Crimean-Congo hemorrhagic fever virus: Infectious substances pathogen safety data sheet

Section I - Infectious agent

Name

Crimean-Congo hemorrhagic fever virus

Agent type

Virus

Taxonomy

Family

Nairoviridae

Genus

Orthonairovirus

Species

Orthonairovirus haemorrhagiae

Synonym or cross - reference

CCHFV, Crimean-Congo hemorrhagic fever (CCHF), Central Asian haemorrhagic fever, and Congo feverFootnote 1Footnote 2Footnote 3Footnote 4Footnote 5Footnote 6Footnote 7Footnote 8. Formerly known as Crimean-Congo hemorrhagic fever orthonairovirus, Crimean-Congo hemorrhagic fever nairovirus, and Crimean-Congo hemorrhagic fever virus, Crimean haemorrhagic fever Congo virus, Crimean haemorrhagic fever virus, and Congo virusFootnote 1Footnote 3Footnote 9Footnote 10Footnote 11. Through history, and in different parts of the world, CCHFV has been referred to as Asian Ebola, Khungribta (blood taking), Khunymuny (nose bleeding), and Karakhalak (Black Death)Footnote 12.

Characteristics

Brief description

Crimean-Congo hemorrhagic fever virus (CCHFV) is a triple segmented, single-stranded, negative-sense RNA virus assigned to the genus Orthonairovirus within the family NairovirideaeFootnote 1Footnote 4Footnote 5Footnote 7Footnote 8Footnote 11Footnote 13. The virions are enveloped, spherical, approximately 100 nm in diameter, and have a bilayer lipid envelope that is approximately 5 to 7 nm thickFootnote 1Footnote 4Footnote 12Footnote 13. Viral particles consist of a host cell-derived lipid envelope with inserted viral glycoproteins Gn and Gc, surrounding the 3 negative-sense, single-stranded RNA genome segments. These genome segments are designated large (L), medium (M), and small (S), which are 12 kb, 6.8 kb, and 3 kb in size, respectively, and are encapsidated by nucleocapsid protein to form ribonucleoprotein complexes associated with viral L proteinFootnote 12Footnote 14. The L segment encodes the viral polymerase, the M segment encodes the viral glycoproteins Gn and Gc, while the S segment encodes the nucleoprotein (N), which is responsible for the encapsidation of the viral RNAFootnote 12. One or two non-structural proteins (NSs) are also encoded by the S and/or M segmentsFootnote 14Footnote 15.

Properties

The initial binding of CCHFV to the host cell surface is mediated by the glycoproteins Gn and/or GcFootnote 16. CCHFV surface glycoproteins are highly N-glycosylated, which is thought to be important for cellular transport, folding, and virus infectivityFootnote 17. After attachment, CCHFV is endocytosed via a clathrin-mediated endocytosis mechanism and then transported to early endosomesFootnote 16. The L protein synthesizes viral mRNA which is followed by glycoprotein maturation, viral assembly, and egress.

Section II - Hazard identification

Pathogenicity and toxicity

CCHFV causes CCHF in humans, which has a sudden onsetFootnote 18. The CCHF clinical course can be divided into 4 stages: incubation, pre-hemorrhagic, hemorrhagic, and convalescenceFootnote 18. The incubation period for the development of CCHF following exposure is dependent on the mode of exposure. Following the bite of a tick, the incubation period generally lasts from 1-3 days, but may range up to 9 days; whereas the incubation period generally lasts 5-6 days with a maximum of 13 days following transmission from infected bloodFootnote 12. The incubation phase is followed by the pre-hemorrhagic stage which lasts an average of 2-4 days, during which there is abrupt onset of nonspecific symptoms such as fever, headache, myalgia, dizziness, neck pain and stiffness, backache, headache, sore eyes, photophobia, sore throat, abdominal pain, nausea, vomiting, and diarrheaFootnote 18. Hyperemia, conjunctivitis, and jaundice may also occur. Changes in mood (e.g., agitation) and sensory perception can manifest in severe cases, and may be followed by somnolence. Hepatomegaly and splenomegaly have also been reported. The hemorrhagic stage is typically short (2-3 days), presenting with petechiae, extended ecchymoses on mucous membranes and skin, epistaxis, melena, hematemesis, hematuria, and hemoptysisFootnote 1Footnote 2Footnote 4Footnote 5Footnote 6Footnote 7Footnote 8Footnote 18. Bleeding from injection sites is common, and occasionally occurs from other sites such as the vagina, uterus, and brainFootnote 18. Laboratory abnormalities include thrombocytopenia, leukopenia, elevated aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and creatine phosphokinase, and proinflammatory cytokine levels. In addition to these symptoms, hemorrhaging from the gums, nose, internal organs, and gastrointestinal system may occurFootnote 12Footnote 19Footnote 20. Hepatitis is usually evident, and patients may suffer from rapid kidney, liver and/or pulmonary failureFootnote 19. Rarely reported complications associated with CCHF include ascending paralysis with rhabdomyolysis, acute pulmonary embolism, and epididymo-orchitisFootnote 21Footnote 22Footnote 23. Severe cases are marked by rapid progression to disseminated intravascular coagulation, excessive bleeding, multiorgan failure, and shock. In fatal cases, death typically occurs in the second week of illness and is often a result of shock from blood loss, neurological complications, pulmonary hemorrhage, or intercurrent infectionsFootnote 4Footnote 5Footnote 6Footnote 18. In survivors, convalescence begins approximately 9 days post-onset, but may be prolonged, and is characterized by hypotension, tachycardia or bradycardia, polyneuritis, breathing issues, xerostomia, vision and hearing deficiencies, hair loss, memory loss, general weakness, headache, poor appetite, and dizzinessFootnote 12Footnote 18. Full recovery from CCHF may take up to 1 yearFootnote 12. It is estimated that 10-20% of infected humans develop clinical signs of infectionFootnote 24Footnote 25. The estimated case fatality rate is between 30 and 50%Footnote 1Footnote 4Footnote 5Footnote 6Footnote 8Footnote 13.

Viremia and antibody detection has been reported in many domestic and wild animals; however, infection appears to be asymptomatic. Migratory birds are thought to be involved in the spread of CCHFV-infected ticks into novel areasFootnote 26Footnote 27. A 2016 seroepidemiologic survey of CCHF in cattle, camels, and sheep yielded prevalence rates of 20-30% in Iraq, Iran, and TurkeyFootnote 28.

Epidemiology

CCHF was first reported in the Crimean peninsula during 1944 to 1945, when a large outbreak of severe hemorrhagic fever in military agricultural workers with a case fatality rate of 10% was recordedFootnote 1Footnote 3Footnote 13. The disease was designated as Crimean hemorrhagic 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 Crimean-Congo hemorrhagic fever virusFootnote 3Footnote 7Footnote 10.

The geographic range of CCHFV is the most extensive of the tickborne viruses affecting humansFootnote 29. Although first discovered in Crimea and the Democratic Republic of Congo, CCHFV has since been reported in many areas in Eastern Europe, particularly the former Soviet Union and the Mediterranean, in northwestern China, Africa, the Middle East, central Asia, and the Indian subcontinentFootnote 30. Currently, CCHFV is considered endemic or potentially endemic in approximately 50 countries throughout Europe, Africa and AsiaFootnote 31Footnote 32. The geographic distribution of CCFHV mimics that of the predominant natural tick vector, Hyalomma, which have a 50° North latitude limitFootnote 30. The recent spread of CCHFV to non-endemic areas may be attributed to human movement, vertebrate host migration, introduction of Hyalomma ticks to areas outside their endemic range due to migratory birds, and climate changeFootnote 33Footnote 34. Phylogenetic analysis of the S segment revealed genetic diversity among CCHFV strains from different regions of the world, with seven major clades identified: clade I (Africa 2), clade II (Africa 1), clade III (Europe 2), clade IV (Africa 3), clade V (Europe 1), clade VI (Asia 1), and clade VII (Asia 2)Footnote 17.

In southeastern Europe, approximately 6,000 cases of human infection with CCHFV were reported from 1953 to 2010Footnote 25. During this period, outbreaks were reported in Crimea, Astrakhan, Rostov, Bulgaria, Albania, Kosovo, Greece, and TurkeyFootnote 5Footnote 17Footnote 25Footnote 35Footnote 36. Five fatal cases of CCHF were reported in Kosovo in 2013Footnote 37. From January 2021 through May 2021, Turkey reported over 240 confirmed cases of CCHF, including 13 deathsFootnote 38Footnote 39. In North Macedonia, 3 cases were reported as of August 14, 2023, one of which was fatalFootnote 40.

Outbreaks were reported in China between 1965 and 1994 (260 cases), in 1997 (26 cases), and in 2001 (51 cases)Footnote 17Footnote 41. Between 1948 and 1968, 75 cases were reported in Kazakhstan, whereas outbreaks reported in Tajikistan between 1943 and 2009 comprised over 200 casesFootnote 17Footnote 41. Only 14 cases were reported in Pakistan up until 2010; however, over 350 cases were reported between 2014 and 2020Footnote 42. Between January 1, 2022, and June 22, 2022, 4 confirmed cases were reported in PakistanFootnote 43. In Russia, 2,361 cases, including 94 deaths, were reported between 1999 and 2020Footnote 44. In India, outbreaks were reported in 2011 (4 deaths), 2012, and 2013. Outbreaks were reported in Afghanistan in 1998 (19 cases; 2 deaths), 2008, 2016, and 2017 (237 confirmed or suspected cases; 41 deaths)Footnote 17Footnote 45. Most recently an outbreak, involving 806 cases and 86 deaths, was reported from January 1, 2023 to August 5, 2023, in 14 provinces in AfghanistanFootnote 46.

Between 1979 and 2022, outbreaks were reported in several Middle Eastern countries, including the United Arab Emirates, Iraq, Saudi Arabia, Oman, and Iran, comprising over 350 confirmed or suspected casesFootnote 17Footnote 29Footnote 36Footnote 47Footnote 48Footnote 49. Outbreaks have also been reported in several African countries including Zaire, Uganda, Mauritania, Burkina Faso, South Africa, Tanzania, Southwest Africa, Kenya, Senegal, Namibia, and SudanFootnote 17Footnote 41Footnote 50Footnote 51Footnote 52Footnote 53Footnote 54Footnote 55Footnote 56.

Populations at increased risk of exposure include those with outdoor activities (e.g., soldiers, farmers, forest workers, and hikers) and those with close contact to livestock (e.g., shepherds, farmers, butchers, slaughterhouse workers, and veterinarians)Footnote 18.

Risk factors that contribute to the development of severe disease remain unknown. It is thought to be related to the route of exposure, amount of inoculating virus, amount of resources for treatment, and host geneticsFootnote 18. Patients with viremic titres exceeding 109 genome copies per milliliter of plasma are more likely to have lethal diseaseFootnote 18. Thrombocytopenia, elevated AST and ALT levels, and elevated levels of proinflammatory cytokines are predictive of a fatal outcomeFootnote 18. Failure to mount an anti-CCHFV humoral immune response is also associated with fatality.

Host range

Natural host(s)

Humans appear to be the only host of CCHFV in which the disease is manifestedFootnote 1Footnote 2Footnote 3Footnote 4Footnote 5Footnote 6Footnote 7Footnote 8Footnote 9Footnote 10Footnote 13Footnote 29Footnote 57Footnote 58. Like other tick-borne zoonotic agents, CCHFV circulates in a tick-vertebrate-tick cycleFootnote 1Footnote 2Footnote 3Footnote 7Footnote 29. The main natural hosts of CCHFV are hares and hedgehogs (for immature ticks); and cattle, sheep, goats, horses, swine, and birds (for adult ticks)Footnote 3Footnote 4Footnote 5Footnote 6Footnote 7Footnote 8.

Other host(s)

Mice, hamsters, and non-human primates are notable experimentally infected hostsFootnote 59Footnote 60Footnote 61.

Infectious dose

Infectious dose is unknown for humans. However, the infective dose (ID50) of CCHFV Hoti in IFNAR-/- mice by subcutaneous inoculation was determined to be 0.002 TCID50Footnote 62.

Incubation period

Ranges from 1 to 13 days depending on the mode of transmissionFootnote 1Footnote 4Footnote 5Footnote 8Footnote 12.

Communicability

In humans, the preferred mode of transmission of CCHFV is through the bite of an infected tick, mainly of the genus Hyalomma, with nearly 70% of infected individuals reporting a recent tick biteFootnote 19. Transmission by contact with mucous membranes or damaged skin is likely, as infection may result from mucosal exposure or exposure to damaged skin with blood, secretions, organs, and other bodily fluids from infected individuals or animalsFootnote 12. Sexual transmission is suspected in the transmission of CCHFVFootnote 63. Transmission of CCHFV by injection is possible; percutaneous contact with blood or other body fluids from infected individuals is considered to be high risk for transmission of CCHFVFootnote 19. Nosocomial transmission has also been reported to occur through needlestick injuriesFootnote 18. Infection may also occur through airborne transmission, particularly in the late stage of disease when CCHFV viral load in blood/body fluids is highFootnote 64. The likelihood of infection following ingestion or contact with intact skin is unknown.

Casual direct contact is unlikely to cause CCHFV infection in humans, whereas CCHFV transmission through intimate direct contact is likely via contact with blood, secretions, organs, and other bodily fluids of infected individualsFootnote 12Footnote 19Footnote 29. Transmission through indirect contact is likely as CCHFV can be transmitted among humans through exposure to infected fomites, especially among health care workers, and through the bite of an infected tickFootnote 19Footnote 29Footnote 41Footnote 65.

Section III - Dissemination

Reservoir

Mammals, including hares, hedgehogs, rodents, and birds have been implicated as reservoirs of CCHFV; however, it is thought that they are more likely to be amplifying hosts rather than true reservoirsFootnote 1Footnote 2Footnote 7Footnote 8Footnote 13. Ticks of the Hyalomma spp. also act as a reservoirFootnote 1Footnote 2Footnote 3Footnote 4Footnote 5Footnote 6Footnote 7Footnote 8Footnote 9Footnote 10.

Zoonosis

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 29. Zoonosis is also possible indirectly via infected tick bitesFootnote 1Footnote 2Footnote 3Footnote 4Footnote 5Footnote 6Footnote 7Footnote 8Footnote 9Footnote 10.

Vectors

Human infection with CCHFV occurs through the bite of an infected tick, mainly of the genus HyalommaFootnote 4Footnote 5Footnote 6Footnote 7Footnote 8Footnote 13. Other tick species vectors of CCHFV include Rhipicephalus, Ornithodoros, Boophilus, Dermatocentor, Haemaphysalis, Amblyomma, and Ixodes speciesFootnote 7Footnote 13Footnote 66.

Section IV - Stability and viability

Drug susceptibility/resistance

There are no specific therapeutic drugs for CCHFFootnote 18. Chloroquine and chlorpromazine are effective antiviral molecules for CCHFV in vitro Footnote 67. CCHFV is also sensitive to ribavirin in vitroFootnote 68; however, the use of ribavirin to treat CCHFV infection is controversialFootnote 69Footnote 70. Favipiravir is effective in suppressing viral replication and preventing mortality following CCHFV infectionFootnote 71. Ribavirin and favipiravir can synergistically inhibit CCHFV in vitro. Methylprednisolone has also been cited as a treatment for CCHFV infectionFootnote 72.

The clinical efficacy of ribavirin in treating CCHF remains unclear and controversialFootnote 73Footnote 74. Data supporting ribavirin efficacy is poor due to confounding factors in data setsFootnote 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 compoundsFootnote 5Footnote 8Footnote 58Footnote 75. 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 hypochloriteFootnote 58.

Physical inactivation

Susceptible to high temperature (56°C for 30 minutes, or 60°C for 15 minutes), gamma irradiation, UV light (1,200 to 3,000 μW/cm2), and low pH (less than 6)Footnote 3Footnote 5Footnote 76. Treatment with ultraviolet C light at a dose of 0.1 J/cm2 or with methylene blue in conjunction with visible light at 30 J/cm2 was shown to inactivate CCHFV in plasma-reduced platelet concentrates and plasma units, respectively, with reduction of CCHFV infectivity levels to the limit of detectionFootnote 76. The virus is also inactivated in 40% ethanol within 2 minutesFootnote 77.

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 77. 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 2Footnote 3Footnote 4Footnote 5Footnote 6Footnote 7Footnote 8Footnote 9Footnote 13. Serological responses consistent with acute infection include presence of anti-CCHFV IgM antibodies or a 4-fold increase in anti-CCHFV IgG titers between serial blood samplesFootnote 78. Assays that directly assess for CCHFV infection, such as viral culture or nucleic acid amplification tests, are most useful during the first week after symptoms onset, whereas serological testing is more likely to be useful after the first week of illness. Diagnostic tests include compliment fixation, serum neutralisation (with newborn mice), indirect haemagglutination inhibition, radial gel diffusion, RT-PCR, ELISA, and immunofluorescenceFootnote 1Footnote 2Footnote 3Footnote 4Footnote 5Footnote 6Footnote 7Footnote 8Footnote 9Footnote 10. The ELISA test is considered the most sensitive and specific, as well as being fast and easily reproducibleFootnote 4.

Note: The specific recommendations for surveillance in the laboratory should come from the medical surveillance program, which is based on a local risk assessment of the pathogens and activities being undertaken, as well as an overarching risk assessment of the biosafety program as a whole. More information on medical surveillance is available in the Canadian Biosafety Handbook (CBH).

First aid/treatment

Intensive supportive therapyFootnote 6Footnote 7. Analgesics for pain, antiemetic for vomiting, anxiolytic for agitation, and antibiotics and/or antimalarial drugs to prevent infection may be prescribedFootnote 79. For patients without hemorrhagic complications, treatment with analgesics and antipyretics is effectiveFootnote 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. Other treatment options that seem to be effective include administration of monoclonal antibodies against surface glycoproteins of CCHFV, interferon therapy, and high-dose steroid in the case of acute hemophagocytic syndrome complicationFootnote 80. Administration of ribavirin, or convalescent plasma with a high neutralising antibody titre are regarded as useful treatmentsFootnote 2Footnote 7Footnote 8. In vivo studies using mice suggest that favipiravir may be a promising antiviral agent in the treatment of CCHF patientsFootnote 80.

Note: The specific recommendations for first aid/treatment in the laboratory should come from the post-exposure response plan, which is developed as part of the medical surveillance program. More information on the post-exposure response plan can be found in the CBH.

Immunization

No vaccine currently available in Canada. An inactivated vaccine prepared from brain tissue of CCHFV-infected newborn mice has been used solely in Bulgaria since 1974; it is not available for use elsewhere due largely to safety concerns and lack of efficacy trialsFootnote 81. The CCHF candidate vaccine "KIRIM-KONGO-VAX" entered phase I clinical trials from December 2014 to June 2017; however, no results are currently availableFootnote 82. Several other candidate CCHF vaccines have been developed, many of which show promise in preclinical animal models; examples include inactivated virus preparations, subunit vaccines, virus-like particles, recombinant live-attenuated viruses, replication-deficient viral vectors, and nucleic acid-based vaccinesFootnote 18.

Note: More information on the medical surveillance program can be found in the CBH, and by consulting the Canadian Immunization Guide.

Prophylaxis

There are no specific antiviral agents for the treatment of CCHFVFootnote 83. 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. Post-exposure administration of high-dose methylprednisolone was effective in treating patients with CCHFFootnote 84.

Note: More information on prophylaxis as part of the medical surveillance program can be found in the CBH.

Section VI - Laboratory hazard

Laboratory-acquired infections

Eight laboratory-acquired infections (LAIs), including one death, were reported in Uganda in the 1960s, where patients had known exposure to infection during the handling or processing of infected miceFootnote 85. In 1986, a laboratory assistant developed CCHF while preparing plasma from a blood sample of a CCHG patient by centrifugation in Russia; the assistant developed overt disease, including hemorrhages, but survived after prolonged convalescenceFootnote 85. A fatal case of CCHF occurred in 2006 in South Africa, involving a technologist who handled blood samples from a deceased CCHF patientFootnote 85. A retrospective study identified two cases of LAI in Turkey between 2002 and 2014, one due to needlestick while drawing blood and one due to handling a blood sample without wearing glovesFootnote 85.

Note: Please consult the Canadian Biosafety Standard (CBS) and CBH for additional details on requirements for reporting exposure incidents. A Canadian biosafety guideline describing notification and reporting procedures is also available.

Sources/specimens

Blood, bodily secretions, and tissues of infected humans and animalsFootnote 1Footnote 2Footnote 4Footnote 5Footnote 6Footnote 8.

Primary hazards

Needlestick and exposure of mucous membrane to infective fluids and/or aerosols, as well as exposure to infected tick vectors, are the primary hazards associated with exposure to CCHFVFootnote 1Footnote 5Footnote 6Footnote 19.

Special hazards

Centrifugation of virus infected samples is considered the most dangerous of all laboratory manipulations involving CCHFVFootnote 5. Several laboratory-acquired CCHFV infections were associated with working with infected mice; as such, handling experimentally infected animals with CCHFV is a special hazardFootnote 85.

Section VII - Exposure controls/personal protection

Risk group classification

Crimean-Congo hemorrhagic fever virus is a Risk Group 4 Human Pathogen and Risk Group 4 Animal PathogenFootnote 86 and a Security Sensitive Biological Agent (SSBA).

Containment requirements

Containment Level 4 facilities, equipment, and operational practices outlined in the CBS for work involving infectious or potentially infectious materials, animals, or cultures.

Note that there are additional security requirements, such as obtaining a Human Pathogens and Toxins Act Security Clearance, for work involving SSBAs.

Protective clothing

The applicable Containment Level 4 requirements for personal protective equipment and clothing outlined in the CBS to be followed. The use of a positive-pressure suit or use of a Class III biological safety cabinet (BSC) line is required for all work with Risk Group (RG4) pathogens.

A local risk assessment will identify the appropriate hand, foot, head, body, eye/face, and respiratory protection, and the personal protective equipment requirements for the containment zone must be documented.

Other precautions

All activities involving open vessels of regulated materials are to be performed in a certified BSC or other appropriate primary containment device. 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 is to be strictly limited. Open wounds, cuts, scratches, and grazes are to be covered with waterproof dressings. Additional precautions must be considered with work involving animal activities.

Section VIII - Handling and storage

Spills

The spill area is to be evacuated and secured. Aerosols must be allowed to settle for a minimum of 30 minutes. For spills outside of a BSC, air supply to positive-pressure suits must be ensured. Positive-pressure suits that have been in contact with the regulated materials must be completely decontaminated by following procedures for gross decontamination of a positive-pressure suit. Plastics to be transferred to a dishpan, which should be moved to the BSC. Spills of potentially contaminated material to be covered with absorbent paper-based material (e.g., paper towels), liberally covered with an effective disinfectant (e.g., 5% MicroChem), and left to soak for at least 5 minutes before being wiped up. Following the removal of the initial material, the disinfection process are to be repeated. After disinfection, inform the appropriate internal authority (e.g., containment zone supervisor, BSO) of the incident.

Disposal

All materials/substances that have come in contact with the regulated materials must be completely decontaminated before they are removed from the containment zone. This can be achieved by using decontamination technologies and processes that have been demonstrated to be effective against the regulated materials, such as chemical disinfectants, autoclaving, irradiation, incineration, an effluent treatment system, or gaseous decontamination (CBH).

Storage

The applicable Containment Level 4 requirements for storage outlined in the CBS are to be followed. Pathogens, toxins, and other regulated materials to be stored inside the containment zone.

SSBA: Containers of high-security biological agents (SSBA) stored outside the containment area must be labeled, leak-proof, shock-resistant and kept in locked storage equipment in a fixed location (i.e., not mobile) and in an area with limited access.

Inventory of Risk Group 4 (RG4) pathogens and SSBAs in long-term storage to be maintained and to include:

  • specific identification of the pathogens, toxins, and other regulated materials
  • a means to allow for the detection of a missing or stolen sample in a timely manner

Section IX - Regulatory and other information

Canadian regulatory information

Controlled activities with Crimean-Congo hemorrhagic fever virus require a Human Pathogen and Toxins licence issued by the Public Health Agency of Canada.

Note that there are additional security requirements, such as obtaining a Human Pathogens and Toxins Act Security Clearance, for work involving SSBAs.

The following is a non-exhaustive list of applicable designations, regulations, or legislations:

Last file update

August 2023

Prepared by

Centre for Biosecurity, Public Health Agency of Canada.

Disclaimer

The scientific information, opinions, and recommendations contained in this Pathogen Safety Data Sheet have been developed based on or compiled from trusted sources available at the time of publication. Newly discovered hazards are frequent and this information may not be completely up to date. The Government of Canada accepts no responsibility for the accuracy, sufficiency, or reliability or for any loss or injury resulting from the use of the information.

Persons in Canada are responsible for complying with the relevant laws, including regulations, guidelines and standards applicable to the import, transport, and use of pathogens in Canada set by relevant regulatory authorities, including the Public Health Agency of Canada, Health Canada, Canadian Food Inspection Agency, Environment and Climate Change Canada, and Transport Canada. The risk classification and related regulatory requirements referenced in this Pathogen Safety Data Sheet, such as those found in the Canadian Biosafety Standard, may be incomplete and are specific to the Canadian context. Other jurisdictions will have their own requirements.

Copyright © Public Health Agency of Canada, 2023, Canada

References

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Footnote 12

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Footnote 15

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Footnote 17

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Footnote 18

Hawman, D. W., and H. Feldmann. 2023. Crimean-Congo haemorrhagic fever virus. Nat. Rev. Microbiol. 21:463-477.

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Footnote 20

Aslam, S., M. S. Latif, M. Daud, Z. U. Rahman, B. Tabassum, M. S. Riaz, A. Khan, M. Tariq, and T. Husnain. 2016. Crimean-congo hemorrhagic fever: Risk factors and control measures for the infection abatement (Review). Biomed. Rep. 4:15-20.

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Footnote 21

Kerget, F., Ş O. Demirdöğen, and B. Kerget. 2021. Case Report: A Rare Case of Crimean-Congo Hemorrhagic Fever Associated with Epididymo-Orchitis. Am. J. Trop. Med. Hyg. 104:1055-1057.

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Footnote 22

Prasad, H. R., A. Sharma, N. Kothari, V. Vyas, and S. Goyal. 2020. Atypical Presentation of Crimean-Congo Hemorrhagic Fever as Ascending Paralysis with Rhabdomyolysis. Indian. J. Crit. Care. Med. 24:143-144.

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Footnote 23

Ture, Z., and G. Kalin-Unuvar. 2021. A case of Crimean Congo hemorrhagic fever complicated with acute pulmonary embolism. J. Med. Virol. 93:3925-3928.

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Footnote 24

Bodur, H., E. Akinci, S. Ascioglu, P. Öngürü, and Y. Uyar. 2012. Subclinical infections with Crimean-Congo hemorrhagic fever virus, Turkey. Emerg. Infect. Dis. 18:640-642.

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Footnote 25

Goldfarb, L. G., M. P. Chumakov, A. A. Myskin, V. F. Kondratenko, and O. Y. Reznikova. 1980. An epidemiological model of Crimean hemorrhagic fever. Am. J. Trop. Med. Hyg. 29:260-264.

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Footnote 26

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