Knowledge and Attitudes Regarding Crimean-Congo Hemorrhagic Fever Among Slaughterhouse Workers in Sana'a and Dhamar Cities-Yemen: A Cross-Sectional Study.

Background: Crimean-Congo Hemorrhagic Fever (CCHF) is a viral infection spread through tick bites or contact with secretions from infected animals or humans, posing a risk to slaughterhouse workers. This study aimed to evaluate the knowledge and attitudes of slaughterhouse workers in Yemen towards CCHF. Methods: A cross-sectional study conducted on 173 adults working at slaughterhouses in Sana'a and Dhamar cities, Yemen using a multi-stage sampling. The questionnaire used in the study was a reliable survey instrument (with a Cronbach's alpha coefficient of 0.71) employed for the purpose of data collection. The questionnaire encompassed three distinct sections: 1)- demographic inquiries pertaining to age, gender, marital status, level of education, and occupation; 2)- knowledge-based inquiries consisting of 27 items;3)- the attitude section consisted of 11 questions. After completing the questionnaire, the data were analyzed by SPSS version 24, using percentages, chi-square test, and Spearman correlation coefficient. Results: The mean age of the participants was 30.6 years with a SD of 11.2 years, with 84.4% male and 15.6% female. Most slaughterhouse workers were butchers (78.6%) and some were shepherds (21.4%). The participants had poor knowledge (86.7%) and attitude (72.3%) towards CCHF. There exists a noteworthy association between the knowledge scores and the gender, education level, and occupation (P=0.035, P=0.039, P=0.001). A significant positive correlation was identified between knowledge and attitude scores (r = 0.715, P<0.001). Conclusion: The majority of respondents had poor knowledge of CCHF. Educational programs are essential for increasing community awareness, with involvement of technical experts crucial for disseminating information on preventing and managing CCHF.

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.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Looking Beyond the Lens of Crimean-Congo Hemorrhagic Fever in Africa.

Crimean-Congo hemorrhagic fever (CCHF) is a lethal viral disease that has severe public health effects throughout Africa and a case fatality rate of 10%-40%. CCHF virus was first discovered in Crimea in 1944 and has since caused a substantial disease burden in Africa. The shortage of diagnostic tools, ineffective tick control efforts, slow adoption of preventive measures, and cultural hurdles to public education are among the problems associated with continued CCHF virus transmission. Progress in preventing virus spread is also hampered by the dearth of effective serodiagnostic testing for animals and absence of precise surveillance protocols. Intergovernmental coordination, creation of regional reference laboratories, multiinstitutional public education partnerships, investments in healthcare infrastructure, vaccine development, and a One Health approach are strategic methods for solving prevention challenges. Coordinated efforts and financial commitments are needed to combat Crimean-Congo hemorrhagic fever and improve all-around readiness for newly developing infectious illnesses in Africa.

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

BACKGROUND: In 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. METHODS: Cases 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. RESULTS: A 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. CONCLUSION: This 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.

Urgent call for holistic action: Addressing the Crimean-Congo hemorrhagic fever (CCHF) crisis in Pakistan's healthcare system.

•Urgent plea for global collaboration as Crimean-Congo Hemorrhagic Fever ravages Pakistan's healthcare system.•Crisis deepens with 41 confirmed cases, 15 fatalities, and a call to fortify healthcare infrastructure.•Government measures in Balochistan deemed a prelude; urgent actions and long-term strategies imperative.•Strategic recommendations unveiled for a holistic approach: from healthcare infrastructure to rapid response teams.

Convalescent human plasma candidate reference materials protect against Crimean-Congo haemorrhagic fever virus (CCHFV) challenge in an A129 mouse model.

Crimean-Congo Haemorrhagic Fever Virus (CCHFV) is spread by infected ticks or direct contact with blood, tissues and fluids from infected patients or livestock. Infection with CCHFV causes severe haemorrhagic fever in humans which is fatal in up to 83 % of cases. CCHFV is listed as a priority pathogen by the World Health Organization (WHO) and there are currently no widely-approved vaccines. Defining a serological correlate of protection against CCHFV infection would support the development of vaccines by providing a 'target threshold' for pre-clinical and clinical immunogenicity studies to achieve in subjects and potentially obviate the need for in vivo protection studies. We therefore sought to establish titratable protection against CCHFV using pooled human convalescent plasma, in a mouse model. Convalescent plasma collected from seven individuals with a known previous CCHFV virus infection were characterised using binding antibody and neutralisation assays. All plasma recognised nucleoprotein and the Gc glycoprotein, but some had a lower Gn glycoprotein response by ELISA. Pooled plasma and two individual donations from convalescent donors were administered intraperitoneally to A129 mice 24 h prior to intradermal challenge with CCHFV (strain IbAr10200). A partial protective effect was observed with all three convalescent plasmas characterised by longer survival post-challenge and reduced clinical score. These protective responses were titratable. Further characterisation of the serological reactivities within these samples will establish their value as reference materials to support assay harmonisation and accelerate vaccine development for CCHFV.

The Risk of Crimean Congo Haemorrhagic Fever in India as a Growing Health Concern.

Every year witnesses an outbreak of some or the other zoonotic disease that causes the unparalled loss of human life. The year 2022 presented the outbreak of Crimean Congo haemorrhagic fever (CCHF), which brought unprecedented challenges to individuals as well as to the healthcare system all around the world, making it a serious health concern. Rising health concerns have highlighted the importance of managing and decreasing the further transmission of the CCHF virus. CCHF is one of tick-borne viral diseases, which spreads due to various reasons like changes in global warming, environmental influences, and other ecological factors. All these factors somehow impact the disease prevalence. This disease has a negative impact on both humans and livestock. The diverse climate and significant livestock population of India make it susceptible to the prevalence of CCHF. Therefore, it is the need of the hour to develop some strategies in order to tackle the challenges posed by CCHF. This article includes all the cases of CCHF that have occurred in India from the year 2011, along with the fatality rates associated with this disease. Also this study discusses the need to explore some specific drugs for the management and prevention of such diseases. In addition, the pathogenesis of the disease progression, along with some protective measures suggested by the government has been described for prevention of CCHF. Subsequently, this article attempted to draw attention towards the risk that may be posed by CCHF in the coming scenario, emphasizing the importance of taking proactive measures in anticipation of such risks.

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.

Alarming update on incidence of Crimean-Congo hemorrhagic fever in Iraq in 2023.

Objectives: In 2021, large outbreak of Crimean-Congo hemorrhagic fever (CCHF) was reported in Iraq and cases have increased without any significant control measures. To raise awareness about the increasing cases in different regions of Iraq, hence remind the necessity to tackle contributing factors and potential outbreak interventions. Methods: The study included 511 polymerase chain reaction-confirmed CCHF infection cases out of 1827 suspected cases from 18 Provinces from January to August 2023. Approval from the Ministry of Health for data analyzed. Results: Out of 1827 suspected cases, 511 were confirmed positive by polymerase chain reaction. The total case fatality rate (CFR) was 12.7 with varying severity levels among provinces. Erbil had the highest CFR, 38.5, while Sulaimaniya and Anbar report no deaths. Independent t-test showed a significant difference in CFR between provinces west and south of Baghdad compared to north (P <0.05). Trend showed significant surges after Iftar and Adha holidays. Conclusion: Differences in CFR among provinces around the religious ceremonies, highlight the need for one public health intervention strategy. Increased temperatures affected vector behavior. Uncontrolled animal movement with neighboring countries is an important factor. Virus or host determinants can shape the clinical case outcomes, which need clinical and extensive laboratory studies to unravel the reasons leading to death.

Crimean-Congo Hemorrhagic Fever: An Emerging Viral Infection in India, Revisited and Lessons Learned.

Crimean-Congo hemorrhagic fever (CCHF) is a zoonotic disease caused by the CCHF virus. It was first recognized in 1944 in the Crimea region of the former Soviet Union and then was subsequently isolated in Congo, from a child with similar symptoms. Hence, the virus was termed the Crimean-Congo hemorrhagic fever virus. CCHF is an emerging disease with more than 1000 human cases being reported every year from South-Eastern Europe and Western Asia. The disease is endemic in Africa, the Balkans, the Middle East, and Asia, with an estimated 10,000 to 15,000 CCHF infections each year. The geographic range of the CCHF virus is most extensive among the tick-borne viruses that infect humans. The first outbreak of CCHF in India was described in 2011 in the state of Gujarat with four cases being reported. Since then, there have been sporadic cases in India occurring in small clusters with community and nosocomial spread. Here, we describe three cases that were treated at a tertiary care teaching hospital in the Gujarat state of India. All of them had nonspecific symptoms of viremia initially, followed by rapid deterioration of the general condition. Two of the three patients died. Because of its resemblance with other hemorrhagic fevers, diagnosis of CCHF remains a challenge, especially in non-endemic areas. We aim to sensitize the readers to this emerging arboviral disease because the virus is highly infectious and carries high mortality, and hence, it is crucial to suspect and diagnose the index case at the earliest.

The Spatial Distribution of Crimean-Congo Haemorrhagic Fever and Its Potential Vectors in Europe and Beyond.

Crimean-Congo haemorrhagic fever (CCHF) is considered to be spreading across the globe, with many countries reporting new human CCHF cases in recent decades including Georgia, Türkiye, Albania, and, most recently, Spain. We update a human CCHF distribution map produced in 2015 to include global disease occurrence records to June 2022, and we include the recent records for Europe. The predicted distributions are based on long-established spatial modelling methods and are extended to include all European countries and the surrounding areas. The map produced shows the environmental suitability for the disease, taking into account the distribution of the most important known and potential tick vectors Hyalomma marginatum and Hyalomma lusitanicum, without which the disease cannot occur. This limits the disease's predicted distribution to the Iberian Peninsula, the Mediterranean seaboard, along with Türkiye and the Caucasus, with a more patchy suitability predicted for inland Greece, the southern Balkans, and extending north to north-west France and central Europe. These updated CCHF maps can be used to identify the areas with the highest probability of disease and to therefore target areas where mitigation measures should currently be focused.

Seroprevalence of Crimean Congo Hemorrhagic Fever Virus in Occupational Settings: Systematic Review and Meta-Analysis.

Crimean Congo Hemorrhagic Fever (CCHF) Virus can cause a serious human disease, with the case fatality ratio previously estimated to be 30-40%. Our study summarized seroprevalence data from occupational settings, focusing on the following occupational groups: animal handlers, abattoir workers, farmers, healthcare workers, veterinarians, rangers, and hunters. Systematic research was performed on three databases (PubMed, EMBASE, MedRxiv), and all studies reporting seroprevalence rates (IgG-positive status) for CCHF virus were retrieved and their results were reported, summarized, and compared. We identified a total of 33 articles, including a total of 20,195 samples, i.e., 13,197 workers from index occupational groups and 6998 individuals from the general population. Pooled seroprevalence rates ranged from 4.751% (95% confidence intervals (95% CI) 1.834 to 11.702) among animal handlers, to 3.403% (95% CI 2.44 to 3.932) for farmers, 2.737% (95% CI 0.896 to 8.054) among rangers and hunters, 1.900% (95% CI 0.738 to 4.808) for abattoir workers, and 0.644% (95% CI 0.223-1.849) for healthcare workers, with the lowest estimate found in veterinarians (0.283%, 95% CI 0.040-1.977). Seroprevalence rates for abattoir workers (odds ratio (OR) 4.198, 95% CI 1.060-16.464), animal handlers (OR 2.399, 95% CI 1.318-4.369), and farmers (OR 2.280, 95% CI 1.419 to 3.662) largely exceeded the official notification rates for CCHF in the general population. CCHF is reasonably underreported, and pooled estimates stress the importance of improving the adherence to personal protective equipment use and appropriate preventive habits.

Cases of Crimean-Congo haemorrhagic fever in North Macedonia, July to August 2023.

The last report of Crimean-Congo haemorrhagic fever (CCHF) in North Macedonia was more than 50 years ago in the northwest. We report on a fatal CCHF case following a Hyalomma tick bite in the east of the country in July 2023. Tracing of 67 contacts identified CCHF in one healthcare worker (HCW) providing care for the patient. Monitoring of contacts is concluded (including further 11 HCW contacts), thus far 28 days after the death of the case no additional cases were identified.

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.

Status of Crimean-Congo haemorrhagic fever virus in ticks in Iran: A systematic review with meta-analysis.

Crimean-Congo haemorrhagic fever (CCHF) is a re-emerging viral haemorrhagic fever causing outbreaks in Iran in the last 15 years. In this systematic review and meta-analysis, the status of Crimean-Congo haemorrhagic fever virus (CCHFV) in ticks would be evaluated. PubMed, Google Scholar and Web of Science were searched for peer-reviewed original papers published between 2000 and 1 July 2022. We included papers that evaluated the prevalence of CCHFV in individual ticks using reverse transcription polymerase chain reaction (RT-PCR). The pooled prevalence of CCHFV was 6.0% (95% confidence interval [CI]: 4.5-7.9%), with heterogeneity (I2 = 82.706; P < 0.0001). The prevalence of CCHFV was higher related to regions with above sea level of 1001-1500m (6.4%; 95% CI: 4.3-9.5%), an average temperature of ≤15 °C (8.3%; 95% CI: 5.6-12.0%), latitude of ≥36° (8.1%; 95% CI: 5.2-12.3%), an annual rainfall of 101-300 mm (9.8%; 95% CI: 6.1-15.4%) and humidity of ≥61% (10.2%; 95% CI: 5.1-19.3%). Due to the importance of CCHF, it is better to do new epidemiologic studies on ticks by related organizations and adjacent regions of some provinces in which human cases have been previously reported.

Can Fractional Exhaled Nitric Oxide (FeNO) Serve as a Clinical Indicator for Patients Hospitalized with Crimean-Congo Hemorrhagic Fever?

Crimean-Congo hemorrhagic fever (CCHF), a zoonotic disease spread by infected viruses, can be a significant cause of morbidity and mortality in endemic areas. This prospective study aimed to establish the relationship between fractional exhaled nitric oxide (FeNO) levels and clinical prognosis of CCHF. The study included 85 participants: 55 patients followed up for CCHF from May to August 2022, and 30 healthy controls. FeNO levels were measured upon hospital admission and were 7.6 ± 3.3 parts per billion (ppb) in patients with mild/moderate CCHF, 2.5 ± 2.1 ppb in patients with severe CCHF, and 6.7 ± 1.7 ppb in the healthy control group. There was no statistically significant difference in FeNO levels between the control group and patients with mild/moderate CCHF (P = 0.09), whereas patients with severe CCHF had lower FeNO levels than those in the control group and patients with mild/moderate CCHF (P < 0.001 for both). FeNO measurement may offer a noninvasive and easily applied approach for predicting the clinical course and prognosis of CCHF in the early stages of the disease.

Distribution pattern of Crimean-Congo Hemorrhagic Fever in Asia and the Middle East.

Crimean-Congo Hemorrhagic Fever (CCHF) is one of the most important vector-borne diseases of zoonotic potential that can be acquired following the bite of the Hyalomma species of ticks. It is a highly prevalent disease in Asia and the Middle East. The risk factors of this disease are contact with infected tissue, blood, patient, or livestock in the acute viremic phase, infected tick bites, or the manual removal of ticks. The disease is clinically described as progressive hemorrhages, fever, and pain in musculature. Biochemical tests reveal elevated levels of creatinine phosphokinase, alanine transaminase, aspartate aminotransferase, and lactate dehydrogenase. Clotting time is prolonged in pro-thrombin tests, and pathogenesis is mostly related to the disruption of the epithelium during viral replication and indirectly by secreting cytotoxic molecules. These molecules cause endothelial activation and result in the loss of function. Supportive therapy is given through blood or plasma infusions to treat or manage the patients. According to the most advanced studies, CCHF can be treated by Ribavirin, which is an antiviral drug that shows excellent results in preventing the disease. Health-care staff are more prone to infection. The hemorrhagic phase represents a high risk for accidental exposures. This literature review presents a comprehensive overview of the viral epidemiology, zoonotic perspectives, and significant risk factors of CCHF in various Middle East and Asian countries. Furthermore, the pathophysiology and preventive strategies of CCHF have also been discussed as well as legislation and policies regarding public outreach programs, research, and development aimed at infection prevention and control that are required at a global level.

In silico formulation of a next-generation multiepitope vaccine for use as a prophylactic candidate against Crimean-Congo hemorrhagic fever.

BACKGROUND: Crimean-Congo hemorrhagic fever (CCHF) is a widespread disease transmitted to humans and livestock animals through the bite of infected ticks or close contact with infected persons' blood, organs, or other bodily fluids. The virus is responsible for severe viral hemorrhagic fever outbreaks, with a case fatality rate of up to 40%. Despite having the highest fatality rate of the virus, a suitable treatment option or vaccination has not been developed yet. Therefore, this study aimed to formulate a multiepitope vaccine against CCHF through computational vaccine design approaches. METHODS: The glycoprotein, nucleoprotein, and RNA-dependent RNA polymerase of CCHF were utilized to determine immunodominant T- and B-cell epitopes. Subsequently, an integrative computational vaccinology approach was used to formulate a multi-epitopes vaccine candidate against the virus. RESULTS: After rigorous assessment, a multiepitope vaccine was constructed, which was antigenic, immunogenic, and non-allergenic with desired physicochemical properties. Molecular dynamics (MD) simulations of the vaccine-receptor complex show strong stability of the vaccine candidates to the targeted immune receptor. Additionally, the immune simulation of the vaccine candidates found that the vaccine could trigger real-life-like immune responses upon administration to humans. CONCLUSIONS: Finally, we concluded that the formulated multiepitope vaccine candidates would provide excellent prophylactic properties against CCHF.