Crimean-Congo Hemorrhagic Fever Research Articles

The current pathogenicity and potential risk evaluation of Crimean-Congo hemorrhagic fever virus to cause mysterious "Disease X"-An updated literature review.

Crimean-Congo hemorrhagic fever (CCHF) is a severe and potentially lethal illness. Tick bites of the Hyalomma genus are the primary source of transmission of CCHF to humans. The virus responsible for CCHF is the CCHF virus (CCHFV). It is a single-stranded negative sensed RNA virus. The virus belongs to the Orthonairoviridae genus within the Nairoviridae family. It occurs in an extensive geographical area spanning the Middle East, western China, southern Asia, southeastern Europe, and much of Africa. The current study aimed to evaluate the pathogenicity and potential risk of CCHFV to cause a public health emergency of international concern. We searched updated relevant information from PubMed, Google Scholar, and Scopus databases using Crimean-Congo hemorrhagic fever, tick-borne virus, and Nairovirus as keywords. The case fatality rate (CFR) varies by region. It can be more than 30% in some cases. Three segments in the genome of CCHFV (L, M, and S) are different in size and function. It is unknown whether the pathogenicity of CCHFV varied based on the genomic diversity. CCHFV can be transmitted through tick bites, handling of infected ticks, contact with infected humans, contaminated body fluids, and so on. A wide range of severity is associated with CCHF, ranging from a moderate fever with no apparent cause to increased vascular permeability, failure of several organs, bleeding, and shock. Hospitals with high-level isolation units should be the first choice for treating CCHF patients. Individual safety equipment is crucial in healthcare to prevent the spread of the virus. In the farm environment, using integrated pest management techniques, minimizing activity in tick-infested regions, and dressing appropriately in long sleeves and pants will help to reduce the risk of CCHFV infection via tick bites. There are no approved vaccinations or therapeutics for CCHF except supportive therapeutic approaches. Therefore, scientists recommend early ribavirin therapy for cases of high-risk exposures.

Can we predict bleeding at admission in Crimean-Congo hemorrhagic fever?

BackgroundIn Crimean-Congo hemorrhagic fever, bleeding has a significant impact on the prognosis of the disease. In our study, we aimed to identify independent risk factors for the development of bleeding in Crimean-Congo hemorrhagic fever and to contribute to the management of the disease. MethodsCases with a definitive diagnosis of Crimean-Congo hemorrhagic fever were divided into two groups: those who developed bleeding and those who did not. Demographic, clinical and laboratory parameters were subjected to logistic regression analysis in terms of risk factors for bleeding development. Cut-off values for numerical variables were determined by receiver operating characteristics. ResultsA total of 74 patients diagnosed with CCHF were included in the study. Bleeding occurred in at least one defined focus in 21 patients. In the multivariate logistic regression model, procalcitonin, days from symptom onset to admission, platelet count, and d-dimer were identified as independent risk factors for bleeding development. Procalcitonin had the most significant effect, with an approximately 5.3-fold increase in bleeding risk for each unit increase in its level. For discriminate bleeding, LDH and ferritin exhibited the highest sensitivity, while procalcitonin showed the highest specificity. ConclusionThis study demonstrates the potential use of specific clinical and laboratory variables to predict bleeding development in CCHF patients. Procalcitonin elevation and the time from symptom onset to hospital admission have a significant effect in predicting bleeding.

News Items of Russian and Foreign News Agencies on WHO Priority Pathogens: A Comparative Analysis

Introduction: Broadcasting socially important information, including that on infectious disease outbreaks, news agencies are one of the key open sources of epidemic intelligence. Objective: To compare news items on World Health Organization priority pathogens published by Russian and foreign news agencies. Materials and methods: Using the variants of the names of World Health Organization priority pathogens as search queries, among all Google search results on the websites of four agencies (Associated Press, Reuters, Novosti Russian Information Agency, and TASS Russian News Agency) we found 714 news items published in 2018–2022 that have one of the following diseases as the main topic: Crimean-Congo hemorrhagic fever; Ebola virus disease, Marburg virus disease, Lassa fever, Middle East respiratory syndrome, Nipah and henipavirus infections, Rift Valley fever, and Zika fever. We carried out a quantitative (number of news items) and qualitative (topics) content analysis of the sample comparing the findings by agency and pathogen. Results: Each news agency accounted for 20 to 30 % of the sample (approximately 57 % in case of foreign ones), with greater genre diversity among foreign agencies. The vast majority of news items across all agencies were on Ebola (506 stories in total), while in 27 instances the number of the agency news stories on the pathogen was less than 20, and the largest gap between the news agencies regarding the number of the news stories on a single pathogen was seventeen fold (for Lassa). Disease incidence was the predominant topic of the news items. Discussion: Russian and foreign news agencies provided similarly intensive and topically diverse news flows on World Health Organization priority pathogens, with frequent non-reporting on different outbreaks (except for Ebola and Marburg virus diseases), and complemented each other with information relevant to Russian and Western audiences, respectively.

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

First Broad-Range Serological Survey of Crimean-Congo Hemorrhagic Fever among Hungarian Livestock.

(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.

A Novel Drug Candidate for Sepsis Targeting Heparanase by Inhibiting Cytokine Storm.

Sepsis is an infection-triggered, rapidly progressive systemic inflammatory syndrome with a high mortality rate. Currently, there are no promising therapeutic strategies for managing this disease in the clinic. Heparanase plays a crucial role in the pathology of sepsis, and its inhibition can significantly relieve related symptoms. Here, a novel heparanase inhibitor CV122 is rationally designed and synthesized, and its therapeutic potential for sepsis with Lipopolysaccharide (LPS) and Cecal Ligation and Puncture (CLP)-induced sepsis mouse models are evaluated. It is found that CV122 potently inhibits heparanase activity in vitro, protects cell surface glycocalyx structure, and reduces the expression of adhesion molecules. In vivo, CV122 significantly reduces the systemic levels of proinflammatory cytokines, prevents organ damage, improves vitality, and efficiently protects mice from sepsis-induced death. Mechanistically, CV122 inhibits the activity of heparanase, reduces its expression in the lungs, and protects glycocalyx structure of lung tissue. It is also found that CV122 provides effective protection from organ damage and death caused by Crimean-Congo hemorrhagic fever virus (CCHFV) infection. These results suggest that CV122 is a potential drug candidate for sepsis therapy targeting heparanase by inhibiting cytokine storm.

The low-density lipoprotein receptor and apolipoprotein E associated with CCHFV particles mediate CCHFV entry into cells

The Crimean-Congo hemorrhagic fever virus (CCHFV) is an emerging pathogen of the Orthonairovirus genus that can cause severe and often lethal hemorrhagic diseases in humans. CCHFV has a broad tropism and can infect a variety of species and tissues. Here, by using gene silencing, blocking antibodies or soluble receptor fragments, we identify the low-density lipoprotein receptor (LDL-R) as a CCHFV entry factor. The LDL-R facilitates binding of CCHFV particles but does not allow entry of Hazara virus (HAZV), another member of the genus. In addition, we show that apolipoprotein E (apoE), an exchangeable protein that mediates LDL/LDL-R interaction, is incorporated on CCHFV particles, though not on HAZV particles, and enhances their specific infectivity by promoting an LDL-R dependent entry. Finally, we show that molecules that decrease LDL-R from the surface of target cells could inhibit CCHFV infection. Our study highlights that CCHFV takes advantage of a lipoprotein receptor and recruits its natural ligand to promote entry into cells.

Vaccine approaches and treatment aspects against Crimean Congo hemorrhagic fever.

Crimean-Congo hemorrhagic fever [CCHF] is a severe infectious viral disease caused by a tick borne virus which can lead to fatal hemorrhagic disease in humans. It has been reported from some continents including Africa, Asia and Europe. Virus is transmitted to human mainly through tick bite, whose acquire infection from reservoirs wild and domesticated mammalians and ostriches. Currently no approved vaccine or drug is available for CCHF and prevention is mainly based on biosecurity measures. Ribavirin is the only approved drug that has been used in some countries to treat human disease, however some new studies did not prove the Ribavirin efficacy. Different strategies to design effective vaccines, have been conducted through years, from inactivated virus to nucleotide-based ones including DNA and mRNA vaccines. In this study we review of pioneering vaccine candidate platforms.

Replicon particle vaccination induces non-neutralizing anti-nucleoprotein antibody-mediated control of Crimean-Congo hemorrhagic fever virus

Crimean-Congo hemorrhagic fever virus (CCHFV) can cause severe human disease and is considered a WHO priority pathogen due to the lack of efficacious vaccines and antivirals. A CCHF virus replicon particle (VRP) has previously shown protective efficacy in a lethal Ifnar-/- mouse model when administered as a single dose at least 3 days prior to challenge. Here, we determine that non-specific immune responses are not sufficient to confer short-term protection, since Lassa virus VRP vaccination 3 days prior to CCHFV challenge was not protective. We also investigate how CCHF VRP vaccination confers protective efficacy by examining viral kinetics, histopathology, clinical analytes and immunity early after challenge (3 and 6 days post infection) and compare to unvaccinated controls. We characterize how these effects differ based on vaccination period and correspond to previously reported CCHF VRP-mediated protection. Vaccinating Ifnar-/- mice with CCHF VRP 28, 14, 7, or 3 days prior to challenge, all known to confer complete protection, significantly reduced CCHFV viral load, mucosal shedding, and markers of clinical disease, with greater reductions associated with longer vaccination periods. Interestingly, there were no significant differences in innate immune responses, T cell activation, or antibody titers after challenge between groups of mice vaccinated a week or more before challenge, but higher anti-NP antibody avidity and effector function (ADCD) were positively associated with longer vaccination periods. These findings support the importance of antibody-mediated responses in VRP vaccine-mediated protection against CCHFV infection.

Antibodies targeting Crimean-Congo hemorrhagic fever virus GP38 limit vascular leak and viral spread.

Crimean-Congo hemorrhagic fever virus (CCHFV) is a priority pathogen transmitted by tick bites, with no vaccines or specific therapeutics approved to date. Severe disease manifestations include hemorrhage, endothelial dysfunction, and multiorgan failure. Infected cells secrete the viral glycoprotein GP38, whose extracellular function is presently unknown. GP38 is considered an important target for vaccine and therapeutic design as GP38-specific antibodies can protect against severe disease in animal models, albeit through a currently unknown mechanism of action. Here, we show that GP38 induces endothelial barrier dysfunction in vitro, and that CCHFV infection, and GP38 alone, can trigger vascular leak in a mouse model. Protective antibodies that recognize specific antigenic sites on GP38, but not a protective neutralizing antibody binding the structural protein Gc, potently inhibit endothelial hyperpermeability in vitro and vascular leak in vivo during CCHFV infection. This work uncovers a function of the secreted viral protein GP38 as a viral toxin in CCHFV pathogenesis and elucidates the mode of action of non-neutralizing GP38-specific antibodies.

Bioinformatics Characteristics and Genomic Patterns of the Envelope Glycoproteins of the Crimean-congo Hemorrhagic Fever Viruses

Background: Rodents and many wild and domestic animals, including cattle, donkeys, goats, hares, ostriches, and sheep, spread the Crimean-Congo Hemorrhagic Fever Virus (CCHFV), acting as hosts for infected ticks primarily of the Hyalomma genus, which serve as vectors and reservoirs of the virus. CCHF is a severe, potentially lethal, and widespread disease, making it a serious public health issue. Environmental changes impacting rodent populations affect their global distribution and, therefore, play a role in the spread of CCHFV. Objective: This study aims togain a deeper understanding of the envelope glycoproteins expressed by the CCHFV. Methods: Multiple computational algorithms determined the Intrinsic Disorder Predisposition (PIDP), Polarity Index, and genomic profiles of each sequence of the glycoproteins. Results: When examining the Polarity Index Method Profile, 3.0v profile, and the PIDP profile, the envelope glycoproteins of the CCHFV showed different patterns. With these patterns, it was possible to identify structural and morphological similarities. Conclusion: With the PIM 3.0v profile, our computer programs were able to identify isolated CCHFV envelope glycoproteins. We believe that this research provides a deeper understanding of this virus. conclusion: Using the PIM 3.0v profile, our computer programs were able to identify isolates of the CCHFV envelope glycoproteins. We believe that this research contributes to a deeper understanding of this emerging virus.

We Need More Accuracy in Crimean-Congo Hemorrhagic Fever Diagnosis upon Initial Presentation in Endemic Areas.

Background: The primary aim of this study was to highlight the considerable rate of misdiagnosis associated with Crimean-Congo Hemorrhagic Fever (CCHF) during initial hospital admission. Materials and Methods: A comprehensive face-to-face survey was carried out on hospitalized patients living in endemic areas with confirmed diagnosis of CCHF. The structured questionnaire covered demographic information, specifics of hospital admissions before diagnosis, and adherence to the diagnostic criteria for CCHF as determined by the Ministry of Health (MoH). Results: This cohort consisted of 100 patients with a mean age of 44 (20-77) years, of which 65 (65%) were male. Each patient had undergone at least one hospital visit (0-3) before receiving the confirmed diagnosis of CCHF. Only 45 (45%) patients were thoroughly evaluated in line with the clinical diagnostic criteria set forth by the MoH, while 21% had initially received provisional CCHF diagnoses before final confirmation. Conclusions: This study indicates the urgent necessity to improve diagnostic accuracy for CCHF during the initial presentation in endemic regions.

A replicating RNA vaccine confers protection in a rhesus macaque model of Crimean-Congo hemorrhagic fever

Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne febrile illness with a wide geographic distribution. In recent years the geographic range of Crimean-Congo hemorrhagic fever virus (CCHFV) and its tick vector have increased, placing an increasing number of people at risk of CCHFV infection. Currently, there are no widely available vaccines, and although the World Health Organization recommends ribavirin for treatment, its efficacy is unclear. Here we evaluate a promising replicating RNA vaccine in a rhesus macaque (Macaca mulatta) model of CCHF. This model provides an alternative to the established cynomolgus macaque model and recapitulates mild-to-moderate human disease. Rhesus macaques infected with CCHFV consistently exhibit viremia, detectable viral RNA in a multitude of tissues, and moderate pathology in the liver and spleen. We used this model to evaluate the immunogenicity and protective efficacy of a replicating RNA vaccine. Rhesus macaques vaccinated with RNAs expressing the CCHFV nucleoprotein and glycoprotein precursor developed robust non-neutralizing humoral immunity against the CCHFV nucleoprotein and had significant protection against the CCHFV challenge. Together, our data report a model of CCHF using rhesus macaques and demonstrate that our replicating RNA vaccine is immunogenic and protective in non-human primates after a prime-boost immunization.

A Luciferase Immunosorbent Assay Based on Attachment Glycoprotein for the Rapid and Easy Detection of Nipah Virus IgG Antibodies.

Nipah virus (NiV) is a virulent zoonotic disease whose natural host is the fruit bat (Pteropus medius), which can coexist with and transmit the virus. Due to its high pathogenicity, wide host range, and pandemic potential, establishing a sensitive, specific, and rapid diagnostic method for NiV is key to preventing and controlling its spread and any outbreaks. Here, we established a luciferase immunosorbent assay (LISA) based on the NiV attachment glycoprotein (G) to detect NiV-specific immunoglobulin G by expressing a fusion protein of nanoluciferase (NanoLuc) and the target antigen. Sensitivity analysis was performed and compared to an indirect enzyme-linked immunosorbent assay (ELISA), and specificity and cross-reactivity assessments were performed using NiV-positive horse serum and Ebola virus-, Crimean-Congo hemorrhagic fever virus-, and West Nile virus-positive horse sera. The optimal structural domain for NiV detection was located within amino acids 176-602 of the NiV G protein head domain. Moreover, the LISA showed at least fourfold more sensitivity than the indirect ELISA, and the cross-reactivity results suggested that the LISA had good specificity and was capable of detecting NiV-specific immunoglobulin G in both mouse and horse serum. In conclusion, the establishment of a rapid, simple NiV LISA using the G protein head domain provides a resource for NiV monitoring.

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.

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.

Epidemiologic Features and Risk Factors for Crimean-Congo Hemorrhagic Fever in Dhi Qar Province, Iraq.

Crimean-Congo hemorrhagic fever virus (CCHFV) is endemic in Iraq, where recurrent epidemics have been constantly observed during the last five years. The present study aimed to determine the factors associated with Crimean-Congo hemorrhagic fever (CCHF) cases in Dhi Qar province during the year 2022. A test-negative case-control design was used to analyze 621 CCHF patients, of which 162 were confirmed and 459 were suspected cases. To identify the confirmed and suspected cases, reverse transcriptase polymerase chain reaction (RT-PCR) was used. Suspected patients whose PCR test results were negative were selected as the control group. Data on potential risk factors for CCHF were collected as existing data for previous years for the same geographical locations in Dhi Qar province. Logistic regression analyses were used to determine the correlation between probable risk factors and confirmed CCHF cases. The incidence rate of CCHF was 6.8% per 100,000 people. The total number of deaths was 48 for patients with a case fatality rate of 7.7%. The patients' ages ranged from one year to 65 years, with an overall mean ± SD of 36.08 ± 18.29 years. A total of 98.2% of the patients were between 15 and 65 years of age; 58% of the reported patients were male, and the male-to-female ratio was 1.4:1. Additionally, contact with raw meat, animal contact, and tick bite had the highest percentages for CCHF positivity cases. Male gender, high-risk jobs like housewives, health staff, shepherds, butchers, animal dealers, slaughterhouse workers, veterinary staff, and farmers, tick bites, and contact with raw meat were statistically significant predictors for increasing CCHF incidence in Dhi Qar province during the year 2022.

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.