CRIMEAN-CONGO HAEMORRHAGIC FEVER VIRUS

PATHOGEN SAFETY DATA SHEET - INFECTIOUS SUBSTANCES

SECTION I - INFECTIOUS AGENT

NAME: Crimean-Congo haemorrhagic fever virus

SYNONYM OR CROSS REFERENCE: CCHFV, CCHF, Central Asian haemorrhagic fever, and Congo fever ^(1-8). Formerly known as Crimean haemorrhagic fever Congo virus, Crimean haemorrhagic fever virus, and Congo virus ^{(1, 3, 9, 10)}.

CHARACTERISTICS: CCHFV is a triple segmented, single-stranded, negative-sense RNA genome virus belonging to the genus Nairovirus, family Bunyaviridae ^{(1, 4, 5, 7, 8, 11)}. The virions are spherical, measure approximately 85 to 105 nm in diameter, and have a bilayered lipid envelope that is approximately 5 to 7 nm thick ^{(1, 4, 11)}.

SECTION II – HAZARD IDENTIFICATION

PATHOGENICITY/TOXICITY: Crimean-Congo haemorrhagic fever (CCHF) has a sudden onset, with high fever, chills, malaise, diffuse myalgia, photophobia, irritability, vertigo, and head-, limb-, and back-aches ^{(1, 2, 4-8, 11)}. Fever can last between 5 and 12 days and may be continuous or biphasic ^{(5, 8)}. Other frequent symptoms include abdominal pain, anorexia, nausea and vomiting, diarrhoea, bradycardia, hyperaemia and oedema of the face and neck, and conjunctival congestion ^{(1, 2, 4-6, 8, 9, 11)}. Leucopenia and thrombocytopenia are almost always present, as is proteinuria ⁽⁴⁾.

The haemorrhagic phase of the disease usually begins on day 4, with the most common manifestations being petechia, epistaxis, haemorrhaging of the gums, haematuria, bleeding from the vagina, and haemorrhaging of the gastric mucosa ^{(1, 2, 4-8)}. When death occurs, it is usually due to shock brought on by the loss of blood, or by neurological complications, pulmonary haemorrhages, or incurrent infections ^(4-6). For those who do not succumb to the disease, the convalescence period begins about 15 to 20 days after the onset of illness ⁽¹⁾. It is generally characterised by generalised weakness, weak pulse, and sometimes complete loss of hair ⁽¹⁾. Additional sequelae can include polyneuritis, sweating, headache, vertigo, nausea, poor appetite, laboured breathing, poor vision, loss of hearing, and loss of memory ⁽³⁾. The case fatality rate is estimated to be between 30 and 50% ^{(1, 4-6, 8, 11)}.

EPIDEMIOLOGY: CCHF was first reported in the Crimean peninsula during 1944 to 1945, when a large outbreak of severe haemorrhagic fever with a case fatality rate of 10% was recorded ^{(3, 11)}. The disease was designated as Crimean haemorrhagic fever and was later reported throughout the European and central Asian republics of the former Soviet Union, and other countries ^{(3, 7)}. The virus was later shown to be antigenically identical to Congo virus which was isolated from a febrile patient in the Democratic Republic of Congo in 1956, and was subsequently named CCHFV ^{(3, 7, 10)}.

The geographic range of CCHFV is the most extensive of the tick-borne viruses affecting humans ⁽¹²⁾. Infection with CCHFV has been described in over 30 countries, with major outbreaks reported in Southeast Europe, Asia, the Middle East, and Africa ^{(5, 12)}.

Southeast Europe: outbreaks recorded in Crimea (1944-45), Astrakhan (1953-63), Rostov (1963-1969), Bulgaria (1953-74, 1975-96, 1997-2003), Albania (2001), Kosovo (2001), and Turkey (2002-2005 & 2007-2008) ^{(5, 13)}.

Asia: outbreaks recorded in China (1965-94, 1994-1995), Kazakhstan (1948-1968), Tajikistan (1943-1970), and Pakistan (1976, 1994, 2000) ⁽¹²⁾.

Middle East: outbreaks recorded in United Arab Emirates (1979, 1994-1995), Sharjah (1980), Iraq (1979-1980), Saudi Arabia (1990), Oman (1995-1996), and Iran (2003) ⁽¹²⁾.

Africa: outbreaks recorded in Zaire (1956), Uganda (1958-1977), Mauritania (1983, 2004), Burkina Faso (1983), South Africa (1981-1986), Tanzania (1986), Southwest Africa (1986), Kenya (2000), and Sudan (2008) ^{(12, 14)}.

Those at the highest risk of contracting CCHF include farmers living in endemic areas, medical personnel, veterinarians, and abattoir workers ^{(1, 2, 4, 5, 8, 11, 12, 15)}.

HOST RANGE: Humans appear to be the only host of CCHFV in which the disease is manifested ^{(1-12, 15-17)}. Like other tick-borne zoonotic agents, CCHFV circulates in a tick-vertebrate-tick cycle ^{(1-3, 7, 12)}. The main natural hosts of CCHFV are hares and hedgehogs (for immature ticks); and cattle, sheep, goats, horses, swine, and birds (for adult ticks) ^(3-8).

INFECTIOUS DOSE: Unknown.

MODE OF TRANSMISSION: Transmitted via the bite of an infective adult tick, particularly Hyalomma marginatum or Hyalomma anatolicum ^{(2, 4-8)}. Infection can also occur via skin lesions when crushing an infected tick ^{(4, 7, 8, 11, 12)}. Nosocomial outbreaks are frequent and have occurred due to exposure to infected blood and secretions ^{(2, 5-9, 11, 12)}. Infections are also associated with the slaughtering of infected animals via small-particle aerosol from infected rodent excreta, and from contaminated needlesticks or infected fomites ^{(1, 2, 4, 6, 8)}.

INCUBATION PERIOD: Ranges from 1 to 12 days depending on the mode of transmission ^{(1, 4, 5, 8)}.

COMMUNICABILITY: Readily transmissible from person-to-person ^{(2, 4, 6, 8)}. Nosocomial infections are common after exposure to infected blood and secretions ^{(2, 5-9, 11, 12)}.

SECTION III - DISSEMINATION

RESERVOIR: Mammals, including hares, hedgehogs, rodents, and birds have been implicated as reservoirs of CCHFV; however, it is believed that they are more likely to be amplifying hosts rather than true reservoirs ^{(1, 2, 7, 8, 11)}. Ticks of the Hyalomma spp. also act as a reservoir ^(1-10).

ZOONOSIS: Yes, CCHFV can be transmitted to humans via exposure to infected tissues/secretions during the slaughtering of infected animals, and via exposure to small-particle aerosols from infected rodent excreta ^{(2, 4, 6, 8, 12)}. Zoonosis is also possible indirectly via infected tick bites ^(1-10).

VECTORS: The Hyalomma species of tick are the most important vector for CCHFV ^{(4-8, 11)}. Other tick species vectors of CCHFV include Rhipicephalus, Ornithodoros, Boophilus, Dermatocentor, and Ixodes species ^{(7, 11)}.

SECTION IV – STABILITY AND VIABILITY

DRUG SUSCEPTIBILITY: Sensitive to ribavirin in vitro ⁽¹⁸⁾.

SUSCEPTIBILITY TO DISINFECTANTS: Like all lipid enveloped viruses, CCHFV is readily inactivated by common fixatives such as glutaraldehyde, formalin, and paraformaldehyde; chlorine-based disinfectants, such as 1% sodium hypochlorite; and by 70% alcohol, hydrogen peroxide, peracetic acid, and iodophor compounds ^{(5, 8, 17, 19)}. Typically, areas and or objects that have come into contact with viral haemorrhagic fever viruses can be disinfected with a 1:100 dilution of sodium hypochlorite ⁽¹⁷⁾.

PHYSICAL INACTIVATION: Susceptible to high temperature (56°C for 30 minutes, or 60°C for 15 minutes), UV light (1,200 to 3,000 μW/cm²), and low pH (less than 6) ^{(3, 5, 15)}. Virus does not survive in matured meat ⁽¹⁵⁾. The virus is also inactivated in 40% ethanol within 2 minutes ⁽²⁰⁾.

SURVIVAL OUTSIDE HOST: The virus is stable under wet conditions for 7 hours at 37 °C, 11 days at 20 °C, and 15 days at 4 °C ⁽²⁰⁾. Under dry conditions, the virus is stable for at least 90 minutes, but less than 24 hours.

SECTION V – FIRST AID / MEDICAL

SURVEILLANCE: Monitor for symptoms (a diagnosis cannot be made during the incubation period of the disease) and confirm by virus isolation from a blood sample (inoculation of cell cultures or suckling mice) ^{(2-9, 11)}. Diagnostic tests include compliment fixation, serum neutralisation (with newborn mice), indirect haemagglutination inhibition, radial gel diffusion, RT-PCR, ELISA, and immunofluorescence ^(1-10). The ELISA test is considered the most sensitive and specific, as well as being fast and easily reproducible ⁽⁴⁾.

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

FIRST AID/TREATMENT: Intensive supportive therapy ^{(6, 7)}. For patients without haemorrhagic complications, treatment with analgesics and antipyretics is effective ⁽⁴⁾. Patients with haemorrhagic manifestations are given therapy aimed at maintaining fluid and electrolyte balance, circulatory volume, and blood pressure ^{(2, 4)}. In severe cases, fresh platelets, fresh frozen plasma, albumin, or coagulation factors are administered ^{(4, 5)}. Administration of ribavirin, or convalescent plasma with a high neutralising antibody titre are regarded as useful treatments ^{(2, 7, 8)}.

IMMUNIZATION: None available. Vaccines based on the inactivated virus have been investigated since the 1970s, and more recently, possible DNA vaccines have been studies, although the safety and efficacy of these vaccines have not been demonstrated for humans ^{(7, 8)}.

PROPHYLAXIS: Control of tick populations with insecticides, and application of insect repellent to limit tick bites in endemic areas ^{(1, 3, 11, 15)}. Post-exposure prophylaxis with oral ribavirin for those considered to have been in contact with highly viraemic patients (200 mg twice daily, for 5 days) ⁽²⁾.

SECTION VI - LABORATORY HAZARDS

LABORATORY-ACQUIRED INFECTIONS: Eight cases were reported with 1 death up to 1980 ⁽²¹⁾.

SOURCES/SPECIMENS: Blood, and bodily secretions and tissues of infected animals and humans ^{(1, 2, 4-6, 8)}.

PRIMARY HAZARDS: Needlestick and exposure of mucous membrane to infective fluids and/or aerosols ^{(1, 5, 6)}.

SPECIAL HAZARDS: Centrifugation of virus infected samples is considered the most dangerous of all laboratory manipulations involving CCHFV ⁽⁵⁾.

SECTION VII – EXPOSURE CONTROLS / PERSONAL PROTECTION

RISK GROUP CLASSIFICATION: Risk Group 4 ⁽²²⁾.

CONTAINMENT REQUIREMENTS: Containment Level 4 facilities, equipment, and operational practices for work involving infectious or potentially infectious materials, animals, and 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 ⁽²³⁾.

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 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. ⁽²³⁾. Additional precautions should be considered with work involving animals.

SECTION VIII - HANDLING AND STORAGE

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 ⁽²³⁾.

DISPOSAL: Decontaminate all materials for disposal from the containment laboratory by steam sterilisation, chemical disinfection, incineration or by gaseous methods. Contaminated materials include both liquid and solid wastes ⁽²³⁾.

STORAGE: In sealed, leak-proof containers that are appropriately labelled and locked in a Containment Level 4 laboratory ⁽²³⁾.

SECTION IX – REGULATORY AND OTHER 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: September 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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