Crimean-Congo hemorrhagic fever (CCHF) is a serious viral disease that spreads to humans mainly through tick bites or contact with the blood or tissues of infected animals and people. It begins suddenly with high fever, headache, muscle pain, and dizziness. In severe cases, it can cause bleeding under the skin (petechiae), nosebleeds, and bleeding in the stomach or intestines. The disease can be fatal in 10% to 40% of cases, depending on the outbreak and the level of medical care available. CCHF was first recognized in Crimea in 1944 and later in the Congo in 1969, which led to its current name.
The disease is common in areas where Hyalomma ticks live, including sub-Saharan Africa, the Middle East, Eastern Europe, and parts of Asia. These ticks both carry and spread the virus. People most at risk include farmers, livestock handlers, slaughterhouse workers, and healthcare staff. Human-to-human spread can also occur in hospitals if proper infection control is not followed.
The virus that causes the disease, Crimean-Congo hemorrhagic fever virus (CCHFV), belongs to the Nairoviridae family and is one of the most widespread tick-borne viruses known to affect humans. There is currently no specific cure. Treatment focuses on supportive care, such as giving fluids, oxygen, blood transfusions, and medications to stabilize blood pressure. The antiviral drug ribavirin has shown some benefit, but its effectiveness is not certain.
Prevention mainly involves avoiding tick bites by using protective clothing and insect repellents, removing ticks safely, and controlling tick populations in animals and their environment. Because of its severity, high death rate, and ability to spread in healthcare settings, the World Health Organization lists CCHF as a priority disease for research and vaccine development.
History of Outbreaks
Crimean-Congo hemorrhagic fever (CCHF) was first described in 1944 during an outbreak among Soviet military personnel in the Crimea region, where more than 200 cases were reported. The virus was later isolated in 1956 in the Democratic Republic of the Congo (then Belgian Congo), which led to the combined name of the disease.
Since its discovery, CCHF has been reported in more than 30 countries across Africa, the Middle East, Eastern Europe, and Asia. Outbreaks have often occurred in rural areas where people have close contact with livestock and ticks. Notable outbreaks have included:
- Bulgaria (1950s–1970s): Repeated clusters of cases occurred, with early recognition of person-to-person transmission in hospitals.
- Pakistan (1976 onward): Sporadic outbreaks have continued, with higher numbers reported in the 2000s and 2010s.
- Iran (1999–present): Hundreds of confirmed cases have been reported annually, with the disease now considered endemic.
- Turkey (2002–present): Thousands of cases have been recorded, making Turkey one of the most affected countries worldwide.
- Kosovo and other parts of the Balkans (1990s–2000s): Multiple outbreaks highlighted the risks to healthcare workers.
- Oman and United Arab Emirates (1990s): Outbreaks were linked to livestock trade and slaughterhouse exposure.
Large epidemics have also occurred in Sudan (2008, 2010) and Uganda (2013, 2017), with case fatality rates exceeding 30% in some outbreaks. In many regions, the number of cases increases during spring and summer when tick activity is highest.
Transmission and Risk Factors
Crimean-Congo Hemorrhagic Fever (CCHF) spreads primarily through tick bites, contact with infected animal blood or tissues, and direct human exposure to bodily fluids. Certain individuals and activities increase the likelihood of infection due to closer contact with vectors or infected persons.
Vectors and Animal Hosts
Ticks of the genus Hyalomma are the principal vectors of the CCHF virus (CCHFV). These ticks act as both reservoirs and transmitters of the virus. They acquire the pathogen when feeding on viremic animals, which include a wide range of wild and domestic hosts such as cattle, sheep, goats, and hares. Although many of these animals develop no symptoms of disease, they play an important role in maintaining the virus in nature.
Once infected, ticks can harbor the virus for life. Transmission can occur during subsequent feedings on new hosts, a process known as transstadial transmission (persistence of the virus as the tick develops from larva to nymph to adult). In addition, transovarial transmission, where the virus is passed from female ticks to their offspring, ensures long-term survival of the virus within tick populations.
Humans typically become infected after being bitten by infected ticks or through direct handling of infected animal tissues and blood. Such exposures commonly occur during agricultural activities, livestock rearing, slaughtering, or veterinary care.
Human-to-Human Transmission
Direct transmission between humans occurs through contact with blood, secretions, or other bodily fluids of infected individuals. This mode of spread is of particular concern in healthcare settings, where medical staff may be exposed during patient care, invasive procedures, or improper handling of contaminated needles.
Nosocomial outbreaks have been documented in several countries, often linked to inadequate infection control measures. Household transmission can also occur when family members care for sick relatives without protective precautions. Use of personal protective equipment (PPE), safe needle practices, and strict adherence to infection prevention protocols significantly reduce the risk of human-to-human spread.
High-Risk Populations
Risk of infection varies according to occupation, environment, and activities:
- Agricultural workers and farmers are at heightened risk due to frequent exposure to ticks in fields and pastures.
- Livestock handlers, butchers, and slaughterhouse employees face risks through direct contact with infected animal blood and tissues during slaughtering and processing.
- Veterinary staff may be exposed when treating or handling infected animals.
- Healthcare workers are especially vulnerable during outbreaks, particularly when treating severely ill patients without adequate protective gear.
- Travelers to endemic regions generally face a lower but notable risk, especially if engaging in outdoor or rural activities where tick bites are more likely.
Clinical Presentation
Crimean-Congo Hemorrhagic Fever (CCHF) typically begins with an initial silent phase followed by distinct clinical features. The signs may escalate rapidly to severe bleeding and organ dysfunction.
Incubation Period
The incubation period of CCHF depends on the route of exposure. When infection occurs through a tick bite, symptoms generally develop within 1 to 3 days, with a maximum of 9 days reported. In cases where infection results from contact with infected blood or tissues, the incubation period is slightly longer, typically 5 to 6 days, with a maximum of 13 days.
This variability is attributed to differences in the viral load (amount of virus entering the body) and the site of entry. The incubation period ends with the sudden onset of symptoms, marking the beginning of the acute illness.
Signs and Symptoms
Patients initially present with high fever, severe headache, dizziness, and muscle pains. Gastrointestinal symptoms including nausea, vomiting, and diarrhea frequently occur.
Facial flushing, red eyes, and photophobia are common early signs. As the disease progresses, petechiae, ecchymosis, and bleeding from mucous membranes appear.
The rash and bleeding result from vascular damage and thrombocytopenia. Neurological symptoms such as confusion or agitation may develop in some cases.
Complications
Severe CCHF can lead to hemorrhagic shock due to widespread bleeding. Liver damage is common, causing elevated liver enzymes and jaundice.
Multiorgan failure frequently occurs in fatal cases, involving kidneys and lungs. Secondary bacterial infections may complicate the clinical course.
Mortality rates range from 10% to 40%, emphasizing the need for early diagnosis and supportive care.
Diagnosis and Laboratory Testing
Confirmation of Crimean-Congo Hemorrhagic Fever (CCHF) requires specific laboratory tests targeting viral RNA, antigens, or antibodies. Correct identification involves distinguishing CCHF from other diseases with similar symptoms while maintaining strict biosafety throughout the diagnostic process.
Diagnostic Methods
The most widely used and reliable method for early diagnosis of CCHF is reverse transcription polymerase chain reaction (RT-PCR), which identifies CCHFV RNA in blood or tissue samples. RT-PCR is highly sensitive and specific, enabling detection of the virus during the acute phase of illness, often within the first few days of symptom onset. Quantitative RT-PCR (qRT-PCR) assays can also provide viral load data, which may correlate with disease severity and prognosis.
Serological methods, such as enzyme-linked immunosorbent assay (ELISA), are used to detect host antibodies against CCHFV. Detection of IgM antibodies indicates recent or ongoing infection, while IgG antibodies suggest past exposure and can be useful in epidemiological investigations. Serology is particularly valuable when patients present in later stages of illness or after viral RNA has become undetectable. Immunohistochemistry and antigen-capture ELISA can identify viral proteins in patient tissues or fluids. These methods require specialized laboratories and are typically used in research settings or retrospective analyses rather than routine clinical practice.
Although isolation of live CCHFV in cell culture is possible and provides definitive evidence of infection, it is rarely undertaken outside of reference laboratories due to the extreme biosafety risks. Virus isolation requires Biosafety Level 4 (BSL-4) facilities, limiting its use to specialized centers engaged in research or outbreak investigation. Accurate diagnosis depends heavily on the timing of specimen collection. During the early viremic phase, molecular assays yield the highest sensitivity, while serological methods are more informative after the first week of illness, when the host immune response develops. Collecting multiple samples at different time points can increase diagnostic reliability. Diagnostic facilities must adhere to validated protocols to avoid false results.
Differential Diagnosis
CCHF must be differentiated from a wide range of infectious diseases that share overlapping clinical manifestations, particularly in tropical and subtropical regions where multiple pathogens are endemic.
- Malaria: Often presents with fever, chills, and anemia; blood smear or rapid diagnostic tests confirm Plasmodium infection.
- Dengue fever: May resemble CCHF in early febrile and hemorrhagic stages. The NS1 antigen test and dengue-specific RT-PCR or serology help distinguish it.
- Leptospirosis: Characterized by fever, jaundice, and renal involvement; diagnosed by serology (MAT) or PCR.
- Other viral hemorrhagic fevers (VHFs): Including Ebola virus disease, Marburg virus disease, and Lassa fever. Differentiation requires molecular and serological assays specific to each pathogen.
- Septicemia and other bacterial infections: May mimic hemorrhagic presentations; blood cultures are necessary for exclusion.
Supporting laboratory findings in CCHF, such as thrombocytopenia, leukopenia, elevated liver enzymes, and coagulopathy, contribute to differentiation but are not disease-specific.
Biosafety Procedures
Because of the high infectivity and mortality associated with Crimean-Congo Hemorrhagic Fever virus (CCHFV), strict biosafety measures are essential when handling clinical specimens. The virus poses a significant risk of laboratory-acquired infection, and even small errors in sample processing or containment can lead to severe consequences. For this reason, the choice of laboratory containment level is a critical consideration. Diagnostic work that involves live virus must be performed in Biosafety Level 4 (BSL-4) facilities, which provide the highest level of protection against dangerous pathogens. However, certain molecular and serological assays may be conducted in BSL-3 laboratories, provided that enhanced precautions are in place and inactivation protocols are rigorously followed to neutralize the virus before testing.
The use of personal protective equipment (PPE) is another cornerstone of laboratory safety. Personnel handling suspected CCHF samples are required to wear comprehensive protective gear to minimize exposure risk. Standard PPE includes impermeable gowns or coveralls, double layers of gloves, and protective footwear. To guard against inhalation of infectious aerosols, respiratory protection in the form of N95 respirators or powered air-purifying respirators is mandatory. In addition, face shields or goggles are used to prevent contamination of the eyes and mucous membranes, ensuring that every potential route of infection is covered.
Specimen handling must also be carefully controlled to reduce the risk of accidental exposure. All processing should take place inside Class II or higher biological safety cabinets, which provide an enclosed, ventilated workspace that protects both the laboratory worker and the surrounding environment. Procedures that generate aerosols, such as centrifugation, require additional precautions. Centrifuge rotors or safety cups must be sealed, and specimens should only be opened within the safety cabinet after centrifugation is complete, minimizing the chance of airborne contamination.
Thorough decontamination of laboratory environments and equipment is vital for maintaining biosafety. Surfaces, instruments, and protective equipment must be treated with disinfectants proven effective against enveloped RNA viruses. Commonly used agents include sodium hypochlorite solutions, 70% ethanol, and aldehyde-based disinfectants. Regular and validated cleaning protocols not only ensure safe handling of CCHF samples but also reduce the risk of cross-contamination that could compromise diagnostic accuracy.
Safe transport of specimens is equally important, particularly when samples are moved from the point of collection to diagnostic laboratories. International and national regulations require the use of a triple-containment system. This includes a primary sealed container holding the sample, a secondary leak-proof container to provide an additional layer of security, and a rigid outer container that can withstand physical stress during transit. Each container must be clearly labeled in accordance with international regulations for infectious substances, specifically UN 2814, to alert handlers of the potential hazard.
Finally, training and exposure management are fundamental components of biosafety. Laboratory staff must undergo specialized training that prepares them for the unique risks associated with handling high-consequence pathogens like CCHFV. This training includes safe laboratory practices, correct use of PPE, and emergency procedures for accidental exposures. Institutions must also establish clear protocols for exposure management, including immediate medical surveillance of affected personnel and access to post-exposure treatment options where available. By combining rigorous training with systematic preparedness, laboratories can reduce the risk of occupational infections and maintain the highest standards of biosafety.
Treatment and Management
Treatment of Crimean-Congo Hemorrhagic Fever (CCHF) primarily involves supportive care, antiviral medications when appropriate, and specialized management for severe cases. Early intervention can improve outcomes, although no specific cure exists.
Supportive Care Strategies
Supportive care is vital and focuses on stabilizing the patient’s condition. This includes maintaining fluid and electrolyte balance through intravenous fluids to prevent dehydration and shock.
Pain management with acetaminophen is preferred; nonsteroidal anti-inflammatory drugs (NSAIDs) are avoided due to bleeding risks. Monitoring for bleeding, organ function, and signs of secondary infections is essential, with blood transfusions considered if severe hemorrhaging occurs.
Hospitalization is often necessary for close observation, especially during the critical hemorrhagic phase.
Antiviral Therapies
Although pharmacological options for CCHF are limited, the nucleoside analogue ribavirin has been used most widely. Ribavirin can be administered orally or intravenously, typically beginning with a high loading dose followed by several days of maintenance doses. It is thought to act by inhibiting viral RNA synthesis, thereby reducing viral replication. Clinical observations suggest that early administration of ribavirin, ideally within the first few days of symptom onset, may reduce the severity of illness and improve survival outcomes.
Despite these potential benefits, the effectiveness of ribavirin remains controversial. Results from clinical studies vary, and robust randomized controlled trials are lacking. Moreover, the drug carries risks of adverse effects, including hemolytic anemia, liver toxicity, and gastrointestinal discomfort, which can complicate its use in severely ill patients. Alternative antivirals, such as favipiravir and monoclonal antibodies directed against the CCHF virus, are currently under investigation. However, these experimental therapies have not yet been proven effective enough for routine clinical application.
Management of Severe Cases
Patients with severe or fulminant forms of CCHF often require intensive care management. Respiratory complications such as pulmonary hemorrhage or acute respiratory distress may necessitate supplemental oxygen therapy or mechanical ventilation. In cases where renal failure develops often as a consequence of multi-organ dysfunction or rhabdomyolysis, renal replacement therapies such as hemodialysis may become essential.
Coagulopathy represents a significant challenge in advanced cases. Management strategies can include platelet transfusions, plasma infusions, and administration of clotting factor concentrates to control bleeding. Treatment must be individualized, guided by the severity of bleeding and laboratory test results. Secondary bacterial infections occasionally complicate the course of CCHF, and while broad-spectrum antibiotics may be administered if infection is suspected, their routine use is not recommended unless bacterial involvement is confirmed.
Infection Control and Nosocomial Prevention
Given the high transmissibility of the virus through blood and bodily fluids, infection control forms a vital part of CCHF management. Patients are ideally treated in isolation rooms equipped with negative-pressure ventilation, and the number of staff involved in their care should be minimized. Healthcare workers must consistently wear personal protective equipment (PPE), including gloves, gowns, masks, and eye protection, to reduce the risk of exposure.
Handling of biological specimens requires adherence to biosafety level-4 (BSL-4) laboratory protocols. Similarly, medical waste generated in the care of CCHF patients must be disposed of as high-risk infectious material to prevent environmental contamination. Post-exposure prophylaxis with ribavirin has been administered in cases of high-risk exposure among healthcare workers, but evidence for its efficacy remains limited and inconclusive.
Prevention and Control Measures
Effective prevention and control of Crimean-Congo Hemorrhagic Fever (CCHF) rely on minimizing exposure to ticks and infected materials. Measures focus on protecting individuals, reducing tick populations, and raising public awareness.
Personal Protective Equipment
Personal protective equipment (PPE) is a cornerstone of prevention for individuals at high risk, including livestock handlers, slaughterhouse workers, veterinarians, and healthcare providers. In agricultural or rural environments, protective clothing such as long-sleeved shirts, trousers, gloves, and boots helps reduce skin exposure to tick bites.
Treating clothing with insect repellents, especially permethrin-based formulations, further enhances protection. Routine inspection and prompt removal of ticks from clothing and skin immediately after outdoor exposure are strongly recommended.
In healthcare settings, PPE is essential to prevent human-to-human transmission. Gloves, gowns, masks, and eye protection serve as physical barriers against infected blood and body fluids. Strict adherence to infection prevention protocols, including the safe disposal of sharps and other contaminated medical waste, reduces the risk of accidental exposure.
Education and regular training on the correct use of PPE enhance compliance and improve overall protective effectiveness, especially in high-burden regions.
Vector Control Programs
Controlling tick populations is a vital component of reducing CCHF transmission in endemic regions.
Acaricides, or tick-killing chemicals, are commonly applied to livestock to reduce tick infestations, thereby lowering the chances of virus transmission to humans.
Regular treatment of animal shelters and spraying of pasture areas help break the tick–livestock–human transmission cycle.
In addition to chemical interventions, integrated pest management strategies combine acaricide use with environmental control. This may include clearing overgrown vegetation, maintaining animal enclosures in hygienic conditions, and limiting contact between wild and domestic animals in areas where ticks are abundant.
Monitoring tick populations and testing them for viral presence provides valuable information for implementing targeted control measures. Close collaboration between veterinary and public health authorities ensures that interventions are coordinated, sustainable, and effective in preventing outbreaks.
Community Education
Public education focuses on informing communities about tick avoidance and CCHF transmission routes. Clear instructions on wearing protective clothing and checking for ticks after outdoor activities reduce bite incidents.
Communities are taught how to handle livestock safely, avoid contact with animal blood, and report suspected cases promptly to health authorities. Awareness campaigns utilize local languages and culturally appropriate materials for effective communication.
Training healthcare workers and community leaders enhances early detection and response. Emphasizing practical preventive actions enables individuals to protect themselves and their families efficiently.
Epidemiology
Crimean–Congo Hemorrhagic Fever (CCHF) is endemic across wide geographic regions including Africa, the Balkans, the Middle East, Eastern Europe, Central Asia, and parts of Asia south of the 50th parallel north. The disease was first identified in the Crimea in 1944 and later recognized in the Congo, which together gave rise to its name. Its wide distribution reflects both the ecology of its tick vectors and the presence of suitable animal hosts, making it one of the most geographically widespread tick-borne viral infections affecting humans.
Countries that report regular cases include Turkey, Iran, Pakistan, Afghanistan, Iraq, and Russia. In these regions, CCHF has become a recurring public health concern, with seasonal surges corresponding to heightened tick activity and increased human contact with livestock. Sporadic outbreaks have also been recorded in parts of Southern Europe, notably Spain and Portugal, where ecological changes and climate factors have expanded the habitat range of infected ticks.
Epidemiological data illustrate the varied burden of CCHF across different countries. In Turkey, since the first recognized outbreak in 2002, more than 9,700 cases have been documented. Although the overall mortality rate has remained relatively low compared to other regions, this has been attributed in part to improved surveillance and clinical management. In Iran, Khuzestan Province reported 42 probable cases between 1999 and 2015, with a case fatality rate of 28.6 percent. Nationally, over 1,600 probable cases were registered between 2000 and 2009, with mortality rates of about 5 percent. Afghanistan has seen a steady increase in incidence, rising from just four cases in 2007 to nearly 500 by 2018. This escalation has been linked to livestock migration, environmental stressors such as drought, and expanded surveillance systems.
In Iraq, outbreaks have been particularly severe in recent years. In 2022, the country recorded over 200 cases, nearly half of them laboratory confirmed, with 27 deaths. The following year, between January and August 2023, more than 500 confirmed cases were reported with a fatality rate of 12.7 percent, and much higher in some provinces such as Erbil. These patterns have been associated with increased animal slaughter during religious festivals, cross-border animal movements, and the influence of climate change on tick populations. Afghanistan also reported major outbreaks in 2023 and 2024, with more than a thousand suspected cases each year and case fatality rates approaching 10 percent. Spain and Portugal, although outside the traditional endemic zone, documented autochthonous cases during 2023 and 2024, with Portugal reporting its first confirmed and fatal case in 2024. Global estimates suggest that between 10,000 and 15,000 human infections occur annually, resulting in approximately 500 deaths.
The public health impact of CCHF is considerable. Clinically, the disease carries a high case fatality rate, typically ranging from 10 to 40 percent, and in some outbreaks exceeding this level. Patients often present with fever, severe hemorrhagic manifestations, and, in critical cases, multiorgan failure. These clinical features necessitate advanced supportive care, including intensive monitoring, blood transfusions, and mechanical ventilation in severe cases.
In several countries, nosocomial infections have been documented when infection prevention and control measures were insufficient. For example, in Iran, at least a dozen healthcare-associated infections were confirmed over two decades.