Ebola virus causes Ebola hemorrhagic fever (EHF), a severe
disease (the fatality rate is 55 - 60%) that occurs in humans and some other
primates including gorillas and chimpanzees.
It was first thought that humans contracted disease as a
result of eating gorilla or chimpanzee meat but that is now thought to be
unlikely. EHF is a zoonotic disease and although the reservoir host is not know
precisely, much evidence points (as in several other important zoonotic
diseases) to bats. Specifically, contact with bat urine, saliva or feces.
The virus was first associated with human disease in 1976
when an outbreak occurred in the Democratic Republic of the Congo (DRC) near the
Ebola River in which there were 602 reported cases of hemorrhagic fever and 431
patients died. There have been several more recent outbreaks including in 1995
also in the DRC (315 cases and 254 deaths), in 2000 in Uganda (425 cases and 224
deaths), and in 2007 in Uganda and the DRC again (413 cases and 214 deaths).
In 2014, the largest Ebola outbreak so far occurred. By
April 2016, the number of suspected and confirmed cases was 28,652 with 15,261
laboratory confirmed cases and 11,325 deaths (figs. 1 and 2). This epidemic is thought to have started in a village in Guinea in an
area in which people often hunt bats.
Outbreaks of EHF are sporadic and exactly how humans pick
up the virus from the reservoir host is unknown. Indeed, though highly suspected
to be bats, the reservoir host has yet to be unequivocally identified. It is
probable that humans acquire the virus from saliva, feces and urine of infected
bats such as by eating contaminated food. The virus is usually not transmitted
in aerosols (as is the case with flu) but is spread by direct, close personal
contact with the bodily fluids (blood, urine, sweat) of an infected person.
Thus, if the infected patient is isolated and contact personnel wear protective
clothing, the outbreak should be contained. Most common transmission is to
persons who care for a patient (such as washing) or other close contact. In
areas where outbreaks occur, the hospital facilities are often unsanitary and
nosocomial infections occur as a result of direct contact with bodily fluids,
unsterilized needles and medical equipment.
It has been found that even after an apparent recovery, the
virus may remain in some body fluids, including semen. It appears that the rate
of elimination of Ebola from the semen is different for each man. It may last
for three to nine months. It appears that the amount of virus decreases over
Classically, Ebola virus is transmitted via body fluids
such as urine and blood of an infected person. In 2015, it was shown that
men who have survived the disease can have the virus in their semen. The
testis is an immune-privileged site and viruses that might be cleared from
elsewhere in the body may persist here. Viral RNA could be detected by
RT-PCR for up to 9 months from the start of the infection. In the current
2014 outbreak, there are estimated to be about 8,000 male survivors but
there have been only about 20 suspected cases of sexual Ebola virus
The Centers for Disease Control (CDC) list the following
symptoms for EHF:
Joint and muscle aches
Lack of appetite
Some patients may experience:
Symptoms may appear anywhere from 2 to 21 days after
exposure to the virus although 8-10 days is most common. Some who become sick
with EHF are able to recover, while others do not. The reasons behind this are
not yet fully understood. However, it is known that patients who die usually
have not developed a significant immune response to the virus at the time of
In about half of cases, the disease progresses to EHF.
Internal hemorrhage leads to blood in vomit, urine and feces. It can also be
seen under the skin and around the eyes and mouth. Unseen bleeding also occurs
internally and this loss of fluid causes a dramatic drop in blood pressure
leading to organ failure. It is the latter that kills the patient.
Countries in which
EHF has occurred
In Africa, confirmed cases of Ebola HF have been reported
Democratic Republic of the Congo (DRC)
of the Congo (ROC)
Initial diagnosis is difficult because of the non-specific
nature of the symptoms. If the initial stages of EHF are suspected (such as
recent travel in an Ebola virus-infected area), there are specific tests
available. ELIZA tests for specific Ebola proteins, PCR and direct isolation of
the virus may be used. Later the patient develops IgM and IgG antibodies.
In most situations, treatment is palliative. The patientís
electrolytes and body fluids, oxygen levels and blood pressure are normalized.
Any other infections that the patient has are also treated.
Antibody treatment -
There is a more specific experimental treatment that has
been tried with two Americans who were infected in Africa in the 2014 outbreak
and returned to Emory University Hospital in the United States for further care.
This therapy is now being made available in West Africa. The treatment is
called ZMapp (because it is made by Mapp Biopharmaceuticals). It is not a
vaccine because vaccines consist of antigens from the pathogen that stimulate
the hostís own immune response. Rather, ZMapp consists of already formed
exogenous antibodies against Ebola virus proteins. Hybridomas are produced from
mice that have been injected with Ebola proteins and the genes encoding the
anti-Ebola antibodies (the antigen binding site (Fab)) extracted. The genes are
then genetically engineered to produce a gene that has much of the mouse
antibody protein replaced by human protein. Only the active site, the antigen
binding site, remains as a mouse amino acid sequence. This is called
humanization of the mouse monoclonal antibody. The engineered gene is then
cloned into a plant transformation vector and using a system based on Agrobacterium,
Nicotiniana (tobacco) plants are infected. The tobacco
plants then produce the humanized antibody. ZMapp contains two monoclonal
antibodies (MB003 and ZMab) both of which have been shown to be effective in
very small post-exposure trials with rhesus macaques.
Natural Immunity of
EHF is a very uncommon disease and, though alarming, kills
far fewer people than diseases such as malaria. The French Institut de Recherche
pour la Developpment (IRD) found that a large number of people in Gabon have
anti-Ebola antibodies. In rural communities, IRD found that 15.3% of the
population had these antibodies but they had never had EHF or any disease
symptoms. Indeed, many Gabonese people in areas that have never experienced an
Ebola outbreak have these antibodies. Presumably they have nevertheless come in
contact with infected bat excrement. In some villages the prevalence of
anti-Ebola antibodies is as high as 33.8%. Further studies have shown that the
people expressing anti-Ebola antibodies have a higher number of T8 lymphocytes.
They appear to have a specific immune memory to Ebola virus. IRD researchers
suspect that these people have had a mild form of Ebola virus infection that did
not produce symptoms. It is likely that these people have developed a natural
immunity to subsequent Ebola infection. But why they never developed symptoms is
a mystery. Clearly the symptoms of even a non-hemorrhagic Ebola infection are
severe and likely to have been remembered.
There is no currently approved vaccine against Ebola;
however, several are in development, many of which are based on
replication-deficient and replication-competent viruses. A trial is underway
in West Africa using a vaccine (rVSV-ZEBOV) based in replication competent
vesicular stomatitis virus (VSV) which normally infects cows and other
animals but is harmless to humans. The recombinant VSV has been engineered
to express the surface glycoprotein of Zaire Ebola virus. In December 2016,
it was reported that this vaccine is 70 - 100% effective.
Several other Ebola vaccines are being tested.