Molecular epidemiology of Crimean–Congo hemorrhagic fever in Bulgaria—An update

Abstract

Crimean-Congo hemorrhagic fever (CCHF) is endemic in Bulgaria. During 2013-2014, 11 confirmed CCHF cases have been reported in the country (seven in 2013 and four in 2014). The present study provides the CCHF molecular epidemiology in Bulgaria based on all currently available S, M, and L RNA segment nucleotide sequences spanning the years 1978-2014. A relatively low genetic difference (0-6%, the maximum seen in the M RNA segment) was seen among the CCHFV sequences suggesting that a slow evolving CCHFV strain belonging to "Europe 1" clade is present in Bulgaria. Although the virus emerged in new foci during the recent years, it is more active in the established endemic foci which seem to offer the most suitable ecosystem and environment. Understanding the CCHF epidemiology and virus evolution is the basis for public health programs and vaccine design.

Development of vaccines against Crimean-Congo haemorrhagic fever virus

“…Data from the Bulgarian Ministry of Health suggest a fourfold reduction in reported CCHF cases over a 22 year time period (1953–1974: 1105 cases; 1975–1996, 279 cases) [61]. Unfortunately, however, this was the extent of the efficacy studies at the time and while there has been a reduction in cases, data indicates that this may not necessarily be the result of the vaccine but due to a multitude of factors which have decreased tick exposure in the region per se [62]. In addition, there is a lack of data regarding the incidence of CCHF in the same time frame in neighbouring countries, which also brings into question the analysis of vaccine efficacy at the time [63].…”

Immunization with DNA Plasmids Coding for Crimean-Congo Hemorrhagic Fever Virus Capsid and Envelope Proteins and/or Virus-Like Particles Induces Protection and Survival in Challenged Mice

“…Since 1974 it has been used to immunize mainly military and medical personnel, farmers, and persons living or working in regions of endemicity. A 4-fold reduction in the number of reported Crimean-Congo hemorrhagic fever cases in Bulgaria has been observed over a 21-year period following initiation of vaccination (8, 9). A recent study found that this vaccine elicited both a cellular and humoral response to CCHFV (9), but neutralizing antibody titers were low, even in individuals that who had received four doses (3, 7).…”

“…A 4-fold reduction in the number of reported Crimean-Congo hemorrhagic fever cases in Bulgaria has been observed over a 21-year period following initiation of vaccination (8, 9). A recent study found that this vaccine elicited both a cellular and humoral response to CCHFV (9), but neutralizing antibody titers were low, even in individuals that who had received four doses (3, 7). Controlled studies on protective efficacy have not been reported with this vaccine, and, due to its crude preparation, it is unlikely to gain widespread international regulatory approval.…”

MicroRNA expression profiles in patients with acute Crimean Congo hemorrhagic fever reveal possible adjustments to cellular pathways

“…Expression of hsa‐miR‐451 also increases PBMCs infected with Dengue virus serotype 2, with a concomitant elevation of proinflammatory cytokines such as CCL5, IL‐6, and IL‐8 [Qi et al, ]. These findings correlate with the cytokine profiles observed in individuals with CCHF [Papa et al, , ], as well as in Hantavirus‐induced hemorrhagic fever with renal syndrome (HFRS) [Kyriakidis and Papa, ]. A similar cytokine imbalance is associated with disease progression and occurs during viral hemorrhagic fevers, regardless of the etiologic agent.…”