Ebola and Marburg Hemorrhagic Fevers

I

Introduction

Ebola and Marburg Hemorrhagic Fevers, deadly viral diseases characterized by massive bleeding and destruction of internal tissues. The closely related Ebola and Marburg viruses can be highly contagious through contact with infected bodily fluids. Both diseases have high fatality rates and together have caused more than 1,500 deaths in parts of Africa since the 1970s. Ebola virus is named for the Ebola River in the Democratic Republic of the Congo, where the virus was first identified in 1976. Marburg virus is named for Marburg, Germany, where the virus was isolated in 1967 after an outbreak among laboratory workers who came in contact with body parts of African monkeys. As well as affecting humans, Ebola has killed large numbers of gorillas and chimpanzees in some areas of Africa.

II

Cause

Ebola and Marburg hemorrhagic fevers belong to the filovirus family of viruses and are zoonoses—that is, diseases that animals spread to humans. The animal hosts of the viruses remain largely unknown, but evidence points to the role of fruit bats as possible natural hosts (called reservoir hosts) of Ebola virus. Infected bats did not show clinical signs of infection, but carried the virus, viral RNA, and antibodies against the virus. Otherwise, the life cycles of both viruses are still mysterious—we do not know how the viruses jump from reservoir hosts to humans.

Each outbreak of Ebola and Marburg hemorrhagic fever has been traced to what is known as an index case, a person who became infected by coming into contact with a reservoir host animal. From the index case, transmission of virus between humans occurs by direct contact with infected blood or other body fluids, usually involving health-care personnel and family members caring for sick patients. Transmission of Ebola virus has also occurred by handling ill or dead infected chimpanzees.

Filoviruses can be identified by a distinctive thread-like appearance under an electron microscope. Ebola and Marburg virus virions (virus particles) appear similar, with a range of shapes. They occur as long strands, often with branched forms, circular forms, or forms shaped like the letter “U” or the numeral “6.” The virions are composed of a coiled strand of ribonucleic acid (RNA) surrounded by an envelope covered with spikes. Laboratory tests that measure antiviral antibodies or viral RNA easily distinguish between the two viruses.

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III

Symptoms

The incubation period for Ebola and Marburg virus infection—that is, the time between exposure and the onset of illness—is typically four to ten days and is followed by abrupt onset of severe headache, fever, chills, sore throat, muscle aches, and weakness. These early symptoms are followed by vomiting, abdominal pain, diarrhea, and conjunctivitis (inflammation of the mucous membranes in the eye). There is usually bleeding from body openings and a rash, and evidence of abnormal blood-clotting that is associated with profound shock. Death often follows quickly, usually six to nine days after clinical onset of the disease. In a pregnant woman, abortion is a common consequence of infection, and when women who are dying of infection give birth, their infants invariably die. Convalescence is slow and marked by physical weakness, weight loss, and often by amnesia for the period of acute illness.

Marburg and Ebola viruses cause similar disease-related changes in the body. The most striking disease changes are found in liver, spleen and kidney—there is widespread necrosis (cell death) of tissues.

Marburg and Ebola viruses are Biosafety Level 4 (BSL-4) pathogens requiring the highest level of containment in the lab and in the field to prevent the accidental escape or intentional spread of the viruses. Governments of most countries strictly regulate the importation or possession of either virus. People experienced with handling such material must use a strict set of practices and procedures. To ensure maximum safety, scientists studying the Ebola or Marburg virus must work in special protective clothing, including hoods with controlled air flow, and full-body, air-supplied suits that are pressurized to keep surrounding air from entering. Laboratories are in special buildings that must contain equipment such as filtered air exhaust and decontamination systems, as well as other protective features to block release of the viruses.

IV

Diagnosis

In those places in the world where Ebola and Marburg viruses are found diagnosis may be difficult, partly because of the presence of other severe, acute, fever-causing diseases that may show similar symptoms. Such diseases include malaria, typhoid fever, shigellosis, plague, leptospirosis, anthrax, relapsing fever, typhus, murine typhus, yellow fever, Chikungunya fever, Rift Valley fever, hemorrhagic fever with renal syndrome, Crimean-Congo hemorrhagic fever, Lassa fever, and fulminant viral hepatitis. When a cluster of cases with symptoms of such diseases is seen in those parts of Africa where either Ebola or Marburg virus has been found in the past, diagnosis is still difficult. Recent experiences with quite large outbreaks show that correct diagnosis is becoming more and more important, however. Person-to-person spread and clinical signs suggestive of viral hemorrhagic fever may provide the first indication. When a suspect patient is seen in developed countries, determining a history of recent travel, especially from Africa, is an important clue.

Laboratory confirmation of clinical diagnosis is crucial, and recently has become more practical in some developing countries because of modern technology. Three kinds of tests are used: (1) tests that detect antibody to Ebola or Marburg viruses, which prove that the patient has been infected; (2) tests for viral antigen (substances that stimulate antibodies), which prove that the patient is currently suffering an acute infection; and (3) special tests for viral genomic RNA. Electron microscopy has also been useful in diagnosis of Ebola or Marburg virus infections—the distinctive virions are easy to see in cell cultures inoculated with blood or tissues from patients. Tests using specially labeled antibodies to find antigens in the tissues of people who have died (a technique called immunohistochemistry) have also been valuable when such tissues are the only specimens available.

When infection is suspected, local health officials must institute strict procedures to prevent spreading the infection. Called barrier nursing, these procedures include the use of gowns, gloves, masks, and lots of disinfectants. Local officials usually call on experts from the World Health Organization (WHO), and in the United States the Centers for Disease Control and Prevention (CDC) and the United States Army, to provide help with diagnosis, patient care, and epidemic control measures.

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