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Marburg and Ebola Virus Infections

By

Thomas M. Yuill

, PhD, University of Wisconsin-Madison

Last full review/revision Mar 2020| Content last modified Mar 2020
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Marburg and Ebola are filoviruses that cause hemorrhage, multiple organ failure, and high mortality rates. Diagnosis is with enzyme-linked immunosorbent assay, polymerase chain reaction (PCR), or electron microscopy. Treatment is supportive. Strict isolation and quarantine measures are necessary to contain outbreaks.

Marburg and Ebola viruses are filamentous filoviruses that are distinct from each other but that cause clinically similar diseases characterized by hemorrhagic fevers and capillary leakage. Ebola virus infection is slightly more virulent than Marburg virus infection.

Ebola virus isolates have been differentiated into 5 species:

  • Zaire Ebola virus

  • Sudan Ebola virus

  • Tai Forest Ebola virus (formerly, Côte d'Ivoire Ebola virus [the Tai forest is located in Côte D'Ivoire])

  • Bundibugyo Ebola virus

  • Reston Ebola virus (which is present in Asia but does not cause disease in humans)

Most previous outbreaks of Marburg and Ebola virus infections have originated in sub-Saharan Central and West Africa. Past outbreaks have been rare and sporadic; they have been contained partly because they have occurred in isolated areas. Spread to other areas, when it occurs, has usually resulted from travelers returning from Africa. However, in 1967, a small Marburg hemorrhagic fever outbreak occurred in Germany and Yugoslavia among laboratory workers who had been exposed to tissues from imported green monkeys.

In December 2013, a large Ebola virus outbreak began in rural Guinea (West Africa), then spread to densely populated urban regions in Guinea and to neighboring Liberia and Sierra Leone. It was first recognized in March 2014. It involved thousands of people and had a case fatality rate of about 59%. Infected travelers have spread Ebola virus to Nigeria, Europe, and North America. Cases of Ebola continued to occur in the first few months of 2016; Sierra Leone was finally declared Ebola-free in March 2016, Guinea, in May 2016, and Liberia, in June 2016. In 2017, a small outbreak was reported in a remote region of the Democratic Republic of the Congo (DRC); the World Health Organization (WHO) declared an end to this outbreak on July 2, 2017 (1). In May 2018, another outbreak occurred in the DRC and, as of February 2020 is ongoing (2).

Transmission of Marburg and Ebola viruses

Most index cases involve exposure to nonhuman primates in sub-Saharan Africa. The vector and reservoir are not known precisely, although the Marburg virus has been identified in bats, and cases have occurred in people exposed to bats (eg, in mines or caves). Ebola virus outbreaks have been linked to consumption of meat from wild animals in affected areas (bush meat) or soup made from bats. Ebola and Marburg virus infections have also occurred after handling tissues from infected animals.

Filoviruses are highly contagious. Human-to-human transmission occurs via skin and mucous membrane contact with body fluids (saliva, blood, vomit, urine, stool, sweat, breast milk, semen) of an infected symptomatic person or rarely a nonhuman primate. Humans are not infectious until they develop symptoms. Symptoms and signs persist in surviving patients for as long as it takes to develop an effective immune response. Typically, surviving patients eliminate the virus entirely and no longer transmit the virus; however, Ebola virus may persist in certain immune-privileged sites (eye, brain, testes). The virus may re-emerge from these sites and cause late sequelae or relapse, and sexual transmission from survivors to susceptible individuals is suspected.

Marburg virus transmission via infected semen has been documented up to 7 weeks after clinical recovery (3). Ebola virus genetic material persisted for a year or longer in the semen of 63% men who recovered from Ebola. However, tests cannot determine whether live Ebola virus is present and capable of spreading disease. However, one man transmitted the virus to his sex partner > 500 days after he first had symptoms of the infection, indicating that the infectious virus can persist and be transmitted. It is possible that Ebola can be spread through sexual or other contact with semen (4).

Aerosol transmission has been postulated; however, if it occurs, it is probably rare.

During an outbreak, transmission is mainly human-to-human, resulting from close contact with the blood, secretions, other body fluids, or organs of infected people. Burial ceremonies in which the body is washed and in which mourners have direct contact with the deceased have played an important role in transmission of infection.

General references

Symptoms and Signs

Symptoms of Marburg and Ebola virus infection are very similar.

After an incubation period of 2 to 20 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 2nd week of symptoms, either defervescence occurs and patients begin recovery, or patients develop fatal multiple organ failure. Recovery is prolonged and may be complicated by recurrent hepatitis, transverse myelitis, and orchitis. The case fatality rate ranges from 25 to 90%.

Eye lesions (eg, severe cataracts in children) may develop after recovery from Ebola virus infection. In one adult, severe acute unilateral uveitis developed during the convalescent phase after infection.

A recent follow-up study of patients during convalescence after Ebola virus infection reported that many survivors had major limitations in cognition and vision and in mobility due to joint pain (1).

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

Symptoms and signs reference

  • 1. Jagadesh S, Sevalie S, Fatoma R, et al: Disability among Ebola survivors and their close contacts in Sierra Leone: A retrospective case-controlled cohort study. Clin Infect Dis 66 (1):131–133, 2018. doi: 10.1093/cid/cix705.

Diagnosis

  • 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 has issued guidelines for evaluating travelers returning from endemic areas (see Think Ebola: Early recognition). A similar approach can be used if Marburg virus is suspected.

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

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.

Treatment

  • Supportive care

  • Drug 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

Drugs are being tested in the current Ebola epidemic in eastern DRC. Two monoclonal antibodies, REGN-EB3 and mAb-114, given as a single IV infusion, have demonstrated excellent efficacy with cure rates of about 90% in patients with low viral loads (which suggests treatment was begun within the first few days after infection). This is compared to a death rate that is thought to be over 70% in untreated and unvaccinated patients and is a significant improvement over previous experimental drugs for Ebola (ZMapp, remdesivir). REGN-EB3 and mAb-114 are now being offered to all patients with Ebola infection in the current outbreak in DRC.

Until the two monoclonal antibodies or others are shown to neutralize Marburg virus, there is still no effective treatment for that virus infection.

Prevention

Several vaccines are in clinical trials. One Ebola vaccine, rVSV-ZEBOV, is being used in the current outbreak in the DRC with good results and was used successfully on a limited scale at the end of the 2016 Ebola outbreak in West Africa. The Ebola vaccine rVSV-ZEBOV was approved by the US Food and Drug Administration in December 2019 for use in people 18 years of age and older. The DRC Ministry of Health has approved the use of a second vaccine combination of Ad26.ZEBOV and MVA-BN-Filo for use in the country outside of the outbreak zone.

To prevent spread, 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 (see the Centers for Disease Control and Prevention: Sequence for Donning Personal Protective Equipment).

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

All suspected cases, including the cadavers, require strict isolation and special handling.

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

  • Until 2 tests for the virus are negative

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

Key Points

  • Ebola and Marburg viruses, although distinct, cause similar hemorrhagic fevers; outbreaks are perpetuated mainly by human-to-human transmission via contact with infected body fluids, organs of infected people, or cadavers.

  • Suspect Marburg or Ebola virus infection in patients with bleeding tendencies, fever, other compatible symptoms, and travel from endemic areas.

  • Isolate patients with possible infection in dedicated containment facilities, and use strict procedures to protect workers who care for these patients.

  • Ebola vaccines are being developed; one is currently in routine use in the DRC.

  • Plan diagnosis, management, and prevention of transmission with public health authorities.

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