Abstract
Crimean-Congo Hemorrhagic Fever (CCHF) is a life threatening acute viral infection characterized by fever, bleeding, leukopenia and thrombocytopenia. It is a major emerging infectious diseases threat, but its pathogenesis remains poorly understood and few data exist for the role of apoptosis in acute infection. We aimed to assess apoptotic gene expression in leukocytes in a cross-sectional cohort study of adults with CCHF. Twenty participants with CCHF and 10 healthy controls were recruited at a tertiary CCHF unit in Turkey; at admission baseline blood tests were collected and total RNA was isolated. The RealTime ready Human Apoptosis Panel was used for real-time PCR, detecting differences in gene expression. Participants had CCHF severity grading scores (SGS) with low risk score (10 out of 20) and intermediate or high risk scores (10 out of 20) for mortality. Five of 20 participants had a fatal outcome. Gene expression analysis showed modulation of pro-apoptotic and anti-apoptotic genes that facilitate apoptosis in the CCHF patient group. Dominant extrinsic pathway activation, mostly related with TNF family members was observed. Severe and fatal cases suggest additional intrinsic pathway activation. The clinical significance of relative gene expression is not clear, and larger longitudinal studies with simultaneous measurement of host and viral factors are recommended.
Highlights
Crimean Congo Hemorrhagic Fever (CCHF) is a life threatening acute viral infection caused by a RNA virus belonging to the family Bunyaviridae
The pathogenesis of CCHF remains poorly understood despite significant recent scientific progress and research efforts [2]
Viral factors and an impaired host immune response including an exaggerated pro-inflammatory cytokine effect, all play a role in the severity and prognosis of viral haemorrhagic fevers including CCHF [15,16]
Summary
Crimean Congo Hemorrhagic Fever (CCHF) is a life threatening acute viral infection caused by a RNA virus belonging to the family Bunyaviridae. The first documented infection was observed in 1944 in the Crimea region of Ukraine and was designated as Crimean haemorrhagic fever. It was later observed in Congo in 1956 and the name was changed to CCHF [1]. Turkey reports up to 1000 cases per year and CCHFV is predominantly transmitted to humans via Hyalomma spp. ticks [3]. Clinical features of disease represent a spectrum of disease severity, characterized by fever, bleeding and lethargy, and has a case fatality rate of 5–50%. At present there is no approved vaccine or therapeutic agent, ribavirin and hyper immune serum are utilized by some clinicians
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