April 15, 2014

What is Ebola Virus Disease (EVD)?

EBOLA VIRAL DISEASE (EVD)

Ebola virus disease (formerly, Ebola haemorrhagic fever) is one of the Viral Hemorrhagic Fevers. It is a severe, often fatal disease in humans and nonhuman primates (such as monkeys, gorillas, and chimpanzees). It is one of the world’s deadliest and most virulent diseases.

The first Ebolavirus species was discovered in 1976 in two simultaneous outbreaks, in Sudan and in what is now the Democratic Republic of Congo. The DRC outbreak was near the Ebola River, from which the disease takes its name.

Since then, outbreaks have appeared sporadically, and the disease has since killed more than 1,500 people in parts of Africa.

Ebola virus
The Ebola virus
The outbreak that began in Guinea in early 2014 is the first among humans in West Africa. The virus strain detected is Zaire, the most virulent.

Causes

Ebola Virus Disease (EVD) is caused by infection with a virus of the family Filoviridae, genus Ebolavirus.

There are five identified subspecies of Ebolavirus. Four of the five have caused disease in humans:
  1. Ebola virus (Zaire ebolavirus);
  2. Sudan virus (Sudan ebolavirus);
  3. Taï Forest virus (Taï Forest ebolavirus, formerly Côte d’Ivoire ebolavirus); and
  4. Bundibugyo virus (Bundibugyo ebolavirus).
The fifth, Reston virus (Reston ebolavirus), has caused disease in nonhuman primates, but not in humans.

Mode of Transmission

The natural reservoir host of ebolaviruses remains unknown. However, on the basis of available evidence and the nature of similar viruses, researchers believe that the virus is zoonotic (animal-borne) with fruit bats being the most likely reservoir. Infected bats are believed to transmit the disease directly to humans, or indirectly through other animals which are hunted for their meat.

Four of the five subtypes of the virus occur in an animal host native to Africa.

A host of similar species is probably associated with Reston virus, which was isolated from infected cynomolgous monkeys imported to the United States and Italy from the Philippines. Several workers in the Philippines and in US holding facility outbreaks became infected with the virus, but did not become ill.

The virus can be transmitted by direct contact with the blood, body fluids and tissues of infected animals or people.

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.

Pathophysiology of Ebola virus disease
Pathogenesis schematic (source: Wikipedia)
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.

Clinical features

When infection occurs, symptoms usually begin abruptly.

Symptoms are non-specific, however, making the disease difficult to diagnose. The symptoms can appear from two to 21 days after exposure.

Many of those infected with the virus quickly get flu-like symptoms such as fever, intense weakness, muscle pain, headache and sore throat. This is followed by vomiting, diarrhoea, rash, impaired kidney and liver function, and in some cases, both internal and external bleeding.

Severely ill patients require intensive supportive care.

Investigations

Diagnosing Ebola HF in an individual who has been infected for only a few days is difficult, because the early symptoms, such as red eyes and a skin rash, are nonspecific to ebolavirus infection and are seen often in patients with more commonly occurring diseases.

However, if a person has the early symptoms of Ebola HF and there is reason to believe that EVD should be considered, the patient should be isolated and samples collected and tested to confirm infection.

Timeline of InfectionDiagnostic tests available
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

Treatment

There is no specific vaccine or cure available for the disease. The most serious cases require intensive care and intravenous fluids to combat dehydration.

Preventive measures

Ebola can be caught from both humans and animals. It spreads by direct contact with blood, body fluids or tissues of the infected.

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.

Funeral rituals in which relatives and friends touch the body of the dead play an important role in transmission, as does handling dead (or living) animals carrying the virus. Touching these dead bodies must be avoided.

Prognosis

Ebola Virus Disease is one of the world’s deadliest and most virulent diseases, with a case fatality rate of up to 90%.

During an outbreak, those at higher risk of infection are health workers, family members and others in close contact with sick people and deceased patients.

Ebola virus disease outbreaks can devastate families and communities, but the infection can be controlled through the use of recommended protective measures in clinics and hospitals, at community gatherings, or at home.

References:
  1. WHO Global Alert and Response (GAR): Ebola virus disease (EVD) - World Health Organization. Downloaded on 15/04/2014. Available online at http://www.who.int/csr/disease/ebola/en/.
  2. CDC: 2014: Ebola Hemorrhagic Fever Outbreak in Guinea and Liberia - Centers for Disease Control and Prevention. Downloaded on 15/04/2014. Available online at http://www.cdc.gov/vhf/ebola/outbreaks/guinea/index.html.
  3. Wikipedia: Ebola virus disease. Downloaded on 15/04/2014. Available online at http://en.wikipedia.org/wiki/Ebola_virus_disease.

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