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 outbreaks of Marburg and Ebola virus infections have originated in sub-Saharan Central and West Africa. Outbreaks have been rare and sporadic; they have been contained partly because they have occurred in isolated areas. When spread to other areas occurs, it has usually resulted from travelers 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 Zaire 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 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 due to Zaire Ebola virus 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 in July 2017 (1). In May 2018, another outbreak occurred in the DRC (2). Control was complicated by the widespread distribution of cases across 3 provinces and the presence of dozens of hostile armed insurgent groups. Case identification and contact tracing were difficult. Treatment centers were established and staffed by local and international health care professionals. By the end of 2019, both the United States and the European Union had approved the Ebola Zaire vaccine [rVSV-ZEBOV] that helped bring the epidemic to an end in June 2020. A second vaccine, the 2-dose vaccine known as Ad26.ZEBOV/MVA-BN-Filo, was approved and put into use later. In June 2020, another Ebola outbreak occurred in the Équateur Province of the DRC, and ended in March 2021 (3). In October 2021 there was an outbreak in the DRC province of North Kivu that ended in December 2021 with 11 confirmed cases and 9 deaths (4). In April 2022 there was another small outbreak in Équateur Province of the DRC with 4 confirmed cases and 1 probable case, all of whom died. The outbreak was declared over by July 2022 (5). In August 2022 there was an outbreak in North Kivu with only one confirmed case; the outbreak was declared over in September 2022 (6).
In September 2022, Uganda reported a case of Ebola disease caused by the Sudan ebolavirus, the first in a decade. This outbreak was declared over in January 2023, after 142 confirmed cases and 77 deaths (7).
There was a small outbreak starting in February 2021 in Guinea that is speculated to have started with the wife of a man who had recovered from an Ebola virus infection 5 years earlier and was thought to have transmitted the virus to his wife. This persistent infection and delayed transmission was suggested by the fact that the genetically sequenced virus was remarkably similar to that of the West Africa outbreak 5 to 7 years earlier.
Передача вірусів Марбург і Ебола
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 (8). Ebola virus genetic material persisted for a year or longer in the semen of 63% men who recovered from Ebola. However, PCR 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 (9).
Aerosol transmission has been suspected in a few instances; 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 physical contact with the deceased have played an important role in transmission of infection.
Довідкові матеріали загального характеру
1. Centers for Disease Control and Prevention (CDC): Ebola: 2017 Democratic Republic of the Congo, Bas Uélé District. 2017.
2. World Health Organization (WHO): New Ebola outbreak declared in Democratic Republic of the Congo, May 2018.
3. CDC: Ebola: 2020 Democratic Republic of the Congo, Equateur Province.
4. WHO: Ebola virus disease – Democratic Republic of the Congo, December 2021
5. WHO: Ebola outbreak 2022 - Équateur Province, DRC
6. WHO: Ebola Virus Disease –Democratic Republic of the Congo, September 2022
7. WHO: Ebola disease caused by Sudan ebolavirus – Uganda
8. WHO: Fact Sheet: Marburg virus disease. February 15, 2018.
9. Bausch DG, Crozier I: The Liberia Men's Health Screening Program for Ebola virus: Win-win-win for survivor, scientist, and public health. Lancet Glob Health 4 (10):e672–673, 2016. doi: 10.1016/S2214-109X(16)30207-8. Epub 2016 Aug 30.
Symptoms and Signs of Marburg and Ebola Virus Infections
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.
Довідковий матеріал щодо симптомів та ознак
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 of Marburg and Ebola Virus Infections
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 (see CDC: Interim Guidance on Risk Assessment and Management of Persons with Potential Ebolavirus Exposure). 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 of Marburg and Ebola Virus Infections
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 are currently available to treat Ebola virus infection caused by the Zaire ebolavirus. These are REGN-EB3 and mAb114. REGN-EB3 was approved by the US Food and Drug Administration (FDA) in October 2020 and is a combination of three monoclonal antibodies (atoltivimab/maftivimab/odesivimab). The second medication, mAb114, is a single monoclonal antibody (ansuvimab) that was approved in December 2020. Both of these treatments were proven effective during the 2018 to 2020 Ebola outbreak in the DRC demonstrating 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 medications for Ebola (ZMapp, remdesivir).
Until the two monoclonal antibodies or others are shown to neutralize Marburg virus, there is still no effective treatment for that virus infection.
Prevention of Marburg and Ebola Virus Infections
Several Ebola vaccines are in clinical trials. rVSV-ZEBOV was used successfully on a limited scale at the end of the 2016 Ebola outbreak in West Africa and on a greater scale in the 2018 outbreak in the DRC and was approved by the FDA in December 2019 for prevention of disease caused by Zaire ebolavirus in people 18 years of age and older. In 2020, the European Medicines Agency granted marketing authorization to a second new vaccine delivered in 2 doses, one each of Ad26.ZEBOV and MVA-BN-Filo, 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. For the Sudan ebolavirus, there were 3 candidate vaccines recommended for the trial during the Uganda outbreak by an independent WHO expert panel. The outbreak ended before the ring vaccination (vaccinating a ring of people around cases, rather than vaccinating an entire population) vaccine trials could be done.
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
For more information, see the WHO: Interim recommendations for infection prevention and control, WHO: Marburg virus disease, and WHO: Interim advice on the sexual transmission of the Ebola virus disease.
Ключові моменти
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 for Zaire ebolavirus, and 2 are currently in routine use in the DRC. Three candidate vaccines have been developed for Sudan ebolavirus.
Plan diagnosis, management, and prevention of transmission with public health authorities.
Додаткова інформація
The following English-language resources may be useful. Please note that THE MANUAL is not responsible for the content of these resources.
Centers for Disease Control and Prevention (CDC): Think Ebola: Early recognition: Infographic for health care providers approaching a patient who may have Ebola
CDC: Sequence for Donning and Removing Personal Protective Equipment
World Health Organization (WHO): Outbreaks and Emergencies Bulletin
