Recent Progress in the Treatment of Crimean–Congo Hemorrhagic Fever and Future Perspectives

Masayuki Saijo; Shigeru Morikawa; Ichiro Kurane

Disclosures

Future Virology. 2010;5(6):801-809. 

In This Article

Diagnosis

The precise diagnosis of CCHF is necessary in order to reduce the mortality and morbidity associated with CCHF. The establishment of diagnostic systems for CCHFV infections in regional laboratories and reference hospitals near the sites of CCHF outbreaks is, therefore, an issue that needs to be resolved. CCHFV is regarded as a biosafety level-4 (BSL-4) pathogen in some countries, indicating the manipulation of CCHFV is restricted to high-containment laboratories. The materials for virological tests should be handled very carefully to reduce the risk of nosocomial infections. The detection of both IgG and IgM CCHFV-antibodies is required for diagnosis. CCHFV antibody detection tests such as indirect immunofluorescent assay (IFA) and ELISA, are available only in a limited number of laboratories. CCHFV antigen-detection assay is useful for the proper diagnosis of CCHF and assessment of the clinical course of CCHF in patients.[56,57] CCHFV genome amplification tests are also important and practically useful virological tests for the diagnosis of CCHF.[12,47,58,59] Nested RT-PCR is commonly used for diagnostic purposes, while, recently, quantitative real-time RT-PCR assays for the amplification of the CCHFV genome were also reported.[60–62] Although the sensitivity and specificity of the real-time RT-PCR require further evaluation, this assay might prove to be an efficacious tool for the assessment of the clinical course of CCHF and its outcome in patients.

As mentioned previously, CCHFV must be handled in a high-containment laboratory. This restriction makes it difficult to prepare diagnostic materials and to perform virological tests for CCHFV infections. To overcome this difficulty, recombinant viral antigen-based antibody- and antigen-detection assay systems have been developed. A recombinant CCHFV nucleoprotein N-based ELISA for the detection of IgG and IgM antibodies was developed, and was shown to have high sensitivity and specificity.[44,47,63,64] A recombinant CCHFV nucleoprotein N-based indirect IFA has also been developed.[65] Garcia et al. also developed a recombinant N-based antibody detection assays (IFA and ELISA) using the recombinant nucleoprotein N expressed in mammalian cells via the recombinant Semliki Forest α-virus replicon.[66] Furthermore, a CCHFV antigen-detection sandwich ELISA was developed using a novel monoclonal antibody to recombinant CCHFV nucleoprotein N.[56] The advantage of these recombinant protein-based diagnostic systems is that these diagnostics can be employed in regional and reference institutes without a BSL-4 laboratory.

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