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New geographical area on the map of Crimean-Congo hemorrhagic fever virus: First serological evidence in the Hungarian population
Abstract
Crimean-Congo hemorrhagic fever (CCHF) is an emerging tick-borne disease that is endemic in Africa, Asia, the Middle East, and the Balkan region of Europe; the disease is spreading northwards following widespread distribution of the main vector, Hyalomma marginatum, which was first found in Hungary in 2011. The aim of this pilot sero-surveillance study was to assess CCHF seroprevalence in Hungary. A total of 2700 serum samples obtained from healthy volunteer blood donors were screened using an in-house immunofluorescence assay and a commercially available ELISA kit. We found ten (0.37 %) seropositive donors. The western and central regions proved to be the most affected areas, with a prevalence of 2.97 %. Higher positivity was found among male donors (0.55 %) and younger donors (18–34 years; 0.78 %). Based on these results, a more extended surveillance focusing on specific at-risk populations and animals is advised. The results should also raise the awareness of clinicians and other high-risk populations, such as foresters and hunters, about the emerging threat of CCHF in Hungary.
... High-risk occupations for CCHFV infection include veterinarians, farmers, foresters, hunters, and abattoir workers who are in close proximity to livestock or can acquire tick bites [25]. In Hungary, CCHFV seropositivity has been detected in the last decade, both among animals (rodents and brown hares) and in the general human population [27][28][29]. CCHFV seroprevalence among animals is also increasing in neighboring countries, such as Romania and the Balkan states south of Hungary, where CCHFV is an endemic pathogen [21,[30][31][32]. ...
... HM452307.1) were produced in Vero E6 cells and validated at the National Biosafety Laboratory, as previously described [29]. Individual serum samples were diluted in 1:20 in phosphate-buffered saline (PBS), added to IIFA slides, and incubated for 1 h at 37 • C. ...
... According to the latest technical report published by the European Centre for Disease Prevention and Control in December 2023, and based on vector presence and serological . Red dots represent data from a previous study with identified CCHFV seropositive human blood donors [29]. Blue squares show historical data on the identification of Hyalomma spp. ...
(1) Background: Crimean–Congo hemorrhagic fever (CCHF) is an emerging tick-borne disease endemic in Africa, Asia, the Middle East, and the Balkan and Mediterranean regions of Europe. Although no human CCHF cases have been reported, based on vector presence, serological evidence among small vertebrates, and the general human population, Hungary lies within high evidence consensus for potential CCHF introduction and future human infection. Thus, the aim of our pilot serosurvey was to assess CCHF seropositivity among cattle and sheep as indicator animals for virus circulation in the country. (2) Methods: In total, 1905 serum samples taken from free-range cattle and sheep in 2017 were tested for the presence of anti-CCHF virus IgG antibodies using commercial ELISA and commercial and in-house immunofluorescent assays. (3) Results: We found a total of eleven reactive samples (0.58%) from five administrative districts of Hungary comprising 8 cattle and 3 sheep. The most affected regions were the south–central and northwestern parts of the country. (4) Conclusions: Based on these results, more extended surveillance is advised, especially in the affected areas, and there should be greater awareness among clinicians and other high-risk populations of the emerging threat of CCHF in Hungary and Central Europe.
... Three Hy. rufipes nymphs were reported from a common whitethroat (Sylvia communis) in another study (Hornok et al., 2016). The presence of antibodies against CCHFV has also been detected in Hungarian hares (Lepus europaeus) (Németh et al., 2013), rodents (Földes et al., 2019) and recently in humans as well (Magyar et al., 2021). ...
... rufipes nymphs from a common whitethroat (Sylvia communis) in 2014 (Hornok et al., 2013;Hornok et al., 2016). Red crosses indicate origin of CCHFV seropositive blood donors collected between 2008 and 2017 (Magyar et al., 2021). Red dots indicate the origin of the two Hyalomma specimens of the present study where D. reticulatus is the most common species of this genus (Földvári et al., 2016), the above study detected only D. marginatus. ...
... ). There was also a reported human case of CCHF with unknown origin in 2004(Országos Epidemiológiai Központ, 2008) and CCHFV seropositives were detected in 12 healthy blood donors collected between 2008 and 2017(Magyar et al., 2021). All these data indicate that CCHFV might be transmitted by tick species other than Hyalomma spp. ...
Hyalomma ticks are important vectors of Crimean‐Congo Haemorrhagic Fever Virus (CCHFV) and other pathogens. They are frequently carried as immatures from Africa, the Middle East and Mediterranean areas to temperate Europe via migratory birds and emergence of adults has been reported in many countries where it has so far been considered non‐endemic. This study aimed to implement the first steps of the DAMA (Document, Assess, Monitor, Act) protocol by monitoring the potential arrival of adult Hyalomma ticks in Hungary applying citizen‐science methods. Ticks were collected from April to December 2021 by asking volunteer participants through a self‐made website to look for large, quickly moving, striped‐legged hard ticks on themselves, their pets and livestock. Owing to an intensive media campaign, the project website had more than 31,000 visitors within seven months; 137 specimens and several hundred photos of hard ticks were submitted by citizen scientists from all over the country. Beside Ixodes ricinus, Dermacentor reticulatus, Dermacentor marginatus and Haemaphysalis inermis, a specimen from a dog was morphologically identified as a male Hyalomma marginatum and another removed from a cow as a male Hyalomma rufipes. The dog and the cow had never been abroad, lived approximately 280 km apart, so the two Hyalomma observations can be considered separate introductions. Amplification of the partial mitochondrial cytochrome C oxidase subunit I gene was successfully run for both specimens. Sequencing confirmed morphological identification for both ticks. Based on the phylogenetic analyses, the Hy. marginatum individual most likely belongs to the Eurasian population and the Hy. rufipes tick to a clade of mixed sequences from Europe and Africa. We summarize the scattered historical reports about the occurrence of Hyalomma ticks and CCHFV in Hungary. Our data highlight the effectiveness of citizens science programmes in the monitoring and risk assessment of CCHFV emergence and preparedness in the study area. This article is protected by copyright. All rights reserved
... Azerbajian and Hungary are countries in the WHO European region that despite having positive human seroprevalence studies (as reported by Blair et al. [61,91]) have never reported clinical cases of CCHF. ...
Background: The World Health Organization has identified Crimean-Congo hemorrhagic fever (CCHF) as a priority disease for research and development in emergency contexts. The epidemiology of CCHF is evolving and this review highlights travel-associated cases and focuses on the need for a One Health approach in Europe. Methods: For this narrative review, two searches were performed in PubMed and Google Scholar for the period 1980-October 2024. The first search identified travel-associated CCHF cases globally, additional cases were identified in the ProMED mail database and through healthmap.org. The second search, with a focus on the European region, aimed to analyse reports of CCHF virus (CCHFV) detected in ticks, CCHF seroprevalence studies in animals and/or humans, and autochthonous CCHF cases. Results: Seventeen cases of imported CCHF, the majority acquired in Africa, were identified. Importation to European countries accounted for eight of the cases. Most patients presented with fever and hemorrhagic manifestations and the estimated case fatality rate was 35 %. In the WHO European region, at least 13 countries have reported ticks infected with different genotypes of CCHFV; 17 countries were found to have animals/ humans with positive CCHF serology. Finally, 16 countries in the WHO European region have notified human cases of CCHF. The Russian Federation, Turkey, and several former USSR countries are considered highly endemic, followed by the Balkanic region, with sporadic cases emerging in Bulgaria, Greece, Spain, and recently Portugal. Conclusions: Travel-associated CCHF is infrequent. However, given the recently reported increased geographical distribution in ticks and animals in the European region, additional human cases may be anticipated in the near future. Europe receives over half of all international tourist arrivals annually, so healthcare professionals should be aware of risk factors and current protocols for the management of suspected and confirmed cases.
... During the last decades, CCHF outbreaks in humans have been reported in eastern and south-eastern Europe, especially in Albania [4], Kosovo ‡ [5] and Bulgaria [6]. Alongside human cases, there have been reports of seropositivity among wild animals and humans in the region, extending as far north to Hungary [7][8][9] and Romania [10] Although several tick species are capable to act as vectors for CCHFV, ticks of the genus Hyalomma are the primary vectors of concern since they are highly adapted for virus maintenance and transmission of multiple CCHFV genotypes, acting as both a vector and a reservoir [2,11]. As Hyalomma ticks are emerging and spreading in Europe, there is a high risk of CCHF emergence and re-emergence across the continent, influenced by multiple factors such as climate or human behaviour [12,13]. ...
Background
Crimean–Congo haemorrhagic fever (CCHF) is a severe illness characterised by fever, bleeding and high case-fatality rates. The disease is caused by CCHF virus (CCHFV), transmitted by ticks and infectious body fluids and tissues.
Aim
After CCHF was diagnosed in three persons in 2023, we aimed to investigate the presence of antibodies against CCHFV in healthcare workers (HCW), sheep and goats, and of CCHFV in ticks, in an area in North Macedonia and characterise virus strains.
Methods
In 2023, we collected blood samples from HCWs involved in treating CCHF patients and sera and ticks from sheep and goats in the village in North Macedonia where the index case resided. The blood samples were analysed by ELISA. Ticks were tested for presence of CCHFV, and the virus from a CCHF case was sequenced.
Results
Samples from four of 52 HCWs and 10 of 17 small ruminants had antibodies against CCHFV. The virus was not detected from any of the 24 Rhipicephalus bursa ticks. The virus strain from the index case clustered with regional strains within the Europe-1 lineage (genotype V) group and was closest to strains from Kosovo‡.
Conclusion
This report shows CCHFV is endemic in North Macedonia. Raising awareness of the risk factors and educating people about the measures they can take to reduce exposure to the virus is important. Healthcare workers need to be aware of the disease. Early detection, robust diagnostic methods, surveillance and collaborative efforts are necessary to prevent and control CCHF in the affected regions.
... Locally acquired immatures of Hy. ru pes were recently found on birds in the country raising the possibility of a local population [11]. Additionally, there is evidence that both humans [12] and animals [13; 14] have antibodies against the CCHFV virus. ...
Hyalomma marginatum , a vector for the high-consequence pathogen, the Crimean–Congo hemorrhagic fever virus (CCHFV), needs particular attention due to its impact on public health. Although it is a known vector for CCHFV, its general virome is largely unexplored. Here, we report findings from a citizen science monitoring program aimed to understand the prevalence and diversity of tick-borne pathogens, particularly focusing on Hyalomma ticks in Hungary. In 2021, we identified one adult specimen of Hyalomma marginatum and subjected it to Illumina-based viral metagenomic sequencing. Our analysis revealed sequences of the uncharacterized Volzhskoe tick virus, an unclassified member of the Bunyavirales order. The in silico analysis uncovered key genetic regions, including the glycoprotein and the RNA-dependent RNA polymerase (RdRp) coding regions. Phylogenetic analysis indicated a close relationship between our Volzhskoe tick virus sequences and other unclassified Bunyavirales species. These related species of unclassified Bunyavirales were detected in vastly different geolocations. These findings highlight the remarkable diversity of tick specific viruses and emphasize the need for further research to understand the transmissibility, seroreactivity or the potential pathogenicity of Volzhskoe tick virus and related species.
... During the last decades, territories of Eastern and Southeastern Europe were a hotspot for CCHFV with multiple and regular human outbreaks, especially in Albania [4], Kosovo* [5] and Bulgaria [6]. Alongside human cases, there have been reports of seropositivity among wild animals and humans in the region, extending as far north to Hungary [7][8][9] and Romania [10] Altough several tick species are capable to act as a vector for CCHFV, genus Hyalomma is identi ed as biggest public health threat since it is highly adapted for virus maintanence and transmission of multiple CCHFV genotypes, acting as a vector and reservoir in the same time [2,11]. Due to expanding presence of Hyalomma tick species in Europe, there is a high risk of CCHF emergence and re-emergence across the continent, in uenced by multiple factors such as climate or human behaviour [12,13]. ...
Crimean-Congo Hemorrhagic Fever (CCHF) is a severe illness transmitted by ticks and infectious body fluids, characterized by fever, hemorrhagic syndrome, and high fatality rates. This study investigates the recent outbreak of CCHF in North Macedonia, where cases had not been reported for over 50 years, aiming to elucidate factors contributing to its re-emergence and inform public health strategies.
Through a multidisciplinary approach encompassing epidemiological, clinical, and molecular analyses, we garnered pivotal insights into the outbreak dynamics. Centralized in Kuchica village, our serosurveys conducted among local livestock populations disclosed a significant rate of CCHFV exposure, which underlines the urgent necessity for persistent monitoring of the virus's circulation. The phylogenetic analysis distinctly pointed to the autochthonous nature of the CCHFV Hoti strain implicated in the outbreak. This local strain circulation may be influenced by ecological changes, probably climate change, which is likely altering tick distribution, activity patterns and the extrinsic incubation of the virus in North Macedonia.
This report underscores the importance of clinical vigilance, proactive surveillance, early detection, and collaborative efforts in combating emerging infectious diseases like CCHF. By prioritizing monitoring, risk assessment, and preparedness measures, we can effectively mitigate the impact of CCHF and protect public health in affected regions.
... (Gargili et al., 2017). Areas where the virus has been shown to circulate include regions in Africa, the middle East, southern Asia as well as countries in Eastern and Southern Europe such as Spain, where autochthonous human cases of CCHF have been reported since 2013 (Febrer-Sendra et al., 2023;Hoogstraal, 1979;Lorenzo Juanes et al., 2023;Magyar et al., 2021;Messina et al., 2015;Negredo et al., 2017). In addition, global warming is largely discussed to contribute to the spread of this tick species to new areas, e.g. ...
... 4). In einer Seroprävalenzstudie an gesunden Blutspendern aus Ungarn wurde eine CCHF-Seropositivität von 0,37 % detektiert (2,97 % in den westlichen und zentralen Regionen des Landes) [42]. Seit dem sehr warmen Jahr 2018 wurde eine zunehmende Anzahl von Exemplaren der Spezies H. marginatum und H. rufipes (ebenfalls ein CCHFV-Vektor) in mehreren Teilen Deutschlands gefunden [43,44]. ...
ZUSAMMENFASSUNG
Die zunehmenden Auswirkungen des Klimawandels und globaler Umweltveränderungen haben erhebliche Konsequenzen für das Infektionsrisiko von vektorübertragenen Erkrankungen. Dies wirkt sich insbesondere auch auf die temperaturabhängige Aktivität und das Vorkommen von Zecken in Europa aus. Veränderungen in den Verbreitungsgebieten der Vektoren, verbunden mit einem gesteigerten Übertragungsrisiko durch verhaltensbedingte Faktoren, führen zu einem Anstieg der durch Zecken übertragenen Erkrankungen, darunter Borreliose, Frühsommer-Meningoenzephalitis (FSME) und Tularämie. Insbesondere steigende Temperaturen und eine Zunahme der Luftfeuchtigkeit begünstigen die Vermehrung von Zecken. Vor diesem Hintergrund ist eine verstärkte Implementierung von Präventions- und Überwachungsmaßnahmen im Kontext zeckenübertragener Infektionskrankheiten von entscheidender Bedeutung.
... However, our model predicted its distribution across all countries in Central Europe and provided strong evidence for extensive medium to very high suitability in Germany, Poland, Hungary, and the Czech Republic, followed by Austria and Slovakia. A recent study conducted in Hungary revealed seropositivity for CCHF, indicating that Hungary could be a novel geographical region for the distribution of CCHFV [71]. Sporadic records of H. marginatum in other central European countries, apart from Hungary, indicate potential breeding habitats for this tick vector. ...
Crimean-Congo haemorrhagic fever (CCHF) is the most widely distributed tick-borne viral disease in humans and is caused by the Crimean-Congo haemorrhagic fever virus (CCHFV). The virus has a broader distribution, expanding from western China and South Asia to the Middle East, southeast Europe, and Africa. The historical known distribution of the CCHFV vector Hyalomma marginatum in Europe includes most of the Mediterranean and the Balkan countries, Ukraine, and southern Russia. Further expansion of its potential distribution may have occurred in and out of the Mediterranean region. This study updated the distributional map of the principal vector of CCHFV, H. marginatum, in the Old World using an ecological niche modeling approach based on occurrence records from the Global Biodiversity Information Facility (GBIF) and a set of covariates. The model predicted higher suitability of H. marginatum occurrences in diverse regions of Africa and Asia. Furthermore, the model estimated the environmental suitability of H. marginatum across Europe. On a continental scale, the model anticipated a widespread potential distribution encompassing the southern, western, central, and eastern parts of Europe, reaching as far north as the southern regions of Scandinavian countries. The distribution of H. marginatum also covered countries across Central Europe where the species is not autochthonous. All models were statistically robust and performed better than random expectations (p < 0.001). Based on the model results, climatic conditions could hamper the successful overwintering of H. marginatum and their survival as adults in many regions of the Old World. Regular updates of the models are still required to continually assess the areas at risk using up-to-date occurrence and climatic data in present-day and future conditions.
... Crimean-Congo hemorrhagic fever (CCHF) is an emerging highly contagious, tick-borne, potentially fatal disease with a case fatality rate of up to 30% (Ma and Hamza, 2021;Monsalve-Arteaga et al., 2020). The causative agent of this viral infection is the Crimean-Congo hemorrhagic fever virus (CCHFV), an enveloped RNA virus of the genus Orthonairovirus in the family Nairoviridae (Balinandi et al., 2022;Magyar et al., 2021;Nasirian, 2020). Although CCHFV infection in animals is generally asymptomatic, animal-to-human transmission occurs through infected blood or body fluids, which has raised public concern at the human-animal interface, especially for farmers, herders, veterinarians, hunters, butchers, and merchants involved in the above-mentioned sectors of activity. ...
... The virus is circulating among small ruminants in Bosnia and Hercegovina and Romania [11,12]. Additionally, there are reports of the emergence of Hyalomma marginatum and Hyalomma rufipes, ticks known to carry CCHFV in Hungary, along with human exposure to the virus [13,14]. ...
The last report of Crimean-Congo haemorrhagic fever (CCHF) in North Macedonia was more than 50 years ago in the northwest. We report on a fatal CCHF case following a Hyalomma tick bite in the east of the country in July 2023. Tracing of 67 contacts identified CCHF in one healthcare worker (HCW) providing care for the patient. Monitoring of contacts is concluded (including further 11 HCW contacts), thus far 28 days after the death of the case no additional cases were identified.
... [15][16][17][18] Of the WHO blueprint priority pathogens, 19,20 CCHFV covers one of the vastest geographic ranges 5,21,22 due to tick reservoirs and climate change facilitating further spread of the Hyalomma genus ticks. 23,24 There remain no approved targeted treatments for CCHF, though the nucleoside analogue drug ribavirin is sometimes given despite its questioned clinical efficacy. [25][26][27][28] Similarly, at present there is a single vaccine against CCHFV which has limited licensure in Eastern Europe due to possible safety concerns and poor immunogenicity. ...
Background:
The tick-borne bunyavirus, Crimean-Congo Haemorrhagic Fever virus (CCHFV), can cause severe febrile illness in humans and has a wide geographic range that continues to expand due to tick migration. Currently, there are no licensed vaccines against CCHFV for widespread usage.
Methods:
In this study, we describe the preclinical assessment of a chimpanzee adenoviral vectored vaccine (ChAdOx2 CCHF) which encodes the glycoprotein precursor (GPC) from CCHFV.
Findings:
We demonstrate here that vaccination with ChAdOx2 CCHF induces both a humoral and cellular immune response in mice and 100% protection in a lethal CCHF challenge model. Delivery of the adenoviral vaccine in a heterologous vaccine regimen with a Modified Vaccinia Ankara vaccine (MVA CCHF) induces the highest levels of CCHFV-specific cell-mediated and antibody responses in mice. Histopathological examination and viral load analysis of the tissues of ChAdOx2 CCHF immunised mice reveals an absence of both microscopic changes and viral antigen associated with CCHF infection, further demonstrating protection against disease.
Interpretation:
There is the continued need for an effective vaccine against CCHFV to protect humans from lethal haemorrhagic disease. Our findings support further development of the ChAd platform expressing the CCHFV GPC to seek an effective vaccine against CCHFV.
Funding:
This research was supported by funding from the Biotechnology and Biological Sciences Research Council (UKRI-BBSRC) [BB/R019991/1 and BB/T008784/1].
... In Bulgaria and Hungary, countries that are on the border with Romania, CCHFV is endemic, which suggests that the virus could also circulate in Romania. Small ruminants have been recognized as CCHFV hosts in certain endemic regions and have been epidemiologically linked to human cases (Gergova and Kamarinchev 2013, Földes et al. 2019, Magyar et al. 2021. ...
Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne disease that can be contracted by direct contact with viremic animals or humans. Domestic animals are accidental hosts and contribute to the spread and amplification of the virus. The main objective of this study was to provide updated information related to CCHF virus (CCHFV) infection in Southern Romania by assessing the seroprevalence of CCHF in small ruminants (sheep and goats) using a double-antigen sandwich enzyme-linked immunosorbent assay and by detection of CCHFV in engorged ticks and serum samples using real-time RT-PCR. The overall seroprevalence of CCHF in small ruminants was 37.7% (95% CI 31.7 to 43.7). No statistical seroprevalence difference was observed between the two species of ruminants (p = 0.76), but a significant difference was established between the locations (p < 0.01). No CCHFV RNA was detected in tick pools and small ruminant's sera tested by real-time RT-PCR, although the high seroprevalence to CCHFV among ruminants indicates that CCHV or a closely related virus circulates in Southern Romania.
Hyalomma marginatum, a vector for the high-consequence pathogen, the Crimean–Congo hemorrhagic fever virus (CCHFV), needs particular attention due to its impact on public health. Although it is a known vector for CCHFV, its general virome is largely unexplored. Here, we report findings from a citizen science monitoring program aimed to understand the prevalence and diversity of tick-borne pathogens, particularly focusing on Hyalomma ticks in Hungary. In 2021, we identified one adult specimen of Hyalomma marginatum and subjected it to Illumina-based viral metagenomic sequencing. Our analysis revealed sequences of the uncharacterized Volzhskoe tick virus, an unclassified member of the class Bunyaviricetes. The in silico analysis uncovered key genetic regions, including the glycoprotein and the RNA-dependent RNA polymerase (RdRp) coding regions. Phylogenetic analysis indicated a close relationship between our Volzhskoe tick virus sequences and other unclassified Bunyaviricetes species. These related species of unclassified Bunyaviricetes were detected in vastly different geolocations. These findings highlight the remarkable diversity of tick specific viruses and emphasize the need for further research to understand the transmissibility, seroreactivity or the potential pathogenicity of Volzhskoe tick virus and related species.
Hyalomma ticks are important vectors of Crimean-Congo Haemorrhagic Fever Virus (CCHFV) and other pathogens. They are frequently carried as immatures from Africa, the Middle East and Mediterranean areas to temperate Europe via migratory birds and emergence of its adults has been reported in many countries where it has so far been non-endemic. Our aim was to implement the first steps of the DAMA (Document, Assess, Monitor, Act) protocol by monitoring the potential arrival of adult Hyalomma ticks in Hungary applying citizen-science methods. Ticks were collected from April-December 2021 by asking volunteer participants through a self-made website to look for unusual hard ticks on themselves, their pets and livestock. Owing to the intensive media campaign, the project website had over 31 thousand visitors within seven months and 137 specimens and several hundreds of photos of hard ticks were submitted by citizen scientists from all over the country. Beside Ixodes ricinus , Dermacentor reticulatus, Dermacentor marginatus and Haemaphysalis inermis, a specimen from a dog was morphologically identified as a male Hyalomma marginatum and another removed from a cattle as a male Hyalomma rufipes . The dog and the cattle had never been abroad, they were approximately 280 km apart, thus the two Hyalomma observations can be considered as separate introductions. Amplification of the partial mitochondrial cytochrome C oxidase subunit I gene was successful for both specimens. Sequencing verified the previous morphological identification for both ticks. Based on the phylogenetic analyses the Hy. marginatum individual most likely belongs to the Eurasian population and the Hy. rufipes to a clade of mixed sequences from Europe and Africa. We summarize the scattered historical reports about the occurrence of Hyalomma ticks and CCHFV in Hungary. Our data highlight the effectiveness of citizens science programmes in the monitoring and risk assessment of CCHFV emergence and preparedness in our region.
Outbreaks that occur as a result of zoonotic spillover from an animal reservoir continue to highlight the importance of studying the disease interface between species. One Health approaches recognise the interdependence of human and animal health and the environmental interplay. Improving the understanding and prevention of zoonotic diseases may be achieved through greater consideration of these relationships, potentially leading to better health outcomes across species. In this review, special emphasis is given on the emerging and outbreak pathogen Crimean-Congo Haemorrhagic Fever virus (CCHFV) that can cause severe disease in humans. We discuss the efforts undertaken to better understand CCHF and the importance of integrating veterinary and human research for this pathogen. Furthermore, we consider the use of closely related nairoviruses to model human disease caused by CCHFV. We discuss intervention approaches with potential application for managing CCHFV spread, and how this concept may benefit both animal and human health.
Crimean-Congo hemorrhagic fever (CCHF) and hantavirus infections are the two viral hemorrhagic fevers spread in Europe. To test actual circulation of CCHF virus (CCHFV) and hantaviruses in Bulgaria, we conducted country-wide seroepidemiological studies. Serum samples were collected prospectively from 1500 residents of all 28 districts in Bulgaria. CCHFV seroprevalence of 3.7% was revealed. Anamnesis for tick bites, contact with livestock, age over 40 years and residency in Haskovo district were found as risk factors. The highest CCHFV seroprevalence was observed in the known endemic districts in southeastern Bulgaria: Haskovo (28%) and Yambol (12%). Reactive samples were found in residents of 20 out of the 28 districts in Bulgaria. In comparison with the previous studies, the data presented indicate that CCHFV increased substantially its circulation in the endemic regions and was introduced in many new areas. Hantavirus seroprevalence was based on results of the immunoblot and estimated as 3.1%. Surprisingly, contrary to all available data, Puumala virus seroprevalence rate was 2.3% versus 0.8% of Dobrava-Belgrade virus. Evidence for hantavirus IgG seropositivity was found in residents of 23 of the 28 districts in the country. The first hantavirus seroprevalence study in Bulgaria showed that Puumala virus is probably more wide-spread in the country than Dobrava-Belgrade virus. This article is protected by copyright. All rights reserved.
Crimean-Congo hemorrhagic fever virus (CCHFV) is a member of the Bunyaviridae family and Nairovirus genus. The viral genome consists of 3 RNA segments of 12 kb (L), 6.8 kb (M), and 3 kb (S). Crimean-Congo hemorrhagic fever (CCHF) is the most widespread tickborne viral infection worldwide: it has been reported in many regions of Africa, the Middle East, and Asia. The geographical distribution of CCHFV corresponds most closely with the distribution of members of the tick genera, and Hyalomma ticks are the principal source of human infection. In contrast to human infection, CCHFV infection is asymptomatic in all species. Treatment options for CCHF are limited; immunotherapy and ribavirin are effective in the treatment of CCHF; the efficacy of ribavirin in the treatment of CCHF has not yet been proven. This article reviews the history, epidemiology, clinical symptoms, pathogenesis, diagnosis, and treatment of CCHFV, as well as the development of a vaccine against it.
Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne infection caused by a virus (CCHFV) from the Bunyaviridae family. Domestic and wild vertebrates are asymptomatic reservoirs for the virus, putting animal handlers, slaughter-house workers and agricultural labourers at highest risk in endemic areas, with secondary transmission possible through contact with infected blood and other bodily fluids. Human infection is characterised by severe symptoms that often result in death. While it is known that CCHFV transmission is limited to Africa, Asia and Europe, definitive global extents and risk patterns within these limits have not been well described.
We used an exhaustive database of human CCHF occurrence records and a niche modelling framework to map the global distribution of risk for human CCHF occurrence.
A greater proportion of shrub or grass land cover was the most important contributor to our model, which predicts highest levels of risk around the Black Sea, Turkey, and some parts of central Asia. Sub-Saharan Africa shows more focalized areas of risk throughout the Sahel and the Cape region.
These new risk maps provide a valuable starting point for understanding the zoonotic niche of CCHF, its extent and the risk it poses to humans.
© The Author 2015. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.
Crimean-Congo hemorrhagic fever (CCHF) is an acute, tick borne disease often associated with hemorrhagic presentations and high case fatality rate. Kosovo is a highly endemic area for CCHF, with a significant case fatality rate. The aim of our study was to determine the prevalence of CCHF in Kosovo. We tested 1105 serum samples from healthy population in both endemic and non-endemic areas in the country. Our results revealed a seroprevalence of 4.0% (range 0-9.3%) which is comparable to the seroprevalence in other countries. We show that seroprevalence is correlated to the disease incidence in each studied municipality. We also tested 401 animal sera (353 cow, 30 sheep, 10 goat and 8 chicken) in four endemic municipalities in Kosovo. We detected specific antibodies in all animals except in chicken. Seroprevalence in cows is comparable to other endemic areas and correlates to the seroprevalence in humans. No CCHF RNA could be detected in 105 tick samples obtained in 2012 and 2013. Sequencing of CCHFV positive ticks from 2001 revealed that the virus is most closely related to viral strains that were detected in CCHF patients from Kosovo. Results suggest that mild CCHF cases are most probably underdiagnosed and consequently that the burden of disease is higher than reported. Our study provides key information for CCHF surveillance and raises awareness for possible imported cases in CCHF non-endemic countries.
Background:
Crimean-Congo hemorrhagic fever (CCHF) is a viral disease with fatality rate up to 30%. Up to date, only one CCHF case has been reported in Greece, while a distinct virus strain (AP92) had been isolated in 1975 from ticks in Imathia prefecture, northern Greece. The aim of the present study was to estimate the CCHF virus (CCHFV) seroprevalence among humans residing in the prefecture of Imathia, and the neighboring prefecture of Pella, and to investigate the risk factors associated with the seropositivity.
Material and methods:
A total of 277 persons randomly selected from the general population were tested for the presence of CCHFV IgG antibodies. Additional 51 persons belonging in groups with risk for acquisition of CCHFV infection (19 slaughterhouse workers and 32 hunters) were also tested. All participants filled in a questionnaire related to demographics and probable risk factors (e.g. occupation, former tick bite, animal contact).
Results:
Six of the 277 (2.2%) persons were found to carry CCHFV IgG antibodies: 3 in Imathia and 3 in Pella prefecture, resulting in seroprevalence of 1.7% and 2.9%, respectively. History of tick bite, residence in a hilly territory and increased age were significantly associated with CCHFV seropositivity. None of the slaughterers was found IgG-positive, while CCHFV IgG antibodies were detected in a 67-year old hunter who reported agricultural activities and a former tick bite.
Conclusions:
A relatively low seroprevalence is observed in the area where the AP92 strain has been isolated, with tick bite being significantly associated with CCHFV seropositivity. Further studies in ticks in the area will show whether are they infected by the AP92 strain or other more pathogenic CCHFV strains and at which rate.
Crimean-Congo haemorrhagic fever (CCHF) is an infectious viral disease that has (re-)emerged in the last decade in south-eastern Europe, and there is a risk for further geographical expansion to western Europe. Here we report the results of a survey covering 28 countries, conducted in 2012 among the member laboratories of the European Network for Diagnostics of ‘Imported’ Viral Diseases (ENIVD) to assess laboratory preparedness and response capacities for CCHF. The answers of 31 laboratories of the European region regarding CCHF case definition, training necessity, biosafety, quality assurance and diagnostic tests are presented. In addition, we identified the lack of a Regional Reference Expert Laboratory in or near endemic areas. Moreover, a comprehensive review of the biosafety level suitable to the reality of endemic areas is needed. These issues are challenges that should be addressed by European public health authorities. However, all respondent laboratories have suitable diagnostic capacities for the current situation.
The Crimean-Congo hemorrhagic fever virus (CCHFV) presents a wide distribution, with the Balkan Peninsula being among the endemic regions. To date, only one CCHF case has been reported in Greece; however, based on seroprevalence data, there is evidence that CCHFV circulates in the country. Achaia is a prefecture in western Greece that has not previously been studied for CCHFV.
The aim of this study was to estimate the seroprevalence of CCHFV in humans in Achaia Prefecture, Greece, and to assess possible factors playing a role in seropositivity.
A total of 207 serum samples from people of all age groups, from both urban and rural areas, were prospectively collected and tested for IgG antibodies against CCHFV.
The overall seroprevalence was 3.4%, with significant differences among municipalities. An agro-pastoral occupation, contact with sheep and goats, former tick bite, increasing age, and living at an altitude of ≥400 m, on specific land cover types, were significantly associated with CCHFV seropositivity.
A relatively high seroprevalence was detected in a previously unstudied region of Greece, where CCHFV infection seems to occur mainly through tick bites. Further investigations are needed to identify the circulating CCHFV strains in Greece, in order to gain a better understanding of CCHFV ecology and epidemiology in the country.
Abstract Diagnosed cases of tick-borne encephalitis (TBE) and Lyme disease (LD) have been reportable infectious diseases in Hungary since 1977 and 1998, respectively. Clinically diagnosed cases have been registered in the National Database of Epidemiological Surveillance System (NDESS). All reported TBE cases are confirmed by laboratory serological and, if necessary, PCR tests, whereas the registered cases of LD are mainly based on the appearance of erythema migrans concurring with possible exposure of tick bite. Our work is the first comparative epidemiological and geographical information analysis of these 2 diseases together. The following demographic data from each individual case (703 TBE and 13,606 LD) recorded in the NDESS were used: Sex, age, the starting date and place of the onset of disease, and a short report from the affected person. The descriptive epidemiological analysis of incidence was carried out using directly standardized rates, and smoothed indirectly standardized incidence ratios were calculated by hierarchical Bayesian methods at the municipality level using a Rapid Inquiry Facility (RIF). The average yearly incidence rate of TBE was 0.64 per 100,000 inhabitants (range, 0.46-0.84) and of LD was 12.37 per 100,000 inhabitants (range, 9.9-18.1), with the highest incidence rates in 1998 for TBE and 2008 for LD. The most affected age groups were men between 15 and 59 years of age for TBE, and women between 45 and 64 years of age for LD. Seasonality, based on the starting date of the illness, was also characterized. Extended areas of high risk were identified in western and northern Hungary, illustrated on high-resolution (municipality level) maps. On the basis of our analysis, it is possible to associate areas and periods of high-risk with characteristics (sex, age, residence) of groups most affected by tick-borne diseases in Hungary.
Abstract Crimean-Congo hemorrhagic fever virus (CCHFV) is a typical tick-borne pathogen that causes an increasing number of severe infections in many parts of Africa, Asia, the Middle East, and the Balkans, as well as in some other parts of Europe. The virus is transmitted primarily by Hyalomma spp., and the spectrum of natural hosts for CCHFV is broad, including wild and domestic animals. Although, the presence of CCHFV was hypothesized in Hungary, no significant research activity has been carried out in the past 30 years. In the present study, we provide serological evidence of CCHFV infection in Lepus europeus using newly developed antibody detection assays. Of 198 samples, 12 (6%) were positive for immunoglobulin G antibody against CCHFV, with 2 independent detection assays. This observation indicates a need for a large-scale surveillance to estimate the potential public health risk of CCHFV in Hungary.
Crimean-Congo hemorrhagic fever (CCHF) is a highly contagious viral tick-borne disease with case-fatality rates as high as 50%. We describe a collaborative evaluation of the characteristics, performance, and on-site applicability of serologic and molecular assays for diagnosis of CCHF. We evaluated ELISA, immunofluorescence, quantitative reverse transcription PCR, and low-density macroarray assays for detection of CCHF virus using precharacterized archived patient serum samples. Compared with results of local, in-house methods, test sensitivities were 87.8%-93.9% for IgM serology, 80.4%-86.1% for IgG serology, and 79.6%-83.3% for genome detection. Specificity was excellent for all assays; molecular test results were influenced by patient country of origin. Our findings demonstrate that well-characterized, reliable tools are available for CCHF diagnosis and surveillance. The on-site use of such assays by health laboratories would greatly diminish the time, costs, and risks posed by the handling, packaging, and shipping of highly infectious biologic material.
South Hungary is being monitored for the northward spreading of thermophilic ixodid species, therefore ticks were collected from cattle and wild ruminants (red, fallow and roe deer) in the autumn of 2011.
Besides indigenous species (1185 Dermacentor reticulatus and 976 Ixodes ricinus), two Hyalomma marginatum rufipes males were found on two cows, in September eight days apart.
This is the northernmost autochthonous infestation of the type host (cattle) with H. m. rufipes, vector of Crimean-Congo haemorrhagic fever virus. The present findings are suggestive of the moulting success of this Afro-Mediterranean tick species in a continental climate in Central Europe.
Crimean-Congo Hemorrhagic Fever (CCHF) is a fatal infection, but no clinical case due to AP92 strain was reported. We described the first clinical case due to AP92 like CCHFV.
A case infected by a AP92 like CCHFV was detected in Balkanian part of Turkey. Diagnosis was confirmed by RT-PCR and sequencing. A human serologic and tick survey studies were performed in the region, where the case detected.
Thirty eight individuals out of 741 were found to be anti CCHFV IgM positive. The attack rate for overall CCHFV was calculated as 5.2%. In univariate analyses, CCHFV IgM positivity was found to be associated with the age (p < 0.001), male gender (p = 0.001), agricultural activity (p = 0.036), and history of tick bite (p = 0.014). In multivariate analysis, older age (OR: 1.03, CI:1.01-1.05, p < 0.001), male gender were found to be the risk factors (OR: 2.5, CI:1.15-5.63, p = 0.020) for CCHFV infection.
This is the first human case with AP92 like CCHFV infection. Furthermore, this is the first report of AP92 like strain in Turkey. In the region, elderly males carry the highest risk for CCHFV infection.
Crimean-Congo haemorrhagic fever (CCHF) is a viral zoonotic disease with a high mortality rate in humans. The CCHF virus (CCHFV) is transmitted to humans through the bite of Ixodid ticks or by contact with blood or tissues of infected livestock. In addition to zoonotic transmission, CCHFV can be spread from person to person and is one of the rare haemorrhagic fever viruses able to cause nosocomial outbreaks in hospitals. Crimean-Congo haemorrhagic fever is a public health problem in many regions of the world such as Eastern Europe, Asia, the Middle East and Africa. In addition to clinical symptoms, the diagnosis of CCHF is based on the use of serological tests for the detection of immunoglobulin M and immunoglobulin G antibodies and on the use of molecular tools such as RT-PCR. From 1970 to 1978, serological and epidemiological studies were performed in humans and in livestock of Iran. After two decades and observations of CCHF in some provinces of Iran, a CCHF surveillance and detection system was established in 1999, leading to a dramatically decreased mortality rate from 20% (year 2000) to 2% (year 2007).
During the years 2000 to 2004, of 248 serologically confirmed cases of Crimean-Congo hemorrhagic fever (CCHF) that occurred in several parts of Iran, 169 were reported from Sistan-va-Baluchestan province. To assess the seroprevalence of CCHF virus infection within the Zahedan and Zabol districts of the Sistan-va-Baluchestan province in Iran, 300 subjects were sampled from the general population. In addition to blood sampling, a questionnaire was completed for every subject. All but just 3 of our 300 sampled subjects participated in blood sampling, and just 7 out of the 297 serum samples were found to be IgG ELISA positive. The point estimate of the seroprevalence was 0.024 (95% confidence interval: 0.003-0.044). A history of keeping livestock in houses (even for short periods) showed an association with seropositivity (P = 0.018). It seems that even occasional contact with livestock could be effective in transmission of the virus.
Rhipicephalus sanguineus (the brown dog tick, kennel tick) has a world-wide geographical distribution. In Europe its original habitat is the Mediterranian basin, with sporadic introduction to northern countries. It is a three-host tick species, the dog being the primary host for all three developmental stages, but occasionally these can also attach to other mammals, even humans. This hard tick species is known for its capability to survive indoors, in houses. The authors review the geographical distribution, life-cycle, and significance of R. sanguineus as a vector that can transmit numerous pathogens. In August 2005, in North Hungary (Nógrád county, Zsunypuszta) on a beef cattle farm five engorged hard ticks were removed from the eyelids of a 2 year old, short-haired mixed breed male dog. Upon morphological examination all turned out to be nymphs of R. sanguineus. Sixteen days later a further engorged nymph was found on the same animal. To examine the presence of some important pathogens transmitted by this tick species, blood smears and serum samples of the dog were analysed, but they did not contain babesia developmental stages, or specific antibodies to Borrelia burgdorferi and Coxiella burnetii, respectively. Five further dogs were examined in the neighbourhood and were found tick-free. Extensive tick collection (by dragging/flagging) in four nearby forests revealed only 3 nymphs of Ixodes ricinus. However, 6 days later another dog became infested with R. sanguineus on the same farm. Both infested dogs were herding local cattle throughout their lives and neither the owners nor the dogs ever left the area (especially the country). The most likely introduction of these ticks in a younger stage (e.g. eggs in a fertilized female) was by a truck coming from Croatia to transport calves 40 days before the infestation was first detected.
Larval Hyalomma truncatum ticks were infected with Crimean-Congo hemorrhagic fever (CCHF) virus by allowing them to engorge on viremic newborn mice. The overall tick infection rate was 4.4% (24/542). Virus was detected in specimens for greater than or equal to 160 days postinfection. Transstadial transmission to the adult tick stage was observed and horizontal transmission to a mammalian host was demonstrated. Horizontal transmission of CCHF virus to uninfected adult ticks occurred while feeding with transstadially infected ticks on the same host. No evidence of transovarial virus transmission from infected female ticks to their 1st generation progeny was observed.
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