What is Crimean-Congo Hemorrhagic Fever?

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Crimean-Congo hemorrhagic fever, or CCHF, is a severe tick-borne disease. The CCHF virus is transmitted to humans by tick bites or contact with infected animal blood or tissues during and immediately following slaughter.

Ixodid (hard) ticks, particularly those of the genus, Hyalomma, can be both a vector and reservoir and a for CCHF virus. Image Credit: Gertjan Hooijer/Shutterstock.com

Affected patients are mainly those working in the livestock business, such as farmers, slaughterhouse workers, and veterinarians. In patients with CCHF, common laboratory results include leukopenia and thrombocytopenia. It is one of the world's most widespread arboviral infections, with a 40-60% fatality rate.

Cause and mechanism

The causative agent of CCHF is a nairovirus of the Bunyaviridae family. Infected animals are usually asymptomatic, while the infection is usually fatal in humans. Serological research suggests that CCHF can infect a wide range of wild and domestic animals without causing disease.

Furthermore, CCHF infection is frequently subclinical or asymptomatic in people. Thus, Crimean-Congo hemorrhagic fever is a severe, deadly infection most likely influenced by host and viral factors. Kupffer cells, hepatic endothelial cells, and hepatocytes are thought to be key CCHF targets.

Humans are primarily dead-end hosts for CCHF. The severe disease is thus an unintended consequence of selective pressures in ticks and mammalian species that serve as a reservoir and amplify hosts.

Symptoms

Crimean-Congo hemorrhagic fever begins with nonspecific febrile symptoms and progresses to hemorrhagic syndrome. Infection typically progresses through four stages: incubation, pre-hemorrhagic, hemorrhagic, and convalescent.

The incubation period ranges between three and seven days and depends on the route of infection, viral load, and source of infection-blood or tissue from livestock. A minimum of 1-10 viruses are necessary for disease transmission.

The symptoms appear in the second, pre-hemorrhagic phase, which lasts for about four to five days and consists of high fever, abdominal pain, headache, and nausea, among other symptoms. Hypotension with relative bradycardia, conjunctivitis, and rash, can also be observed.

In most cases, the pre-hemorrhagic phase progresses to the hemorrhagic phase. This third phase is short and involves symptoms like petechiae, conjunctival hemorrhage, hematemesis, and melena.

Death happens in severe cases due to multiorgan failure, disseminated intravascular coagulation, and circulatory shock.

The convalescent period occurs 10-20 days following the commencement of disease in survivors. During this stage, patients may experience a weak pulse, and tachycardia, with hearing, memory, and hair loss.

Crimean-Congo hemorrhagic fever virus

The CCHF virions are spherical (diameter ̴ 100 nm) and have a lipid envelope produced from the host. CCHFV is a negative-sense, single-stranded RNA virus with three genomic segments labeled large (L), medium (M), and small (S). The L segment is 11,942 nucleotides long and contains only one projected open reading frame (ORF) with 3,442 residues.

Near the N-terminus of the ORF is an ovarian tumor protease (OTU) domain. The M segment can code for up to 240 KDa of protein. The M gene is essential for immunity, pathogenicity, and vaccine production.

The S segment of the genome is divided into eight genetically different clades and, together with the viral polymerase, aids in viral transcription and replication.

Crimean-Congo Hemorrhagic fever || CCHF || Cause, Symptoms, Diagnosis & Prevention of CCHF

Epidemiology

The geographic distribution of Crimean-Congo hemorrhagic fever virus is extensive. Most cases were recorded from the former Soviet Union in the early years after the virus was originally characterized in 1967.

Since the disease's discovery in Crimea the Congo basin, it has been recorded in numerous parts of Africa, the Middle East, Europe, and Asia. Fifty-two countries have been designated as endemic or potentially endemic zones, with many cases reported yearly.

The majority of the reports came from Turkey, Russia, Iran, and Bulgaria. Climate, population growth, travel, agriculture, ecological changes, and animal movement may create opportunities for CCHF virus to spread to previously unaffected areas.

The primary outbreak sites are in the Middle East (Turkey and Iran), with over 10,000 cases confirmed in Turkey since 2002. The prevalence of CCHF increased between 2008 and 2012.

Diagnosis and treatment

Because of the potential for nosocomial transmission, early detection is critical for patient management and preventing additional disease transmission. Demonstrating the virus or viral genome is the most conclusive method of diagnosis. Viral isolation, RT-PCR, and serological assays can all help in the diagnosing process.

The main approach in treating individuals with CCHF virus infection is to manage fluid and electrolyte imbalances, depending on the severity of the clinical manifestation.

Early diagnoses and supportive therapy, such as blood, platelet, and plasma replacement, can save lives, particularly in patients with hemorrhagic manifestations. There are currently two CCHF virus vaccines  – the first is a formalin-inactivated vaccine created in Bulgaria using infected suckling mouse brains, and the second is a DNA vaccine tested in mice. Neither vaccine has undergone formal randomized clinical trials.

Due to the epidemic potential, high mortality rate, propensity for nosocomial infection, and difficulty in treatment and prevention, CCHF outbreaks pose a hazard to global health.

Reference

  • Rodriguez SE, Hawman DW, Sorvillo TE, et al. (2022). Immunobiology of Crimean-Congo hemorrhagic fever. Antiviral Research, 199, 105244. doi: 10.1016/j.antiviral.2022.105244. https://pubmed.ncbi.nlm.nih.gov/35026307/
  • Fillâtre P, Revest M & Tattevin P (2019). Crimean-Congo hemorrhagic fever: An update. Medecine et Maladies Infectieuses, 49(8), 574–585. doi: 10.1016/j.medmal.2019.09.005. https://pubmed.ncbi.nlm.nih.gov/31607406/
  • Leblebicioglu H, Ozaras R, Irmak H et al. (2016). Crimean-Congo hemorrhagic fever in Turkey: Current status and future challenges. Antiviral Research, 126, 21–34. doi: 10.1016/j.antiviral.2015.12.003. https://pubmed.ncbi.nlm.nih.gov/26695860/
  • Papa A, Mirazimi A, Köksal I, et al. (2015). Recent advances in research on Crimean-Congo hemorrhagic fever. Journal of Clinical Virology: the official publication of the Pan American Society for Clinical Virology, 64, 137–143. doi: 10.1016/j.jcv.2014.08.029. https://pubmed.ncbi.nlm.nih.gov/25453328/
  • Messina JP, Pigott DM, Golding N, et al. (2015). The global distribution of Crimean-Congo hemorrhagic fever. Transactions of the Royal Society of Tropical Medicine and Hygiene, 109(8), 503–513. doi: 10.1093/trstmh/trv050. https://academic.oup.com/trstmh/article/109/8/503/1910424
  • Shayan S, Bokaean M, Shahrivar MR, et al. (2015). Crimean-Congo Hemorrhagic Fever. Laboratory Medicine, 46(3), 180–189. doi: 10.1309/LMN1P2FRZ7BKZSCO. https://academic.oup.com/labmed/article/46/3/180/2657762
  • Appannanavar SB & Mishra B (2011). An update on crimean congo hemorrhagic Fever. Journal of Global Infectious Diseases, 3(3), 285–292. doi: 10.4103/0974-777X.83537. https://pubmed.ncbi.nlm.nih.gov/21887063/

Further Reading

  • All Tick-borne Diseases Content

Last Updated: Aug 17, 2023