[57][63] Spread of EBOV by water, or food other than
bushmeat, has not been observed.[62][63] No spread by mosquitos or other insects
has been reported.[62] Other possible methods of transmission are being studied.
[64]
