Immunohistochemical and in situ localization of Crimean-Congo hemorrhagic fever (CCHF) virus in human tissues and implications for CCHF pathogenesis

J. Butt, Robert Swanepoel, Wun Ju Shieh, Jonathan F. Smith, A. Leman, W. Greer, Lisa M. Coffield, Pierre E. Rollin, Thomas Ksiazek, Clarence J. Peters, Sherif R. Zaki

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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. Design. - 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 imrnunohistochemistry, and 5 by in situ hybridization. Immunohistochemistry and in situ hybridization analyses showed that the munonuclear 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 vital 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.

Original languageEnglish (US)
Pages (from-to)839-846
Number of pages8
JournalArchives of Pathology and Laboratory Medicine
Volume121
Issue number8
StatePublished - 1997
Externally publishedYes

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Crimean-Congo hemorrhagic fever virus
Crimean Hemorrhagic Fever
Congo
Virus Diseases
Serology
Viruses
In Situ Hybridization
Immunohistochemistry
Phagocytes
Infection
Hepatocytes
Viral Cytopathogenic Effect
Viral Hemorrhagic Fevers
Endothelial Cells
Orthobunyavirus
Eastern Europe
Virology
Tropism
Clinical Laboratory Techniques
South Africa

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Medical Laboratory Technology

Cite this

Immunohistochemical and in situ localization of Crimean-Congo hemorrhagic fever (CCHF) virus in human tissues and implications for CCHF pathogenesis. / Butt, J.; Swanepoel, Robert; Shieh, Wun Ju; Smith, Jonathan F.; Leman, A.; Greer, W.; Coffield, Lisa M.; Rollin, Pierre E.; Ksiazek, Thomas; Peters, Clarence J.; Zaki, Sherif R.

In: Archives of Pathology and Laboratory Medicine, Vol. 121, No. 8, 1997, p. 839-846.

Research output: Contribution to journalArticle

Butt, J, Swanepoel, R, Shieh, WJ, Smith, JF, Leman, A, Greer, W, Coffield, LM, Rollin, PE, Ksiazek, T, Peters, CJ & Zaki, SR 1997, 'Immunohistochemical and in situ localization of Crimean-Congo hemorrhagic fever (CCHF) virus in human tissues and implications for CCHF pathogenesis', Archives of Pathology and Laboratory Medicine, vol. 121, no. 8, pp. 839-846.
Butt, J. ; Swanepoel, Robert ; Shieh, Wun Ju ; Smith, Jonathan F. ; Leman, A. ; Greer, W. ; Coffield, Lisa M. ; Rollin, Pierre E. ; Ksiazek, Thomas ; Peters, Clarence J. ; Zaki, Sherif R. / Immunohistochemical and in situ localization of Crimean-Congo hemorrhagic fever (CCHF) virus in human tissues and implications for CCHF pathogenesis. In: Archives of Pathology and Laboratory Medicine. 1997 ; Vol. 121, No. 8. pp. 839-846.
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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. Design. - 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 imrnunohistochemistry, and 5 by in situ hybridization. Immunohistochemistry and in situ hybridization analyses showed that the munonuclear 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 vital 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.",
author = "J. Butt and Robert Swanepoel and Shieh, {Wun Ju} and Smith, {Jonathan F.} and A. Leman and W. Greer and Coffield, {Lisa M.} and Rollin, {Pierre E.} and Thomas Ksiazek and Peters, {Clarence J.} and Zaki, {Sherif R.}",
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T1 - Immunohistochemical and in situ localization of Crimean-Congo hemorrhagic fever (CCHF) virus in human tissues and implications for CCHF pathogenesis

AU - Butt, J.

AU - Swanepoel, Robert

AU - Shieh, Wun Ju

AU - Smith, Jonathan F.

AU - Leman, A.

AU - Greer, W.

AU - Coffield, Lisa M.

AU - Rollin, Pierre E.

AU - Ksiazek, Thomas

AU - Peters, Clarence J.

AU - Zaki, Sherif R.

PY - 1997

Y1 - 1997

N2 - 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. Design. - 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 imrnunohistochemistry, and 5 by in situ hybridization. Immunohistochemistry and in situ hybridization analyses showed that the munonuclear 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 vital 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.

AB - 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. Design. - 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 imrnunohistochemistry, and 5 by in situ hybridization. Immunohistochemistry and in situ hybridization analyses showed that the munonuclear 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 vital 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.

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