What is Crimean Congo Hemorrhagic Fever (CCHF): Epidemiology, Symptoms, Diagnosis, and Prevention

How is Crimean-Congo Hemorrhagic Fever Transmitted to Humans? 

The primary vectors for CCHF are ixodid (hard) ticks belonging to the Hyalomma genus. The Hyalomma genus of ixodid ticks acts as a vector and a reservoir for the CCHF virus. Main species include H.marginatum, H.rufipes, H.anatolicum, and H.asiaticum [3]. 

CCHF cases are most prevalent during the spring and summer when the Hyalomma ticks find the environment most suitable. CCHF-carrying ticks infest many types of animals, including domesticated sheep, cattle, goats, hares, hedgehogs, and more, but these animals mostly remain asymptomatic. This viral hemorrhagic fever is transmitted to humans when they come in contact with the infected ticks themselves or the blood of an infected animal host. Birds are not usually susceptible to CCHF infections, but migratory birds can carry and spread the virus [4, 12]. 

Human to human transmission occurs through the exchange of body fluids or contact with infected blood. Another way is through healthcare-associated infections (HAI) or nosocomial transmission through contaminated medical equipment. 

People most at risk are butchers or those who work with livestock or in slaughterhouses, and healthcare workers [1]. The risk of contracting CCHF from travel is rare, but instances have been reported. 

CCHF and Travel

Reports of Crimean-Congo hemorrhagic fever (CCHF) related to travel are rare. The following chronology is abstracted from GIDEON. [1]

• 1985 – South Africa ex. Democratic Republic of Congo (fatal).
• 1986 – South Africa ex. Tanzania (nonfatal)
• 1997 – An English traveler died of probable CCHF contracted in Zimbabwe.
• 2001 – A German tourist acquired Crimean-Congo hemorrhagic fever in Bulgaria.
• 2004 – A case of imported Crimean-Congo hemorrhagic fever (nonfatal) was reported in a traveler returning to France from Senegal. Infection in a second French national was diagnosed locally in Senegal.
• 2009 – An American soldier died in a hospital in Germany after contracting Crimean-Congo hemorrhagic fever in Afghanistan.
• 2011 – An outbreak (4 cases) in a Pakistan hospital was related to an index patient who had arrived from Afghanistan.
• 2012 – A patient died of Crimean-Congo hemorrhagic fever in Scotland following the acquisition of the disease in Afghanistan.
• 2013 – A woman died of Crimean-Congo hemorrhagic fever in Uganda following contact with her infected husband in South Sudan.
• 2014 – A British traveler acquired Crimean-Congo hemorrhagic fever in Bulgaria.

Epidemiology and Risk Factors 

CCHF was first described in Crimea in 1944. In 1969, it was the cause of severe illness in the Congo. CCHF-carrying ticks are endemic to a wide geographical area, including Africa, Asia, the Middle East, and Eastern and Southwestern Europe. Turkey leads with the highest number of laboratory-confirmed cases of CCHF among endemic countries [5,6].

With climate change and the rise in global temperatures, experts are concerned about the growing spread of CCHF disease outbreaks. In recent years, CCHF has been reported in even northern European countries like Sweden that were previously unaffected by it [7, 12]. 

Lower levels of rainfall and environmental changes can trigger community outbreaks. Altering agricultural lands may also play a role.

Symptoms

With an infection by a tick bite, the incubation period is 1-3 days. With nosocomial infections through blood or body fluids, the incubation period is about 5-6 days [1]. 

Symptoms can appear suddenly. Symptoms can appear suddenly. Initially, individuals with a Crimean congo hemorrhagic fever virus infection may experience headaches, dizziness, a high fever, joint and back pain (myalgia), pain in the stomach, and even nausea and vomiting. These symptoms may be accompanied by conjunctivitis (pink eye), pharyngitis (sore throat), and photophobia (sensitivity to light). Infected individuals may also demonstrate sharp mood swings and confusion but become lethargic, depressed, and sleepy after 2-4 days. The liver may also be enlarged (hepatomegaly) [9]. 

As the viral hemorrhagic fever progresses, the hemorrhaging or bleeding characteristic of this infection begins. There are many regions with bruising and severe bleeding from the nose and injection sites. The bleeding starts on the fourth or fifth day and can last for two weeks.   

Lymph node enlargement (lymphadenopathy), petechiae (tiny red or brown clusters of spots on the skin that appear due to bleeding). Severely ill patients may experience kidney, liver, or lung failure after five days of illness [1,14]. 

Diagnosis

According to WHO, laboratory tests are the best way to diagnose CCHF. Diagnostic tests include ELISA (enzyme-linked immunosorbent assay), antigen detection, serum neutralization, RT-PCR (reverse transcriptase polymerase chain reaction), and cell culture. In survivors, IgG antibodies can be detected after recovery [1,9].  

CCHF is categorized as an extreme biohazard risk and classified as a biosafety level 4 pathogen. This means it has a high risk of transmission or outbreak through aerosol droplets, can be fatal, and does not have an effective treatment. Biosafety protocols must be followed when collecting and handling samples from suspected or confirmed cases of CCHF.  

Unfortunately, there is no ‘universal gold standard’ for CCHF diagnostic tests. Virus isolation is the ideal method. However, since CCHFV needs biosafety level 4 protocols, it is currently impractical to implement viral isolation as a standard practice. This is because CCHF is primarily found in rural or other areas where access to specialized labs and equipment is limited [10].   

Treatment 

There is no specific medication effective against CCHF, but treatment is supportive. The virus does show sensitivity to the antiviral medicine ribavirin, which has been used to treat CCHF patients [11]. 

Prevention 

There are no licensed vaccines available to protect humans from the CCHF virus [12]. However, there may be hope on the horizon. In September 2023, volunteers got a vaccine for a Crimean Congo Hemorrhagic fever vaccine as part of an Oxford clinical trial.

The best way to prevent CCHF, with or without a vaccine, is to educate individuals working with livestock or butchers on the right safety precautions. Wearing protective clothing and paying attention to ticks are recommended steps. 

In healthcare facilities, patients with confirmed or suspected nosocomial CCHF infections must be isolated. Healthcare professionals must follow standard infection control, including hand hygiene, and PPE, and protect their eyes and face from potential exposure to droplets carrying infections [1,12]. 

Unfortunately, though there is an urgent need to find a cure and preventive vaccine for this disease, the CCHF virus (CCHFV) is under-researched. Standard murine models are not applicable because adult mice, rats, hamsters, and guinea pigs are resistant to the CCHF virus (CCHFV). Until now, only newborn mice have been used, but they are too sensitive to the virus and not effective when trying to understand adult immune responses [13]. 

Researchers identified new murine and non-human primate models that respond to the virus. Additionally, in 2021, researchers identified mouse-adapted CCHFV variants that opened the door to more investigations. These immunocompetent mice demonstrated differences in how males and females reacted to CCHFV.  Male mice infected with CCHFV developed a severe disease with high viral loads, cytokine inflammatory response, and liver disease. Female mice infected with Crimean Congo hemorrhagic fever had similar viral loads to the male mice initially but experienced milder levels of disease and inflammatory response [13,14]. 

Hopefully, the development of new murine models and mouse-adapted CCHFV will accelerate research into effective treatments and vaccines for this highly fatal disease.