Generality

The Ebola virus is a pathogen that causes severe hemorrhagic fever, often fatal, not only in humans but also in non-human primates. The viral agent was identified in 1976, during an epidemic in the Democratic Republic of the Congo (formerly Zaire), near the Ebola river valley.

Since its first survey, several outbreaks of hemorrhagic fever have appeared sporadically in Africa, with mortality rates ranging from 50 to 90%.

The disease is transmitted by animal infection or by direct contact with blood, body fluids and tissues of infected individuals. The natural host of the Ebola virus is unknown, so it is not possible to implement programs to control or eliminate the natural reservoirs of the pathogen.

The rapid progression of the infection further complicates the management of this disease, as it offers little chance for the human host to develop adequate acquired immunity. The predominant treatment is general support. Currently, there is no specific antiviral therapy or vaccine that is effective against Ebola virus infection.

Ebola virus

The Ebola virus is a member of the Filoviridae family (genus Filovirus ). Each virion contains an anti-sense RNA molecule.

Currently, it is possible to distinguish five viral strains:

  • Zaire ebolavirus (ZEBOV);
  • Sudan ebolavirus (SEBOV);
  • Ivory Coast ebolavirus (or Tai ebolavirus);
  • Bundibugyo ebolavirus;
  • Reston ebolavirus.

All these pathogens are found in Africa, with the exception of Reston ebolavirus, located in the Philippines. The Reston Ebola virus is also the only subtype that does not cause the disease in humans, but infects pigs and non-human primates (such as monkeys, gorillas and chimpanzees). The Ebola Zaire virus is highly pathogenic and is associated with the highest mortality rate.

Ebola is clinically almost indistinguishable from Marburg hemorrhagic fever. The pathogenic agent that causes it, in fact, presents morphological analogies with ebolavirus, but it has different antigenic characteristics.

Evolution

The incubation period of the Ebola virus varies from 2 to 25 days (on average, 12 days). The onset of the disease is sudden and the infection presents with non-specific flu-like symptoms, such as fever, myalgia and malaise. As the condition progresses, patients experience bleeding symptoms, coagulation abnormalities and skin rashes. Cytokines are released when the cells of the reticulo-endothelial system encounter the virus and can contribute to triggering exaggerated inflammatory responses, which are not protective. Liver damage, combined with massive viremia, leads to disseminated intravascular coagulopathy. The virus infects the endothelial cells of the microcirculation and compromises the integrity of the blood vessels. The terminal stages of Ebola virus infection include gastrointestinal bleeding, hypovolemic shock and multiple organ dysfunction syndrome.

Although the clinical course of hemorrhagic fever is well known, the specific mechanisms related to the pathogenicity of the Ebola virus have not been clearly delineated. This is due, in part, to the difficulty of obtaining samples and studying the disease in relatively remote areas where epidemics occur. Furthermore, a high degree of biological risk containment is required for laboratory studies and clinical analyzes.

Contagion

The Ebola virus is transmitted with the body fluids of animals and infected people. Man can become infected by direct contact with blood, saliva, sperm, vaginal fluid, vomiting, urine or faeces. Even objects, needles or dirty clothes can be contaminated with infected secretions.

Transmission from animals to humans

The virus can be transmitted to humans through exposure to the body fluids of an infected animal. In addition to primates, the viral agent has also been found in pigs, antelopes and fruit bats. According to the World Health Organization, it is possible to become infected by managing a sick or dead wild animal that has been infected. Slaughtering or eating infected carcasses can help spread the Ebola virus.

Transmission from person to person

Infected people generally remain NON-contagious until the first symptoms occur. Medical personnel can become infected by close contact with sick patients and inadequate use of protective devices, such as surgical masks, shirts, latex gloves and glasses. Epidemics have also been fueled by traditional burial practices, which expose grieving family members to direct contact with the bodies of the dead.

For most people, the risk of contracting Ebola is extremely low. This risk, however, increases if you visit regions of Africa where the virus is present or epidemics have occurred in the past. Confirmed cases of the disease have been reported in the Democratic Republic of the Congo, as well as in Sudan, Gabon, Uganda and Ivory Coast.

Viral vectors

The Ebola virus is considered zoonotic, however the natural reservoir is still unknown, although in this regard extensive investigations have been carried out. Non-human primates (such as chimpanzees, gorillas and monkeys), exposed to the pathogen, develop a fatal disease and represent a source of human infection, however they are not considered the vector of the Ebola virus. A large number of dead animals were found in Gabon and the Democratic Republic of the Congo, before the outbreaks developed. Furthermore, the samples recovered from the carcasses showed the simultaneous presence of several Ebola strains. This suggests that animals have been infected by more than one source, so they are not the carriers of the virus. Currently, it is believed that man and non-human primates are susceptible to the same reservoir species or transmission chain that originates from it.

Immune response

The Ebola virus replicates at an unusually high rate and overwhelms the protein synthesis apparatus of infected cells. At the same time, the immune system responds to infection, but some types of cells (in particular, monocytes and macrophages) are relevant targets for the pathogenesis of the disease. The main objectives of viral replication are endothelial cells, mononuclear phagocytes and hepatocytes.

The components of the immune system, which may protect against ebolavirus infection, have not been defined. Antibody titres against the viral agent are readily detectable in patients recovering from the disease, however, other reports have indicated that the serum of healed subjects does not always protect against cultured infection. Furthermore, the passive transfer of antibodies in animal models only delays the onset of symptoms and does not change overall survival.

Signs and Symptoms

To learn more: Ebola symptoms

After the incubation period, the first signs and symptoms of Ebola include:

  • Fever with chills;
  • Headache;
  • Sore throat;
  • Joint and muscle pain;
  • Asthenia.

Over time, the symptoms become increasingly severe and may include:

  • Nausea, abdominal pain, diarrhea and vomiting;
  • Swelling and redness in the eyes;
  • Swelling of the genitals (big lips and scrotum);
  • Chest pain and cough (sometimes, with hemoptysis);
  • Severe weight loss;
  • Bleeding from eyes, ears and nose;
  • Bleeding from mucous membranes (vagina, mouth and rectum);
  • Rash (petechiae, maculo-papular rash and purpura) all over the body, often hemorrhagic.

Complications

Ebola hemorrhagic fever can cause:

  • Multiple organ failure (liver damage, kidney failure etc.)
  • Gastrointestinal hemorrhage, with hematemesis (presence of blood coming from the stomach, esophagus or duodenum) and melena (blood in the stool);
  • Jaundice;
  • Loss of consciousness;
  • Coma;
  • Hypovolemic shock;

One of the reasons why the disease is so fatal is based on the viral pathogenesis, which interferes with the immune system's ability to organize an effective defense.

For patients who survive, recovery is slow and can take several months. The viremia persists for about 2-3 weeks.

During the convalescence phase, people can experiment:

  • Hair loss;
  • Hepatitis;
  • Weakness;
  • Headache;
  • Inflammation of the eyes;
  • Disorders of the central nervous system.

Diagnosis

The clinical diagnosis of Ebola is difficult in the initial stages of infection: the first symptoms are non-specific and similar to those of other infectious diseases, such as typhoid and malaria. In case of suspected exposure to the virus, doctors can use some laboratory tests to confirm the responsible viral agent within a few days. Patient samples present an extreme biological risk and the tests must be conducted only in conditions of maximum safety.

Blood tests show a series of haematological irregularities, such as lymphopenia, neutrophilia and thrombocytopenia. Furthermore, it is possible to observe an increase in liver enzymes, such as the elevation of transaminases and hyperamylasemia.

The Ebola virus can be isolated by inoculation of a blood sample in cell cultures, within a few days of the onset of symptoms. Immunoenzymatic methods (ELISA, Enzyme-Linked ImmunoSorbent Assay) and RT-PCR (retro-transcription polymerase chain reaction) allow the detection of antigens and the viral genome or antibodies (IgM and IgG) against the virus. New tests have been developed to test the Ebola virus in saliva, urine and inactivated samples, to allow an early diagnosis.

Treatment

To learn more: Drugs to cure Ebola

There are no specific treatments or vaccines for Ebola hemorrhagic fever. For this reason, the therapy consists of supportive hospital treatment designed to alleviate symptoms. These may include:

  • Oxygen therapy;
  • Intravenous or oral liquids, to maintain hydro-electrolyte balance;
  • Blood transfusions;
  • Measures to maintain adequate blood pressure and avoid superinfections;
  • Pain medications.

New drug therapies have shown promising results in laboratory studies and are currently being evaluated.

Prevention

The Ebola virus is highly infectious and contagious. Therefore, prevention presents many challenges. First of all, a broader knowledge of the natural vector of the virus and the transmission modalities must be acquired in order to effectively prevent future epidemics.

Risk for travelers

The risk for most travelers of contracting Ebola is low; however, it depends on the possibility of being exposed to the viral agent and increases with any of the following activities:

  • Burial ceremonies, in which there is direct contact with an infected deceased;
  • Handling of infected chimpanzees, gorillas, monkeys, forest antelopes, pigs, porcupines or fruit bats (living or dead);
  • Management of infected patients in a healthcare environment.

The risk of contracting the infection with the Ebola virus can be reduced by avoiding travel to areas of known outbreaks.

Reduce the risk of Ebola infection in people

In the absence of effective treatment and vaccine, taking some primary prevention measures is the only way to reduce human infection. These focus on several factors:

  • To reduce the risk of human-to-human transmission close physical or close contact with infected patients should be avoided. Gloves and appropriate personal protective equipment must be worn during the visit of sick relatives in the hospital.
  • Communities affected by ebola should inform the population about the nature of the disease and the measures to contain the infection, including the burial of the dead. Deceased infected people must be buried quickly and safely.
  • In order to avoid Ebola infection, it is useful to reduce or avoid contact with wildlife. Carcasses of infected animals should be handled with gloves and other suitable protective clothing. Precautionary measures are also needed to avoid transmission from farms and slaughter of pigs. In regions where the Ebola virus has been detected in pigs, all products of animal origin (blood, meat and milk) must not be eaten raw.

Infection control in healthcare facilities

To avoid transmission of the Ebola virus from person to person, suspected cases must be isolated from other patients. Invasive procedures, such as the introduction of intravenous lines, the manipulation of blood, secretions, catheters and suction devices, represent a particular biological risk, therefore rigorous barrier nursing techniques must be practiced. Hospital personnel must properly use disposable protective devices, such as gowns, gloves, masks and glasses. Other Ebola infection control measures include disinfection and disposal of tools and equipment used in the care of infected individuals. Any person who has had close physical contact with the patient should be kept under strict surveillance.

Possibility of survival

The Ebola virus is one of the most aggressive pathogens known to science, fatal in about 50-90% of cases. The viral agent infects the liver, destroys the lining of blood vessels, causes coagulopathies and bleeding. Death is usually due to hypovolemic shock. Survival depends on the viral strain and the initial or innate immune response to the infection. However, it is not yet known why some people survive Ebola hemorrhagic fever, while others do not.