title: Immunohistochemical and in situ localization of Crimean-Congo hemorrhagic fever (CCHF) virus in human tissues and implications for CCHF pathogenesis.
abstract: BACKGROUND
  Crimean-Congo hemorrhagic fever (CCHF) is a potentially fatal disease that occurs in parts of Africa, Asia, and eastern Europe, and that is caused by a recently emerged bunyavirus. Rapid laboratory diagnosis of CCHF infection is essential and is currently performed by virus isolation and serology. Histopathologic studies have been limited to a small number of cases, and little is known about the cellular tropism of CCHF virus and the pathogenesis of this disease.
  
  
  METHODS
  We conducted a retrospective case analysis of 12 patients with a diagnosis of CCHF infection, confirmed by virus isolation, who were evaluated at the Special Pathogens Unit, National Institute for Virology, South Africa. The clinicopathologic features of CCHF and the diagnostic role of virus isolation as compared with serology, immunohistochemistry, and in situ hybridization were evaluated. Additionally, the distribution of CCHF virus in human tissues was examined.
  
  
  RESULTS
  The clinical and histopathologic features of CCHF resemble those of other viral hemorrhagic fevers. Of the 12 patients with virus isolation-confirmed CCHF infection, 5 were positive by serology, 10 by immunohistochemistry, and 5 by in situ hybridization. Immunohistochemistry and in situ hybridization analyses showed that the mononuclear phagocytes, endothelial cells, and hepatocytes are main targets of infection. Association of parenchymal necrosis in liver with viral infection suggests that cell damage may be mediated by a direct viral cytopathic effect.
  
  
  CONCLUSIONS
  The diagnosis of CCHF, suspected by history and clinical features, can be supported histopathologically. However, since the pathologic features resemble those of other viral hemorrhagic fevers, an unequivocal diagnosis can be made only by laboratory tests. The utility of immunohistochemistry as a sensitive and rapid diagnostic modality was established by the high degree of concordance with virus isolation. Infection of mononuclear phagocytes, endothelial cells, and hepatocytes may play a critical role in the pathogenesis of CCHF.
authors.affiliation: Department of Virology, University of the Witwatersrand, Sandringham, South Africa.
authors.forename: F J
authors.initials: FJ
authors.lastname: Burt
authors.forename: R
authors.initials: R
authors.lastname: Swanepoel
authors.forename: W J
authors.initials: WJ
authors.lastname: Shieh
authors.forename: J F
authors.initials: JF
authors.lastname: Smith
authors.forename: P A
authors.initials: PA
authors.lastname: Leman
authors.forename: P W
authors.initials: PW
authors.lastname: Greer
authors.forename: L M
authors.initials: LM
authors.lastname: Coffield
authors.forename: P E
authors.initials: PE
authors.lastname: Rollin
authors.forename: T G
authors.initials: TG
authors.lastname: Ksiazek
authors.forename: C J
authors.initials: CJ
authors.lastname: Peters
authors.forename: S R
authors.initials: SR
authors.lastname: Zaki
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000914:Antibodies, Viral / Q000276:immunology; D000956:Antigens, Viral / Q000032:analysis; D001483:Base Sequence; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D003225:Hemorrhagic Fever Virus, Crimean-Congo / Q000276:immunology / Q000302:isolation & purification*; D006479:Hemorrhagic Fever, Crimean / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007422:Intestines / Q000276:immunology / Q000473:pathology / Q000821:virology; D008099:Liver / Q000276:immunology / Q000473:pathology / Q000821:virology*; D008168:Lung / Q000276:immunology / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D015347:RNA Probes; D012189:Retrospective Studies; D013154:Spleen / Q000276:immunology / Q000473:pathology / Q000821:virology
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D017931:DNA Primers; D015347:RNA Probes