MARBURG VIRUS

PATHOGEN SAFETY DATA SHEET - INFECTIOUS SUBSTANCES

SECTION I - INFECTIOUS AGENT

NAME: Marburg virus

SYNONYM OR CROSS REFERENCE: Marburg disease, Marburg haemorrhagic fever, African haemorrhagic fever, and green monkey disease^(1,2).

CHARACTERISTICS: Marburg virus is a member of the Filoviridae family, and is an elongated filamentous molecule, highly variable in length, but typically around 1000 nm long with a uniform diameter of 80 nm^(2,3). The viral fragment is pleomorphic, and may appear in the shape of a "6", a "U", or a circle, and it is contained within a lipid membrane^(2,3). Each virion contains one molecule of single-stranded, negative-sense viral genomic RNA^(1,4), complexed with the proteins NP, VP35, VP30, and L⁽³⁾.

SECTION II – HAZARD IDENTIFICATION

PATHOGENICITY/TOXICITY: A rare, severe haemorrhagic fever in humans and non-human primates⁽¹⁾, characterised by a sudden onset with high fever, chills, headache, myalgia, and maculopapular rash, possibly followed by vomiting, chest pain, sore throat, abdominal pain, and diarrhoea⁽²⁾. Symptoms become increasingly severe and may include inflammation of the pancreas, jaundice, severe weight loss, delirium, shock, liver failure, massive haemorrhage, and multi-organ dysfunction. Marburg disease has a fatality rate of approximately 25 %^(1,2).

EPIDEMIOLOGY: Occurrence of Marburg haemorrhagic fever has been primarily limited to countries in sub-Saharan Africa.

In 1967, simultaneous outbreaks in Marburg, Frankfurt (Germany), and Belgrade (Yugoslavia, now Serbia) were reported following the handling of viscera, body fluids, and/or kidney tissue cultures from African green monkeys imported from Uganda. Thirty-one cases and 9 deaths were reported^(1,2,4,5,6). Between 1975 and 1987, isolated cases were reported in South Africa (originating from Zimbabwe), Kenya, Zimbabwe, Kenya, and the Democratic Republic of Congo^(1,2,4,6). The large long running outbreak occurred between 1998 and 2000 in the Democratic Republic of Congo⁽⁷⁾, resulting in 149 cases and 123 deaths^(6,8). The largest outbreak to date occurred in 2004 and 2005 centered in Uige, Angola where 252 cases were reported with 227deaths^(6,8). Since 2007, a number of cases have been reported in Uganda, some of which have been diagnosed into other countries (i.e. USA, Netherlands) in individuals returning from Uganda^(6,9,10).

HOST RANGE: Humans and non-human primates (e.g. the African green monkey)^(1,2).

INFECTIOUS DOSE: One to 10 aerosolized organisms⁽⁵⁾.

MODE OF TRANSMISSION: Primary mode of transmission appears to be via close personal contact with an infected individual or their body fluids⁽¹⁾. In the laboratory, the virus displays some capability of infection through small-particle aerosols; however, airborne spread among humans has not been clearly demonstrated⁽²⁾. Individuals handling the infected monkeys or their fluids and cell cultures of Marburg virus have become ill.

INCUBATION PERIOD: Three to 10 days⁽¹⁾.

COMMUNICABILITY: Person-to-person transmission can occur via close personal contact between an infected individual or their body fluids⁽¹⁾. Communicable as long as blood and secretions contain the virus^(1,2). Semen can contain the virus for 3 months and is infective until semen is virus-free^(1,2). Mother-to-child transmission while nurturing has also been documented⁽⁷⁾.

SECTION III - DISSEMINATION

RESERVOIR: The natural reservoir is unknown⁽²⁾, but is likely African fruit bats (Rousettus aegyptiacus), and/or other fauna of the goldmine area in Congo⁽⁸⁾. Monkeys are susceptible but are incidental hosts^(11,12,13).

ZOONOSIS: Yes, via contact with monkeys or bats, or handling their viscera and/or body fluids^(1,2,4,5).

VECTORS: Unknown, but it is suggested that the index case in South Africa (1975) had been bitten by arthropods while sleeping outdoors in Zimbabwe⁽²⁾.

SECTION IV – STABILITY AND VIABILITY

DRUG SUSCEPTIBILITY: Unknown⁽⁸⁾.

SUSCEPTIBILITY TO DISINFECTANTS: Sodium hypochlorite⁽⁴⁾, β-propiolactone^(4,14), 3 % acetic acid (pH 2.5)⁽¹⁵⁾, phenolic disinfectants⁽⁴⁾, formaldehyde and paraformaldehyde⁽¹⁶⁾, 1 % glutaraldehyde⁽¹⁷⁾, formalin⁽¹⁾, lipid solvents⁽⁴⁾, and detergents such as SDS⁽¹⁷⁾. Note: Decontamination requires specific, controlled use of virus-inactivating agents⁽⁴⁾.

PHYSICAL INACTIVATION: Heating for 30 minutes⁽⁴⁾ to 60 minutes⁽¹⁵⁾ at 60°C, boiling for 5 minutes⁽¹⁷⁾, gamma irradiation (1.2 x10⁶ rads to 1.27 x10⁶ rads)^(4,14,15,17), and UV radiation^(4,14).

SURVIVAL OUTSIDE HOST: Can survive for up to 4 to 5 days on contaminated surfaces⁽¹⁸⁾, and can survive in liquid or dried material for a number of days^(3,19,20,21).

SECTION V – FIRST AID / MEDICAL

SURVEILLANCE: Monitor for symptoms. Diagnosis can be confirmed by virus isolation^(1,2,4,7), ELISA to detect viral antigens or patient antibodies^(1,7), serum or organ homogenates⁽¹⁾, RT- PCR, immunohistochemistry⁽¹⁾, and electron microscopy of tissue sections and/or biopsies^(1,2).

Other tests include indirect immunofluorescence to detect virus⁽²⁾, or antiviral antibodies⁽¹⁾. Laboratory studies are extremely hazardous and should be performed in a Containment Level 4 facility⁽¹⁾.

Note: All diagnostic methods are not necessarily available in all countries.

FIRST AID/TREATMENT: No anti-viral therapy currently available^(4,6,20). Supportive therapy should be provided to maintain renal function, fluid and electrolyte balance, oxygen status and blood pressure, replace lost blood and clotting factors, and complicating infections^(4,21). Transfusion of convalescent serum may be beneficial⁽⁴⁾. Ribavirin has poor in vitro and in vivo activity against filoviruses⁽²¹⁾.

IMMUNIZATION: None⁽²⁰⁾.

PROPHYLAXIS: None⁽²²⁾.

SECTION VI - LABORATORY HAZARDS

LABORATORY-ACQUIRED INFECTIONS: In 1967 in Marburg, Frankfurt (Germany), and Belgrade (Yugoslavia, now Serbia), there were 25 reported primary cases with 7 deaths. The cases arose from contact and accidents with blood and tissues from infected African green monkeys^(1,2,4,5,23). Six secondary cases (medical personnel, one spouse) developed from the primary cases⁽²⁾.

SOURCES/SPECIMENS: Blood^(1,21); serum⁽²⁾; secretions⁽²¹⁾, including respiratory and throat secretions⁽⁷⁾; semen^(1,2,7,21); urine; and various tissues and organs from human or animal hosts, or their homogenates^(2,19,22).

PRIMARY HAZARDS: Accidental parenteral inoculation, respiratory exposure to infectious aerosols, and mucous membrane exposure to infectious droplets⁽²⁰⁾.

SPECIAL HAZARDS: None.

SECTION VII – EXPOSURE CONTROLS / PERSONAL PROTECTION

RISK GROUP CLASSIFICATION: Risk Group 4⁽²⁴⁾.

CONTAINMENT REQUIREMENTS: Containment Level 4 facilities, equipment, and operational practices for work involving infectious or potentially infectious materials, animals, or cultures.

PROTECTIVE CLOTHING: Personnel entering the laboratory must remove street clothing, including undergarments, and jewellery, and change into dedicated laboratory clothing and shoes, or don full coverage protective clothing (i.e., completely covering all street clothing). Additional protection may be worn over laboratory clothing when infectious materials are directly handled, such as solid-front gowns with tight fitting wrists, gloves, and respiratory protection. Eye protection must be used where there is a known or potential risk of exposure to splashes⁽²⁵⁾.

OTHER PRECAUTIONS: All activities with infectious material should be conducted in a biological safety cabinet (BSC) in combination with a positive pressure suit, or within a class III BSC line. Centrifugation of infected materials must be carried out in closed containers placed in sealed safety cups, or in rotors that are loaded or unloaded in a biological safety cabinet. The integrity of positive pressure suits must be routinely checked for leaks. The use of needles, syringes, and other sharp objects should be strictly limited. Open wounds, cuts, scratches, and grazes should be covered with waterproof dressings. Additional precautions should be considered with work involving animal activities⁽²⁵⁾.

SECTION VIII - HANDLING INFORMATION

SPILLS: Allow aerosols to settle and, wearing protective clothing, gently cover spill with paper towels and apply suitable disinfectant, starting at the perimeter and working towards the centre. Allow sufficient contact time before clean up (30 min)⁽²⁵⁾.

DISPOSAL: Decontaminate all materials for disposal from the containment laboratory by steam sterilization, chemical disinfection, incineration or by gaseous methods. Contaminated materials include both liquid and solid wastes⁽²⁵⁾.

STORAGE: In sealed, leak-proof containers that are appropriately labelled and locked in a Containment Level 4 laboratory⁽²⁵⁾.

SECTION IX - MISCELLANEOUS INFORMATION

REGULATORY INFORMATION: The import, transport, and use of pathogens in Canada is regulated under many regulatory bodies, including the Public Health Agency of Canada, Health Canada, Canadian Food Inspection Agency, Environment Canada, and Transport Canada. Users are responsible for ensuring they are compliant with all relevant acts, regulations, guidelines, and standards.

UPDATED: August 2010.

PREPARED BY: Pathogen Regulation Directorate, Public Health Agency of Canada.

Although the information, opinions and recommendations contained in this Pathogen Safety Data Sheet are compiled from sources believed to be reliable, we accept no responsibility for the accuracy, sufficiency, or reliability or for any loss or injury resulting from the use of the information. Newly discovered hazards are frequent and this information may not be completely up to date.

Copyright ©
Public Health Agency of Canada, 2010
Canada

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