Ebola Virus Disease & Marburg Virus Disease

Infectious Agent

The family Filoviridae includes viruses of the Ebolavirus and Marburgvirus genuses, which can cause hemorrhagic fever in humans and nonhuman primates. Five species within the genus Ebolavirus have been identified: Tai Forest ebolavirus (Taï Forest virus), Sudan ebolavirus (Sudan virus), Zaire ebolavirus (Ebola virus), Bundibugyo ebolavirus (Bundibugyo virus), and Reston ebolavirus (Reston virus). Marburg marburgvirus is the single species in its genus.

Transmission

Bats are the suspected reservoir species for the viruses within the genus Ebolavirus . Fruit bats (Rousettus aegypticacus ) are the natural reservoirs for Marburg virus. Outbreaks occur when a person becomes infected after exposure to the reservoir species or a secondarily infected nonhuman primate or antelope species and then transmits the virus to other people in the community. In the community, Ebola virus and Marburg virus are generally transmitted by direct physical contact between unprotected skin or mucous membranes and blood or other infected body fluids of patients in the acute phase of Ebola virus disease (EVD) or Marburg virus disease (MVD) or from patients who have died from EVD or MVD. Aerosol transmission of Ebola virus in humans has not been documented.

After recovery from acute disease, the virus or its RNA persists in some specific body fluids of convalescent EVD or MVD patients. Ebola virus RNA has been detected in breast milk up to 21 days after the onset of the disease and in vaginal secretions up to 33 days after onset. Ebola virus has also been shown to persist in “immune-privileged” sites (such as the central nervous system, eye, testes). Ebola virus and Marburg virus have been cultured from ocular aqueous humor at 2 and 3 months after disease onset, respectively.

Evidence suggests that Ebola and Marbug viruses can be sexually transmitted from a male survivor to his female partner months after onset of disease. In pregnant women with EVD, there can be in utero transmission of Ebola virus to the fetus.

Epidemiology

People at greatest risk of EVD or MVD include family members, health care workers or others who come into direct contact with infected patients or corpses without protective equipment, people who have come into contact or close proximity to bats (visiting bat caves), and those who have handled infected primates or carcasses. Additionally, sexual partners of recent male EVD or MVD survivors may be at risk if they have had contact with virus-infected semen.

Countries where domestically acquired EVD cases have been reported and that should be considered areas where future epidemics could occur include Republic of the Congo, Côte d’Ivoire, Democratic Republic of the Congo, Gabon, Uganda, Guinea, Liberia, and Sierra Leone.

Typically, previous Ebola outbreaks had been limited in scope and geographic extent. However, in March of 2014, an outbreak of Ebola virus was detected in a rural area of Guinea near the border with Liberia and Sierra Leone. By June of 2014, cases were reported in all three countries and across many districts. The outbreak was the largest and most complex Ebola epidemic ever reported. Additional cases occurred in Nigeria, Senegal, Mali, Spain, the United Kingdom, Italy, and the United States after infected people traveled from West Africa.

Countries with confirmed human cases of Marburg hemorrhagic fever include Uganda, Kenya, Democratic Republic of the Congo, Angola, and possibly Zimbabwe. Four cases of Marburg hemorrhagic fever have occurred in travelers visiting caves harboring bats, including Kitum cave in Kenya and Python cave in Maramagambo Forest, Uganda. Miners in the Democratic Republic of the Congo and Uganda have also acquired Marburg virus infection from working in underground mines harboring bats.

Reston virus is believed to be endemic in the Philippines but has not been shown to cause human disease.

Clinical Presentation

The incubation period for EVD and MVD ranges from 2–21 days, although most people develop symptoms after 7–10 days. Signs and symptoms of EVD and MVD can vary but, in general, patients present with an abrupt-onset fever, weakness, myalgias, arthralgias, and headache. This is often followed by gastrointestinal symptoms including anorexia, abdominal discomfort, nausea, vomiting, and diarrhea. Conjunctival injection, rash, and hiccups have also been reported. In the West African EVD epidemic, diarrhea was severe with up to 10 L of output reported per 24 hours. Intravascular volume depletion is common and may be associated with profound electrolyte depletion, hypoprofusion, and shock. Coagulopathy is a late manifestation and can present with a petechial rash, ecchymoses, and sometimes overt bleeding (epistaxis, melena, bloody diarrhea). Hypoxia, another late manifestation, was noted in half of EVD patients (median oxygen saturation 84.5%). Laboratory abnormalities include elevations in liver enzymes, initial drop in leukocyte count, and thrombocytopenia. Because the incubation period may be as long as 21 days, patients may not develop illness until returning from travel; therefore, a thorough travel and exposure history is critical. Fatality ratios for EVD vary, ranging from 19%–90% depending on Ebolavirus species and the availability of medical care.

Pregnant women with EVD appear to be at high risk of spontaneous abortions, stillbirth, and pregnancy-related hemorrhage. Limited evidence suggests that the prognosis for neonates born to mothers with EVD is poor, and most die within 19 days of birth.

Diagnosis

US-based clinicians should notify local health authorities immediately of any suspected cases of viral hemorrhagic fevers occurring in patients residing in the United States, or notify the CDC directly regarding any patients requiring evacuation to the United States (contact the CDC Emergency Operations Center at 770-488-7100). Personal protective equipment is indicated for any patients where EVD or MVD is suspected and includes droplet and contact precautions. Whole blood, plasma, or serum may be tested for virologic (RT-PCR, antigen detection, virus isolation) and immunologic (IgM, IgG) evidence of infection. Tissue may be tested by immunohistochemistry, RT-PCR, and virus isolation. Postmortem skin biopsies fixed in formalin and blood collected within a few hours after death by cardiac puncture can be used for diagnosis. Diagnostic testing of blood and other body fluid specimens calls for special handling procedures.

Treatment

Currently, there is no proven specific therapy for EVD. The mainstay of treatment is early aggressive supportive care directed at maintaining effective intravascular volume and correcting electrolyte imbalances. Several additional experimental immune therapy treatments and antivirals are currently under investigation. With aggressive supportive care, reported case-fatality ratios were 43% among EVD patients treated in West Africa and 18.5% among patients treated in the United States and Europe. EVD patients may also have concomitant malaria infection. As such, empiric use of antimalarial therapy should be considered when rapid diagnostic testing is not immediately available. In general, NSAIDs such as ibuprofen and diclofenac are not recommended due to their platelet activity.

Currently there is no FDA-approved vaccine to prevent EVD. Experimental Ebola vaccines are under development, including a recombinant vesicular stomatitis virus–based vaccine and a chimpanzee adenovirus–based vaccine. However, these investigational products are in the early stages of product development and are not yet available.

CDC website: www.cdc.gov/vhf/ebola

Bibliography

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Authors

Mary Choi, Barbara Knust