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Background: Crimean-Congo Haemorrhagic Fever (CCHF) is a viral haemorrhagic fever with a case fatality rate of 5-25% that has been prioritised for research and development by the World Health Organisation. There are no CCHF rapid diagnostic tests (RDTs) commercially available. We describe the development and evaluation of an antigen-targeting lateral flow immunoassay RDT for CCHF., Methods: Prospective clinical samples were collected and tested between July and October 2023 in Türkiye. Retrospective stored samples were obtained from the Central Public Health Laboratory, Baghdad, Iraq. The sensitivity and specificity of the CCHF RDT was compared to reverse transcription quantitative polymerase chain reaction assays., Findings: On prospective clinical samples in Türkiye, the sensitivity and specificity of the CCHF RDT was 90.4% [95% CI 81.5-95.3%] (n = 73) and 96.2% [95% CI 87.0-99.3%] (n = 52), respectively with a sensitivity of 92.9% [95% CI 84.3-96.9%] (n = 70) in samples with a cycle threshold (Ct) ≤30. On retrospective stored samples in Iraq, sensitivity and specificity of the RDT was 71.7% [95% CI 59.2-81.5%] (n = 60) and 92.5% [95% CI 80.1-97.8%] (n = 40), respectively with a sensitivity of 82.2% [95% CI 68.7-90.7%] (n = 45) in samples of Ct ≤30., Interpretation: The CCHF RDT was an effective rapid diagnostic test in this preliminary clinical evaluation, showing this RDT has the potential diagnostic capability for use at the point-of-care. Definitive evaluation is now required to ensure the RDT meets the regulatory requirements for commercialisation., Funding: The Liverpool School of Tropical Medicine, National Institute for Health Research Health Protection Research Unit in Emerging Zoonotic Infections, The Medical Research Council and The Pandemic Institute., Competing Interests: Declaration of interests LSTM intends to out-license the antibodies to facilitate the future commercialisation of the rapid diagnostic test (RDT). Additionally, we are evaluating the potential for filing a patent application for the antibodies. EA collects salary from the Liverpool School of Tropical Medicine and Global Access Diagnostics., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Crimean-Congo hemorrhagic fever virus (CCHFV) causes a highly contagious tick-borne disease with high case-fatality rates in humans. It is circulating not only in many Asian and African countries, but also spreading to and within Europe. To cope better with future outbreaks of Crimean-Congo hemorrhagic fever (CCHF), the WHO has prioritized the need for the development and validation of CCHF diagnostics, including serological assays. In this study, we evaluated the performance of the new EUROIMMUN anti-CCHFV IgM and IgG enzyme-linked immunosorbent assays (ELISAs). Materials and Methods: Both ELISAs were compared to the Vector-Best VectoCrimean-CHF-IgM and -IgG ELISAs using the EUROIMMUN CCHFV Mosaic 2 IgM and IgG indirect immunofluorescence assays (IFA) as reference. Forty-nine acute-phase serum samples from patients with CCHFV infection confirmed by reverse transcription-polymerase chain reaction (RT-PCR) and/or anti-CCHFV IgM IFA positivity were used to determine assay sensitivity. The assessment of specificity was based on sera from 30 control patients, 30 healthy blood donors, and 29 patients with hantavirus or sandfly fever virus infections. All samples originated from Turkey. Results: Sensitivity of the EUROIMMUN ELISAs (IgM 98.0%, IgG 47.1%) exceeded that of the Vector-Best ELISAs (IgM 95.9%, IgG 35.3%). Specificity of the EUROIMMUN ELISA IgM (86.4%) was slightly higher compared with the Vector-Best ELISA IgM (84.7%), while specificity for IgG was 100% for both assays. Qualitative agreement between the EUROIMMUN and Vector-Best ELISAs was substantial for detecting anti-CCHFV IgM (84.1%, ĸ = 0.673) and IgG (94.9%, ĸ = 0.791), whereas the quantitative results indicated a very strong positive correlation (IgM: r = 0.868, IgG: r = 0.913). Conclusion: The new EUROIMMUN anti-CCHFV ELISAs are standardized and easy-to-use tools that reliably support the identification of acute CCHF cases, and thus suitable for laboratories involved in on-site outbreak support.

Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne disease caused by the arbovirus Crimean-Congo hemorrhagic fever virus (CCHFV). The CCHFV has a single-stranded RNA genome of negative sense. MicroRNAs (miRNAs) are key players in virus-host interactions and viral pathogenesis. We investigated the miRNA gene expression profiles in patients with CCHF using microarray for the first time in the world. Microarray analysis was performed using mirBase Ver 21 (Agilent Technologies, Santa Clara, CA). All statistical analyses were performed across the case-control, fatal-control, and fatal-nonfatal case groups using Genespring (Ver 3.0). Fifteen miRNAs were statistical significant in patients with CCHF compared with the controls (5 were upregulated, 10 were downregulated). Seventy-five and sixty-six miRNAs are in fatal compared with control and nonfatal case, respectively (fold change ([FC] ≥50) were statistically significant. In this study, the target genes of important miRNAs were identified and Gene Ontology analyses were performed across all groups. As a result of this study, we propose that the detection of miRNAs in patients with CCHF will allow the determination of therapeutic targets in diseases. CCHF is an important public health problem that can often be fatal. In this study, we investigated miRNA expression in case-control, fatal-control, and fatal-nonfatal case groups. Significant miRNAs associated with fatality were detected in CCHF. This study will serve as a source of data for the development of an antagomir-based therapy against CCHF using miRNAs in the future., (© 2019 Wiley Periodicals, Inc.)