Pathogen Safety Data Sheets: Infectious Substances – 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 Footnote 1 - Footnote 8. Formerly known as Crimean haemorrhagic fever Congo virus, Crimean haemorrhagic fever virus, and Congo virus Footnote 1Footnote 3Footnote 9Footnote 10.
CHARACTERISTICS: CCHFV is a triple segmented, single-stranded, negative-sense RNA genome virus belonging to the genus Nairovirus, family Bunyaviridae Footnote 1Footnote 4Footnote 5Footnote 7Footnote 8Footnote 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 Footnote 1Footnote 4Footnote 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-achesFootnote 1Footnote 2Footnote 4 - Footnote 8Footnote 11. Fever can last between 5 and 12 days and may be continuous or biphasicFootnote 5-Footnote 8. Other frequent symptoms include abdominal pain, anorexia, nausea and vomiting, diarrhoea, bradycardia, hyperaemia and oedema of the face and neck, and conjunctival congestionFootnote 1Footnote 2Footnote 4 - Footnote 6Footnote 8Footnote 9Footnote 11. Leucopenia and thrombocytopenia are almost always present, as is proteinuriaFootnote 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 mucosaFootnote 1Footnote 2Footnote 4 - Footnote 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 infectionsFootnote 4 - Footnote 6. For those who do not succumb to the disease, the convalescence period begins about 15 to 20 days after the onset of illnessFootnote 1. It is generally characterised by generalised weakness, weak pulse, and sometimes complete loss of hairFootnote 1. Additional sequelae can include polyneuritis, sweating, headache, vertigo, nausea, poor appetite, laboured breathing, poor vision, loss of hearing, and loss of memoryFootnote 3. The case fatality rate is estimated to be between 30 and 50%Footnote 1Footnote 4 - Footnote 6Footnote 8Footnote 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 recordedFootnote 3Footnote 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 countriesFootnote 3Footnote 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 CCHFVFootnote 3Footnote 7Footnote 10.
The geographic range of CCHFV is the most extensive of the tick-borne viruses affecting humansFootnote 12. Infection with CCHFV has been described in over 30 countries, with major outbreaks reported in Southeast Europe, Asia, the Middle East, and AfricaFootnote 5Footnote 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)Footnote 5Footnote 13.
Asia: outbreaks recorded in China (1965-94, 1994-1995), Kazakhstan (1948-1968), Tajikistan (1943-1970), and Pakistan (1976, 1994, 2000)Footnote 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)Footnote 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)Footnote 12Footnote 14.
Those at the highest risk of contracting CCHF include farmers living in endemic areas, medical personnel, veterinarians, and abattoir workersFootnote 1Footnote 2Footnote 4Footnote 5Footnote 8Footnote 11Footnote 12Footnote 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. Footnote 2Footnote 4 - Footnote 8 Infection can also occur via skin lesions when crushing an infected tickFootnote 4Footnote 7Footnote 8Footnote 11Footnote 12. Nosocomial outbreaks are frequent and have occurred due to exposure to infected blood and secretionsFootnote 2Footnote 5 - Footnote 9Footnote 11Footnote 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 fomitesFootnote 1Footnote 2Footnote 4Footnote 6Footnote 8.
COMMUNICABILITY: Readily transmissible from person-to-personFootnote 2Footnote 4Footnote 6Footnote 8. Nosocomial infections are common after exposure to infected blood and secretionsFootnote 2Footnote 5 - Footnote 9Footnote 11Footnote 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 Footnote 1Footnote 2Footnote 7Footnote 8Footnote 11. Ticks of the Hyalomma spp. also act as a reservoir Footnote 1 - Footnote 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 excretaFootnote 2Footnote 4Footnote 6Footnote 8Footnote 12. Zoonosis is also possible indirectly via infected tick bitesFootnote 1 - Footnote 10.
VECTORS: The Hyalomma species of tick are the most important vector for CCHFVFootnote 4 - Footnote 8Footnote 11. Other tick species vectors of CCHFV include Rhipicephalus, Ornithodoros, Boophilus, Dermatocentor, and Ixodes speciesFootnote 7Footnote 11.
SECTION IV – STABILITY AND VIABILITY
DRUG SUSCEPTIBILITY: Sensitive to ribavirin in vitroFootnote 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 Footnote 5Footnote 8Footnote 17Footnote 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)Footnote 3Footnote 5Footnote 15. Virus does not survive in matured meatFootnote 15 The virus is also inactivated in 40% ethanol within 2 minutesFootnote 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 °CFootnote 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)Footnote 2 - Footnote 9Footnote 10. Diagnostic tests include compliment fixation, serum neutralisation (with newborn mice), indirect haemagglutination inhibition, radial gel diffusion, RT-PCR, ELISA, and immunofluorescenceFootnote 1 - Footnote 10. The ELISA test is considered the most sensitive and specific, as well as being fast and easily reproducibleFootnote 4.
Note: All diagnostic methods are not necessarily available in all countries.
FIRST AID/TREATMENT: Intensive supportive therapyFootnote 6Footnote 7. For patients without haemorrhagic complications, treatment with analgesics and antipyretics is effective Footnote 4. Patients with haemorrhagic manifestations are given therapy aimed at maintaining fluid and electrolyte balance, circulatory volume, and blood pressureFootnote 2Footnote 4. In severe cases, fresh platelets, fresh frozen plasma, albumin, or coagulation factors are administeredFootnote 4Footnote 5. Administration of ribavirin, or convalescent plasma with a high neutralising antibody titre are regarded as useful treatmentsFootnote 2Footnote 7Footnote 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 humansFootnote 7Footnote 8.
PROPHYLAXIS: Control of tick populations with insecticides, and application of insect repellent to limit tick bites in endemic areasFootnote 1Footnote 3Footnote 11Footnote 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)Footnote 2.
SECTION VI - LABORATORY HAZARDS
LABORATORY-ACQUIRED INFECTIONS: Eight cases were reported with 1 death up to 1980Footnote 21
SPECIAL HAZARDS: Centrifugation of virus infected samples is considered the most dangerous of all laboratory manipulations involving CCHFVFootnote 5.
SECTION VII – EXPOSURE CONTROLS / PERSONAL PROTECTION
RISK GROUP CLASSIFICATION: Risk Group 4Footnote 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 splashesFootnote 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.Footnote 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 upFootnote 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 wastesFootnote 23.
STORAGE: In sealed, leak-proof containers that are appropriately labelled and locked in a Containment Level 4 laboratoryFootnote 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.
Public Health Agency of Canada, 2010
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