Comparative pathogenesis of Crimean-Congo hemorrhagic fever and Ebola hemorrhagic fever

Abstract

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 [38]. 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].