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Laboratory diagnosis of Crimean–Congo hemorrhagic fever virus infections

    Felicity Jane Burt

    Department of Medical Microbiology & Virology, National Health Laboratory Services Universitas/Faculty of Health Sciences, University of the Free State, Bloemfontein, South Africa.

    Published Online:https://doi.org/10.2217/fvl.11.47

    Crimean–Congo hemorrhagic fever virus is a tick-borne viral zoonosis widely distributed in Africa, Asia, Russia and the Balkans. The emergence and re-emergence of Crimean–Congo hemorrhagic fever virus emphasizes the importance of developing standardized, rapid and sensitive assays. Confirmation of infection in the acute phase of illness is currently achieved by detection of viral nucleic acid in serum samples using reverse transcriptase (RT)-PCR, or by isolation of the virus. RT-PCR has provided a rapid and reliable method for early diagnosis. In addition, real-time RT-PCR can be used to determine viral load, which has application as a prognostic indicator. In convalescent samples collected from nonfatal cases, the diagnosis is confirmed by demonstration of an immune response. Patients with fatal infections almost always do not develop a demonstrable antibody response. Accurate interpretation of laboratory findings is dependent on the kinetics of viremia and antibody responses in humans as well as an accurate history of onset date and clinical pathology.

    Papers of special note have been highlighted as: ▪ of interest

    Bibliography

    • Hoogstraal H. The epidemiology of tick-borne Crimean–Congo hemorrhagic fever in Asia, Europe, and Africa. J. Med. Entomol.15(4),307–417 (1979).
    • Maltezou HC, Andonova L, Andraghetti R et al. Crimean–Congo hemorrhagic fever in Europe: current situation calls for preparedness. Euro. Surveill.15(10),19504–19508 (2010).
    • Davies FG, Casals J, Jesset DM, Ochieng P. The serological relationships of Nairobi sheep disease virus. J. Comp. Path.88(4),519–523 (1978).
    • Karabatsos N. International Catalogue of Arboviruses Including Certain Other Viruses of Vertebrates. (3rd Edition). San Antonio, TX, USA. Am. Soc. Trop. Med. Hyg. (1985).
    • Clerx JP, Casals J, Bishop DH. Structural characteristics of nairoviruses (genus Nairovirus, Bunyaviridae). J. Gen. Virol.55(1),165–178 (1981).
    • Sanchez AJ, Vincent MJ, Nichol ST. Characterization of the glycoproteins of Crimean–Congo hemorrhagic fever virus. J. Virol.76(14),7263–7275 (2002).
    • Casals J. Antigenic similarity between the virus causing Crimean hemorrhagic fever and Congo virus. Proc. Soc. Exp. Biol. Med.131(1),233–236 (1969).
    • Hewson R, Chamberlain J, Mioulet V et al. Crimean–Congo haemorrhagic fever virus: sequence analysis of the small RNA segments from a collection of viruses worldwide. Virus Res.102(2),185–189 (2004).
    • Burt FJ, Swanepoel R. Molecular epidemiology of African and Asian Crimean–Congo haemorrhagic fever isolates. Epidemiol. Infect.133(4),659–666 (2005).
    • 10  Deyde VM, Khristova ML, Rollin PE, Ksiazek TG, Nichol ST. Crimean–Congo hemorrhagic fever virus genomics and global diversity. J. Virol.80(17),8834–8842 (2006).
    • 11  Swanepoel R, Shepherd AJ, Leman PA et al. Epidemiologic and clinical features of Crimean–Congo hemorrhagic fever in southern Africa. Am. J. Trop. Med. Hyg.36(1),120–132 (1987).
    • 12  Swanepoel R, Gill DE, Shepherd AJ, Leman PA, Mynhardt JH, Harvey S. The clinical pathology of Crimean–Congo hemorrhagic fever. Rev. Infect. Dis.11(Suppl. 4),S794–S800 (1989).
    • 13  Ergonul O. Crimean–Congo haemorrhagic fever. Lancet Inf. Dis.6(4),203–214 (2006).
    • 14  Kuhn JH, Seregin SV, Morzunov SP et al. Genetic analysis of the mRNA segment of Crimean-Congo haemorrhagic fever virus involved in the recent outbreaks in Russia. Arch. Virol.149(11),2199–2213 (2004).
    • 15  Vorou R, Pierroutsakos IN, Maltezou HC. Crimean–Congo hemorrhagic fever. Curr. Opin. Infect. Dis.20(5),495–500 (2007).
    • 16  Maltezou HC, Papa A. Crimean–Congo hemorrhagic fever: risk for emergence of new endemic foci in Europe? Travel Med. Infect. Dis.8(3),139–143 (2010).
    • 17  Drosten C, Kummerer BM, Schmitz H, Gunther S. Molecular diagnostics of viral haemorrhagic fevers. Antiviral Res.57(1–2),61–87 (2003).
    • 18  Burt FJ, Swanepoel R, Shieh WJ et al. Immunohistochemical and in situ localization of Crimean–Congo hemorrhagic fever (CCHF) virus in human tissues and implications for CCHF pathogenesis. Arch. Pathol. Lab. Med.121(8),839–846 (1997).
    • 19  Bodur H, Akinci E, Onguru P et al. Detection of Crimean–Congo hemorrhagic fever virus genome in saliva and urine. Int. J. Infect. Dis.14(3),247–249 (2010).
    • 20  Butenko AM, Chumakov MP. Isolation of Crimean–Congo hemorrhagic fever virus from patients and from autopsy specimens. Arch. Virol.1(Suppl.),295–301 (1990).
    • 21  Watts DM, Ksiazek TG, Linthicum KJ, Hoogstraal H. Crimean–Congo haemorrhagic fever. In: The Arboviruses: Epidemiology and Ecology. Volume II. Monath TP (Ed.). CRC Press Inc. FL, USA (1989).
    • 22  Shepherd AJ, Swanepoel R, Leman PA, Shepherd SP. Comparison of methods for isolation and titration of Crimean–Congo hemorrhagic fever virus. J. Clin. Microbiol.24(4),654–656 (1986).
    • 23  Hewson R, Gmyl A, Gmyl L et al. Evidence of segment reassortment in Crimean–Congo haemorrhagic fever virus. J. Gen. Virol.85(10),3059–3070 (2004).
    • 24  Burt FJ, Paweska JT, Ashkettle B, Swanepoel R. Genetic relationship among southern African Crimean-Congo haemorrhagic fever virus isolates and evidence for occurrence of reassortment. Epidemiol. Inf.137(9),1302–1308 (2009).
    • 25  Schwarz TF, Nitschko H, Jager G et al. Crimean–Congo haemorrhagic fever in Oman. Lancet346(8984),1230 (1995).
    • 26  Rodriguez LL, Maupin GO, Ksiazek TG et al. Molecular investigation of a multisource outbreak of Crimean–Congo hemorrhagic fever in the United Arab Emirates. Am. J. Trop. Med. Hyg.57(5),512–518 (1997).
    • 27  Burt FJ, Leman PA, Smith JF, Swanepoel R. The use of a reverse transcription-polymerase chain reaction for the detection of viral nucleic acid in the diagnosis of Crimean–Congo haemorrhagic fever. J. Virol. Methods70(2),129–137 (1998).
    • 28  Drosten CS, Gottig S, Schilling M et al. Rapid detection and quantification of RNA of Ebola and Marburg viruses, Lassa virus, dengue virus, and yellow fever virus by real-time reverse transcription-PCR. J. Clin. Microbiol.40(7),2323–2330 (2002).▪ First real-time real time-PCR for detection of Crimean–Congo hemorrhagic fever virus (CCHFV).
    • 29  Yapar M, Aydogan H, Pahsa A et al. Rapid and quantitative detection of Crimean–Congo hemorrhagic fever virus by one-step real-time reverse transcriptase-PCR. Jpn. J. Infect. Dis.58(6),358–362 (2005).▪ First quantification of CCHFV RNA.
    • 30  Duh D, Saksida A, Petrovec M, Dedushaj I, Avsic-Zupanc T. Novel one-step real-time RT-PCR assay for rapid and specific diagnosis of Crimean–Congo hemorrhagic fever encountered in the Balkans. J. Virol. Methods133(2),175–179 (2006).
    • 31  Duh D, Saksida A, Petrovec M et al. Viral load as predictor of Crimean–Congo hemorrhagic fever outcome. Emerg. Infect. Dis.13(11),1769–1772 (2007).▪ Results indicate levels of viral load suggestive of fatal outcome and influence of antibody on viral load.
    • 32  Papa A, Drosten C, Bino S et al. Viral load and Crimean–Congo hemorrhagic fever. Emerg. Infect. Dis.13(5),805–806 (2007).
    • 33  Garrison AR, Alakbarova S, Kulesh DA et al. Development of a TaqMan minor groove binding protein assay for the detection and quantification of Crimean–Congo hemorrhagic fever virus. Am. J. Trop. Med. Hyg.77(3),514–520 (2007).
    • 34  Wolfel R, Paweska JT, Petersen N et al. Virus detection and monitoring of viral load in Crimean–Congo hemorrhagic fever virus patients. Emerg. Infect. Dis.13(7),1097–1100 (2007).
    • 35  Wolfel R, Paweska JT, Petersen N et al. Low-density macroarray for rapid detection and identification of Crimean–Congo hemorrhagic fever virus. J. Clin. Microbiol.47(4),1025–1030 (2009).▪ Biotinylated amplification products hybridized to DNA macroarrays and detected colorimetrically using streptavidin horseradish peroxidase.
    • 36  Kondiah K, Swanepoel R, Paweska JT, Burt FJ. A aimple-probe real-time PCR assay for genotyping reassorted and non-reassorted isolates of Crimean–Congo hemorrhagic fever virus in southern Africa. J. Virol. Methods169(1),34–38 (2010).
    • 37  Cevik MA, Erbay A, Bodur H et al. Viral load as a predictor of outcome in Crimean–Congo hemorrhagic fever. Clin. Infect. Dis.45(7),96–100 (2007).
    • 38  Shepherd AJ, Swanepoel R, Gill DE. Evaluation of enzyme-linked immunosorbent assay and reversed passive hemagglutination for detection of Crimean–Congo hemorrhagic fever virus antigen. J. Clin. Microbiol.26(2),347–353 (1988).
    • 39  Saijo M, Tang Q, Shimayi B et al. Antigen-capture enzyme-linked immunosorbent assayfor the diagnosis of Crimean–Congo hemorrhagic fever using a novel monoclonal antibody. J. Med. Virol.77(1),83–88 (2005).
    • 40  Casals J, Tignor GH. The Nairovirus genus: serological relationships. Intervirology14(3–4),144–147 (1980).
    • 41  Swanepoel R, Struthers JK, McGillivray GM. Reversed passive hemagglutination and inhibition with Rift Valley fever and Crimean–Congo hemorrhagic fever viruses. Am. J. Trop. Med. Hyg.32(3),610–617 (1983).
    • 42  Shepherd AJ, Swanepoel R, Leman PA. Antibody response in Crimean–Congo hemorrhagic fever. Rev. Infect. Dis.11(Suppl. 4),S801–S806 (1989).▪ Kinetics of antibody response in nonfatal and fatal cases. The study includes largest number of patients tested by immunofluorescence with days after onset.
    • 43  Burt FJ, Leman PA, Abbott JC, Swanepoel R. Serodiagnosis of Crimean–Congo haemorrhagic fever. Epidemiol. Infect.113(3),551–562 (1994).▪ Kinetics of antibody response in nonfatal and fatal cases. Includes largest number of patients tested by ELISA with days after onset.
    • 44  Saijo M, Qing T, Niikura M et al. Immunofluorescence technique using HeLa cells expressing recombinant nucleoprotein for detection of immunoglobulin G antibodies to Crimean–Congo hemorrhagic fever virus. J. Clin. Microbiol.40(2),372–375 (2002).
    • 45  Garcia S, Chinikar S, Coudrier D et al. Evaluation of a Crimean–Congo hemorrhagic fever virus recombinant antigen expressed by Semliki Forest suicide virus for IgM and IgG antibody detection in human and animal sera collected in Iran. J. Clin. Virol.35(2),154–159 (2006).
    • 46  Saijo M, Qing T, Niikura M et al. Recombinant nucleoprotein-based enzyme-linked immunosorbent assay for detection of immunoglobulin G antibodies to Crimean–Congo hemorrhagic fever virus. J. Clin. Microbiol.40(5),1587–1591 (2002).
    • 47  Saijo M, Tang Q, Shimayi B et al. Recombinant nucleoprotein-based serological diagnosis of Crimean–Congo hemorrhagic fever virus infections. J. Med. Virol.75(2),295–299 (2005).▪ Application of recombinant CCHFV nucleocapsid protein in diagnostic ELISA.
    • 48  Tang Q, Saijo M, Zhang Y et al. A patient with Crimean–Congo hemorrhagic fever serologically diagnosed by recombinant nucleoprotein-based antibody detection systems. Clin. Diagn. Lab. Immunol.10(3),489–491 (2003).
    • 49  Yu X-J, Liang M-F, Zhang S-Y et al. Fever with thrombocytopenia associated with a novel bunyavirus in China. N. Engl. J. Med.364(16),1523–1532 (2011).
    • 50  Randolph SE, Rigers DJ. Ecology of tick-borne disease and the role of climate. In: Crimean–Congo Haemorrhagic Fever. A Global Perspective. Ergonul O, Whitehouse CA (Eds). Springer, The Netherlands, 167–1186 (2007).
    • 51  Ahmed J, bouloy M, Ergonul O et al. International network for capacity building for the control of emerging viral vector-borne zoonotic diseases: ARBO-ZOONET. Euro. Surveill.14(12),19160 (2009).
    • 52  Bereczky S, Lindegren G, Karlberg H, Akerstrom S, Klingstrom J, Mirazimi A. Crimean–Congo hemorrhagic fever virus infection is lethal for adult type 1 interferon receptor-knockout mice. J. Gen. Virol.91(Pt 6),1473–1477 (2010).
    • 53  Bente DA, Alimonti JB, Shieh W-J et al. Pathogenesis and immune response of Crimean–Congo hemorrhagic fever virus in a STAT-1 knockout mouse model. J. Virol.84(21),11089–11100 (2010).