Crimean-Congo haemorrhagic fever (CCHF)

Crimean-Congo haemorrhagic fever (CCHF) is a widespread zoonotic disease caused by a Nairovirus (tick-borne virus) of the Bunyaviridae family and primarily transmitted to humans through bites from infected Hyalomma ticks. It can also spread through direct contact with blood or tissues from infected animals. Human-to-human transmission can also occur via contact with infected blood, making healthcare workers particularly vulnerable during outbreaks.

The CCHF virus causes severe viral haemorrhagic fever outbreaks, with a case fatality rate of 10–40%. It is characterised with a rapid disease progression and possible severe bleedings and organ failures.

CCHF is endemic in Africa, the Balkans, the Middle East and Asian countries south of the 50th parallel north – the geographical limit of the principal tick vector. 

The following are standard case definitions to allow national health authorities to interpret data in an international context. However, during an outbreak case definitions may be adapted to the local context and the Red Cross Red Crescent should use those agreed/established by national health authorities. NB: Consider that during community-based surveillance, volunteers should use broad (simplified) case definitions (referred to as community case definitions) to recognize most or all possible cases, provide relevant risk communication and appropriate actions and encourage them to seek care. Other actors such as healthcare workers or investigators studying the cause of a disease, on the other hand, can use more specific case definitions that may require laboratory confirmation.

As with other zoonotic and vector-borne diseases, control of CCHF among humans is highly dependent on the integration of the human health, veterinary surveillance and vector control systems. The following include case definitions for human surveillance and exclude case definitions for veterinary surveillance. For more information on veterinary surveillance or clinical presentations, please visit WOAH’s page on CCHF.  

Clinical Criteria:

• Abrupt onset of fever (>38°C)
• Severe headache
• Muscle pain (myalgia)
• Dizziness
• Chills
• Neck pain and stiffness
• Back pain
• Sore eyes and sensitivity to light (photophobia)
• Nausea, vomiting, diarrhoea, or abdominal pain
• Sore throat
• Weakness or fatigue
• Depression and lassitude
• Rapid progression to hemorrhagic symptoms, including bleeding from gums, nose (epistaxis), or other mucous membranes
• Bruising or a rash due to bleeding under the skin (petechiae or ecchymoses)
• Detectable enlargement of the liver
• Tachycardia
• Swelling of the lymph nodes
• Nose bleeding
• Blood in vomit, stool, or urine
• Heavy menstrual bleeding or other unexplained bleeding

Epidemiological Criteria:

• History of tick bites (particularly from Hyalomma ticks) or crushed a tick with bare hands within the past 15 days
• Recent travel to or residence in an endemic area for CCHF within the past 15 days
• Contact with blood, bodily fluids, or tissues of livestock (such as cattle, sheep, goats) in an endemic area within the past 15 days
• Close contact with a confirmed or probable case of CCHF within the past 15 days
• Healthcare workers who have been exposed to blood or bodily fluids of a CCHF patient without adequate protective measures within the past 15 days

Suspected Case - an individual who meets both the clinical and epidemiological criteria.

Probable Case - a suspected case with a strong epidemiological link such as:

• History of direct contact with a confirmed CCHF case.
• Exposure to contaminated materials (e.g., needles, equipment) from a confirmed CCHF case.
• History of caring for a patient with CCHF.

Confirmed Case - a suspected or probable case with one or more of the following laboratory confirmations: 

Laboratory Criteria:

• Detection of CCHF virus-specific nucleic acid by reverse transcription-polymerase chain reaction (RT-PCR).
• Isolation of CCHF virus from a clinical specimen.
• Detection of CCHF-specific IgM or a fourfold rise in IgG antibody titers in paired serum samples (acute and convalescent phases).
• Detection of CCHF virus antigens in a clinical specimen.

Discarded case - a suspected or probable case with a negative laboratory result (showing no specific antibodies, RNA or specific detectable antigens)

Single confirmed case in non-endemic regions and abrupt rise in tick populations or incidence in endemic regions. 

• People who spend time in tick-infested areas, such as farmers, herders, hunters, and outdoor workers, are at higher risk of exposure.
• People who provide care to CCHF patients are at risk of infection due to direct contact with infected blood or bodily fluids.  
• Livestock farmers and people who work in slaughterhouses, and veterinarians are at increased risk due to potential exposure to ticks and infected animal blood or tissues.
• Laboratory personnel who handle samples from suspected or confirmed CCHF cases may be at risk if biosafety precautions are not strictly followed.
• Caregivers, family members and other people who have direct contact with the blood, secretions, or other bodily fluids of an infected person, especially during the acute phase of illness.
• Travellers to and residents of endemic communities
• Immunocompromised persons 

Attack rates will vary from one outbreak to another. In case of an outbreak, consult the latest information provided by health authorities.

Differences in the attack rates depend on several factors, including exposure risks to infected ticks and humans, geographic location, population immunity, and the effectiveness of public health interventions.  

• Healthcare workers, if they are exposed to high levels of the virus while caring for CCHF patients
• Children
• Elderly individuals
• Persons with chronic illnesses such as diabetes, hypertension, cardiovascular diseases, or other age-related health issues
• Individuals with weakened immune systems, whether due to HIV/AIDS, cancer, organ transplantation, or immunosuppressive therapy.
• Pregnant women 

Crimean-Congo haemorrhagic fever (CCHF) virus is a Nairovirus (tick-borne virus) of the Bunyaviridae family and primarily transmitted to humans through bites from infected Hyalomma ticks.  

Zoonotic disease: Domestic and wild animals such as cattle, sheep, goats, hares, hedgehogs, and various species of wild ungulates (e.g., deer) are significant reservoir hosts. Birds, including ostriches, have been found to carry the CCHF virus, especially in regions like South Africa. Ticks, particularly those of the Hyalomma genus, are both primary vectors and reservoirs of the CCHF virus. 

• Bites from infected ticks, particularly ticks of the Hyalomma genus.
• Contact with infected animal blood or tissues during activities like slaughtering, butchering, or handling livestock.
• Human-to-Human transmission via contact with the blood, bodily fluids, or tissues of an infected person.
• Nosocomial transmission via contact with contaminated medical equipment or inadequate use of personal protective equipment (PPE).
• Laboratory exposure in case of laboratory workers who handle specimens from infected individuals or animals, if appropriate biosafety precautions are not observed. 

If the virus is transmitted through a tick bite, the incubation period ranges from 1 to 3 days. However, it can be as long as 9 days in some cases.

If a person is infected through contact with the blood or tissues of an infected animal or human, the incubation period ranges from 5 to 6 days, but it can extend up to 13 days. 

This period ranges from the acute phase of infection (within the first two weeks after symptoms onset) till recovery. In some cases, CCHF virus can persist in bodily fluids such as urine and semen even after recovery.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078823/  

Initial (Pre-hemorrhagic) Phase - lasts for about 3-7 days and characterised by non-specific symptoms including:

• Sudden onset of high-grade fever
• Severe headache
• Muscle pain (myalgia)
• Dizziness and neck pain, often accompanied by stiffness.
• Sore eyes and aversion to light
• Nausea, vomiting, and diarrhoea
• Abdominal pain
• Sore throat: A common symptom during the early phase.
• Flushed face and red eyes
• Mood changes: Anxiety, depression, and confusion can occur.

Hemorrhagic Phase - lasts for 2-3 days and characterised by the severe hemorrhagic clinical signs including:

• Petechiae: Small red or purple spots on the skin due to minor bleeding.
• Bruising (ecchymosis): Larger areas of bruising on the skin.
• Bleeding from body openings including nosebleeds (epistaxis), gum bleeding, hematuria (blood in urine), and bleeding from the gastrointestinal tract.
• Hematomas: Swelling caused by clotted blood within the tissues.
• Hemoptysis: Coughing up blood in severe cases.
• Vaginal bleeding: In women, abnormal bleeding may occur.

Organ dysfunction -  

• Liver dysfunction leading to jaundice (yellowing of the skin and eyes), and failure
• Kidney failure
• Lungs failure
• Shock due to low blood pressure

Neurological Symptoms

• Agitation and confusion
• Somnolence or coma
• Memory loss and sensory changes 

Diseases with similar clinical signs and symptoms include Dengue Fever, Ebola virus disease (EVD), Marburg virus disease, Lassa fever, Rift Valley fever (RVF), Yellow Fever, malaria (severe form), Leptospirosis, Typhoid Fever, and severe COVID-19.

Diagnosing Crimean-Congo Hemorrhagic Fever (CCHF) can be challenging due to its non-specific early symptoms, similar to many other febrile illnesses.

Clinical Assessment

• Patient History: information on recent travels to endemic areas, tick bites, occupation (e.g., healthcare workers, farmers, slaughterhouse workers), and contact with livestock or other animals and exposure to individuals with similar symptoms can be clues.
• Symptoms: Abrupt onset of high fever, severe headache, muscle pain, dizziness, and hemorrhagic symptoms such as petechiae, ecchymosis, and bleeding from various sites.
• Physical Examination: Signs of haemorrhage, jaundice, and neurological symptoms.

Laboratory Diagnosis

• Enzyme-linked immunosorbent assay (ELISA);
• Antigen detection;
• Serum neutralisation;
• Reverse transcriptase polymerase chain reaction (RT-PCR) assay; and
• Virus isolation by cell culture.

Please refer to the appropriate local or international guidelines for clinical management. All clinical management including the administration of a treatment or vaccine should be conducted by a health professional.  

• General supportive care with treatment of symptoms is the main approach to managing CCHF in people.
• Antivirals are being used to treat cases of CCHF infection effectively
• There are no vaccine available for use in either humans or animals.  

There is a possibility of long-term immunity after infection. Further studies are ongoing.

https://doi.org/10.3390%2Fdiagnostics13162708