Ebola overview

# Overview
Ebola virus disease (EVD) is one of numerous viral hemorrhagic fevers (VHF). It is a severe, often fatal disease in human and nonhuman primates. Ebola virus is spread by direct contact with the blood or body fluids (such as urine, saliva, feces, vomit and semen) of an infected person or by being exposed to objects that have been contaminated with infected blood or body fluids. The incubation period is usually 810 days (rarely ranging from 2 to 21 days). Patients can transmit the virus once symptoms appear and through the later stages of disease, as well as postmortem.  Ebola has caused a number of serious and highly publicized outbreaks since its discovery.

# Historical Perspective
The Ebola virus was named after the Ebola River Valley in the Democratic Republic of the Congo (formerly Zaire), near the site of a 1976 outbreak at a mission run by Flemish nuns. Since the initial discovery of the virus, five subtypes have subsequently been identified.

# Classification
Ebola virus can be classified into 5 subtypes: Zaire, Sudan, Reston, Tai (Ivory Coast) and Bundibugyo, according to the place of discovery.

# Pathophysiology
The Ebola virus infects the mononuclear phagocyte system, but also other cells such as hepatocytes, spongiocytes, fibroblasts and endothelial cells, inducing tissue necrosis and disrupting the hematological and coagulation systems. The Ebola virus is transmitted by direct contact with infected patients or animals. The natural reservoir has not been identified.

# Causes
Ebola infection is caused by a virus that belongs to the family Filoviridae. Three viral subtypes have been reported to cause disease in humans: Ebola-Zaire virus, Ebola-Sudan virus, and Ebola-Ivory Coast virus. The human disease has so far been limited to parts of Africa. A very small number of people in the United States who were infected with the fourth type of the virus, known as Ebola Reston, did not develop any signs of disease.

# Differentiating Ebola from other Diseases
Ebola must be differentiated from other diseases that cause hemorrhage and/or high fever as part of their presentation such as Marburg virus, Lassa fever, Typhoid fever  and Malaria.  The clinician must first rule out other more common causes of the fever before considering a viral hemorrhagic fever (VHF) such as Ebola, and the consideration of a VHF should be based upon epidemiology and demographics as well as sign and symptoms. A VHF such as Ebola, should be suspected in febrile persons who, within 3 weeks before onset of fever, have either: 1) traveled in the specific local area of a country where VHF has recently occurred; 2) had direct unprotected contact with blood, other body fluids, secretions, or excretions of a person or animal with VHF; 3) if the patient had any contact with someone who was ill with fever and bleeding or who died from an unexplained illness with fever and bleeding; 4) had a possible exposure when working in a laboratory that handles hemorrhagic fever viruses; 5) If a fever continues after 3 days of empiric treatment, and if the patient has signs such as bleeding or shock, the clinician must consider a VHF; 6) if no other cause is found for the patients signs and symptoms, the clinician must suspect a VHF.

# Epidemiology and Demographics
Outbreaks of Ebola have been generally restricted to Africa. Governments and individuals should quickly quarantine the area. Lack of roads and transportation help to contain the outbreak in remote areas.  The potential for widespread Ebola virus disease epidemics is considered low due to the high case-fatality rate, the rapidity of demise of patients, and the often remote areas where infections occur.

# Risk Factors
The main risk factors for Ebola virus disease are traveling to endemic areas, to be a health professional taking care of infected patients and researchers working with animal models of the Ebola virus disease.

# Natural History
Ebola infection rapidly progresses to death in the absence of supportive care.  Ebola infection can be complicated by multiorgan failure and shock. The prognosis of Ebola infection is poor, and depends upon the Ebola virus strain. The Zaire Ebola virus has mortality rate as high as 90%.

# Diagnosis

## History and Symptoms
Ebola causes a variety of symptoms which may include fever, chills vomiting, diarrhea, generalized pain or malaise, and sometimes internal and external bleeding, that follow an incubation period of 2-21 days.  These symptoms are common to all species of Ebola virus, but the different species may present with differences in the severity of symptoms.

## Physical Examination
Ebola is commonly associated with the acute onset of high fever, chills and hemorrhage as well as swollen joints, weakness, rash and red eyes.

## Laboratory Findings
Ebola infection is associated with nonspecific laboratory abnormalities including alterations in the white blood cell count, blood chemistry tests and liver function tests, all of which may contribute to a disruption in the clotting process and bleeding.

## Other Diagnostic Studies
While the diagnosis of Ebola may be suspected based on clinical findings, the diagnosis of Ebola can be confirmed by antigen-capture enzyme-linked immunosorbent assay (ELISA) testing, IgM ELISA, polymerase chain reaction (PCR), and virus isolation, within few days of the onset of symptoms. Persons tested later in the course of the disease, or after recovery, can be tested for IgM and IgG antibodies. The disease can also be diagnosed in deceased patients by using immunohistochemistry testing, virus isolation, or PCR.

# Treatment

## Medical Therapy
The treatment of Ebola infection is primarily supportive and includes maintaining fluids and electrolytes, homeostasis, adequate oxygen levels and blood pressure and treating any complicating superimposed infections. All patients with a confirmed or suspected viral hemorrhagic fever should be put in isolation with adequate contact precautions. No vaccine is currently available.

## Primary Prevention
The transmission of Ebola can be limited by implementing preventive measures in both endemic and nonendemic areas which include isolation of infected patients; using gloves/masks/gowns and other standard barrier precautions; routine hand-washing; careful handling, disposal and/or maintenance of sharp objects; proper waste management and proper handling of human remains after death.

## Future or Investigational Therapies
Although there is no effective human vaccine against Ebola currently available, there are promising results for antisense prevention therapies targeting the Ebola virus in monkey studies. Administration of an inhibitor of coagulation (rNAPc2) has demonstrated some benefit in monkey studies. There are non-conclusive results in human survivors from post-exposure vaccination, passive immunization with blood or serum or with recombinant human monoclonal antibodies.