Ebola Virus Disease: What You Should Know

WebMD

Ebola Virus Disease:

Ebola virus disease (EVD), formerly known as Ebola haemorrhagic fever, is a severe, often fatal illness in humans. The virus is transmitted to people from wild animals and spreads in the human population through human-to-human transmission. The average EVD case fatality rate is around 50%. Case fatality rates have varied from 25% to 90% in past outbreaks.

The first EVD outbreaks occurred in remote villages in Central Africa, near tropical rainforests, but the most recent outbreak in west Africa has involved major urban as well as rural areas. Community engagement is key to successfully controlling outbreaks. Good outbreak control relies on applying a package of interventions, namely case management, surveillance and contact tracing, a good laboratory service, safe burials and social mobilisation. Early supportive care with rehydration, symptomatic treatment improves survival. There is as yet no licensed treatment proven to neutralise the virus but a range of blood, immunological and drug therapies are under development.

Risk of Exposure to Ebola:

Healthcare providers caring for Ebola patients and the family and friends in close contact with Ebola patients are at the highest risk of getting sick because they may come in contact with the blood or body fluids of sick patients. People also can become sick with Ebola after coming in contact with infected wildlife. For example, in Africa, Ebola may spread as a result of handling bushmeat (wild animals hunted for food) and contact with infected bats. The virus also can be spread through contact with objects (like clothes, bedding, needles, syringes/sharps or medical equipment) that have been contaminated with the virus or with infected animals.

Transmission of Ebola:

It is thought that fruit bats of the Pteropodidae family are natural Ebola virus hosts. Ebola is introduced into the human population through close contact with the blood, secretions, organs or other bodily fluids of infected animals such as chimpanzees, gorillas, fruit bats, monkeys, forest antelope and porcupines found ill or dead or in the rainforest.

Ebola then spreads through human-to-human transmission via direct contact (through broken skin or mucous membranes) with the blood, secretions, organs or other bodily fluids of infected people, and with surfaces and materials (e.g. bedding, clothing) contaminated with these fluids.

Health-care workers have frequently been infected while treating patients with suspected or confirmed EVD. This has occurred through close contact with patients when infection control precautions are not strictly practiced.

Burial ceremonies in which mourners have direct contact with the body of the deceased person can also play a role in the transmission of Ebola.

People remain infectious as long as their blood and body fluids, including semen and breast milk, contain the virus. Men who have recovered from the disease can still transmit the virus through their semen for up to 7 weeks after recovery from illness.

Pathophysiology of Ebola:

Cells lining the inside of blood vessels (endothelial cells), macrophages, monocytes, and liver cells are the main targets of infection. Macrophages are the first cells to be infected with the virus and this infection results in cellular death. Endothelial cells can be infected within three days after exposure to the virus. After infection, a secreted glycoprotein, known as small soluble glycoprotein (sGP) or as the Ebola virus glycoprotein (GP), is synthesized. Ebola virus 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. 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. The presence of viral particles and cell damage resulting from viruses budding out of the cell causes the release of chemical signals (such as TNF-α, IL-6, and IL-8), which are molecular signals for fever and inflammation.

The damage to human cells, caused by infection of the endothelial cells, decreases blood vessel integrity. This loss of vascular integrity is furthered with the synthesis of GP, which reduces specific integrins responsible for cell adhesion to the intercellular structure, and damage to the liver, which leads to improper clotting.

Filoviral infection is also known to interfere with proper functioning of the innate immune system. Ebola virus proteins blunt the human immune system’s response to viral infections by interfering with cells’ ability to produce and respond to interferon proteins such as interferon-alpha, interferon-beta, and interferon gamma. This interference is accomplished by the VP24 and VP35 ebola virus structural proteins.

When a cell is infected with ebola virus, receptors located in the cell’s cytosol (such as RIG-I and MDA5) or outside of the cytosol (such as Toll-like receptor 3, Toll-like receptor 7, Toll-like receptor 8, and Toll-like receptor 9), recognize infectious molecules associated with the virus.

After these receptors are activated, proteins including interferon regulatory factor 3 and interferon regulatory factor 7 start a signaling cascade that leads to the expression of type 1 interferons. Type 1 interferons are then released and bind to the IFNAR1 and IFNAR2 receptors expressed on the surface of the neighboring cell.

Once interferon has bound to its receptors on the neighboring cell, the signaling proteins STAT1 and STAT2 are activated and move to the cell’s nucleus. This triggers the expression of interferon-stimulated genes, which code for proteins that have antiviral properties.

Ebolavirus’ V24 protein prevents the STAT1 signaling protein in the neighboring cell from entering the nucleus and therefore prevents the creation of these antiviral proteins. A separate ebola virus protein, known as VP35, directly inhibits the production of interferon-beta. The ability to inhibit these immune responses creates an environment in which Ebolavirus can quickly spread throughout the body.

Signs and Symptoms of Ebola:

Signs and Symptoms of Ebola.

Symptoms usually begin with a sudden influenza-like stage characterized by feeling tired, fever, pain in the muscles and joints, headache, and sore throat. The fever is usually greater than 38.3 °C (100.9 °F). This is often followed by: vomiting, diarrhea and abdominal pain. Shortness of breath and chest pain may occur next along with swelling, headaches and confusion. In about half of cases the skin may develop a maculopapular rash (a flat red area covered with small bumps).

In some cases, internal and external bleeding may occur. This typically begins five to seven days after first symptoms. All people show some decreased blood clotting. Bleeding from mucous membranes or from sites of needle punctures is reported in 40–50% of cases. This may result in the vomiting of blood, coughing up of blood, or blood in stool.

Bleeding into the skin may create petechiae, purpura, ecchymoses, or hematomas (especially around needle injection sites). There may also be bleeding into the whites of the eyes. Heavy bleeding is uncommon and if it occurs is usually within the gastrointestinal tract.

Recovery may begin between 7 and 14 days after the start of symptoms. Death, if it occurs, is typically 6 to 16 days from the start of symptoms and is often due to low blood pressure from fluid loss. In general, the development of bleeding often indicates a worse outcome and this blood loss can result in death. People are often in a coma near the end of life. Those who survive often have ongoing muscle and joint pain, liver inflammation, and decreased hearing among other difficulties.

Prevention:

There is no FDA-approved vaccine available for Ebola.

If you travel to or are in an area affected by an Ebola outbreak, make sure to do the following:

• Practice careful hygiene. For example, wash your hands with soap and water or an alcohol-based hand sanitizer and avoid contact with blood and body fluids.
• Do not handle items that may have come in contact with an infected person’s blood or body fluids (such as clothes, bedding, needles, and medical equipment).
• Avoid funeral or burial rituals that require handling the body of someone who has died from Ebola.
• Avoid contact with bats and nonhuman primates or blood, fluids, and raw meat prepared from these animals.
• Avoid hospitals in West Africa where Ebola patients are being treated. The U.S. embassy or consulate is often able to provide advice on facilities.
• After you return, monitor your health for 21 days and seek medical care immediately if you develop symptoms of Ebola.

Healthcare workers who may be exposed to people with Ebola should follow these steps:

• Wear appropriate PPE.
• Practice proper infection control and sterilization measures. For more information, see Ebola Information for Non-U.S. Healthcare Settings.
• Isolate patients with Ebola from other patients.
• Avoid direct contact with the bodies of people who have died from Ebola.
• Notify health officials if you have had direct contact with the blood or body fluids, such as but not limited to, feces, saliva, urine, vomit, and semen of a person who is sick with Ebola. The virus can enter the body through broken skin or unprotected mucous membranes in, for example, the eyes, nose, or mouth.

Diagnosis:

Diagnosing Ebola in an person who has been infected for only a few days is difficult, because the early symptoms, such as fever, are nonspecific to Ebola infection and are seen often in patients with more commonly occurring diseases, such as malaria and typhoid fever.

However, if a person has the early symptoms of Ebola and has had contact with the blood or body fluids of a person sick with Ebola, contact with objects that have been contaminated with the blood or body fluids of a person sick with Ebola, or contact with infected animals, they should be isolated and public health professionals notified. Samples from the patient can then be collected and tested to confirm infection.

Laboratory tests used in diagnosis include:

Treatment of Ebola:

As of right now there is no FDA-approved vaccine or medicine (e.g., antiviral drug) available for Ebola.
Experimental vaccines and treatments for Ebola are under development, but they have not yet been fully tested for safety or effectiveness.

Symptoms of Ebola are treated as they appear. The following basic interventions, when used early, can significantly improve the chances of survival:
– Providing intravenous fluids (IV) and balancing electrolytes (body salts)
– Maintaining oxygen status and blood pressure
– Treating other infections if they occur

Recovery from Ebola depends on good supportive care and the patient’s immune response. People who recover from Ebola infection develop antibodies that last for at least 10 years, possibly longer. It isn’t known if people who recover are immune for life or if they can become infected with a different species of Ebola. Some people who have recovered from Ebola have developed long-term complications, such as joint and vision problems.

References: 1, 2, 3, 4