Crimean-Congo Hemorrhagic Fever Virus Genome Research Articles

Identification and evaluation of multi-antigenic epitopes of immunodominant protein from the selected Crimean–Congo hemorrhagic fever virus genome towards the development of diagnostic and vaccine candidates by reverse vaccinology approach

Identification and evaluation of multi-antigenic epitopes of immunodominant protein from the selected Crimean–Congo hemorrhagic fever virus genome towards the development of diagnostic and vaccine candidates by reverse vaccinology approach

Seromolecular survey and risk factor analysis of Crimean-Congo haemorrhagic fever orthonairovirus in occupationally exposed herdsmen and unexposed febrile patients in Kwara State, Nigeria.

Crimean-Congo haemorrhagic fever virus (CCHFV) is a globally significant tick-borne zoonotic pathogen that causes fatal haemorrhagic disease in humans. Despite constituting an ongoing public health threat, limited research exists on the presence of CCHFV among herdsmen, an occupationally exposed population that has prolonged contact with ruminants and ticks. This cross-sectional study, conducted between October 2018 and February 2020 in Kwara State, Nigeria, was aimed at assessing CCHFV seroprevalence among herdsmen and non-herdsmen febrile patients, and identifying the associated risk factors. Blood samples from herdsmen (n = 91) and febrile patients in hospitals (n = 646) were analyzed for anti-CCHFV IgG antibodies and CCHFV S-segment RNA using ELISA and RT-PCR, respectively. Results revealed a remarkably high CCHFV seroprevalence of 92.3% (84/91) among herdsmen compared to 7.1% (46/646) in febrile patients. Occupational risk factors like animal and tick contact, tick bites, and hand crushing of ticks significantly contributed to higher seroprevalence in the herdsmen (p<0.0001). Herdsmen were 156.5 times more likely (p<0.0001) to be exposed to CCHFV than febrile patients. Notably, the odds of exposure were significantly higher (OR = 191.3; p<0.0001) in herdsmen with a history of tick bites. Although CCHFV genome was not detectable in the tested sera, our findings reveal that the virus is endemic among herdsmen in Kwara State, Nigeria. CCHFV should be considered as a probable cause of febrile illness among humans in the study area. Given the nomadic lifestyle of herdsmen, further investigations into CCHF epidemiology in this neglected population are crucial. This study enhances our understanding of CCHFV dynamics and emphasizes the need for targeted interventions in at-risk communities.

Molecular identification of Crimean-Congo haemorrhagic fever virus in Hyalomma rufipes and Amblyomma variegatum in the Upper East Region of Ghana.

Sampled ticks were screened for Crimean-Congo haemorrhagic fever virus (CCHFV) using an assay that targets the nucleoprotein gene region of the S segment, a conserved region of the CCHFV genome. Minimum infection rates of 0.34% and 0.10% were obtained when testing pools of Hyalomma rufipes and Amblyomma variegatum, respectively. Next-generation sequencing and phylogenetic analysis showed that the S and L segments of the CCHFV isolate clustered with those of similar isolates of genotype III. However, analysis of the M segment showed that reassortment had occurred, causing this segment to cluster with those of isolates of genotype I, providing the first evidence of such an occurrence in Ghana.

Detection of the Crimean-Congo Hemorrhagic Fever Virus Genome in Questing Ixodes spp. and Haemaphysalis spp. in the Periurban Forestry Areas of Istanbul: Has a New Biorisk Emerged?

Background: Istanbul is one of the world's most densely populated metropolitan cities, with various geographical areas that possess distinct characteristics. These areas have different climates, vegetation, and host populations that can support the survival of diverse tick species. Turkey is a region with a high risk of Crimean-Congo hemorrhagic fever (CCHF) disease, making it crucial to screen for this risk, especially in densely populated regions such as Istanbul and its surrounding areas. However, the presence of potential vectors for CCHF virus (CCHFV) in these areas has not been studied in the past 12 years. Materials and Methods: In this study, a total of 676 ticks were collected from 6 centers using the flagging and dragging method. Ticks were identified as Ixodes ricinus (7.85%), Ixodes spp. immature form (73.22%), Haemaphysalis parva (0.89%), Haemaphysalis inermis (0.15%), and Haemaphysalis spp. immature form (17.89%). Pooled samples were screened for the CCHFV genome (S segment) by RT-nested PCR. Results: A total of 14.28% of the samples were found as positive. Phylogenetic analysis revealed that all the CCHFV sequences obtained from the positive samples were clustered in clade V: Europe/Turkey genogroup. Conclusion: This study suggests that ixodes spp. and Haemaphysalis spp. may have the potential to pose a biorisk for Crimean-Congo hemorrhagic fever.

Investigating the effect of ribavirin treatment on genetic mutations in Crimean-Congo haemorrhagic fever virus (CCHFV) through next-generation sequencing.

Crimean-Congo haemorrhagic fever (CCHF) is the most widespread tick-borne viral haemorrhagic fever affecting humans, and yet a licensed drug against the virus (CCHFV) is still not available. While several studies have suggested the efficacy of ribavirin against CCHFV, current literature remains inconclusive. In this study, we have utilised next-generation sequencing to investigate the mutagenic effect of ribavirin on the CCHFV genome during clinical disease. Samples collected from CCHF patients receiving ribavirin treatment or supportive care only at Sivas Cumhuriyet University Hospital, Turkey, were analysed. By comparing the frequency of mutations in each group, we found little evidence of an overall mutagenic effect. This suggests that ribavirin, administered at the acute stages of CCHFV infection (at the World Health Organization-recommendeddose) is unable to induce lethal mutagenesis that would cause an extinction event in the CCHFV population and reduce viremia.

Molecular detection of Crimean-Congo Haemorrhagic Fever (CCHF) virus in hard ticks from South Khorasan, east of Iran.

Crimean-Congo Hemorrhagic Fever (CCHF) is a deadly viral infection reported from more than 30 countries. It is considered a zoonosis↱ and tick bites are the main route of transmission in nature. So far, the virus has been identified in 31 species of hard (Ixodidae) and soft (Argasidae) ticks. The aim of this study was to determine the rate of CCHF virus infection in hard ticks from South-Khorasan province, east of Iran. In this study, 684 livestock including 302 sheep, 344 goats, 16 cows and 22 camels were sampled from Birjand, Qaen, Khusf, Darmian and Sarbisheh counties. Genus and species of the ticks were diagnosed under stereomicroscope according to valid morphological keys. Reverse transcription-polymerase chain reaction (RT-PCR) method was used to detect the CCHF virus genome based on S segment in 100 ticks. RT-PCR detected CCHF virus genome in 7 out of 100 ticks. Positive ticks belonged to Hyalomma and Rhipicephalus genera. CCHF virus infected species were Rhipicephalus sanguineus, Hyalomma detritium and Hyalomma asiaticum. All the infected ticks were isolated from goat and sheep and were from Birjand county. Our results suggest that Hyalomma and Rhipicephalus may be the main vectors of CCHF virus in the study area.

Molecular epidemiology of Crimean-Congo hemorrhagic fever virus in Russia.

In this report, we present new data on the diversity and geographical distribution of genetic variants in Crimean-Congo hemorrhagic fever virus (CCHFV) in Russia. Partial S, M, and L segment sequences of the CCHFV genome were obtained from 500 serum samples from CCHF patients and 103 pools of ticks collected in the south of the European region of Russia in 2007–2017. The investigated viral strains belonged to the lineages Europe 1 (596 samples), Africa 3 (1 sample) and a new genetic lineage, Europe 3 (6 samples). The Russian CCHFV strains of the Europe 1 lineage formed four subgroups (Va-Vd) correlated with the geographical site of virus isolation. Segment reassortment events between strains of different subgroups within lineage Europe 1 were revealed. The complete S, M and L genome segments of 18 CCHFV strains belonging to different subgroups of the Europe 1 lineage and the complete S segments of 3 strains of the Europe 3 lineage and 1 strain of the Africa 3 lineage were sequenced. The analysis of the geographical distribution of CCHFV genetic variants in southern Russia revealed local viral populations with partially overlapping boundaries.

Molecular Epidemiology and Phylogeny of Crimean-Congo Haemorrhagic Fever (CCHF) Virus of Ixodid Ticks in Khorasan Razavi Province of Iran.

Background:Crimean–Congo hemorrhagic fever (CCHF) is a fatal disease caused by Nairovirus classified within the Bunyaviridae family. The virus is transmitted to humans through the bites of infected ticks or direct contact with viremic animals or humans. The current study aimed to detect the virus genome in ticks from Khorasan Razavi Province.Methods:One hundred hard ticks were collected randomly from 100 sheep in four different areas of the province. Collected ticks were kept alive and identified. All the ticks were analyzed for the presence of CCHF virus genome using reverse transcriptase polymerase chain reactions (RT-PCR).Results:The identified ticks were belonging to Hyalomma marginatum (16% female and 6% male), Rhipicephalus turanicus (52% female and 25% male), and Dermacentor raskemensis (1%). The CCHF virus genome was found in Hyalomma marginatum (5% male from Taibad and Sabzevar region and 1% female from Taibad). Genetic analysis of the virus genome isolated from two regions (Sabzevar and Taibad) showed 100% identity.Conclusion:This study indicated that CCHF should be regarded as a risk-borne infection in this province. Therefore, special health management is needed to control this disease.

High prevalence and different genotypes of Crimean-Congo hemorrhagic fever virus genome in questing unfed adult Hyalomma marginatum in Thrace, Turkey

Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne viral disease in the old continents, in many countries south of the 50 °North Parallel. The agent is known to be the most prevalent and major cause of severe and fatal human hemorrhagic diseases among the tick-borne viruses, and is the second most widespread of all medically critical arboviruses following dengue. Members of the Hyalomma genus are mainly involved in the natural transmission of the CCHF virus (CCHFV); of those, H. marginatum is known to be the primary vector of the disease in the Western Palaearctic. In general, epidemiological studies have been based on serological detections in the hosts and/or virus screening of ticks collected from the hosts. To the best of our knowledge, only a few studies have been carried out to screen the virus in unfed, questing field ticks. Nevertheless, detection of the virus in questing ticks is known to be a crucial parameter to determine the possible vector roles of the ticks and to understand the ecological dynamics of related diseases. In this study, 200 (75 males,125 females) questing H. marginatum adults collected from the field in nine villages in Thrace, located in the European part of Turkey, were screened individually for CCHFV using nested PCR. As a result, 103 (51.5 %) ticks were determined as positive with various strains of CCHFV. High positivity in questing vectors in a region where a significantly lower number of human cases have been encountered suggests that there should be some region-specific drivers that are effective in the natural dynamics of the disease. Detailed etiological and epidemiological studies are needed to reveal the possible reason for this unexpected discrepancy.

Identification of a novel lineage of Crimean-Congo haemorrhagic fever virus in dromedary camels, United Arab Emirates.

Crimean-Congo haemorrhagic fever virus (CCHFV) is a tick-borne virus causing Crimean-Congo haemorrhagic fever (CCHF), a disease reported to have a high fatality rate in numerous countries. The virus is geographically widespread due to its vector, and numerous wild and domestic animals can develop asymptomatic infection. Serological and limited molecular evidence of CCHFV has previously been reported in Camelus dromedarius (the dromedary, or one-humped camel) in the United Arab Emirates (UAE). In this study, 238 camel samples were screened for CCHFV RNA where 16 camel samples were positive for CCHFV by RT-PCR. Analysis of full-length CCHFV genome sequences revealed a novel lineage in camels from the UAE, and potential reassortment of the M segment of the genome.

In Silico Modeling of Crimean Congo Hemorrhagic Fever Virus Glycoprotein-N and Screening of Anti Viral Hits by Virtual Screening.

Crimean-Congo hemorrhagic fever (CCHF) is a widespread zoonotic viral disease, caused by a tick-born virus Crimean-Congo hemorrhagic fever virus (CCHFV). This disease is endemic in Middle East, Asia, Africa and South-Eastern Europe with the mortality rate of 5–30%. CCHFV genome is composed of three segments: large, medium and small segments. M segment encodes a polyprotein (glycoprotein) so called glycoprotein N (Gn) which is considered as a potential druggable target for the effective therapy of CCHF. The complete structure of Gn is still not characterized. The aim of the current study is to predict the complete three-dimensional (3D-) structure of CCHFV Gn protein via threading-based modeling and investigate the residues crucial for binding with CCHFV envelop. The developed model displayed excellent stereo-chemical and geometrical properties. Subsequently structure based virtual screening (SBVS) was applied to discover novel inhibitors of Gn protein. A library of > 1300 anti-virals was selected from PubChem database and directed to the predicted binding site of Gn. The SBVS results led to the identification of thirty-seven compounds that inhibit the protein in computational analysis. Those 37 hits were subject to pharmacokinetic profiling which demonstrated that 30/37 compound possess safer pharmacokinetic properties. Thus, by specifically targeting Gn, less toxic and more potent inhibitors of CCHFV were identified in silico.Electronic supplementary materialThe online version of this article (10.1007/s10989-020-10055-1) contains supplementary material, which is available to authorized users.

Development of quantitative real-time RT-PCR assay for detection and viral load determination of Crimean-Congo Hemorrhagic Fever (CCHF) virus

Background and Aim: The CCHF (Crimean-Congo hemorrhagic fever) virus causes a severe disease in human with a case fatality rate of up to 50%. Since, there is no specific treatment or approved vaccine against CCHF viral infections, an accurate and early detection as well as a reliable surveillance and quantitative determination of viral load is necessary for patient improvement and case management. In this research, our aim was to develop a probe based one-step real-time reverse-transcription polymerase chain reaction (rRT-PCR) assay for in-house quantitative detection of CCHF virus. Methods: At first, the highly conserved S-fragment sequence of CCHF virus genome was adapted from GenBank and the specific probe and primers targeting this region were designed. Then, viral RNAs were extracted from 37 blood samples of different patients from east of Iran (Zahedan). The specificity and sensitivity of the probe and primers were also evaluated in positive blood samples, confirmed to have CCHF virus. A standard (PTG19-T vector containing S-fragment) for quantization was also constructed and the viral load was determined in some of positive samples. Results: From a total of 37 suspicious blood samples, 15 samples were confirmed to be positive for CCHF virus by this probe based one-step rRT-PCR assay and no false-positive result was detected according to sequencing data. The predicted fragment of 176 bp was also confirmed in all positive samples by gel-based electrophoresis analysis. The assay was linear between 10 to 103 copy numbers per each microliter of extracted plasmid for this technique and the viral load determined in one of patient blood samples was 55,000 viral particles per each milliliter, for example. Bioinformatics and experimental evaluations approved the specificity of this assay. The LOD of the assay was 10 (or fewer) copy numbers of viral genome per each microliter of the extracted genome. Conclusions: This research showed that the developed probe based one-step rRT-PCR assay is a specific, rapid, sensitive and the simple tool for detection and viral load determination of the CCHF virus. Keywords: CCHF Virus, Real-time RT-PCR, Quantitative, viral load, S-region.

Epidemiological investigations of Crimean-Congo haemorrhagic fever virus infection in sheep and goats in Balochistan, Pakistan

Crimean-Congo haemorrhagic fever (CCHF) is a tick-borne zoonotic disease caused by the arbovirus Crimean-Congo haemorrhagic fever virus (CCHFV). Livestock serve as a transient reservoir for CCHFV, but do not show clinical signs. In this cross-sectional study, sheep and goats in Balochistan, Pakistan, were examined to determine the CCHFV seroprevalence, spatial distribution of seropositive sheep and goats, and to identify potential risk factors for seropositivity to CCHFV in these animals. To this end, farms and animals were selected by systematic sampling, blood samples from 800 sheep and 800 goats were collected and information regarding farm management and the kept animals were retrieved using a standard questionnaire. Sera were tested for antibodies against CCHFV in two independent ELISA formats and an immunofluorescence assay (IFA) following a hierarchical diagnostic decision tree. By these assays 149 (19 %, 95 %-CI: 16–21 %) out of 800 sheep serum samples and 37 (5 %, 95 %-CI: 3–6 %) out of 800 goat serum samples were positive for CCHFV-specific IgG antibodies. Interestingly, at least 8 (5 %, 95 %-CI: 2–10 %) out of 160 sera pools were from CCHFV viraemic sheep, as sera (in pools of 5) tested positive for CCHFV genome by real-time PCR (RT-qPCR). Risk factor analysis revealed that the open type of housing (OR = 3.76, 95 %-CI:1.57-9.56, p-value = 0.003), grazing (OR = 4.18, 95 %-CI:1.79-10.37, p-value = 0.001), presence of vegetation in or around the farm (OR = 3.13, 95 %-CI: 1.07–10.15, p-value = 0.043), lack of treatment against ticks (OR = 3.31, 95 %-CI: 1.16–10.21, p-value = 0.029), absence of rural poultry (OR = 2.93, 95 %-CI: 1.41–6.29, p-value = 0.004), animals with age ≥ 2 years (OR = 4.15, 95 %-CI: 2.84–6.19, p-value<0.001), animals infested with ticks (OR = 2.35, 95 %-CI: 1.59–3.52, p-value<0.001), and sheep species (OR = 4.72, 95 %-CI:3.24-6.86, p-value<0.001) represented statistically significant risk factors associated with seropositivity to CCHFV. Taken together this study confirms the circulation of CCHFV in livestock in Balochistan, Pakistan. The identification of risk factors might help to reduce the risk of infection in sheep and goats, which may also mitigate the risk for human infection. An interesting option for reducing the risk of CCHFV infection in small ruminants is keeping also chickens, since they pick ticks that transmit CCHFV.

Molecular and seroepidemiological survey on Crimean-Congo Hemorrhagic Fever Virus in Northeast of Iran.

Background: Crimean-Congo hemorrhagic fever (CCHF) is a prevalent tick-borne disease in different regions of Iran. This molecular and serologic study was performed to investigate the Crimean-Congo hemorrhagic fever virus (CCHFV) in collected ticks and in blood samples of some domestic animals in North Khorasan, Northeast of Iran. Methods: In this cross sectional study, 136 blood samples from domestic animals (sheep, goats, and cows) collected in the Northeast region in Iran were examined using IgG ELISA assay. Ticks (n = 1478) were collected from sheep, goats, and cows. Out of all collected ticks, 62 specimens were investigated for CCHF virus genome using RT-PCR technique. The data were descriptively presented by median and 95% confidence interval (CI). Results: CCHFV infection rate was 8.1% in studied ticks. Two species of ticks, Hy. anatolicum (n=3; 15%, 95% CI 9.41–20.59) and Rh. sanguineus (n=2; 6.9%, 95%CI 4.33–8.58), were infected with CCHFV genome and were probable vectors of CCHF virus in the area. Infection rate was 15.4% for CCHFV in tested domestic animals. Serologic tests detected CCHFV specific IgG antibodies in 16.2% (95% CI 13.49–18.83) (99/16) and 19.2% (95% CI 13.26–25.20) (26/5) of sheep and goats, respectively. Conclusion: The present study showed that domestic animals and ticks were infected with Crimean-Congo hemorrhagic fever virus and that the disease was endemic in North Khorasan province, Iran. However, further surveillance and prevention programs are recommended.

Molecular detection of Crimean-Congo haemorrhagic fever virus in ticks collected from infested livestock populations in a New Endemic Area, South of Iran.

Crimean-Congo haemorrhagic fever (CCHF) is a viral zoonotic disease with potentially fatal systemic effects on man. We aimed to determine the presence of CCHF virus among collected ticks from domestic livestock from October 2012 to September 2013. A total of 1245 hard and soft ticks were collected from naturally infested ruminants in Marvdasht County, Fars Province, south of Iran. Nine tick species and one unidentified species in four disparate genera were detected. A total of 200 ticks were randomly selected and analysed by reverse transcription-polymerase chain reaction (RT-PCR) for the presence of CCHF virus genome. The viral genome was detected in 4.5% (9 samples) of the studied tick population. The infected ticks belonged to the species of Hyalomma marginatum' Hyalomma anatolicum and Rhipicephalus sanguineus. The viruses detected in these three tick species were clustered in the same lineage as Matin and SR3 strains in Pakistan and some other Iranian strains. These results indicate that the ticks were wildly infected with a genetically closely related CCHF virus in the region. Regular controls and monitoring of livestock to reduce the dispersion of ticks and providing information to those involved in high-risk occupations are urgently required.

Genetic variants of the Crimean-Congo hemorrhagic fever virus circulating in endemic areas of Southern Tajikistan in 2009

506 Hyalomma anatolicum ticks were collected and assayed in two Crimean-Congo hemorrhagic fever (CCHF) endemic regions of Tajikistan. Antigen and RNA of CCHF virus were detected in 3.4% of tick pools from Rudaki district using ELISA and RT-PCR tests. As of Tursunzade district, viral antigen was identified in 9.0% of samples and viral RNA was identified in 8.1% of samples. The multiple alignment of the obtained nucleotide sequences of CCHF virus genome S-segment 287-nt region (996-1282) and multiple alignment of deduced amino acid sequences of the samples, carried out to compare with CCHF virus strains from the GenBank database, as well as phylogenetic analysis, enabled us to conclude that Asia 1 and Asia 2 genotypes of CCHF virus are circulating in Tajikistan. It is important to note that the genotype Asia 1 virus was detected for the first time in Tajikistan.

Molecular detection of Crimean-Congo haemorrhagic fever (CCHF) virus in ticks from southeastern Iran

Crimean-Congo haemorrhagic fever (CCHF) virus is a tick-borne member of the genus Nairovirus, family Bunyaviridae. CCHF virus has been isolated from at least 31 different species of ticks. The virus is transmitted through the bite of an infected tick or by direct contact with CCHF virus-infected patients or the products of infected livestock. This study was conducted to determine the rate of CCHF virus infection in ticks in the district of Zahedan, in the province of Sistan and Baluchistan, southeastern Iran. A total of 140 ticks were collected from Sistan and Baluchistan. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used for the detection of the CCHF virus genome in the tick population. This genome was detected in 4.3% of ticks collected from livestock of different regions of Zahedan. The infected tick genera belonged to Hyalomma and Haemaphysalis. Although in the epidemiology of CCHF virus Hyalomma ticks are considered to be the most important vectors and reservoirs, the virus has also been reported to occur in other genera of ticks, which conforms to the current data in our study from Sistan and Baluchistan. Given that animals are common hosts for Hyalomma and Haemaphysalis, regular monitoring programmes for livestock should be applied for CCHF virus control.

Epitope-based immunoinformatics and molecular docking studies of nucleocapsid protein and ovarian tumor domain of crimean-congo hemorrhagic Fever virus.

Crimean–Congo hemorrhagic fever virus (CCHFV), the fatal human pathogen is transmitted to humans by tick bite, or exposure to infected blood or tissues of infected livestock. The CCHFV genome consists of three RNA segments namely, S, M, and L. The unusual large viral L protein has an ovarian tumor (OTU) protease domain located in the N terminus. It is likely that the protein may be autoproteolytically cleaved to generate the active virus L polymerase with additional functions. Identification of the epitope regions of the virus is important for the diagnosis, phylogeny studies, and drug discovery. Early diagnosis and treatment of CCHF infection is critical to the survival of patients and the control of the disease. In this study, we undertook different in silico approaches using molecular docking and immunoinformatics tools to predict epitopes which can be helpful for vaccine designing. Small molecule ligands against OTU domain and protein–protein interaction between a viral and a host protein have been studied using docking tools.

Crimean–Congo hemorrhagic fever: a molecular survey on hard ticks ( Ixodidae) in Yazd province, Iran

Objective To determine the rate of Crimean-Congo hemorrhagic fever virus (CCHFV) infection in hard ticks (Ixodidae) in Yazd province of Iran. Methods A molecular survey on hard ticks (Ixodidae) was conducted in Yazd province during 2008–2009. A total of 140 hard ticks (three genera and 7 species) were collected from randomly selected villages and were exanimate for presence of CCHFV reverse transcription-polymerase chain reaction (RT-PCR) method. Results CCHFV genome was found in 5.71% of hard ticks. All positive ticks were from Hyalomma genus. Positive ticks including: Hyalomma dromedarii, Hyalomma marginatum, Hyalomma anatolicum, Hyalomma detritum, Hyalomma asiaticum. We were not able to find virus in in Rhipicephalus sanguineus and Dermacentor marginatus. Results exhibited that Hyalomma is the main vector in the study area. Conclusions Due to the presence of virus in 24 provinces' out of 31, we recommend the use of acaricides and repellent to prevent disease transmission among humans. Greta care should be taken by the people who are working in slaughter houses.

Geographical Distribution and Surveillance of Crimean-Congo Hemorrhagic Fever in Iran

Crimean-Congo hemorrhagic fever (CCHF) is viral hemorrhagic fever caused by CCHF virus, which belongs to the family Bunyaviridae and the genus Nairovirus. The virus is transmitted to humans via contact with blood and tissue from infected livestock, a tick bite, or contact with an infected person. Since 2000, we have shown the disease to be prevalent in 23 out of 30 provinces of Iran. Among those, Sistan-va-Baluchistan, Isfahan, Fars, Tehran, Khorasan, and Khuzestan demonstrated the highest infection, respectively. Notably, Sistan-va-Baluchistan province, southeast of Iran, has the highest prevalence of CCHF, and has shown to be present since at least 2000. Phylogenetic study of the CCHF virus genome isolated from Iranian patients showed a close relationship with the CCHF Matin strain (Pakistan). Our epidemiological data in the last decade have implied that the severity and fatality rate of the disease has ranged variably in different provinces of Iran. More pathogenesis and phylogenetic studies should therefore be investigated to clarify these differences.