Transmission Of Crimean-Congo Hemorrhagic Fever Virus Research Articles

Dynamics of Crimean-Congo hemorrhagic fever virus in two wild ungulate hosts during a disease-induced population collapse

Identifying the role that host species play in pathogen transmission and maintenance is crucial for disease control, but it is a difficult task, in particular for vector-borne and multi-host pathogens, and especially when wildlife species are involved. This is the case for a Crimean-Congo hemorrhagic fever virus (CCHFV) hotspot in north-eastern Spain, where Iberian ibex (Capra pyrenaica) and wild boar (Sus scrofa) are involved, but their roles in disease transmission are unclear. In this context, we studied the dynamics of CCHFV transmission in these two species during the collapse of an Iberian ibex population due to a sarcoptic mange outbreak. We carried out a repeated cross-sectional study measuring the trends of CCHFV seroprevalence in Iberian ibex and wild boar and their abundances. In addition, we identified the tick species present in this area on the vegetation and on wild boars, and evaluated relevant meteorological factors. Results show that while the trends in CCHFV seroprevalence in Iberian Ibex and density of wild boars remained constant (p = 1.0 and p = 0.8, respectively), both the trends in Iberian ibex census and CCHFV seroprevalence in wild boars decreased significantly (p = 0.003 and p = 0.0001, respectively), and were correlated (Spearman's rank, 0.02 < p-adjusted<0.05). The correlation between the patterns of reduction of Iberian ibex abundance and the decrease of seroprevalence in wild boars suggests some sort of shared transmission cycle between the two species. Data from tick species in the area suggest a possible role of Rhipicephalus bursa in CCHFV transmission. The dynamics of CCHFV were unlikely caused by changes in meteorological variables such as temperature or water vapor pressure deficit. Further studies will be needed to confirm these hypotheses.

Towards a Sustainable One Health Approach to Crimean-Congo Hemorrhagic Fever Prevention: Focus Areas and Gaps in Knowledge.

Crimean–Congo hemorrhagic fever virus (CCHFV) infection is identified in the 2018 World Health Organization Research and Development Blueprint and the National Institute of Allergy and Infectious Diseases (NIH/NIAID) priority A list due to its high risk to public health and national security. Tick-borne CCHFV is widespread, found in Europe, Asia, Africa, the Middle East, and the Indian subcontinent. It circulates between ticks and several vertebrate hosts without causing overt disease, and thus can be present in areas without being noticed by the public. As a result, the potential for zoonotic spillover from ticks and animals to humans is high. In contrast to other emerging viruses, human-to-human transmission of CCHFV is typically limited; therefore, prevention of spillover events should be prioritized when considering countermeasures. Several factors in the transmission dynamics of CCHFV, including a complex transmission cycle that involves both ticks and vertebrate hosts, lend themselves to a One Health approach for the prevention and control of the disease that are often overlooked by current strategies. Here, we examine critical focus areas to help mitigate CCHFV spillover, including surveillance, risk assessment, and risk reduction strategies concentrated on humans, animals, and ticks; highlight gaps in knowledge; and discuss considerations for a more sustainable One Health approach to disease control.

Detection of New Crimean-Congo Hemorrhagic Fever Virus Genotypes in Ticks Feeding on Deer and Wild Boar, Spain

Background: Crimean-Congo hemorrhagic fever virus (CCHFV) is the causative agent of the severe tick-borne, which is widely distributed worldwide. The CCHFV transmission to humans occurs through tick bite, crushing of engorged ticks, or contact with infected host blood. Previously, CCHFV genotype Africa III was reported in Spain. Methods: A total of 613 ticks, including Hyalomma lusitanicum and Dermacentor marginatus, were collected from hunter-harvested wild ungulates in twenty locations throughout southwestern Spain. Tick RNA was analyzed by a nested RT-PCR targeting CCHFV S segment and the amplicons were sequenced. Findings: The study reports the presence of CCHFV human genotype Europe V in both tick species collected from red deer (Cervus elaphus), fallow deer (Dama dama), and Eurasian wild boar (Sus scrofa). Viral RNA was detected in 129 of the analyzed ticks. Most of the CCHFV S segment sequences showed 99-100% identity to reported sequences of human isolates from Russia and Iran belonging to genotype Europe V. Interpretation: The detection of CCHFV in different tick species collected from various wild host species and localities provided strong evidence of widespread CCHFV presence in the region, suggesting that CCHFV circulation in Spain requires more attention. Additionally, the identification of the CCHFV genotype Europe V in ticks suggested that its introduction in Spain was probably from Eastern Europe. Funding: This study was partially supported by MINECO Plan Nacional grant CGL2017-89866-R and EU-FEDER. Declaration of Interest: The authors declare no commercial or financial conflict of interest. Ethical Approval: Tick sampling were collected according to hunting disease surveillance schemes and in the framework of Spanish and EU laws for notifiable disease surveillance. Therefore, no Animal Ethics Committee approval was required for the collection of ticks from hunter harvested wild ungulates.

Evidence of Crimean-Congo Haemorrhagic Fever Virus Occurrence in Ixodi¬dae Ticks of Armenia

Crimean-Congo hemorrhagic fever (CCHF) causes serious health problems in humans. Though ticks of the genera Hyalomma play a significant role in the CCHF virus transmission it was also found in 31 other tick species. Totally, 1412 ticks from 8 remote sites in Armenia during 2016 were sampled, pooled (3-5 ticks per pool) and tested for the presence of CCHFV antigen using ELISA test. From 359 tick pools, 132 were CCHF virus antigen-positive. From 6 tick species, four species (Rhipicephalus sanguineus, R. annulatus, R. bursa, Hyalomma marginatum) were positive for the virus antigen and R. sanguineus was the most prevalent (37.9%). Dermacentor marginatus and Ixodes ricinus revealed no positive pools, but both revealed delectable but very low virus antigen titers. The highest infection rate (50%) was observed in R. sanguineus, whereas H. marginatus rate of infection was 1 out of 17 pools. For the first time in the last four decades CCHF virus antigen was detected in Ixodid ticks of Armenia. This finding substantiates the role of R. sanguineus in the disease epidemiology; however, the role of H. marginatum in the CCHF virus circulation in the country could not be excluded.

Crimean-Congo Hemorrhagic Fever: Tick-Host-Virus Interactions.

Crimean-Congo hemorrhagic fever virus (CCHFV) is transmitted to humans by bite of infected ticks or by direct contact with blood or tissues of viremic patients or animals. It causes to humans a severe disease with fatality up to 30%. The current knowledge about the vector-host-CCHFV interactions is very limited due to the high-level containment required for CCHFV studies. Among ticks, Hyalomma spp. are considered the most competent virus vectors. CCHFV evades the tick immune response, and following its replication in the lining of the tick's midgut, it is disseminated by the hemolymph in the salivary glands and reproductive organs. The introduction of salivary gland secretions into the host cells is the major route via which CCHFV enters the host. Following an initial amplification at the site of inoculation, the virus is spread to the target organs. Apoptosis is induced via both intrinsic and extrinsic pathways. Genetic factors and immune status of the host may affect the release of cytokines which play a major role in disease progression and outcome. It is expected that the use of new technology of metabolomics, transcriptomics and proteomics will lead to improved understanding of CCHFV-host interactions and identify potential targets for blocking the CCHFV transmission.

Probable Crimean-Congo hemorrhagic fever virus transmission occurred after aerosol-generating medical procedures in Russia: nosocomial cluster

We report here a fatal case of laboratory confirmed Crimean-Congo hemorrhagic fever (CCHF), which caused nosocomial infection in eight health care workers (HCWs), who had provided medical care for the patient. All the HCWs survived. The report demonstrates that airborne transmission of CCHF is a real risk, at least when the CCHF patient is in a ventilator. During performance of any aerosol-generating medical procedures for any CCHF patient airborne precautions should always be added to standard precautions, in particular, airway protective N95 mask or equivalent standard, eye protection, single airborne precaution room, or a well-ventilated setting.

Investigation of Crimean-Congo Hemorrhagic Fever Virus Transmission from Patients to Relatives: A Prospective Contact Tracing Study

We investigated the possibility of transmission of Crimean-Congo hemorrhagic fever (CCHF) virus through respiratory and physical contact. In this prospective study, we traced 116 close relatives of confirmed CCHF cases who were in close contact with the patients during the acute phase of the infection and evaluated the type of contact between patients and their relatives. These relatives were followed for clinical signs or symptoms indicative of CCHF disease, blood samples of those with and without clinical signs were analyzed for CCHF virus immunoglobulin M and G (IgM and IgG, respectively) by enzyme-linked immunosorbent assay. No close relatives developed any signs or symptoms of CCHF and were negative for CCHF virus IgM and IgG. The results suggest that CCHF virus is not easily transmitted from person to person through respiratory or physical contact.

Influence of laboratory animal hosts on the life cycle of Hyalomma marginatum and implications for an in vivo transmission model for Crimean-Congo hemorrhagic fever virus.

Crimean-Congo hemorrhagic fever virus (CCHFV) is one of the most geographically widespread arboviruses and causes a severe hemorrhagic syndrome in humans. The virus circulates in nature in a vertebrate-tick cycle and ticks of the genus Hyalomma are the main vectors and reservoirs. Although the tick vector plays a central role in the maintenance and transmission of CCHFV in nature, comparatively little is known of CCHFV-tick interactions. This is mostly due to the fact that establishing tick colonies is laborious, and working with CCHFV requires a biosafety level 4 laboratory (BSL4) in many countries. Nonetheless, an in vivo transmission model is essential to understand the epidemiology of the transmission cycle of CCHFV. In addition, important parameters such as vectorial capacity of tick species, levels of infection in the host necessary to infect the tick, and aspects of virus transmission by tick bite including the influence of tick saliva, cannot be investigated any other way. Here, we evaluate the influence of different laboratory animal species as hosts supporting the life cycle of Hyalomma marginatum, a two-host tick. Rabbits were considered the host of choice for the maintenance of the uninfected colonies due to high larval attachment rates, shorter larval-nymphal feeding times, higher nymphal molting rates, high egg hatching rates, and higher conversion efficiency index (CEI). Furthermore, we describe the successful establishment of an in vivo transmission model for CCHFV in a BSL4 biocontainment setting using interferon knockout mice. This will give us a new tool to study the transmission and interaction of CCHFV with its tick vector.

Factors driving the circulation and possible expansion of Crimean-Congo haemorrhagic fever virus in the western Palearctic

To produce a spatial risk map regarding spread of Crimean-Congo haemorrhagic fever virus (CCHFV) in the western Palearctic by linking a process-driven model of the main tick vector, Hyalomma marginatum, to a Next Generation Matrix. Process-driven model was composed of deterministic equations that simulate developmental and mortality rates of different tick stages by using temperature and atmospheric water vapour data. The model used climate data at 10-day intervals at a spatial resolution of 10 min over western Palearctic. The model estimated the basic reproduction number, R0, for CCHFV transmission by H. marginatum ticks and evaluated how changes in temperature and biological parameters may alter the geographical range of CCHFV. In particular, variation in the rate of transovarial transmission of CCHFV in the tick produced the greatest change in CCHFV circulation in the tick population. Parameters affecting the rates of tick bite, non-systemic transmission and efficiency of tick-to-tick transmission had little effect on R0. Temperature changes that affect tick development, survival and activity rates increased the suitable area for CCHFV transmission at higher latitudes in the western Palearctic. Non-systemic transmission had little impact on virus transmission under all scenarios. In the area studied, increase of temperature has no impact on the routes of transmission of CCHFV. However, climate conditions favouring tick survival, which increase infected adult tick populations, together with large numbers of hosts for adults were predicted as the most likely scenario for the spread of the virus in the studied area. The proposed framework is able to capture the dynamics and the relative contribution of the different routes (hosts, ticks) in the transmission and spread of an important pathogen affecting human health. The high contribution of the transovarial transmission route makes the process highly dependent upon suitable hosts for adult ticks, like large domestic and wild ungulates. Climate seems to have a very reduced effect on such spread.

Unraveling the Ecological Complexities of Tick-Associated Crimean-Congo Hemorrhagic Fever Virus Transmission: A Gap Analysis for the Western Palearctic

This review aims to summarize the current knowledge of the eco-epidemiology of Crimean-Congo hemorrhagic fever (CCHF) virus transmission reviewing the most recent scientific advances in the last few decades of epidemic and non-epidemic ("silent") periods. We explicitly aim to highlight the dynamics of transmission that are still largely unknown. Recent knowledge gathered from research in Africa and Europe explains the very focal nature of the virus, and indicates that research on the ecology of the virus in the inter-epidemic periods of the disease has not yet been addressed. Hyalomma spp. ticks have been incriminated in the transmission of the virus under field conditions, but the role of other ticks found infected in nature remains to be tested under experimental conditions. Published evidence suggests that the increase in human cases reported in the Balkans, Turkey, and Russia is perhaps less due to the effect of changes in climate, but rather result from the impact of yet unexplored mechanisms of amplification that might be supported by wild animal hosts. Assessment of the available data suggests that epidemics in Eastern Europe are not the result of a spreading viral wave, but more likely are due to a combination of factors, such as habitat abandonment, landscape fragmentation, and proliferation of wildlife hosts that have exacerbated prevalence rates in tick vectors. There is an urgent need to empirically demonstrate these assumptions as well as the role of birds in introducing infected ticks, and also to evaluate the potential for survival of introduced ticks. Either a replacement of the pathogenic virus in the western Mediterranean or a lack of westward dissemination of infected tick populations may explain the absence of the virus in Western Europe.

Crimean‐congo hemorrhagic fever virus–tick survey in endemic areas in Bulgaria

The Balkan Peninsula and Bulgaria in particular, is a well-known endemic region for Crimean-Congo hemorrhagic fever (CCHF). This study describes the prevalence of Crimean-Congo hemorrhagic fever virus (CCHFV) among tick populations from areas, previously recognized with emerging cases of CCHF disease in humans. These include regions from the Southeastern (regions of Kardzhali and Haskovo) and Central (region of Stara Zagora) parts of the country. For the period 2006-2010 a total of 911 adult ticks, collected from livestock in endemic areas were studied for presence of CCHFV by an immunofluorescence-hemocytes assay (IFHA) and a reverse transcription-polymerase chain reaction (RT-PCR). The detection rate of CCHFV in the tick population was 2.09%. The prevalence of the virus was determined between 2.01% and 4.83% in the regions of Kardzhali and Haskovo, respectively (Southeastern Bulgaria). In the Central part of the country CCHFV infestation of the ticks was observed in 1.46% (region of Stara Zagora). The results confirmed the mosaic dispersion of CCHFV in the investigated regions. The principal infection vector in the surveyed areas was confirmed to be Hyalomma marginatum marginatum. Rhipicephalus sanguineus and Ixodes ricinus were also detected and may play a role in the transmission of CCHFV. Species distribution of CCHFV-positive ticks was as follows: H. m. marginatum-4.93%; R. sanguineus-2.33%; I. ricinus-1.02%. The combination of IFHA and RT-PCR that are used in this study are useful tools in the algorithm for monitoring endemic areas in Bulgaria.

Possible Drivers of Crimean-Congo Hemorrhagic Fever Virus Transmission in Kosova

Crimean-Congo hemorrhagic fever (CCHF) has long been a disease of concern in Kosova; however, little is known about the enzootic cycles of the virus in this country. Since the first documented case in 1954, sporadic cases and occasional outbreaks have been recorded with cases more consistently reported following the conflict in 1999. CCHF virus exists in enzootic cycles between wild animal species and ticks. The infection rates within ticks and hence the exposure to humans is determined by both the biology and seasonal dynamics of ticks, and the population dynamics and structure of the wild animals. These, in turn, are affected by complex interactions between climatic variables, changes in agricultural practices, land management, and wild animal density. If we are to understand the spatial and temporal occurrence of human disease, we must understand the ecology of the virus in nature. This article discusses the possible ecological, societal, political, and economic drivers that may impact the enzootic cycle of the virus and contribute to an increase in virus amplification and/or human exposure to infected ticks in Kosova.

Crimean-Congo hemorrhagic fever virus in various ixodid tick species from a highly endemic area

Ticks are major vectors of numerous diseases affecting animals and humans. Presence of various tick-borne pathogens such as Crimean-Congo hemorrhagic fever virus (CCHFV) in various tick species was documented. CCHF is a severe tick-borne illness caused by the CCHFV which is a member of the Nairovirus genus (family: Bunyaviridae). Presence of CCHFV was shown in the most prevalent ixodid tick species such as Hyalomma marginatum and Rhiphicephalus bursa in Turkey. In the present study, prevalence and species diversity of ixodid ticks carrying CCHFV in Tokat province where CCHF is highly endemic were determined by using real-time reverse transcription-polymerase chain reaction (RRT-PCR). As a result, 15 out 745 ticks from various hosts (2%) were found to be CCHFV positive. The CCHFV positive ticks were Haemaphysalis concinna, Hyalomma anatolicum, Hyalomma detritum, Hyalomma marginatum, Hyalomma turanicum, Rhipicephalus bursa, and Rhiphicephalus turanicus indicating that multiple ixodid tick species may contribute to transmission of CCHFV to humans and animals in Turkey.

The lack of Crimean-Congo hemorrhagic fever virus antibodies in healthcare workers in an endemic region

We aimed to detect antibodies against Crimean-Congo hemorrhagic fever virus (CCHFV) in healthcare workers (HCWs) in an endemic region. The study was conducted in a tertiary care hospital that had cared for CCHFV infected patients in the period 2002-2003. The sera from the HCWs were collected one month after the last admitted hospital case (October 2003), and sent to the Pasteur Institute, Lyon, France to be studied for CCHF IgM and IgG by ELISA. The total number of HCWs included in the study was 75; the median age was 30, 68% of the subjects were female, and 83% of the HCWs were at risk of exposure to the body fluids of patients. Only one HCW from the group without risk of exposure was CCHF IgG positive. The adherence rate to universal precautions was high. In conclusion, a lack of CCHFV transmission from patients to HCWs was observed. This result could be related to the high rate of compliance to the universal precautions, which are sufficient to protect against CCHFV infection.

Crimean-Congo hemorrhagic fever in ticks (Acari: Ixodidae) and ruminants: field observations of an epizootic in Bandia, Senegal (1989-1992).

From 1989 to 1992, a longitudinal study of the relationships between different tick species and domestic ungulates in the transmission and amplification of Crimean-Congo hemorrhagic fever (CCHF) virus was undertaken in the Bandia area in Senegal where the presence of the virus had been reported previously. An epizootic occurred in 1991-1992 and 22 strains of CCHF virus were isolated from Hyalomma marginatum rufipes Koch, Amblyomma variegatum (F.), Rhipicephalus guilhoni Morel & Vassiliades, and R. evertsi evertsi Neumann ticks collected from cattle and goats. No human cases were reported. Transmission of CCHF virus in the area involves a complicated pattern including many tick species and hosts. Amplicons of the S fragment (536 bp) of the CCHF genome of 12 isolates from the study were obtained by polymerase chain reaction and analyzed by restriction-length fragment polymorphism. Three different genotypes of CCHF virus were identified and present during the epizootic. One genotype was recovered from A. variegatum, R. guilhoni, and R. e. evertsi and 2 genotypes were isolated from H. m. rufipes.

Sexual and transovarian transmission of Crimean-Congo haemorrhagic fever virus in Hyalomma truncatum ticks

Male Hyalomma truncatum ticks were inoculated with Crimean-Congo haemorrhagic fever (CCHF) virus, hypostomectomized and then allowed to mate with uninfected females feeding on a naive rabbit. After mating, CCHF virus was reisolated from 2 out of 3 males tested and from 4 of 6 mated, engorged females (titre greater than or equal to 2.2 log LD50/ml). Vertical transmission was then demonstrated by virus reisolation from a portion of 2 of the 6 batches of eggs laid by the positive females. From these 2 positive egg batches, 6 larvae pools were tested with successful virus reisolation from one. Attempts to reisolate CCHF virus from 15 nymph pools of this positive batch of larvae were unsuccessful. Virus reisolation from gonopore-closed female H. truncatum which cofed with preinfected males demonstrated transmission in the absence of copulation. Rabbits that served as bloodmeal sources seroconverted after infestation by infected male ticks. However, CCHF virus was not reisolated from 3 gonopore-closed, engorged females, nor from their eggs, after feeding with hypostomectomized preinfected males. Transmission of CCHF virus during mating or cofeeding of adult H. truncatum, and subsequent transovarial transmission, appear to represent additional mechanisms of infection in the tick population, and may contribute to the maintenance of transmission in nature.