RARE DISEASE
Crimean-Congo hemorrhagic fever
Crimean-Congo hemorrhagic fever
Crimean-Congo hemorrhagic fever
Synonyms: CCHF, Congo fever, Congo hemorrhagic fever, Crimean hemorrhagic fever
Synonyms: CCHF, Congo fever, Congo hemorrhagic fever, Crimean hemorrhagic fever
Synonyms: CCHF, Congo fever, Congo hemorrhagic fever, Crimean hemorrhagic fever
Drug discovery
1
drug
With orphan designation
Overview
Crimean-Congo hemorrhagic fever (CCHF) is a tickborne Nairovirus infection causing severe viral hemorrhagic fever. Transmission occurs via Hyalomma ticks, contact with infected animal tissues, or human bodily fluids. Symptoms include sudden fever, myalgia, petechial rash, hemorrhage (days 3–5), and multiorgan failure, with a case fatality rate of 10%–40% [1][7][17]. Diagnosis relies on PCR or serology. Prevention focuses on tick avoidance, PPE in high-risk settings, and ribavirin prophylaxis for exposures [3][11][18].
Burden
Annual global incidence: ~10,000–15,000 cases, with underreporting in low-resource regions [1][4]
CFR ranges from 5% in well-resourced settings to 40% in Africa; indirect costs from livestock trade disruptions [5][9][15]
Emerging threat due to climate-related tick expansion and inadequate surveillance infrastructure [10][12]
Therapies
Supportive care: Fluid resuscitation, blood product transfusions, and organ support [3][11][18]
Ribavirin: Used off-label despite conflicting efficacy data; WHO recommends its use in high-risk exposures [3][7][19]
Infection control: Strict isolation and biocontainment protocols to prevent nosocomial transmission [16][18]
Categories: rare infectious diseases
Research Papers
494 drug discovery papers related to Crimean-Congo hemorrhagic fever, with 3 first-in-class and 4 next-in-class early-stage therapies forecasted to outperform the average preclinical success rate. Recent publications:
494 drug discovery papers related to Crimean-Congo hemorrhagic fever, with 3 first-in-class and 4 next-in-class early-stage therapies forecasted to outperform the average preclinical success rate. Recent publications:
2026-07-11 | Coagulopathy in viral haemorrhagic fevers and beyond: molecular mechanisms and targeted interventions.
Coagulopathy refers to any medical condition which affects the ability of the blood to clot. It can be caused due to genetic conditions like haemophilia, von Willebrand disease, or it can be caused through liver disease or deficiency of Vitamin K. It also involves a broad range of diseases affecting hemostasis as an unbalanced and even bidirectional relationship between thrombosis and bleeding. Coagulopathy can also be caused by thromboinflammation, as seen in VHFs like Ebola, Dengue, Marburg, Crimean-Congo Hemorrhagic Fever, Yellow Fever, and Hantavirus infection. The immune response and coagulation system are intricately linked in such cases. Infections from VHFs cause endothelial cell dysfunction through the immune response, monocytes/macrophages activation, and increased expression of tissue factor (TF), which in turn causes excessive thrombin production and fibrin formation. These conditions result in microvascular thrombosis, organ dysfunction, consumption of platelets and coagulation factors, causing a balanced but fragile state of hemostasis that could tip over towards either thrombosis or bleeding. New therapies have been developed that interfere with these processes, such as interference with the TF pathway (for instance, rNAPc2) and regulation of fibrinolysis (tranexamic acid). The recognition of the double-edged sword of coagulopathy is critical for the development of treatment strategies targeting coagulation disorders. This literature review discusses the molecular basis of immunothrombosis and endothelial dysfunction in VHFs.
2026-07-05 | The Impact of Admission Viral Load and Inflammatory Markers on Mortality and Prognosis in Crimean-Congo Hemorrhagic Fever.
This study aimed to evaluate the impact of admission viral load and biochemical parameters on mortality and disease severity in a large cohort of patients with Crimean-Congo Hemorrhagic Fever (CCHF). This retrospective cohort study included 492 adult patients diagnosed with CCHF between 2022 and 2025. Admission viral loads, laboratory parameters, and clinical findings were compared. Logistic regression and ROC analyses were performed to identify independent predictors and optimal cut-off values. The mortality rate was 9.8% (n = 48). In multivariate analysis, admission log-viral load was identified as a potent independent predictor of mortality (OR: 3.36, p < 0.001 95% CI: 2.88-8.95, p < 0.001), alongside CRP (OR: 1.02, p < 0.001). Notably, advanced age was a significant risk factor, associated with a 2.8% increased risk of mortality (OR: 1.028, p = 0.025). In a separate model for disease severity, log-viral load (OR: 1.71, p < 0.001), age (OR: 1.021, p = 0.002), and CRP (OR: 1.012, p < 0.001) were significant independent predictors of a severe clinical course. Conversely, higher fibrinogen levels (OR: 0.997, p = 0.025) were associated with reduced disease severity. A viral load cut-off of 6.69 log10 copies/mL predicted mortality with 85.4% sensitivity and a negative predictive value of 98%. Admission viral load serves as a primary early marker for both mortality and clinical severity in CCHF. While CRP reflects the host's inflammatory response, admission fibrinogen levels also provide critical prognostic information. Combined use of these markers can optimize early triage and clinical management in endemic regions.
2026-06-22 | Finding the Goldilocks zone: Modulating glycoprotein cleavage and fusogenicity optimizes the efficacy of a candidate Crimean-Congo hemorrhagic fever virus vaccine.
Crimean-Congo hemorrhagic fever virus (CCHFV) is the etiologic agent of a lethal hemorrhagic disease spread by ticks throughout Europe, the Middle East, Africa and Asia. The lack of approved medical countermeasures and fundamental understanding of molecular mechanisms of viral assembly and egress have thus far curtailed disease prevention. Here, we identify and characterize key residues within the viral glycoprotein through forward and reverse genetics for vesicular stomatitis virus (VSV)-based vaccine candidates that are highly protective in animal models. These residues are broadly applicable across divergent CCHFV strains and lead to greater protection in vivo against heterologous challenge. We further characterize the essential role of proteolytic processing in the maintenance of a stable fusogenic state required for effective VSV-based CCHFV vaccines. This study establishes a toolkit for better understanding orthonairovirus glycoprotein processing and vaccine development.
2026-07-11 | Coagulopathy in viral haemorrhagic fevers and beyond: molecular mechanisms and targeted interventions.
Coagulopathy refers to any medical condition which affects the ability of the blood to clot. It can be caused due to genetic conditions like haemophilia, von Willebrand disease, or it can be caused through liver disease or deficiency of Vitamin K. It also involves a broad range of diseases affecting hemostasis as an unbalanced and even bidirectional relationship between thrombosis and bleeding. Coagulopathy can also be caused by thromboinflammation, as seen in VHFs like Ebola, Dengue, Marburg, Crimean-Congo Hemorrhagic Fever, Yellow Fever, and Hantavirus infection. The immune response and coagulation system are intricately linked in such cases. Infections from VHFs cause endothelial cell dysfunction through the immune response, monocytes/macrophages activation, and increased expression of tissue factor (TF), which in turn causes excessive thrombin production and fibrin formation. These conditions result in microvascular thrombosis, organ dysfunction, consumption of platelets and coagulation factors, causing a balanced but fragile state of hemostasis that could tip over towards either thrombosis or bleeding. New therapies have been developed that interfere with these processes, such as interference with the TF pathway (for instance, rNAPc2) and regulation of fibrinolysis (tranexamic acid). The recognition of the double-edged sword of coagulopathy is critical for the development of treatment strategies targeting coagulation disorders. This literature review discusses the molecular basis of immunothrombosis and endothelial dysfunction in VHFs.
2026-07-05 | The Impact of Admission Viral Load and Inflammatory Markers on Mortality and Prognosis in Crimean-Congo Hemorrhagic Fever.
This study aimed to evaluate the impact of admission viral load and biochemical parameters on mortality and disease severity in a large cohort of patients with Crimean-Congo Hemorrhagic Fever (CCHF). This retrospective cohort study included 492 adult patients diagnosed with CCHF between 2022 and 2025. Admission viral loads, laboratory parameters, and clinical findings were compared. Logistic regression and ROC analyses were performed to identify independent predictors and optimal cut-off values. The mortality rate was 9.8% (n = 48). In multivariate analysis, admission log-viral load was identified as a potent independent predictor of mortality (OR: 3.36, p < 0.001 95% CI: 2.88-8.95, p < 0.001), alongside CRP (OR: 1.02, p < 0.001). Notably, advanced age was a significant risk factor, associated with a 2.8% increased risk of mortality (OR: 1.028, p = 0.025). In a separate model for disease severity, log-viral load (OR: 1.71, p < 0.001), age (OR: 1.021, p = 0.002), and CRP (OR: 1.012, p < 0.001) were significant independent predictors of a severe clinical course. Conversely, higher fibrinogen levels (OR: 0.997, p = 0.025) were associated with reduced disease severity. A viral load cut-off of 6.69 log10 copies/mL predicted mortality with 85.4% sensitivity and a negative predictive value of 98%. Admission viral load serves as a primary early marker for both mortality and clinical severity in CCHF. While CRP reflects the host's inflammatory response, admission fibrinogen levels also provide critical prognostic information. Combined use of these markers can optimize early triage and clinical management in endemic regions.
2026-06-22 | Finding the Goldilocks zone: Modulating glycoprotein cleavage and fusogenicity optimizes the efficacy of a candidate Crimean-Congo hemorrhagic fever virus vaccine.
Crimean-Congo hemorrhagic fever virus (CCHFV) is the etiologic agent of a lethal hemorrhagic disease spread by ticks throughout Europe, the Middle East, Africa and Asia. The lack of approved medical countermeasures and fundamental understanding of molecular mechanisms of viral assembly and egress have thus far curtailed disease prevention. Here, we identify and characterize key residues within the viral glycoprotein through forward and reverse genetics for vesicular stomatitis virus (VSV)-based vaccine candidates that are highly protective in animal models. These residues are broadly applicable across divergent CCHFV strains and lead to greater protection in vivo against heterologous challenge. We further characterize the essential role of proteolytic processing in the maintenance of a stable fusogenic state required for effective VSV-based CCHFV vaccines. This study establishes a toolkit for better understanding orthonairovirus glycoprotein processing and vaccine development.
Access all drug discovery articles and probability of success in trials forecasts:
Access all drug discovery articles and probability of success in trials forecasts:
Drug Discovery Landscape
1 orphan drug designation for Crimean-Congo hemorrhagic fever.
1 orphan drug designation for Crimean-Congo hemorrhagic fever.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Ribavirin | small molecules | EMA | 2018-03-21 | — | Pharmadev Healthcare Ltd |
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