Ebola virus disease

Definition

Ebola virus (see the image below) is one of at least 30 known viruses capable of causing viral
hemorrhagic fever syndrome. The genus Ebolavirus is currently classified into 5 separate species: Sudan
ebolavirus, Zaire ebolavirus, Tai Forest (Ivory Coast) ebolavirus, Reston ebolavirus, and Bundibugyo
ebolavirus. The 2014-2016 outbreak of Ebola virus disease in West Africa, involving Zaire ebolavirus,
was the largest outbreak of Ebola virus disease in history. As of September 17, 2019, an active outbreak
of Ebola virus disease (EVD) in the Democratic Republic of the Congo had resulted in 3,034 confirmed
and 111 probable cases of Ebola virus disease, including 2,103 attributable deaths. An experimental
vaccine has been credited with limiting the outbreak’s scope.

Causative agent

Ebola virus disease (EVD; formerly known as Ebola haemorrhagic fever) is caused by infection with
Ebola virus which belongs to the family Filoviridae. EVD in humans has an average case fatality rate of
around 50% (varied from 25% to 90% in previous outbreaks).

EVD first appeared in 1976 in South Sudan and the Democratic Republic of the Congo, the latter in a
village situated near the Ebola River, from which the disease took its name. The disease has appeared
sporadically since then. Confirmed cases of EVD have been reported mainly in sub-Saharan Africa
including the Democratic Republic of the Congo, Gabon, South Sudan, Cote D'Ivoire, Uganda and
Congo. 

The EVD outbreak which occurred in West Africa from March 2014 to January 2016 was the largest
outbreak since Ebola virus was first discovered in 1976. It affected mainly Guinea, Liberia and Sierra
Leone. In August 2018, an EVD outbreak was reported in the Democratic Republic of the Congo, with
more than 3000 cases reported by October 2019. 

Incubation period

The incubation period for Ebola varies from about two to 21 days. People are not contagious for the
disease until the first symptoms appear (sudden onset of fatigue, fever, muscle pain, headache, and/or sore
throat).

Mode of transmission
Scientists think people are initially infected with Ebola virus through contact with an infected animal,
such as a fruit bat or nonhuman primate. This is called a spill over event. After that, the virus spreads
from person to person, potentially affecting a large number of people. The virus spreads through direct
contact (such as through broken skin or mucous membranes in the eyes, nose, or mouth) with:

 Blood or body fluids (urine, saliva, sweat, feces, vomit, breast milk, and semen) of a person who
is sick with or has died from Ebola virus disease (EVD).
  Objects (such as clothes, bedding, needles, and medical equipment) contaminated with body
fluids from a person who is sick with or has died from EVD.
 Infected fruit bats or nonhuman primates (such as apes and monkeys).
 Semen from a man who recovered from EVD (through oral, vaginal, or anal sex). The virus can
remain in certain body fluids (including semen) of a patient who has recovered from EVD, even
if they no longer have symptoms of severe illness. There is no evidence that Ebola can be spread
through sex or other contact with vaginal fluids from a woman who has had Ebola.

When people become infected with Ebola, they do not start developing signs or symptoms right away.
This period between exposure to an illness and having symptoms is known as the incubation period. A
person can only spread Ebola to other people after they develop signs and symptoms of Ebola.

Additionally, Ebola virus is not known to be transmitted through food. However, in certain parts of the
world, Ebola virus may spread through the handling and consumption of wild animal meat or hunted wild
animals infected with Ebola. There is no evidence that mosquitoes or other insects can transmit Ebola
virus.

Signs and symptoms

The following 2 types of exposure history are recognized:

 Primary exposure – This typically involves travel to or work in an Ebola-endemic area

 Secondary exposure – This refers to human-to-human exposure (eg, medical caregivers, family
caregivers, or persons who prepared deceased patients for burial), primate-to-human exposure
(eg, animal care workers who provide care for primates), or persons who collect or prepare bush
meat for human consumption

Physical findings depend on the stage of disease at the time of presentation. With African-derived
Ebolavirus infection, there is an incubation period (typically 3-8 days in primary cases and slightly longer
in secondary cases).

Early findings may include the following:

 Fever  Maculopapular rash (best seen in white

 Pharyngitis patients)
 Severe constitutional signs and  Bilateral conjunctival injection
symptoms

Later findings may include the following:

 Expressionless facies
 Bleeding from intravenous (IV) puncture sites and mucous membranes
 Myocarditis and pulmonary edema
 In terminally ill patients, tachypnea, hypotension, anuria, and coma
Survivors of Ebola virus disease have developed the following late manifestations:

 Myalgias  Fatigue  Tinnitus

 Asymmetric and  Bulimia  Unilateral orchitis
migratory arthralgias  Amenorrhea  Suppurative parotitis
 Headache  Hearing loss

Laboratory/diagnostic tests

Basic blood tests

The early phase of infection is characterized by thrombocytopenia, leukopenia, and a pronounced

lymphopenia. Neutrophilia develops after several days, as do elevations in aspartate aminotransferase and
alanine aminotransferase. Bilirubin may be normal or slightly elevated.

With the onset of anuria, blood urea nitrogen and serum creatinine increase. Terminally ill patients may
develop a metabolic acidosis that may contribute to the observation that these patients often have
tachypnea, which may be an attempt at compensatory hyperventilation.

Studies for isolating virus

Definitive diagnosis rests on isolation of the virus by means of tissue culture or reverse-transcription
polymerase chain reaction (RT-PCR) assay. However, isolation of Ebola virus in tissue culture is a high-
risk procedure that can be performed safely only in a few high-containment laboratories throughout the
world.

Serologic testing for antibody and antigen

The indirect fluorescence antibody test (IFAT) is associated with false-positive results. Concerns over the
sensitivity and utility of this test have resulted in the development of confirmatory serologic tests. In
infected patients who survive long enough to develop an immune response, the immunoglobulin M (IgM)
and immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) tests may be useful in the
diagnosis of Ebola virus infection. Both ELISA tests have been demonstrated to be sensitive and specific.

IgM-capture ELISA uses Zaire ebolavirus antigens grown in Vero E6 cells to detect IgM antibodies to
this strain. Results become positive in experimental primates within 6 days of infection but do not remain
positive for extended periods. These qualities indicate that the IgM test may be used to document acute
Ebola infection. IgG-capture ELISA uses detergent-extracted viral antigens to detect IgG anti-Ebola
antibodies. It is more specific than the IFAT, and it remains positive for long periods. Accordingly, this
test appears to be superior for seroprevalence investigations. An antigen detection ELISA test is available
that identifies Ebola virus antigens.

Other studies

The risks in viral isolation have led to the development of various modalities that better lend themselves
to laboratories with limited containment systems. Tests used to confirm the diagnosis of Ebola virus
infection include an immunohistochemical test performed on formalin-fixed postmortem skin taken from
patients who have died of Ebola hemorrhagic fever. This test is safe, sensitive, and specific, and it can be
used for diagnosis and surveillance. Electron microscopy has been used to identify filoviruses in tissue
but has obvious limitations as a diagnostic modality in the areas where human outbreaks have occurred. It
is not readily available in areas where Ebola virus is endemic.

Treatment/Management

(MANAGEMENT)

General principles of care are as follows:

 Supportive therapy with attention to intravascular volume, electrolytes, nutrition, and comfort
care is of benefit to the patient.
 Such therapy must be administered with strict attention to barrier isolation; all body fluids contain
infectious virions and should be handled with great care.
 No specific therapy is available that has demonstrated efficacy in the treatment of Ebola
hemorrhagic fever.
 Ebola Zaire vaccine is approved in Europe and the United States. The live recombinant vaccine
has shown effectiveness of 97.5% in preventing infection among 90,000 individuals in an active
Ebola virus outbreak in the Democratic Republic of Congo.

At present, no specific anti-Ebolavirus agents are available. Agents that have been studied for the
treatment or prevention of Ebola virus disease include the following:

 Ribavirin (possesses no demonstrable anti- Ebolavirus activity in vitro and has failed to protect
Ebolavirus –infected primates)
 Nucleoside analogue inhibitors of S-adenosylhomocysteine hydrolase (SAH)
 Interferon beta
 Horse- or goat-derived immune globulins
 Human-derived convalescent immune globulin preparations
 Recombinant human interferon alfa-2
 Recombinant human monoclonal antibody against the envelope glycoprotein (GP) of Ebola virus
 DNA vaccines expressing either envelope GP or nucleocapsid protein (NP) genes of Ebola virus
 Activated protein C
 Recombinant inhibitor of factor VIIa/tissue factor

In those patients who do recover, recovery often requires months, and delays may be expected before full
resumption of normal activities. Weight gain and return of strength are slow. Ebola virus continues to be
present for many weeks after resolution of the clinical illness.

(TREATMENT)

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.

Ebola Zaire vaccine (rVSV-ZEBOV; V920; Merck) has been approved in the United States and Europe.
This vaccine is genetically engineered to express a glycoprotein from Zaire ebolavirus to provoke a
neutralizing immune response. It has shown an efficacy of 97.5% in preventing infection among 90,000
individuals in an active Ebola virus outbreak in the Democratic Republic of Congo.[2] In the Ring
vaccination study, in which patients were vaccinated during the 2014 outbreak in the Republic of Guinea,
results among the people who received the vaccine showed no Ebola cases were recorded 10 days or more
after vaccination. In comparison, there were 23 cases 10 days or more after vaccination among those who
did not receive the vaccine.

Prevention

The Centers for Disease Control and Prevention (CDC) recommends the following preventive measures
for people in an area affected by an outbreak:

 Practice careful hygiene (e.g., wash hands with soap and water, alcohol-based hand sanitizer, or
chlorine solution)
 Avoid contact with body fluids
 Do not handle items that have come into contact with an infected person's body fluids (e.g.,
clothes, medical equipment, needles)
 Avoid funeral or burial rituals that require handling of the body of someone who has died from
confirmed or suspected Ebola virus infection
 Avoid contact with nonhuman primates and bats, including body fluids or raw meat prepared
from these animals
 Avoid hospitals in West Africa in which infected patients are being treated (unless going there to
work)
 Returning travelers (including healthcare workers) should follow local policies for surveillance
and monitor their health for 21 days and seek medical attention if symptoms develop, especially
fever.

These same prevention methods apply when living in or traveling to an area affected by an Ebola
outbreak. After returning from an area affected by Ebola, monitor your health for 21 days and seek
medical care immediately if you develop symptoms of EVD.
Prevention in healthcare personnel

Guidance from the CDC recommends that healthcare personnel who care for patients infected with Ebola
virus (ie, physicians, nurses, other clinicians) wear personal protective equipment (PPE) that does not
expose any skin. This includes a surgical hood that covers the head and neck and a single-use full face
shield (rather than goggles), in addition to either a N95 respirator or powered air-purifying respirator
instead of a mask.

The CDC now recommends that clinicians train rigorously at donning and doffing PPE in a stepwise
manner and demonstrate competency. A trained monitor should oversee each time a clinician puts on and
takes off this gear. During patient care, the PPE should not be adjusted, and the worker’s gloved hands
should be disinfected frequently using an alcohol-based hand rub (ABHR), especially after body fluids
are handled.

Ebola Vaccine

The U.S. Food and Drug Administration (FDA) approved the Ebola vaccine rVSV-ZEBOV (tradename
“Ervebo”) on December 19, 2019. The rVSV-ZEBOV vaccine is a single dose vaccine regimen that has
been found to be safe and protective against only the Zaire ebolavirus species of ebolavirus. This is the
first FDA approval of a vaccine for Ebola.

Another investigational vaccine was developed and introduced under a research protocol in 2019 to
combat an Ebola outbreak in the Democratic Republic of the Congo. This vaccine leverages two different
vaccine components (Ad26.ZEBOV and MVA-BN-Filo) and requires two doses with an initial dose
followed by a second “booster” dose 56 days later. The second vaccine is also designed to protect against
only the Zaire ebolavirus species of Ebola.