Filoviruses – Ebola and Marburg Viruses
Boston University
Research Occupational Health Program (ROHP)
617-358-7647
Agent
Ebola – and marburgviruses are members of the Filoviridae family. Ebola- and marburgviruses cause a severe disease in humans. The filamentous viral particles of ebola- and marburgviruses contain a helical nucleocapsid that is enveloped by a host cell-derived membrane. Each virion contains a non-segmented, negative-sense viral RNA genome. Four of the five ebolavirus species have caused disease in humans; Zaire ebolavirus (Ebola virus, EBOV), Sudan ebolavirus (Sudan virus, SUDV), Tai Forest ebolavirus (Tai Forest virus, TAFV), and Bundibugyo ebolavirus (Bundibugyo virus, BDBV). The fifth, Reston ebolavirus (Reston virus, RESTV), has caused disease in nonhuman primates but not humans. The members of the Marburgvirus genus (Marburg virus, MARV; Ravn virus, RAVV) are structurally similar to ebolaviruses.
Bombali virus (BOMV) is a newly discovered member of the Ebolavirus genus. BOMV genomic RNA, but not infectious virus, was isolated in 2016 from insectivorous free-tailed bats (Chaerephon pumilus, Mops condylurus) in the Bombali District of Sierra Leone. BOMV has not been associated with outbreaks in humans yet, and the pathogenic potential of this virus in humans is unknown. The BOMV glycoprotein can mediate entry into human cells. Given the virus similarity to other ebolaviruses, if circulated in humans, BOMV might cause disease in humans with symptoms similar to Ebola Virus Disease.
Mengla virus (MLAV) and Lloviu virus (LLOV) are newly discovered members of the filovirus family and phylogenetically distinct from ebola- and marburgviruses. MLAV genomic RNA, but not infectious virus, was isolated from Rousettus bats in China. LLOV genomic RNA, but not infectious virus, was isolated from Schreibers’s long-fingered bats (Miniopterus schreibersii) in Spain and Hungary in 2002 and 2016, respectively. MLAV and LLOV have not been associated with outbreaks in humans yet, and their pathogenic potential in humans is unknown. The MLAV and LLOV glycoproteins can mediate entry into human cells. Given that MLAV and LLOV belong to the filovirus family, these viruses might cause disease in humans with symptoms similar to Ebola or Marburg Virus Disease.
Disease/Infection
Ebola Virus Disease (EVD)
Marburg Virus Disease (MVD)
Pathogenicity
Ebola Virus Disease (EVD) is a severe, often-fatal disease in humans. 25-90% case fatality rate, dependent on species. The most pathogenic species is Ebola virus with a case fatality rate of 40-90%.
Marburg Virus Disease (MVD) has a case fatality rate of 25-90%
Biosafety Information
Risk Group/BSL
Risk group 4
Biosafety level: BSL4
Modes of Transmission
| Transmission | |
| Skin Exposure (Needlestick, bite, or scratch): | Yes |
| Mucous Membrane Splash to Eye(s), Nose or Mouth: | Yes Person to person transmission by intimate contact is the main route of infection (direct contact with infected blood, secretions, organs, or semen). Viruses can persist for months in immune-privileged sites (e.g. testis) of disease survivors and can be transmitted by sexual contact. Potential transmission by breast milk has been reported. |
| Inhalation: | Transmission via droplets is suspected. |
| Ingestion: | Unlikely in laboratory setting |
HostRange/Reservoir
Humans, non-human primates, and fruit bats
Symptoms
Sudden onset with high fever, malaise, sore throat, abdominal pain, myalgias, vomiting, diarrhea; conjunctival injection, maculopapular rash, renal and hepatic involvement and hemorrhagic diathesis; involvement of liver, pancreas, kidney, and to a much less degree the CNS and heart; leukopenia, thrombocytopenia, and transaminase elevation. Multi organ failure is noted.
Incubation Period
EVD: 2-21 days (4-9 days in most cases)
MVD: 3-10 days
Viability
a. Ebolaviruses: Susceptible to 2% sodium hypochlorite, 2% glutaraldehyde, 5% peracetic acid, phenolic disinfectants, paraformaldehyde and 1% formalin.
Marburgviruses: Sodium hypochlorite, ß-propiolactone, 3% acetic acid (pH2.5), phenolic disinfectants, formaldehyde and paraformaldehyde, 1% glutaraldehyde, formalin, lipid solvents, and detergents such as SDS.
b. Susceptible to ultra-violet irradiation. Triton X-100 will greatly reduce infectivity. Heating to 60°C for 1 hour will render samples noninfectious. Virus is inactivated with 0.3% ß-propiolactone at 37°C for 30 minutes. Serum samples can be inactivated by 2 megarad of gamma irradiation.
Survival Outside Host
Ebolaviruses: Virus can survive in blood specimens for several weeks at room temperature and for several weeks in a corpse. However, the virus does not survive for long periods after drying.
Marburgviruses: 4-5 days on contaminated surfaces, longer in liquid.
Information for Lab Workers
Laboratory PPE
One-piece positive pressure ventilated suit with life support system is utilized. Long sleeve scrubs will be worn under the positive pressure suit with inner gloves providing added protection against outer glove tear.
Containment
All work with infectious virus must be performed in BSL-4/ABSL-4 containment.
PRIMARY HAZARDS:
- Accidental parenteral inoculation, respiratory exposure to infectious droplets, and/or direct contact with broken skin or mucous membranes.
SPECIAL HAZARDS:
- Work with, or exposure to, infected non-human primates, rodents, or their carcasses represents a risk of human infection; use of sharps when handling virus-containing material.
In Case of Exposure/Disease
Immediately after exposure, lab workers should follow the HIGH AND MAXIMUM CONTAINMENT MEDICAL INCIDENT RESPONSE PLAN (ERP C.1) as provided on site and during training.
- For all lab exposures which involve BSL-4 pathogens (needle sticks, punctures, cuts, scratches, etc.) and for all medical events which require immediate evaluation and treatment (traumatic injury, heart attack, stroke, seizure, etc.):
- Medical Campus: call or have a coworker call the Control Center at 617-414–6666. You will be referred to or transported to the appropriate health care location by the emergency response team.
- The Control Center operator will activate a communication tree which includes the BU Research Occupational Health Program (ROHP) Officer will help guide the response.
- To reach the ROHP directly use the 24/7 hour number (617-358-ROHP (7647)).
- You will be connected with the BU Research Occupational Health Program (ROHP) medical officer. ROHP will refer you the appropriate health care location.
- Under any of these scenarios, always inform the physician of your work in the laboratory and the agent(s) that you work with.
- Present the Medical Surveillance Card that every BSL-4 researcher has been provided by ROHP, this wallet size card identifies the agents that the researcher works with; provide the ID card to the treating physician.
Vaccination
None FDA approved. Chimp adenovirus and vesicular stomatitis virus (VSV) based Ebola virus vaccines are leading candidates with the rVsV-EBOV GP vaccine showing promise in a ring vaccination trial in Guinea.
Information for First Responders/Medical Personnel
Public Health Issues
After exposure: Immediately after an exposure to either virus, the lab worker is not considered infectious. He/she can be cared for with standard PPE. On campus exposures will be escorted directly from NEIDL triage room to the Special Pathogens Unit (SPU) at Boston Medical Center (BMC) where lab workers will be received by a team of physicians and nurses. In case of a lab worker presenting to BMC ED or other outside medical facility, either the exposed or the caring physicians should immediately contact ROHP for further instructions.
In case of (suspected) illness: Lab worker should contact ROHP directly and when possible, transport will be arranged to bring the patient to BMC’s Patient Isolation Unit. Patient should prevent close contact with household members pending evaluation, if possible. If the worker presents to BMC ED or other outside medical facility, caring physicians should contact ROHP for further instructions and ROHP will consult with infectious diseases specialists at SPU.
Person-to-person transmission is reported via close personal contact with an infected individual or their body fluids during the late stages of the infection. PPE requirements for care of this patient are listed below.
PPE: SPU staff use PPE including coveralls, fluid proof aprons, PAPR’s, and double gloves. CDC recommendations: Airborne, Droplet Precautions plus Contact Precautions, with face/eye protection, emphasizing safety sharps and barrier precautions when blood exposure likely. Avoid aerosol-generating procedures.
Other guidance for outside providers: No blood work should be drawn until contact is made with ROHP.
Specimen should be handled with extreme care and enclosed in appropriate shatter-proof and leak-proof packing for transport to lab. Diagnostic laboratory staff should be notified of suspicion of infection, and tests should be performed under proper containment. Please contact ROHP immediately for further details.
Public health officials will be notified.
Diagnosis/Surveillance
Virus detection in blood is difficult in the early stages of this disease. PCR is used to diagnose both EVD and MVD. In EVD, PCR is only positive after 3 days of symptoms. Acute and convalescent serologies are to be drawn.
Potential alternate diagnoses with similar presentation should be considered, such as influenza or other respiratory viruses.
First Aid/Post Exposure Prophylaxis
Standard management of potential exposure to Ebola and Marburg viruses is solely based on observation, potential isolation and with symptomatic and supportive treatments.
No approved post exposure prophylaxis or post exposure vaccination is FDA approved. rVsV-EBOV GP vaccine has shown promise in preventing Ebola virus-related disease.
Treatment
Treatment is aggressive supportive care, and is directed at maintaining renal function and electrolyte balance, addressing coagulopathy and combating hemorrhage and shock. Monoclonal antibodies targeted towards Ebola virus particles and small interferring RNA based treatments have been used some success in clinical settings under compassionate use. Less clinical information is available for Marburg virus disease but some of the same type of modalities have shown some success in animal models. Transfusion of convalescent serum may be beneficial. No treatments are FDA approved for either agent.
Medical countermeasures may be available during treatment through CDC and public health bodies and will be done in coordination with the SPU program.
Survivors of both diseases may shed virus for weeks after infection in semen and breast milk.
References
- Biosafety in Microbiological and Biomedical Laboratories (BMBL) 5th Edition. US Government Printing Office, Washington, 2007.
- Ebola Hemorrhagic Fever Fact Sheet, CDC. http://www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/ebola.htm
- Control of Communicable Diseases Manual. David L. Heymann. Washington DC, USA: American Public Health Association Press, 19th edition 2008
- Public Health Agency of Canada. Material Safety Data Sheets. Infectious Substances. Ebola virus. Marburg Virus, http://www.phac-aspc.gc.ca/lab-bio/res/psds-ftss/ebola-eng.php
- Siegel JD, Rhinehart E, Jackson M, Chiarello L. 2007 Guideline for Isolation Precautions: Preventing Transmission of Infectious Agents in Health Care Settings. American journal of infection control 2007 Dec;35(10 Suppl 2):S65-164.
Revised 6/12/19