Infections in Humans
Infections in Animals
Internet Resources
References
Etiology
Ebola and Marburg are caused by Ebola virus and Marburg virus, the only members of the family Filoviridae. These two viruses are closed related and are considered to be serotypes or genotypes within a single genus. Ebola virus is subdivided into three subtypes: Zaire, Sudan, and Reston. An isolate from a 1994 Ivory Coast outbreak is probably a fourth subtype.
Geographic Distribution
Ebola-Zaire, Ebola-Sudan, and Ebola-Ivory Coast outbreaks have been seen in Sudan, Zaire, the Ivory Coast and the Democratic Republic of the Congo. Ebola-Reston outbreaks have occurred in non-human primates in the Italy and United States; these outbreaks were traced to monkeys imported from the Philippines. Wild non-human primates in the Philippines may have antibodies to Ebola-Reston.
Marburg has been seen in Uganda, Kenya, Zimbabwe and South Africa. Outbreaks also occurred in Germany and Yugoslavia, in humans exposed to African green monkeys from East Africa.
Transmission
Human filovirus outbreaks seem to have a zoonotic source, but the reservoir host has not been identified. Transmission among humans and other primates is by direct contact with infected blood, secretions, organs or semen, and on fomites. Virus has also been found in urine. Marburg and Ebola can be transmitted by aerosols and small droplets among monkeys; however, aerosol transmission does not appear to be a major route of spread between humans infected with Ebola. Filoviruses can survive for several weeks in blood and corpses.
Disinfection
Hypochlorite or phenolic disinfectants are generally recommended for disinfection. Ebola virus is susceptible to 2% sodium hypochlorite, 2% glutaraldehyde, 5% peracetic acid and 1% formalin. This virus is also inactivated by ultraviolet light, gamma irradiation, 0.3% betapropiolactone for 30 minutes at 37° C, or heating to 60° C for 1hr. Marburg virus is susceptible to 1% sodium hypochlorite, 2% glutaraldehyde or formaldehyde, ultraviolet light or heat.
Incubation Period
The incubation period is 2 to 21 days for Ebola and 3 to 10 days for Marburg.
Clinical Signs
Ebola usually begins with the abrupt onset of headache, sore throat, fever, myalgia, joint pain and weakness, followed by diarrhea, vomiting and stomach pain. A maculopapular rash on the truck, red eyes and hiccups are also seen. Hemorrhages are common and may include petechiae, ecchymoses, bloody diarrhea, bleeding from puncture sites and mucous membranes, and other internal and external bleeding. Early symptoms may be nonspecific and resemble other illnesses. Ebola-Reston can infect humans but hemorrhagic illnesses have not been seen.
The symptoms of Marburg are very similar to Ebola. This disease also begins with the acute onset of fever, chills, headache and myalgia. Approximately five days later, a maculopapular rash may appear on the trunk, followed by a sore throat, nausea, vomiting, chest pain, abdominal pain or diarrhea. Other symptoms may include severe weight loss, jaundice, delirium, shock, pancreatitis, liver failure, massive hemorrhaging and multi-organ dysfunction.
Communicability
Yes. Filoviruses can be spread between humans by contact with blood, secretions, organs, or semen. Ebola virus has been found in large quantities in the skin. Aerosol transmission is at least theoretically possible.
Diagnostic Tests
Early in the course of infection, Ebola can be diagnosed by an antigen-capture enzyme-linked immunosorbent assay (ELISA), virus isolation, detection of viral RNA by polymerase chain reaction (PCR) or the detection of virus-specific IgM by ELISA. Serology for IgG antibodies is useful later in the disease. At necropsy, immunohistochemistry, virus isolation or PCR can be employed.
Early Marburg infections can de diagnosed by antigen-capture ELISA, virus isolation, polymerase chain reaction (PCR) or an ELISA to detect Ebola-specific IgM. An IgG specific ELISA is useful later in the disease or after recovery. Diagnosis at necropsy is by immunohistochemistry on blood or tissue, virus isolation or PCR.
Treatment and Vaccination
No specific treatment is available for Ebola or Marburg; supportive therapy is given, with appropriate barrier precautions against infection of medical personnel. Transfusions of fresh-frozen plasma and other replacements for clotting proteins have been tried. Heparin has also been used, although its use is controversial.
Morbidity and Mortality
The case fatality rate is 50 to 90% for Ebola and 23 to 25% for Marburg. Bleeding is a poor prognostic sign. Ebola-Reston can infect humans but hemorrhagic illnesses have not been seen.
Species Affected
Ebola-Zaire, Ebola-Sudan and Ebola-Ivory Coast affect humans and non-human primates; Ebola-Reston causes hemorrhagic fever in monkeys but does not seem to be pathogenic for humans. Naturally-occurring Ebola antibodies have been found in rhesus monkeys, African green monkeys, cynomolgus monkeys and baboons. Chimpanzees, gorillas, rhesus monkeys, vervet monkeys, cynomolgus monkeys, newborn mice and guinea pigs can develop clinical illness. Experimentally infected rabbits, pigeons and various species of mice, bats, frogs, geckos, snakes, tortoises and arthropods did not develop clinical signs; however, virus replication was seen in bats and possibly snakes, mice and spiders. The natural reservoir of this virus is unknown.
Marburg virus can infect humans and non-human primates, including African green monkeys. Antibodies have been found in captive vervet monkeys and baboons in Kenya. The natural host is unknown.
Incubation Period
The incubation period for Marburg or Ebola-Zaire infections in rhesus monkeys and African green monkeys is 4 to 16 days. In guinea pigs, the incubation period is 4 to 10 days.
Clinical Signs
Filovirus infections result in severe, often fatal, hemorrhagic fevers in non-human primates. Clinical signs may include fever, anorexia, vomiting, splenomegaly, weight loss and a skin rash. Hemorrhages can occur in any organ and may include petechiae, bleeding into the gastrointestinal tract, or bleeding from puncture wounds and mucous membranes. Guinea pigs infected with unpassaged virus from primates usually develop a fever and weight loss but recover; animals infected with serially passaged virus may develop fatal liver disease.
Communicability
Yes. Blood, secretions, organs, semen and urine may contain infectious virus; virus can probably be found almost anywhere in the body. Aerosol transmission of both Ebola and Marburg viruses has been seen in primates.
Diagnostic Tests
Filovirus infections can be diagnosed by virus isolation; Vero cells or MA-104 cells are commonly used for Ebola virus. In humans, Ebola virus is most reliably isolated from acute-phase serum but can also be found in throat washes, urine, semen, anterior eye fluid and other fluids. In necropsied monkeys, filoviruses have been found in particularly high concentrations in the liver, spleen, lungs and lymph nodes. Electron microscopy can also detect virus particles in tissues: filoviruses are pleomorphic, long and filamentous and may be branched. Some may be U-shaped, b-shaped or circular. Viral antigens can be detected with an enzyme-linked immunosorbent assay (ELISA) or by immunofluorescence. Skin biopsies collected into formalin may be helpful for diagnosis; large amounts of Ebola antigen have been found in skin. A reverse transcriptase-polymerase chain reaction (RT-PCR) assay can identify Marburg or Ebola RNA.
Serologic tests include indirect immunofluorescence assays (IFA), immunoblotting and ELISAs. Neutralization tests are unreliable for filoviruses. Paired serum samples should be tested; low IFA titers in single samples cannot be interpreted. The significance of antibody titers in asymptomatic primates is controversial.
Treatment and Vaccination
No specific therapy or vaccine is available.
Morbidity and Mortality
Marburg and Ebola infections have a very high mortality rate in non-human primates and experimentally infected suckling mice. Guinea pigs infected with Ebola virus from primates usually recover; animals infected with serially passaged virus may develop fatal liver disease.
Post-Mortem Lesions
At necropsy, there may be widespread petechiae and hemorrhages. Hemorrhages can occur in any organ but are particularly common in the gastrointestinal tract, kidneys, and pleural, pericardial and peritoneal spaces. The liver and spleen may be swollen and friable. Animals may have a maculopapular rash. There can also be signs of interstitial pneumonia, nephritis, and necrosis of the liver, lymphoid tissue, adrenal cortex or pulmonary epithelium.
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Centers for Disease Control and Prevention (CDC) – Viral Hemorrhagic Fevers Index |
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“Marburg and Ebola Viruses” in Encyclopedia of Virology |
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Material Safety Data Sheets –Canadian Laboratory Center for Disease Control |
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Medical Microbiology |
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Pathology of Nonhuman Primates from Primate Info Net. Wisconsin Primate Research Center |
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Primate Info Net. Wisconsin Primate Research Center |
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Typhus and Flying Squirrels Southeastern Cooperative Wildlife Disease Study (SCWDS) Briefs |
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Proceedings of an international colloquium on Ebola virus infection and other hemorrhagic fevers held in Antwerp, Belgium, 6-8 December, 1977 |
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USAMRIID’s Medical Management of Biological Casualties Handbook |
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Center for Food Security and Public Health
Iowa State University College of Veterinary Medicine
Ames Iowa USA 50011
Phone: 515 294 7189
Fax: 515 294 8259
Email: cfsph@iastate.edu
