Crimean-Congo Hemorrhagic Fever Research Articles

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.

Development of a Novel Plasmid-based Eukaryotic Model to Investigate Crimean-Congo Hemorrhagic Fever Virus

Development of a Novel Plasmid-based Eukaryotic Model to Investigate Crimean-Congo Hemorrhagic Fever Virus

Crimean-congo hemorrhagic fever outbreak affecting healthcare workers in pakistan; an urgent rising concern

Crimean-congo hemorrhagic fever outbreak affecting healthcare workers in pakistan; an urgent rising concern

Epidemiologic Survey of Crimean-Congo Hemorrhagic Fever Virus in Suids, Spain.

We conducted a cross-sectional study in wild boar and extensively managed Iberian pig populations in a hotspot area of Crimean-Congo hemorrhagic fever virus (CCHFV) in Spain. We tested for antibodies against CCHFV by using 2 ELISAs in parallel. We assessed the presence of CCHFV RNA by means of reverse transcription quantitative PCR protocol, which detects all genotypes. A total of 113 (21.8%) of 518 suids sampled showed antibodies against CCHFV by ELISA. By species, 106 (39.7%) of 267 wild boars and 7 (2.8%) of 251 Iberian pigs analyzed were seropositive. Of the 231 Iberian pigs and 231 wild boars analyzed, none tested positive for CCHFV RNA. These findings indicate high CCHFV exposure in wild boar populations in endemic areas and confirm the susceptibility of extensively reared pigs to CCHFV, even though they may only play a limited role in the enzootic cycle.

Crimean-Congo Hemorrhagic Fever Virus for Clinicians-Epidemiology, Clinical Manifestations, and Prevention.

Crimean-Congo hemorrhagic fever (CCHF) is a tickborne infection that can range from asymptomatic to fatal and has been described in >30 countries. Early identification and isolation of patients with suspected or confirmed CCHF and the use of appropriate prevention and control measures are essential for preventing human-to-human transmission. Here, we provide an overview of the epidemiology, clinical features, and prevention and control of CCHF. CCHF poses a continued public health threat given its wide geographic distribution, potential to spread to new regions, propensity for genetic variability, and potential for severe and fatal illness, in addition to the limited medical countermeasures for prophylaxis and treatment. A high index of suspicion, comprehensive travel and epidemiologic history, and clinical evaluation are essential for prompt diagnosis. Infection control measures can be effective in reducing the risk for transmission but require correct and consistent application.

Crimean Congo Hemorrhagic Fever Virus for Clinicians-Virology, Pathogenesis, and Pathology.

Crimean-Congo hemorrhagic fever (CCHF), caused by CCHF virus, is a tickborne disease that can cause a range of illness outcomes, from asymptomatic infection to fatal viral hemorrhagic fever; the disease has been described in >30 countries. We conducted a literature review to provide an overview of the virology, pathogenesis, and pathology of CCHF for clinicians. The virus life cycle and molecular interactions are complex and not fully described. Although pathogenesis and immunobiology are not yet fully understood, it is clear that multiple processes contribute to viral entry, replication, and pathological damage. Limited autopsy reports describe multiorgan involvement with extravasation and hemorrhages. Advanced understanding of CCHF virus pathogenesis and immunology will improve patient care and accelerate the development of medical countermeasures for CCHF.

Crimean-Congo Hemorrhagic Fever Virus for Clinicians-Diagnosis, Clinical Management, and Therapeutics.

Crimean-Congo hemorrhagic fever virus (CCHFV) is the most geographically widespread tickborne viral infection worldwide and has a fatality rate of up to 62%. Despite its widespread range and high fatality rate, no vaccines or treatments are currently approved by regulatory agencies in the United States or Europe. Supportive treatment remains the standard of care, but the use of antiviral medications developed for other viral infections have been considered. We reviewed published literature to summarize the main aspects of CCHFV infection in humans. We provide an overview of diagnostic testing and management and medical countermeasures, including investigational vaccines and limited therapeutics. CCHFV continues to pose a public health threat because of its wide geographic distribution, potential to spread to new regions, propensity for genetic variability, potential for severe and fatal illness, and limited medical countermeasures for prophylaxis and treatment. Clinicians should become familiar with available diagnostic and management tools for CCHFV infections in humans.

Lessons From the Global SARS-CoV-2 Health Emergency for Potential Future Pandemics

Abstract The emergence of novel infectious agents with pandemic potential remains a critical global concern, as underscored by the COVID-19 pandemic. This study investigates the various factors contributing to the risk of new pandemics and proposes a framework for pandemic prevention and mitigation. We review the characteristics of several infectious agents, including influenza viruses, coronaviruses, filoviruses, paramyxoviruses, Lassa fever virus, Crimean-Congo hemorrhagic fever virus, and the yellow fever virus. These agents are discussed in terms of their transmission modes, reservoirs, potential for human-to-human spread, and historical outbreaks. We emphasize the importance of monitoring and early detection of these agents, especially those with localized outbreaks and zoonotic potential. Our analysis highlights the role of human activities in pandemic risk. Factors such as overuse of antibiotics, environmental changes (deforestation, wildlife habitat encroachment), climate change effects on disease vectors, and increasing global connectivity are examined as drivers of disease emergence. Furthermore, we propose a foursome of critical actions for pandemic prevention and response: early detection and rapid containment; restricting the transmission by social distancing, masking, quarantine, and elimination of vector, which are crucial even before the vaccine is available; global vaccine and treatment distribution; and robust health policy implementation. We emphasize the importance of international collaboration, information sharing, and preparedness to effectively combat pandemics. In conclusion, this commentary provides a comprehensive overview of infectious agents with pandemic potential and their associated risks. It calls for proactive measures to prevent and mitigate future pandemics, emphasizing the need for a global strategy that combines early detection, rapid response, and sustained public health infrastructure.

Establishment of two serological methods for detecting IgG and neutralizing antibodies against Crimean-Congo hemorrhagic fever virus glycoprotein.

The Crimean-Congo hemorrhagic fever virus (CCHFV), the most geographically widespread tick-borne virus, is endemic in Africa, Eastern Europe and Asia, with infection resulting in mortality in up to 30% of cases. Currently, there are no approved vaccines or effective therapies available for CCHF. The CCHFV should only be manipulated in the BSL-4 laboratory, which has severely hampered basic seroprevalence studies. In the present study, two antibody detection methods in the forms of an enzyme-linked immunosorbent assay (ELISA) and a surrogate virus neutralization test (sPVNT) were developed using a recombinant glycoprotein (rGP) and a vesicular stomatitis virus (VSV)-based virus bearing the CCHFV recombinant glycoprotein (rVSV/CCHFV) in a biosafety level 2 (BSL-2) laboratory, respectively. The rGP-based ELISA and rVSV/CCHFV-based sVNT were established by using the anti-CCHFV pre-GC mAb 11E7, known as a broadly cross-reactive, potently neutralizing antibody, and their applications as diagnostic antigens were validated for the specific detection of CCHFV IgG and neutralizing antibodies in experimental animals. In two tests, mAb clone 11E7 (diluted at 1:163840 or 512) still displayed positive binding and neutralization, and the presence of antibodies (IgG and neutralizing) against the rGP and rVSV/CCHFV was also determined in the sera from the experimental animals. Both mAb 11E7 and animal sera showed a high reactivity to both antigens, indicating that bacterially expressed rGP and rVSV/CCHFV have good immunoreactivity. Apart from establishing two serological testing methods, their results also demonstrated an imperfect correlation between IgG and neutralizing antibodies. Within this limited number of samples, the rGP and rVSV/CCHFV could be safe and convenient tools with significant potential for research on specific antibodies and serological samples.

Relation between the Pandemic COVID-19 and the outbreak of Crimean-Congo Hemorrhagic Fever in Iraq, 2023

Objective: This review examines the link between the COVID-19 pandemic and the outbreak of Crimean-Congo Hemorrhagic Fever (CCHF) in Iraq. Methods: We reviewed literature and data to explore potential associations between the two diseases. Results: No direct causative link between COVID-19 and increased CCHF cases in Iraq was found. However, changes in healthcare,agriculture, and human-animal interactions during the pandemic may have indirectly affected CCHF transmission. Conclusion: This review highlights the need for further research to confirm any connections between the COVID-19 pandemic and CCHFoutbreaks in Iraq. Understanding these links is crucial for effective public health responses to emerging infectious diseases.

The PACS-2 protein and trafficking motifs in CCHFV Gn and Gc cytoplasmic tails govern CCHFV assembly

The Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne bunyavirus that causes high mortality in humans with a wide geographic range. This enveloped virus has a tri-segmented negative or ambisense RNA genome that harbors two surface glycoproteins (GP), Gn and Gc. The maturation of the Gn/Gc glycoprotein precursor complex takes place in the ER and is completed through the secretion pathway. Here, we aimed at characterizing the trafficking network exploited by CCHFV GPs during the stages of virus assembly, envelopment, and/or egress. We identified putative membrane trafficking motifs in the cytoplasmic domains (CD) of CCHFV GPs and addressed how they can impact these late stages of the viral life cycle using infection assays, biochemical assays and confocal microscopy in virus-producing cells. Several of the identified CCHFV GP CD motifs could modulate GP transport through the retrograde trafficking network, impacting envelopment and secretion of infectious particles. Finally, we identified the phosphofurin acidic cluster sorting protein 2 (PACS-2) as a crucial host factor that contributes to CCHFV GPs trafficking required for assembly and release of viral particles.

Genetic background of adaptation of Crimean-Congo haemorrhagic fever virus to the different tick hosts.

Crimean-Congo haemorrhagic fever orthonairovirus (CCHFV) is a negative-sense, single-stranded RNA virus with a segmented genome and the causative agent of a severe Crimean-Congo haemorrhagic fever (CCHF) disease. The virus is transmitted mainly by tick species in Hyalomma genus but other ticks such as representatives of genera Dermacentor and Rhipicephalus may also be involved in virus life cycle. To improve our understanding of CCHFV adaptation to its tick species, we compared nucleotide composition and codon usage patterns among the all CCHFV strains i) which sequences and other metadata as locality of collection and date of isolation are available in GenBank and ii) which were isolated from in-field collected tick species. These criteria fulfilled 70 sequences (24 coding for S, 23 for M, and 23 for L segment) of virus isolates originating from different representatives of Hyalomma and Rhipicephalus genera. Phylogenetic analyses confirmed that Hyalomma- and Rhipicephalus-originating CCHFV isolates belong to phylogenetically distinct CCHFV clades. Analyses of nucleotide composition among the Hyalomma- and Rhipicephalus-originating CCHFV isolates also showed significant differences, mainly in nucleotides located at the 3rd codon positions indicating changes in codon usage among these lineages. Analyses of codon adaptation index (CAI), effective number of codons (ENC), and other codon usage statistics revealed significant differences between Hyalomma- and Rhipicephalus-isolated CCHFV strains. Despite both sets of strains displayed a higher adaptation to use codons that are preferred by Hyalomma ticks than Rhipicephalus ticks, there were distinct codon usage preferences observed between the two tick species. These findings suggest that over the course of its long co-evolution with tick vectors, CCHFV has optimized its codon usage to efficiently utilize translational resources of Hyalomma species.

Unveiling the threat: Balochistan's path to congo virus endemicity

Dear Madam, The detection of 16 cases of Crimean Congo Haemorrhagic Fever Virus (CCHFV) in the Balochistan province this year (1) and a 2020 study indicating a seroprevalence of 2.7% in humans and 36.2% in livestock in Pakistan, with Balochistan showing a significantly higher prevalence in the collected samples (2), has raised concerns about the region's susceptibility to becoming an endemic area for this tick-borne zoonotic disease. Balochistan's arid climate creates an ideal environment for Hyalomma Marginatum ticks to thrive, thereby increasing the risk of transmission. Rural areas, which constitute a significant proportion of Balochistan, are generally more affected due to livestock farming, which plays a significant role in Pakistan’s economy. However, urban areas in Pakistan experience higher infection rates during Eid-Ul-Adha when there is a large-scale animal trade, with increased incidence in high-risk groups, like butchers, veterinarians, and healthcare professionals. The region also encounters challenges due to the cross-border movement of livestock and infected individuals with neighbouring countries, like Afghanistan and Iran, where the virus is endemic (3). Another contributing factor to the endemicity of the virus is the perception of neglect, resulting in limited resources, inadequate vector control and healthcare infrastructure, and insufficient awareness and preventive measures (3), which create significant obstacles in the early detection and management of virus-borne diseases. A Bulgarian vaccine introduced in 1974 led to a decline in cases from 1974 to 1996, but there is insufficient statistical evidence to attribute this decline solely to the vaccine. Thus, there is no universally recognised vaccination available for the virus currently. However, researchers are working to create an effective vaccine (4). Currently, treatment for CCHFV involves supportive care and antivirals, like ribavirin. Although treatments-FDA-approved treatments in use, including steroids, convalescent serum, and specific immunoglobulins, it’s important to note that these treatments are experimental and require further evaluation of their efficacy and safety profile (5). The most effective approach to reducing the prevalence of CCHFV in Balochistan is through prevention methods, including raising awareness among high-risk groups, especially butchers who should wear appropriate protection, handle slaughter in designated areas, and ensure proper waste disposal (4). It is also crucial to discourage tourists from visiting areas where ticks are prevalent, and local law enforcement should limit the unrestricted movement of livestock. Additionally, programmes should be introduced to vaccinate animals against the virus, and suspected animals should be quarantined.

Seroprevalence and Risk Factors Associated with Phleboviruses and Crimean-Congo Hemorrhagic Fever Virus among Blood Donors in Central Tunisia.

The aim of this study was to determine the prevalence of six viruses, from two families of the order Bunyavirales, in the general population of central Tunisia. Sera collected from 377 asymptomatic blood donors were serologically assayed for Rift Valley fever virus (RVFV), Crimean-Congo hemorrhagic fever virus (CCHFV), and four sandfly-borne phleboviruses: Toscana virus (TOSV), sandfly fever Naples virus (SFNV), sandfly fever Sicilian virus (SFSV), and sandfly fever Cyprus virus (SFCV). Of the 377 subjects enrolled in this study, 17.3% were IgG positive for at least one of the viruses tested. The most frequently detected antibodies were against TOSV (13.3%), followed by SFCV (2.9%), RVFV (1.9%), SFSV (1.3%), and SFNV (1.1%). Only one sample was IgG positive for CCHFV. Dual reactivity was observed in nine cases: SFSV + SFCV in three cases (0.8%) and TOSV + SFNV, TOSV + SFCV, and TOSV + RVFV in two cases (0.5%) each. 15.9% of donors were IgG positive against sandfly-borne phleboviruses. Among the 65 donors IgG positive for phleboviruses, 50.8% were from rural areas compared to 12.3% from urban areas (p < 0.001); 92.3% had animals in their living quarters (p = 0.009); and 70.8% lived in the vicinity of stagnant water (p = 0.062). Seroprevalence was significantly higher among donors living with chronic diseases (p = 0.039). Furthermore, the seroprevalence of phleboviruses was higher in Kairouan, the central governorate, than in the two coastal governorates: Monastir and Sousse, with 33.4%, 24.2%, and 14.9%, respectively. The presence of antibodies in the general population needs further investigation to better assess the extent of these viruses. Only TOSV was known to have an extensive circulation in Tunisia and in North Africa. Continued surveillance and interventions are necessary to detect the emergence of all arboviruses and to prevent further transmission.

Serological Evidence of Crimean-Congo Haemorrhagic Fever in Livestock in the Omaheke Region of Namibia.

This research examined the positivity ratio of Crimean-Congo haemorrhagic fever (CCHF) antibodies in cattle and sheep within Namibia's Omaheke region after a human disease outbreak in the same geographical area. A total of 200 samples (100 cattle and 100 sheep) were randomly collected from animals brought to two regional auction sites, and then tested using the ID Screen® CCHF Double Antigen Multi-Species Enzyme-Linked Immunosorbent Assay kit. Of the cattle samples, 36% tested positive, while 22% of the sheep samples were seropositive. The cattle had a significantly higher positivity ratio than sheep at the individual animal level (p = 0.0291). At the herd level, 62.5% of cattle herds and 45.5% of sheep flocks had at least one positive animal, but this difference was statistically insignificant (p = 0.2475). The fourteen cattle farms with at least one seropositive animal were dispersed across the Omaheke region. In contrast, the ten sheep farms with seropositive cases were predominantly situated in the southern half of the region. The study concluded that the CCHF is endemic in the Omaheke region and likely in most of Namibia, underscoring the importance of continued surveillance and preventive measures to mitigate the impact of CCHFV on animal health and potential spillover into human populations.

Development of a non-infectious control for viral hemorrhagic fever PCR assays.

Assay validation is an essential component of disease surveillance testing, but can be problematic in settings where access to positive control material is limited and a safety risk for handlers. Here we describe a single non-infectious synthetic control that can help develop and validate the PCR based detection of the viral causes of Crimean-Congo hemorrhagic fever, Ebola virus disease, Lassa fever, Marburg virus disease and Rift Valley fever. We designed non-infectious synthetic DNA oligonucleotide sequences incorporating primer binding sites suitable for five assays, and a T7 promotor site which was used to transcribe the sequence. Transcribed RNA was used as template in a dilution series, extracted and amplified with RT-PCR and RT-qPCR to demonstrate successful recovery and determine limits of detection in a range of laboratory settings. Our results show this approach is adaptable to any diagnostic assay requiring validation of nucleic acid extraction and/or amplification, particularly where sourcing reliable, safe material for positive controls is infeasible.

Prevalence of crimean Congo hemorrhagic fever in Khyber Pakhtunkhwa, Pakistan

BackgroundCCHFV is well recognized as a major public health threat and its prevalence and epidemiological distribution in Pakistan and specifically in KP province is not well documented. MethodsWe used a gold-standard PCR-based diagnostic assay for confirmation of CCHFV among suspected patients. A total of 150 patients were enrolled from June 2022 to September 2022 and their blood samples were collected for PCR confirmation. ResultsThe overall positivity rate for CCHFV was 26.67 %, with the virus mostly prevalent in the middle-aged group (21–40 years). In the July of 2022, a significant spike in the prevalence of CCHFV was observed in provincial capital Peshawar with the highest burden (31.57 %). ConclusionOur findings indicate the necessity of strengthening CCHFV monitoring programs and intensifying efforts to identify hotspot regions for effective surveillance and control of CCHFV. The months before the Eid-ul-Adha are crucial in the context of CCHFV control.

Crimean-Congo haemorrhagic fever virus in questing non-Hyalomma spp. ticks in Northwest Spain, 2021.

Crimean-Congo haemorrhagic fever (CCHF) unexpectedly emerged in humans in Northwest Spain in 2021, and two additional cases were reported in the region in 2022. The 2021 case was associated with a tick bite on the outskirts of the city where the patient lived. PCR analysis of 95 questing ticks collected in the outskirts of that city in 2021, none of the genus Hyalomma, revealed a prevalence of confirmed CCHF virus (CCHFV) infection of 10.5%. Our results in this emerging scenario suggest the need to consider that CCHFV may be effectively spreading to Northwest Spain and to urgently understand any possible role of non-Hyalomma spp. ticks in the eco-epidemiological dynamics of CCHFV.

Animal Exposure Model for Mapping Crimean-Congo Hemorrhagic Fever Virus Emergence Risk.

To estimate the determinants of spatial variation in Crimean-Congo hemorrhagic fever virus (CCHFV) transmission and to create a risk map as a preventive public health tool, we designed a survey of small domestic ruminants in Andalusia, Spain. To assess CCHFV exposure spatial distribution, we analyzed serum from 2,440 sheep and goats by using a double-antigen ELISA and modeled exposure probability with environmental predictors by using generalized linear mixed models. CCHFV antibodies detected in 84 samples confirmed low CCHFV prevalence in small domestic ruminants in the region. The best-fitted statistical model indicated that the most significant predictors of virus exposure risk were cattle/horse density and the normalized difference vegetation index. Model validation showed 99.7% specificity and 10.2% sensitivity for identifying CCHFV circulation areas. To map CCHFV exposure risk, we projected the model at a 1 × 1-km spatial resolution. Our study provides insight into CCHFV ecology that is useful for preventing virus transmission.

Discovery of baloxavir sodium as a novel anti-CCHFV inhibitor: biological evaluation of in vitro and in vivo

Crimean-Congo hemorrhagic fever virus (CCHFV) is a highly pathogenic bunyavirus with a fatality rate of up to 40%. Currently, there are no licensed antiviral drugs for the treatment of CCHF; thus, the World Health Organization (WHO) listed the disease as a priority. A unique viral transcription initiation mechanism called “cap-snatching” is shared by influenza viruses and bunyaviruses. Thus, we tested whether baloxavir (an FDA-approved anti-influenza drug that targets the “cap-snatching” mechanism) could inhibit CCHFV infection. In cell culture, baloxavir acid effectively inhibited CCHFV infection and targeted CCHFV RNA transcription/replication. However, it has weak oral bioavailability. Baloxavir marboxil (the oral prodrug of baloxavir) failed to protect mice against a lethal dose challenge of CCHFV. To solve this problem, baloxavir sodium was synthesized owing to its enhanced aqueous solubility and pharmacokinetic properties. It consistently and significantly improved survival rates and decreased tissue viral loads. This study identified baloxavir sodium as a novel scaffold structure and mechanism of anti-CCHF compound, providing a promising new strategy for clinical treatment of CCHF after further optimization.