Ebola and Marburg Hemorrhagic Fevers

I INTRODUCTION

Ebola

Ebola Virus Infection

The Ebola virus is highly infectious and can spread through the use of unsterilized needles or through contact with an infected individual or the corpse of someone who has died from the disease. About one week after infection, the virus begins attacking blood and liver cells(1). As the disease swiftly progresses, the virus may destroy vital organs such as the liver and kidneys(2), leading to massive internal bleeding (3). Shock and respiratory arrest soon follow, then death.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.

III SYMPTOMS OF EBOLA

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 OF EBOLA

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.

V CARE AND TREATMENT OF EBOLA

Caring for patients infected with Ebola or Marburg includes general steps to maintain blood volume and electrolyte balance in the body. Preventing or managing shock, cerebral edema, kidney failure, blood-clotting disorders, and secondary bacterial infections may be life-saving. No drugs or specific medical treatments have been shown to be effective against Ebola or Marburg infections.

A protective vaccine would be valuable for medical and nursing personnel in Africa and researchers working with the viruses. However, all early attempts to develop vaccines using inactivated Ebola and Marburg viruses grown in cell cultures failed. Some recent vaccine candidates developed using modern molecular biologic technologies have shown more promise. These include a DNA vaccine, using modified DNA from the Ebola virus. A different approach has been to use a non-disease-causing virus (called a vector) to carry certain proteins found on Ebola or Marburg viruses that can cause an immune response. Another potential vaccine is derived from the soluble glycoprotein of Ebola virus. Several of these candidate vaccines have been successful in tests on monkeys, but proceeding to human clinical trials and FDA approval is a formidable challenge and takes years to complete.

VI HISTORY OF OUTBREAKS

Although the Ebola and Marburg viruses were new to science in the 1960s and 1970s, they may have existed in nature for thousands of years. The disease may have occasionally struck humans who came in contact with the still largely unknown natural hosts (called reservoir hosts). Outbreaks in human populations likely remained local and isolated because of the need for direct physical contact to spread the diseases, as well as rapid and high mortality rates. The general similarity of some symptoms to other types of endemic hemorrhagic fevers or acute illnesses also meant that cases of Ebola or Marburg might not be recognized as specific diseases.

The first recognition of the Marburg virus came in 1967, when 31 cases of hemorrhagic fever, with seven deaths, occurred among laboratory workers in Germany and Yugoslavia who were processing kidneys taken from African green monkeys (Cercopithecus aethiops) that had been imported from Uganda. A new virus was isolated from patients and monkeys; it was named Marburg virus, now the prototype of the family Filoviridae or filoviruses.

Nine years later two epidemics of hemorrhagic fever occurred, one in Zaire (now the Democratic Republic of the Congo), the other in Sudan. Altogether there were more than 550 cases and 430 deaths. A virus with a physical shape identical to the Marburg virus but with distinct antigens was isolated—it was named Ebola virus. Later, the viruses from Zaire and Sudan were found to be genetically distinct and are now designated Ebola virus Zaire and Ebola virus Sudan. The two viruses differ in their pathogenicity also, with the Zaire virus causing death in about 80 to 90 percent of infected persons and the Sudan virus in about 50 percent. The Ebola virus Côte d’Ivoire was discovered when a single human case was identified in Côte d’Ivoire. The genetically distinct virus was isolated from a person who had examined the dead body of a wild chimpanzee from a troop of chimps that had suffered high mortality. Since 1976 there have been many more episodes of Ebola hemorrhagic fever, representing an ever increasing geographic range within Africa.

In 1989 and 1990 cynomolgus monkeys (Macaca fascicularis) imported from the Philippines into a facility for the import and sale of laboratory animals in Reston, Virginia, were found to have been infected with another new virus, now called Ebola virus Reston. Infected monkeys at the facility became ill and many died. Four animal caretakers were infected but there was no clinically apparent disease. This virus reappeared in imported monkeys in Italy in 1992 and Texas in 1996.

Cases of Ebola and Marburg hemorrhagic fevers have been increasing in Africa in recent years, occurring as large and small outbreaks, involving an ever-expanding geographic range. Between 1967 and the early 1990s several smaller outbreaks caused by these viruses were recorded in various parts of western and central Africa. From the mid-1990s onward, the viruses have become more common and widespread, usually in settings where there has been environmental degradation of previously uninhabited areas, such as may happen with gold mining. People may have no immunity to new microbes contacted in unfamiliar ecosystems.

Ebola virus has also emerged as a deadly threat to gorilla populations. Researchers reported that more than 5,000 gorillas in the Republic of Congo and in Gabon died from Ebola hemorrhagic disease just between 2002 and 2004. Similarly, there have been reports of large numbers of chimpanzees dying of Ebola hemorrhagic disease in the same areas as the gorilla deaths. The disease has apparently been spread by contact, even between territorial social groups. The loss of such large numbers of gorillas and chimpanzees adds to the extinction threat for these animals.

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