Crimean-Congo hemorrhagic fever: History, epidemiology, pathogenesis, clinical syndrome and genetic diversity

Abstract

Bente, Dennis A.; Forrester, Naomi L.; Watts, Douglas M.; McAuley, Alexander J.; Whitehouse, Chris A.; and Bray, Mike, "CrimeanCongo hemorrhagic fever: History, epidemiology, pathogenesis, clinical syndrome and genetic diversity" (2013 b s t r a c tCrimean-Congo hemorrhagic fever (CCHF) is the most important tick-borne viral disease of humans, causing sporadic cases or outbreaks of severe illness across a huge geographic area, from western China to the Middle East and southeastern Europe and throughout most of Africa. CCHFV is maintained in vertical and horizontal transmission cycles involving ixodid ticks and a variety of wild and domestic vertebrates, which do not show signs of illness. The virus circulates in a number of tick genera, but Hyalomma ticks are the principal source of human infection, probably because both immature and adult forms actively seek hosts for the blood meals required at each stage of maturation. CCHF occurs most frequently among agricultural workers following the bite of an infected tick, and to a lesser extent among slaughterhouse workers exposed to the blood and tissues of infected livestock and medical personnel through contact with the body fluids of infected patients. CCHFV is the most genetically diverse of the arboviruses, with nucleotide sequence differences among isolates ranging from 20% for the viral S segment to 31% for the M segment. Viruses with diverse sequences can be found within the same geographic area, while closely related viruses have been isolated in far distant regions, suggesting that widespread dispersion of CCHFV has occurred at times in the past, possibly by ticks carried on migratory birds or through the international livestock trade. Reassortment among genome segments during co-infection of ticks or vertebrates appears to have played an important role in generating diversity, and represents a potential future source of novel viruses. In this article, we first review current knowledge of CCHFV, summarizing its molecular biology, maintenance and transmission, epidemiology and geographic range. We also include an extensive discussion of CCHFV genetic diversity, including maps of the range of the virus with superimposed phylogenetic trees. We then review the features of CCHF, including the clinical syndrome, diagnosis, treatment, pathogenesis, vaccine development and laboratory animal models of CCHF. The paper ends with a discussion of the possible future geographic range of the virus. For the benefit of researchers, we include a Supplementary Table listing all published reports of CCHF cases and outbreaks in the English-language literature, plus some principal articles in other languages, with total case numbers, case fatality rates and all CCHFV strains on GenBank.

Cutaneous Findings of Crimean-Congo Hemorrhagic Fever: a Study of 269 Cases

“…Despite these data, it remains unclear how tick-induced changes at the tick-dermal interface permeability, resulting in hypotension, shock, multiple organ failure and death (22)(23)(24)(25). The proinflammatory cytokines may be the reason for the CCHF dermatological signs (morbilliform eruptions, petechial lesions, purpura, ecchymosis and oral erythema-petechiae), and they are secreted after endothelial injury.…”

Ectoparasitic Viral Zoonoses in the Southern African Context

“…However the majority of patients deteriorate clinically and haemorrhagic manifestations start to present within 3-5 days after the onset of the illness [29]. Recovery can occur after 9-10 days from when the symptoms started but at least 30% of patients die within the second week after onset of the illness [29]. Clinical pathology during the first five days of illness can be summarised as follows:…”

Biosafety standards for working with Crimean-Congo hemorrhagic fever virus

“…Observed case fatality rates (CFRs) in CCHF vary from 2 to 30 % and are influenced by efficiency of diagnosis, cohort size sampled and speed of clinical intervention (Bente et al, 2013;Ince et al, 2014). Reported CFRs include 25 % from South Africa (Burt, 2015), 26 % from Kosovo (Humolli, 2015) and 15 % from Iran and Bulgaria (Sadegh, 2015;Christova, 2015).…”

“…Crimean-Congo hemorrhagic fever virus (CCHFV), a member of the genus Nairovirus of the family Bunyaviridae, causes a tick-borne zoonotic infection [Crimean-Congo haemorrhagic fever (CCHF)] in parts of Africa and Eurasia (Bente et al, 2013). CCHFV has been classified as a hazard group 4 pathogen (UK) or risk group 4 (Europe, USA, international) in countries that have promulgated biosafety regulations, and should accordingly be handled in containment level 4 (CL-4, UK) or biosafety level 4 (BSL-4, Europe, USA, international) laboratories (Table 1).…”