Crimean-Congo hemorrhagic fever: epidemiological trends and controversies in treatment
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COMMENTARY
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Crimean-Congo hemorrhagic fever: epidemiological trends and controversies in treatment Helena C Maltezou1* and Anna Papa2
Abstract Crimean-Congo hemorrhagic fever (CCHF) virus has the widest geographic range of all tick-borne viruses and is endemic in more than 30 countries in Eurasia and Africa. Over the past decade, new foci have emerged or re-emerged in the Balkans and neighboring areas. Here we discuss the factors influencing CCHF incidence and focus on the main issue of the use of ribavirin for treating this infection. Given the dynamics of CCHF emergence in the past decade, development of new anti-viral drugs and a vaccine is urgently needed to treat and prevent this acute, life-threatening disease. Background Crimean-Congo hemorrhagic fever (CCHF) is an acute, highly-contagious and life-threatening disease caused by a nairovirus of the Bunyaviridae family [1-3]. CCHF was probably described by a physician in Tajikistan in 1100 AD in a patient with hemorrhagic manifestations [2]. In recent times, the disease was first recognized during an outbreak in Crimea in 1944, however, later it became evident that the causative agent was identical to a virus isolated from a patient in Congo in 1956, and the name CCHF was adopted [4]. CCHF virus (CCHFV) circulates in nature in a tick-vertebrate-tick cycle, mainly among cattle, sheep, goats, and hares. The infection is transmitted to humans primarily by ticks of the genus Hyalomma, but also through direct contact with blood or tissues of viremic patients or animals [1,2]. Typical CCHF progresses rapidly with high fever, malaise, severe headache, and gastrointestinal symptoms. CCHF is confirmed either by detection of specific immunoglobulin M antibodies or a four-fold increase of immunoglobulin G titers using enzyme-linked immunoassays, indirect immunofluorescent assays, or
through reverse transcriptase-polymerase chain reaction and microarray techniques [1,5,6]. Prominent hemorrhages may occur at a late stage of disease, with case fatality rates ranging from 5% to 50%. CCHF is a disease of immediate notification to public health authorities because of the potential of nosocomial outbreaks [7-10] and use in bioterrorism [11]. CCHFV has the widest geographic range among all tickborne viruses, being endemic in more than 30 countries in Eurasia and Africa [1,5]. CCHF activity has increased over the past decade and new foci have emerged in several Balkan countries, as well as in neighboring areas (Figure 1) [5,8,12-15]. In a serosurvey conducted in Northeastern Greece after the first human case occurred in June 2008, seroprevalence rates up to 5% were found in well-confined areas compared with 0% found in the same areas 20 years ago [16], suggesting recent introduction of the virus. After almost three decades, CCHF re-emerged in southwest Russia in 1999, with hundreds of cases being reported since then [17]. An essential factor of the CCHF re-emergence in Russia was a rise in the number of Hyalomma marginatum ticks [18]. Enzootic circulation of the CC
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