Comparative Pathogenesis of Crimean-Congo Hemorrhagic Fever and Ebola Hemorrhagic Fever
Crimean-Congo hemorrhagic fever (CCHF) virus has been called “the Asian Ebola virus” – an epithet that recognizes the close clinical resemblance of CCHF and Ebola hemorrhagic fever (EHF), and also suggests that the two illnesses share similar underlying mechanisms . CCHF and EHF both present difficult challenges to pathophysiology research, because they occur principally in regions lacking a modern medical infrastructure and because the high virulence of their causative agents requires laboratory studies to be performed under Biosafety Level 4 (BSL-4) containment. Efforts to elucidate the pathogenesis of CCHF have been even further handicapped by the failure of the virus to cause disease in laboratory animals other than suckling mice. By contrast, models of EHF in adult mice, guinea pigs, and nonhuman primates have been employed extensively for pathogenesis studies [7, 13, 24]. Detailed examination of clinical and laboratory parameters, pathologic changes, and innate immune responses in cynomolgus macaques over the entire course of fatal EHF has been especially valuable in elucidating how the pathogen overcomes host defenses to cause rapidly overwhelming infection. These findings are leading to novel approaches to postexposure prophylaxis and therapy [10, 14, 20, 35].
KeywordsNitrite Diarrhea Interferon Turkey Alanine
Unable to display preview. Download preview PDF.
- 2.Baize S, Leroy EM, Georges-Courbot MC, Capron M, Lansoud-Soukate J, Debre P, Fisher-Hoch SP, McCormick JB, Georges AJ (1999) Defective humoral responses and extensive intravascular apoptosis are associated with fatal outcome in Ebola virus-infected patients. Nat Med 5:423–426.PubMedCrossRefGoogle Scholar
- 11.Burt FJ, Swanepoel R, Shieh WJ, Smith JF, Leman PA, Greer PW, Coffield LM, Rollin PE, Ksiazek TG, 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. Arch Pathol Lab Med 121:839–846.PubMedGoogle Scholar
- 12.Bwaka MA, Bonnet MJ, Calain P, Colebunders R, De Roo A, Guimard Y, Katwidi DR, Kibadi K, Kipasa MA, Kuvula KJ, Mapanda BB, Massamba M, Mupapa KD, Muyembe-Tamfum JJ, Ndaberey E, Peters CJ, Rollin PE, Van den Enden E (1999) Ebola hemorrhagic fever in Kikwit, Democratic Republic of the Congo: clinical observations in 103 patients. J Infect Dis 179 (Suppl 1):S1–7.PubMedCrossRefGoogle Scholar
- 14.Daddario-DiCaprio KM, Geisbert TW, Stroher U, Geisbert JB, Grolla A, Fritz EA, Fernando L, Kagan E, Jahrling PB, Hensley LE, Jones SM, Feldmann H (2006) Postexposure protection against Marburg haemorrhagic fever with recombinant vesicular stomatitis virus vectors in non-human primates: an efficacy assessment. Lancet 367:1399–1404.PubMedCrossRefGoogle Scholar
- 15.Ergonul O (2006) Crimean-Congo haemorrhagic fever. Lancet Infect Dis 203–214.Google Scholar
- 21.Geisbert TW, Hensley LE, Larsen T, Young HA, Reed DS, Geisbert JB, Scott DP, Kagan E, Jahrling PB, Davis KJ (2003) Pathogenesis of Ebola hemorrhagic fever in cynomolgus macaques: evidence that dendritic cells are early and sustained targets of infection. Am J Pathol 163:2347–2370.PubMedGoogle Scholar
- 31.Joubert JR, King JB, Rossouw DJ, Cooper R (1985) A nosocomial outbreak of Crimean-Congo haemorrhagic fever at Tygerberg Hospital. Part III. Clinical pathology and pathogenesis. S Afr Med J 68:722–728.Google Scholar
- 33.Ksiazek TG, Rollin PE, Williams AJ, Bressler DS, Martin ML, Swanepoel R, Burt FJ, Leman PA, Khan AS, Rowe AK, Mukunu R, Sanchez A, Peters CJ (1999) Clinical virology of Ebola hemorrhagic fever (EHF): virus, virus antigen, and IgG and IgM antibody findings among EHF patients in Kikwit, Democratic Republic of the Congo, 1995. J Infect Dis 179 (Suppl 1):S177–187.Google Scholar
- 38.Sanchez A, Lukwiya M, Bausch D, Mahanty S, Sanchez AJ, Wagoner KD, Rollin PE (2004) Analysis of human peripheral blood samples from fatal and nonfatal cases of Ebola (Sudan) hemorrhagic fever: cellular responses, virus load, and nitric oxide levels. J Virol 78:10370–10377.PubMedCrossRefGoogle Scholar
- 40.van Eeden PJ, Joubert JR, van de Wal BW, King JB, de Kock A, Groenewald JH (1985) A nosocomial outbreak of Crimean-Congo haemorrhagic fever at Tygerberg Hospital. Part I. Clinical features. S Afr Med J 68:711–717.Google Scholar
- 41.Villinger F, Rollin PE, Brar SS, Chikkala NF, Winter J, Sundstrom JB, Zaki SR, Swanepoel R, Ansari AA, Peters CJ (1999) Markedly elevated levels of interferon (IFN)–gamma, IFN-alpha, interleukin (IL)–2, IL–10, and tumor necrosis factor-alpha associated with fatal Ebola virus infection. J Infect Dis 179 (Suppl 1):S188–191.PubMedCrossRefGoogle Scholar