Marburg and Ebola Virus Infections

Symptoms of Marburg and Ebola virus infection are very similar.

After an incubation period of 2 to 21 days, fever, myalgia, and headache occur, often with abdominal pain, nausea, and upper respiratory symptoms (cough, chest pain, pharyngitis). Photophobia, conjunctival injection, jaundice, and lymphadenopathy also occur. Vomiting and diarrhea may soon follow. Delirium, stupor, and coma may occur, indicating central nervous system involvement.

Hemorrhagic symptoms begin within the first few days and include petechiae, ecchymoses, and frank bleeding around puncture sites and mucous membranes. A maculopapular rash, primarily on the trunk, begins around day 5.

Severe hypovolemia can develop, resulting from:

• Extensive fluid loss due to diarrhea and vomiting

• Capillary leakage, resulting in hypoalbuminemia and loss of fluid from the intravascular space

Loss of electrolytes can cause severe hyponatremia, hypokalemia, and hypocalcemia. Cardiac arrhythmias can result.

During the second week of symptoms, either defervescence occurs and patients begin recovery, or multiple organ failure develops, leading to fatality. Recovery is prolonged and may be complicated by recurrent hepatitis, transverse myelitis, and orchitis. The case fatality rate ranges from 25 to 90%.

Survivors from Ebola virus infection may have impairments in cognition, vision, and mobility due to joint pain (1). Severe cataracts may occur in children, and uveitis has been reported in adults.

Ebola virus can persist in the central nervous system and ultimately cause a relapse.

• Evaluation and testing per the Centers for Disease Control and Prevention guidelines

• Enzyme-linked immunosorbent blood assay (ELISA) and reverse transcriptase-polymerase chain reaction (RT-PCR)

Marburg or Ebola virus infection is suspected in patients with bleeding tendencies, fever, other symptoms consistent with early filovirus infection, and travel from endemic areas. The Centers for Disease Control and Prevention (CDC) has issued guidelines for evaluating travelers returning from endemic areas (1). A similar approach can be used if Marburg virus is suspected (2).

Testing includes complete blood count, routine blood chemistries, liver and coagulation tests, and urinalysis. Diagnostic tests include ELISA and RT-PCR. The gold standard is detection of characteristic virions with electron microscopy of infected tissue (especially liver) or blood.

Cases should be discussed with public health authorities, who can assist in all facets of management, including:

• Deciding whether to pursue the diagnosis

• Arranging transport of samples for testing

• Treatment, including transport to selected centers and, when indicated, use of novel therapies

• Tracking contacts

• Supportive care

• Antiviral therapy

Supportive care includes the following:

• Maintenance of blood volume and electrolyte balance

• Replacement of depleted coagulation factors

• Minimization of invasive procedures

• Treatment of symptoms, including use of analgesics

Two monoclonal antibody treatments, REGN-EB3 and mAb114, are available to treat Ebola virus infection caused by the Zaire ebolavirus (1). REGN-EB3 is a combination of 3 monoclonal antibodies (atoltivimab/maftivimab/odesivimab), and mAb114 is a single monoclonal antibody (ansuvimab). Both treatments were proven effective during the 2018 to 2020 Ebola outbreak in the DRC with cure rates of about 90% in patients with low viral loads (which suggests treatment was begun within the first few days after infection). The death rate in untreated and unvaccinated patients is over 70%. ). REGN-EB3 is a combination of 3 monoclonal antibodies (atoltivimab/maftivimab/odesivimab), and mAb114 is a single monoclonal antibody (ansuvimab). Both treatments were proven effective during the 2018 to 2020 Ebola outbreak in the DRC with cure rates of about 90% in patients with low viral loads (which suggests treatment was begun within the first few days after infection). The death rate in untreated and unvaccinated patients is over 70%.

Experimental treatments for Marburg virus infection, including antiviral drugs (favipiravir, remdesivir), polyclonal IgG, and monoclonal antibodies, are under investigation but no definitive treatment is available (Experimental treatments for Marburg virus infection, including antiviral drugs (favipiravir, remdesivir), polyclonal IgG, and monoclonal antibodies, are under investigation but no definitive treatment is available (2).

Two Ebola vaccines, rVSV-ZEBOV and a 2-dose combination of Ad26.ZEBOV and MVA-BN-Filo are available (1). rVSV-ZEBOV, used at the end of the 2016 Ebola outbreak in West Africa and in the 2018 outbreak in the DRC, is used for prevention of disease caused by Zaire ebolavirus in people 18 years of age and older. A second vaccine delivered in 2 doses, one each of Ad26.ZEBOV and MVA-BN-Filo, can be used for prevention of disease caused by Ebola virus (Zaire ebolavirus species) in individuals 1 year of age and older. The Zaire Ebola vaccines do not provide cross-protection against the Sudan Ebola virus disease. Three candidate vaccines were recommended for trial during the Uganda outbreak of Sudan ebolavirus, but the outbreak ended before the vaccine trials could be done.

To prevent spread, all suspected cases, including cadavers, require strict isolation and special handling. Symptomatic patients with possible Ebola or Marburg virus infection must be isolated in dedicated containment facilities. Standard intensive care units (ICUs) in public hospitals are not suitable. Special containment facilities provide for total control of fluid effluent and respiratory products.

Staff members in contact with patients must be completely covered in protective suits with internal containment of respiratory gases. Trained staff members must be available to help those in contact with patients remove the protective clothing. Protocols for donning and removing mask, goggles or face shields, gown, and gloves must be followed (2).

Thorough equipment sterilization, hospital closures, and community education have shortened epidemics.

Because Marburg and Ebola viruses can persist in semen and be sexually transmitted, the World Health Organization (WHO) recommends that infected patients and their sex partners should either abstain from all types of sex or use condoms correctly and consistently until one of the following occurs (3, 4, 5):

• Two tests for the virus are negative

• If testing is unavailable, ≥ 12 months have passed since symptom onset