Diseases

Crimean-Congo Haemorrhagic fever

Download as PDF Download as XLS Download summary

Chapter select

Control Tools

  • Diagnostics availability

  • Commercial diagnostic kits available worldwide

    None for animals.

    In humans:

    Commercial ELISA tests: For both IgG and IgM

             ELISA CCHF IgG (Vektor-Best, Russia)

             ELISA CCHF IgM (Vektor-Best, Russia)

    Commercial IFA tests:

    -        CCHF IgG Sandwich ELISA (Biological Diagnostic Supplies Limited, BDSL®)

    -        IFA test based on recombinant antigens GPC and N / biochip technology, under evaluation (Euroimmun®)

    PCR assay AmpliSens CCHF:

    -       Real Time RT-PCR assay by Altona (Germany)Altona Diagnostic PCR (Europe)

    -       Developed and manufactured by Central Institute of Epidemiology, Russia.

    -       Specific for CCHF virus RNA.

    -       Target: S segment RNA; internal control included.

    GAPS:

    Antibody detection detects evidence of exposure not necessarily current infection (unless an IgM test is used).  Little information is available about how quickly antibody levels drop, nor whether the antibodies are protective. 

    Development  of novel bio-safe neutralization assays.

  • Commercial diagnostic kits available in Europe

    Yes. Euroimmune (IFA) and Altona (IFA (as above)

    ELISA (as above).

    PCR (as above).
  • Diagnostic kits validated by International, European or National Standards

    None.
  • Diagnostic method(s) described by International, European or National standards

    No.
  • Commercial potential for diagnostic kits in Europe

    Yes.GAP: Commercial serological tests for humans and animals with increased sensitivity and specificity are needed.
  • DIVA tests required and/or available

    No.
  • Opportunities for new developments

    Very limited in animals.GAP: Development of diagnostic tests for monitoring CCHFV seroprevalence in reservoir animals.
  • Vaccines availability

  • Commercial vaccines availability (globally)

    None in animals. In humans, an inactivated vaccine derived from mouse brain has been used in the former Soviet Union and Bulgaria (not FDA approved).

    GAP: Development of a safe and effective vaccine for human use has a high priority.

  • Commercial vaccines authorised in Europe

    None.
  • Marker vaccines available worldwide

    None.
  • Marker vaccines authorised in Europe

    None.
  • Effectiveness of vaccines / Main shortcomings of current vaccines

    None available.
  • Commercial potential for vaccines in Europe

    None in animals.
  • Regulatory and/or policy challenges to approval

    Not applicable.
  • Commercial feasibility (e.g manufacturing)

    Not feasible at present.
  • Opportunity for barrier protection

    None.

  • Opportunity for new developments

    None in animals. In humans the vaccines may need to be either immunogens derived from several CCHF virus strains, or those that can target the immune response on conserved neutralizing epitopes.GAP: Development of vaccine(s) for key virus reservoir animals to avoid tick-based infection/transmission. A good animal vaccine may inhibit/decrease the future spread of the virus in Europe and worldwide. Development of vaccine effective against all CCHFV strains.
  • Pharmaceutical availability

  • Current therapy (curative and preventive)

    None in animals as no evidence of clinical disease. The World Health Organization recommends ribavirin as the anti-viral medication of choice for CCHF. However, there is no consensus on the role of specific antiviral therapy in the management of patients, with very limited evidence so far on its efficacy.GAP: Development and or characterization of new antivirals should be prioritized.
  • Future therapy

    Not applicable, not enough knowledge.GAP: Testing efficacy of monoclonal neutralizing antibodies as immunotherapeutic agents.
  • Commercial potential for pharmaceuticals in Europe

    Yes, for humans.
  • Regulatory and/or policy challenges to approval

    Not applicable.
  • Commercial feasibility (e.g manufacturing)

    None.
  • Opportunities for new developments

    Limited, due to the endemic nature of the infection in small mammals and ticks.
  • New developments for diagnostic tests

  • Requirements for diagnostics development

    Diagnosis of suspected CCHF must be performed in specially-equipped, high bio-safety level laboratories.GAP: Provided the virus can be easily inactivated, it might be advisable to revise current biosafety requirements for CCHFV diagnosis.
  • Time to develop new or improved diagnostics

    Short, since currently there are good tools available for developing novel and biosafe diagnostics.GAP: Developing more sensitive and biosafe diagnostic tools for CCHF virus.
  • Cost of developing new or improved diagnostics and their validation

    Costly, and difficult in view of the need for biosafety requirements.
  • Research requirements for new or improved diagnostics

    Approaches for diagnostic methods should be standardised and validated.

    Limited requirements for new diagnostics in animals.

    GAPS:

    Developing standards (serum and virus strain panels) for diagnostic validation.

    Establishing a European laboratory network with capacities to test performance of novel diagnostic developments.
  • Technology to determine virus freedom in animals

    Monitoring the absolute number of virus genomic copies in tissues is now possible and affordable using technologies such as digital PCR.
  • New developments for vaccines

  • Requirements for vaccines development / main characteristics for improved vaccines

    It is considered that a major hindrance in developing vaccines against CCHF virus is the wide genetic variation noted in different strains. Nucleic acid sequence analysis has demonstrated extensive genetic diversity, particularly between viruses from different geographic regions. However genetic variation does not correlate with serotype variants, since currently there is only one serotype for CCHFV.

    Animal models for CCHF infection are currently available.GAP: More extensive preclinical trials to confirm whether/how genetic variation affects vaccine efficacy should be performed using currently available animal models.
  • Time to develop new or improved vaccines

    Difficult to assess, but probably no less than 6 years.
  • Cost of developing new or improved vaccines and their validation

    Expensive but difficult to determine.
  • Research requirements for new or improved vaccines

    Animal models to test efficacy of vaccine developments are available. Virus manipulation needs to be performed in BSL4 laboratories.GAP: Perform immunity/efficacy tests in enhanced BSL3Ag laboratories would facilitate more research towards vaccine development in animals.
  • New developments for pharmaceuticals

  • Requirements for pharmaceuticals development

    Currently available antiviral drugs of unknown efficacy.
  • Time to develop new or improved pharmaceuticals

    Unknown.
  • Cost of developing new or improved pharmaceuticals and their validation

    Unknown but likely to be expensive.
  • Research requirements for new or improved pharmaceuticals

    The development of novel prevention and therapeutic strategies for use in humans is important.GAPS:
    • More research on possible additional antiviral drug therapy.
    • Plan randomised clinical trial to ascertain the benefits of ribavirin treatment in humans.
    • Developing new treatment strategies (such as neutralizing Ab).
    • More research on CCHFV pathogenesis to develop new therapeutic strategies.

Disease details

  • Description and characteristics

  • Pathogen

    CCHF is a zoonotic viral disease that is asymptomatic in infected animals, but a serious threat to humans. The virus which causes CCHF is an arbovirus which is a member of the Nairovirus genus, a group of related viruses forming one of the five genera in the Bunyaviridae family of viruses.

    GAP:

    The general knowledge of migration, epidemiology, re-assortment, recombination and pathogenesis of the virus is very limited.

    Knowledge about pathogenicity differences among strains is missing.

  • Variability of the disease

    Based on sequencing data seven genotypes of CCHF virus (CCHFV) have been recognized up to date. CCHFV is transmitted by ticks from diffferent genera (Hyalomma, Dermacentor, Rhipicephalus) and can infect several mammalian species (cattle, sheep, goats, hares, hedgehogs), causing disease only in man. The disease has a seasonal pattern, related to the increased activity of ticks, and peaks between spring and early autumn. GAP: The knowledge on transmission from animal to human is limited (how long infected animals shed the virus, can domestic animals shed the virus in milk, infectious dose and so on).   
  • Stability of the agent/pathogen in the environment

    CCHFV is stable for up to 10 days in blood kept at 40°C (104°F). 
  • Species involved

  • Animal infected/carrier/disease

    The CCHF virus may infect a wide range of domestic and wild animals but there is no evidence that the virus causes disease in animals.  Many birds are resistant to infection, but ostriches are susceptible and may show a high prevalence of infection in endemic areas. CCHFV can be found in ostrich blood for 1 to 4 days and in visceral organs for up to five days after experimental infection.

    GAP: Prevalence needs to be measured in animals in endemic areas.

  • Human infected/disease

    Only three members of the Nairovirus genus have been implicated as causes of human disease: the Dugbe and Nairobi sheep viruses, and CCHFV, which is the most important human pathogen amongst them. Human beings are the only host of CCHFV in whom the disease manifestations are visible. Seroprevalence studies in endemic and non-endemic areas have been published.  GAP: Host and pathogen factors associated with severity and outcome of the disease have to be determined.   
  • Vector cyclical/non-cyclical

    Members of the Nairovirus genus are transmitted by argasid or ixodid ticks. Once infected, the tick remains infected through its developmental stages. The mature tick may transmit the infection to large vertebrates, such as livestock.

    Population dynamics depends on climatic factors — ecologic changes — wildlife and human factors.

    Some studies on CCHFV molecular detection in ticks have been published.

    GAPS:

    • The competence of other hard ticks genera for CCHFV replication should be studied.
    • A standard programme should be planned to achieve knowledge of arthropod vector distribution and dynamics.
    • Introduction of a standard programme to predict tick activities in European counties.
    • Examination of vectors and reservoir hosts for the presence of CCHF virus by using standard, especially molecular diagnostic techniques.
    • Areas of risk for the establishment of the vector, considering climatic and ecological conditions in Europe, need to be identified.
    • Vector surveillance needs to be strengthened.
    • Tick attachement time for efficient virus transmission to the host (animal/human).
  • Reservoir (animal, environment)

    CCHF virus has been found in around 31 species of ticks in seven genera of the family Ixodidae (hard ticks) acting both as vector and reservoir for CCHFV. Ticks of the genus Hyalomma are particularly important to the ecology as they appear to be the most efficient and common vector for the virus. CCHFV has been isolated from a number of species including cattle, sheep, goats, hares, hedgehogs, dogs and mice. Antibodies have been reported in horses, donkeys, pigs, rhinoceroses, giraffes, buffalo and other mammalian species.The virus infection has been commonly demonstrated among smaller vertebrate wildlife such as hares and hedgehogs. They are believed to act as amplifying hosts and maintain the virus in nature and act as a source of the virus for the immature Hyalomma ticks which feed on them. In general adult ticks prefer cattle and immature ticks prefer scrub hares.

    GAP: Tick competence studies in different species needs to be addressed to understand their role as virus reservoirs.

       
  • Description of infection & disease in natural hosts

  • Transmissibility

    Trans-ovarial, transstadial and venereal transmission have been demonstrated amongst some vector species, in particular the Hyalomma ticks. Many species of mammals can transmit CCHFV to ticks when they are viraemic.

    GAPS:

    Tick attachement time for efficient virus transmission to the host (animal/human).

    Knowledge about virus receptors in animals and humans is missing.   

  • Pathogenic life cycle stages

    GAPS:

    CCHFV usually circulates between asymptomatic animals and ticks in an enzootic cycle. 

    An understanding of the pathogenesis and cycle in animals would be of use. Especially the incubation time, length of the viraemic phase and the length of time after the initial infection and viraemic phase that infected animals would continue to be able to infect ticks. Once the viraemic phase is completed is there a low level of circulating virus in the blood which has the potential to infect feeding ticks or does the development of antibodies preclude any circulating virus?

  • Signs/Morbidity

    There is no evidence that the virus causes disease in animals although a wide range of domestic and wild animals may become infected with CCHF virus. Sheep, goats and cattle develop high titers of virus in blood, but tend not to fall ill. Birds are generally resistant with the exception of ostriches.

    GAPS:

    Will the high titres developed reduce the levels of circulating virus resulting in the animals being less infectious to ticks?

    Why animals do not develop any sign of disease?

  • Incubation period

    Mammals become viraemic and can transmit CCHFV in their blood and tissues. Domesticated ruminants including cattle, sheep and goats are viraemic for one week after experimental infection.

  • Mortality

    None in animals: Large herbivores have the highest seroprevalence to CCHFV. Seroprevalence rates of 13–36% have been reported in some studies, while others suggest that more than 50% of adult livestock in endemic regions have antibodies. Animals carry CCHFV asymptomatically. Deaths occur only in newborn rodents. GAP: Update seroprevalence studies in animals in European endemic and non-endemic regions.
  • Shedding kinetic patterns

    Domestic ruminant animals, such as cattle, sheep and goats, are viraemic for around one week after becoming infected.

    GAPS:

    Studies to better understand and reveal the natural cycle of CCHF virus in animals, humans and vectors.

    Virus transmission between animals can occur in the absence of vector? Is there evidence for vertical virus transmission?

  • Mechanism of pathogenicity

    Non-pathogenic in animals.

    GAP: Research on CCHF pathogenesis and immune response in experimentally infected animals.

  • Zoonotic potential

  • Reported incidence in humans

    The disease occurs sporadically throughout much of Africa, Asia, and Europe and results in an approximately 30% fatality rate. GAP: The exact incidence per endemic country is not known.
  • Risk of occurence in humans, populations at risk, specific risk factors

    CCHFV poses a great threat to public health due to its high mortality rate in humans, its modes of transmission, and its large geographical distribution. Ticks are a major route for the transmission of the disease to  humans either through bites or crushing an infected tick on the skin. Secondary cases are frequently seen due to human to human transmission via percutaneous or per mucosal exposure to blood and body fluids containing the virus. Others may acquire the virus from direct contact with blood or other infected tissues from livestock.  Cases have occurred in those involved with the livestock industry, such as agricultural workers, slaughterhouse workers and veterinarians (1).    
  • Symptoms described in humans

    The incubation period in humans is 1-14 days depending on the route of transmission.

    Human infections begin with nonspecific febrile symptoms, but progress to a serious hemorrhagic syndrome with a high case fatality rate. After a short incubation period (1-14 days), the onset of symptoms is sudden, with fever, chills, myalgia (aching muscles), dizziness, neck pain and stiffness, backache, severe headache, sore eyes and photophobia  and back and abdominal pains. There may be nausea, vomiting and sore throat early on, which may be accompanied by diarrhoea and generalised abdominal pain. Over the next few days, the patient may experience sharp mood swings, and may become confused and aggressive. After two to four days, the agitation may be replaced by sleepiness, depression and lassitude, and the abdominal pain may localize to the right upper quadrant, with detectable hepatomegaly (liver enlargement).

    Additional symptoms can include neuropsychiatric, and cardiovascular changes. In severe cases, hemorrhagic manifestations, ranging from petechiae to large areas of ecchymosis, develop. (2)

    Few studies on immune response in CCHF have been published.

    GAP: The knowledge is limited and further research on CCHF pathogenesis and immune response is necessary.

  • Estimated level of under-reporting in humans

    Low due to the severity of the clinical signs. However, there are many mild and asymptomatic cases which remain undetected.    
  • Likelihood of spread in humans

    Although the causative virus is often transmitted by ticks, animal-to-human and human-to-human transmission also occurs. Fortunately, human illness occurs infrequently, although animal infection may be more common. 
  • Impact on animal welfare and biodiversity

  • Both disease and prevention/control measures related

    None.   
  • Endangered wild species affected or not (estimation for Europe / worldwide)

    No impact.   
  • Slaughter necessity according to EU rules or other regions

    Not necessary or required.   
  • Geographical distribution and spread

  • Current occurence/distribution

    CCHF virus is distributed through large areas of Sub-Saharan Africa, South-Eastern Europe, Middle-East, Central Asia, India and North- West of China. It has been found in parts of Europe including southern regions of the former USSR (Crimea, Astrakhan, Rostov, Uzbekistan, Kazakhstan, Tajikistan), Turkey, Bulgaria, Greece (1 case), Albania and Kosovo province of the former Yugoslavia. The geographical distribution of the virus mirrors that of its principal tick vector Hyalomma spp.  Presence of CCHFV genome detected in ticks from deers in southwest Spain. Recent human cases derived from tick bite and nosocomial infection appeared Spain in September 2016 as the first cases in Western Europe.

    GAP: Further evaluation and classification of environmental conditions that can influence the spatiotemporal distribution and dynamics of CCHF.

       

  • Epizootic/endemic- if epidemic frequency of outbreaks

    Endemic in certain areas but with no disease in the animals.   
  • Seasonality

    Climatic factors can influence the numbers of ticks in the environment and the incidence of disease.

    In some countries, CCHF tends to be seasonal. This disease is most common in Iran during August and September, and in Pakistan from March to May and August to October. In Turkey disease appears earlier and ends in October.    
  • Speed of spatial spread during an outbreak

    Outbreaks in animals are not obvious due to the asymptomatic nature of the infection. 
  • Transboundary potential of the disease

    Potential for transboundary movement especially with the movement of potentially asymptomatic carriers which have the potential to infect ticks at their new destination.

    GAP: Do long term asymptomatic carriers exist or is it only the incubating and viraemic animals which pose a problem?

  • Seasonal cycle linked to climate

    Not specifically linked but will depend on the influence of the climate on tick populations.    
  • Distribution of disease or vector linked to climate

    Based on the distribution of the vector.

    Population dynamics depends on climatic factors — ecologic changes — wildlife and human factors.

    GAP: The role of environmental change, including climate change, needs further assessment.

  • Outbreaks linked to extreme weather

    Yes: dry summer time leading to tick aggressiveness    
  • Sensitivity of disease or vectors to the effects of global climate change (climate/environment/land use)

    Changes in climatic conditions could expand the range of the tick vectors, and increase the incidence of disease.

    GAP: Tools to monitor and predict virus migration along with potential movement of the associate ticks as a result of climate change.

  • Route of Transmission

  • Usual mode of transmission (introduction, means of spread)

    Animals become infected with CCHF from the bite of infected ticks.    
  • Occasional mode of transmission

    Direct contact with contaminated fluids (in humans).    
  • Conditions that favour spread

    Factors which impact on tick population.   
  • Detection and Immune response to infection

  • Mechanism of host response

    Unclear.

    Some studies on immune response have been published. A cytokine storm is observed.

    Animal models are available.

    GAP: 

    Today, there is an animal model for developing vaccine and antivirals, however, still we need to identify an animal model for studying host response to infection.

    Further research is needed to study the immune response in animal models and in patients for evaluation of intervention and control strategies.

  • Immunological basis of diagnosis

    Serological tests. Detection of IgM and IgG antibodies (ELISA, IFA).  GAP: Commercial serological tests for humans and animals with increased sensitivity and specificity are needed.   
  • Main means of prevention, detection and control

  • Sanitary measures

    Persons living in endemic areas should use personal protective measures that include avoidance of areas where tick vectors are abundant and when they are active (Spring to Fall); regular examination of clothing and skin for ticks, and their removal; and use of repellents.

    Persons who work with livestock or other animals in the endemic areas can take practical measures to protect themselves. These include the use of repellents on the skin (e.g. DEET) and clothing (e.g. permethrin) and wearing gloves or other protective clothing to prevent skin contact with infected tissue or blood (1).

  • Mechanical and biological control

    The tick vectors are numerous and widespread and tick control with acaricides (chemicals intended to kill ticks) is only a realistic option for well-managed livestock production facilities. 
  • Diagnostic tools

    In humans:

    CCHF can be diagnosed by isolating the virus from blood, plasma or tissues. Cell cultures can only detect high concentrations of the virus, and this technique is most useful during the first five days of illness. Animal inoculation into newborn mice is more sensitive than culture, and can detect the virus for a longer period. CCHFV is identified by indirect immunofluorescence or reverse transcription-polymerase chain reaction (RT-PCR) assays. Virus isolation must be carried out in maximum biocontainment laboratories (BSL-4).

    The use of real-time reverse transcription-polymerase chain reaction (RT-PCR), in clinical and tick samples has allowed for both rapid diagnosis of disease and molecular epidemiology studies. Whilst this technique is highly sensitive the genetic variability in CCHFV strains, means that single set of primers cannot detect all virus variants, and most RT-PCR assays are either designed to detect local variants or lack sensitivity. Viral antigens can be identified with enzyme-linked immunoassay (ELISA) or immunofluorescence, but this test is less sensitive than PCR.

    Tests detect CCHFV-specific IgM, or a rise in IgG titers in paired acute and convalescent sera. IgG and IgM can usually be found with indirect immunofluorescence or ELISA after 7-9 days of illness. Other serologic tests such as complement fixation and hemagglutination inhibition have been used but lacked sensitivity.

    In animals:

    Serology can identify animals that have been infected or exposed to CCHFV. An IgG ELISA can detect antibodies for the remainder of the animal’s life; other tests, including complement fixation and indirect fluorescent antibody, usually detect antibodies for shorter periods. Viraemia can be recognized by virus isolation and other techniques but these tests are not used diagnostically.

    GAP: Commercial kits for serology in animals are missing.

  • Vaccines

    None.

    A mouse-brain derived vaccine is used in specific groups in Bulgaria (not FDA approved).

    Few reports on vaccine potential have been published.

    GAP: 

    To date, a few several candidates available (tested in IFNAR -/- mice), however, the research program needs to further investigate these candidates.

    An FDA approved vaccine for humans is needed.
  • Therapeutics

    Symptomatic treatment in humans. Controversial data on the use of ribavirin (WHO recommends the use of ribavirin). T-705 (favipiravir) was suggested. GAP: Test novel drugs for CCHF control.   
  • Biosecurity measures effective as a preventive measure

    The CCHF virus is also a potential bioterrorist agent; it has been listed in the U.S. as a CDC/NIAID Category C priority pathogen.

  • Border/trade/movement control sufficient for control

    Not applicable although acaricides can be used before movement.    
  • Prevention tools

    Control of ticks.

    Acaricides can be used on livestock and other domesticated animals to control ticks, particularly before slaughter or export,

    In humans in endemic regions, prevention depends on avoiding bites from infected ticks and contact with infected blood or tissues. Measures to avoid tick bites include tick repellents, environmental modification (brush removal, insecticides), avoidance of tick habitat and regular examination of clothing and skin for ticks.

    Protective clothing and gloves should be worn whenever skin or mucous membranes could be exposed to viremic animals, particularly when blood and tissues are handled. Unpasteurized milk should not be drunk. In meat, CCHFV is usually inactivated by post-slaughter acidification. It is also killed by cooking.

    Human outbreaks have occurred after exposure to infected ostriches during slaughter; these infections seem to be preventable by keeping the birds free of ticks for 14 days before slaughter. In some countries, ostriches are subjected to a 30-day pre-slaughter quarantine period at export facilities.

    GAP: The shedding and presence of the virus in meat should be investigated. To date there is possibility to investigate these issues in research facilities with capacities to perform animal experimentation with large animals (bovines, ovines) in BSL-4 conditions.

  • Surveillance

    Serosurveillance of animals.

    Seroprevalence studies in humans available.

    GAP: The seroprevalence in wildlife is not sufficiently studied. 

  • Past experiences on success (and failures) of prevention, control, eradication in regions outside Europe

    Little experience although there appears to be a gradual spread of the CCHF virus into other parts of Europe.    
  • Costs of above measures

    Unknown although apart from acaricide usage there are no specific measures available for control of animal carriers.    
  • Disease information from the OIE

  • Disease notifiable to the OIE

    Yes. 

  • OIE disease card available

    No.    
  • OIE Terrestrial Animal Health Code

    Not available.   
  • Socio-economic impact

  • Zoonosis: impact on affected individuals and/or aggregated DALY figures

    Can have a high mortality in individuals who become infected.    
  • Zoonosis: cost of treatment and control of the disease in humans

    Expensive but limited control measures available.    
  • Direct impact (a) on production

    No impact on production.    
  • Direct impact (b) cost of private and public control measures

    No costs for animals.    
  • Indirect impact

    Limited impact at present although if the disease becomes a major problem could have an impact on tourism, however, the presence of CCHFV, in endemic areas have a big impact for farmers, which in turn may affect the production.

  • Trade implications

  • Impact on international trade/exports from the EU

    None at present, however, illegal trade has an impact for spreading of the virus.    
  • Impact on EU intra-community trade

    None at present.
  • Impact on national trade

    None at present.    
  • Main perceived obstacles for effective prevention and control

    Widespread in nature, recycling of the virus between the small/ large mammals and the ticks. Limited measures available to break the cycle. 
  • Main perceived facilitators for effective prevention and control

    Effective methods to control the  Hyalomma ticks

           Ectoparasitic: acaricidal control

           Develop genetically resistant animals

           Control movement of infected animals

           Anti-tick vaccines

           Pheromone-based tick control

           Integrated control of ticks

           Animal vaccines

    It has been shown that where wild animals run with domestic animals (cattle) tick control on cattle will also reduce tick burden on the wild animals.

    GAPS:

    Information drawn from vector and animal surveillance is crucial for predicting human risk for CCHF infection but

    also for other tick-borne diseases.

           The standardisation of protocols for tick collection from animals, their identification and screening for possible human pathogens would be helpful;

           Diagnostic capacity would need to be developed accordingly

           Vaccine development for domestic animals

    A better understanding of the epidemiology of CCHF in ticks, domestic livestock and wild animal populations, will support the identification of human risk factors for infection and the development of better diagnostics, antiviral drugs and vaccines for humans.

Risk

  • Over the last years, CCHF outbreaks have become more frequent in several European countries and neighbouring areas, and an increase of large outbreaks caused by CCHF virus (CCHFV) has been observed. Climate changes and recent detection of the CCHF Virus vector in southern Europe and Germany are a cause for concern in Europe. The first Western European human CCHF cases reported appeared in August 2016 in Spain.

Main critical gaps

  •  

Conclusion

  • The knowledge on CCHF pathogenesis and immune response is limited.

    The research activities concerning CCHF disease have been restricted to very few institutes/laboratories, for several reasons:

    • The handling of the virus requires high containment laboratories (BSL-4)
    • The occurrence of sporadic outbreaks in endemic countries which do not have the facilities to conduct basic and/or applied research programs,
    • The lack of clinical specimens from patients, animals and ticks (7)
    MAJOR GAPS (6):

    1. Better understanding of the clinical aspects of the disease and the immune response to the virus.

    2. Establishment of rapid and more sensitive diagnostics.

    3. Future research on the virus-vector interaction, the CCHFV dynamics in reservoirs and vectors, the role of birds and wildlife.

    4. Studies on the role of climate change in the distribution of ticks and the establishment of new CCHFV endemic areas.

    5. The development of vaccines and treatment strategies for humans and animals.

Sources of information

  • Expert group composition

    Expert group members are included where permission has been given.

    Alejandro Brun Torres, INIA, Spain - [Leader]

    Ali Mirazimi, Karolinska Institute, Sweden

    Anna Papa, University of Thessaloniki, Greece

  • Reviewed by

    Project Management Board
  • Date of submission by expert group

    30 September 2016
  • References

    1. WHO Fact sheet N°208. Revised November 2001

    http://www.who.int/mediacentre/factsheets/fs208/en/ accessed 29 May 2012

    2. An Update on Crimean Congo Hemorrhagic Fever Suma B Appannanavar and Baijayantimala Mishra Glob Infect Dis. 2011 Jul-Sep; 3(3): 285–292.

    3. Consultation on Crimean-Congo haemorragic fever prevention and control: Stockholm, September 2008; http://www.ecdc.europa.eu/en/publications/Publications/0809_MER_Crimean_Congo_Haemorragic_Fever_Prevention_and_Control.pdf

    4. CCH fever: European research network (Collaborative Project) supported by the European Commission under the Health Cooperation Work Programme of the 7th Framework Programme.

    5. Papa A, Mirazimi A, Köksal I, Estrada-Pena A, Feldmann H. Recent advances in research on Crimean-Congo haemorrhagic Fever. J Clin Virol 2015;64:137-43.

    6. Papa A, Weber F, Hewson R, Weidmann M, Koksal I, Korukluoglu G, Mirazimi A. Meeting report: First International Conference on Crimean-Congo hemorrhagic fever. Antiviral Res. 2015;120:57-65.