Analysis of liver fibrosis equations as a potential role of predictive models in Crimean-Congo hemorrhagic fever.

Crimean-Congo Hemorrhagic Fever (CCHF) is a formidable global health concern, characterized by its rapid onset and high fatality rate. Distinguishing between patients at different stages remains challenging because of overlapping clinical features. This study aimed to evaluate the diagnostic efficacy of 14 hepatic fibrosis indices for distinguishing fatal cases and intensive care unit requirement (ICU) in CCHF. This study enrolled 194 patients with confirmed CCHF. Laboratory measurements were performed using auto analyzers. Indirect indicators of fibrosis were calculated for each patient based on previously described formulas. Time-dependent receiver operating characteristic (tdROC) curve analyses were employed to evaluate the predictive effects of hepatic fibrosis indices on both intensive care unit requirement and overall survival among patients. Regarding the tdROC analyses results, the highest area under the curve statistics were obtained for the baseline S-INDEX, KING, and GPRI scores (0.920, 0.913, and 0.909 respectively) in the estimation of ten-day survival, and the baseline KING, Goteborg University cirrhosis index (GUCI), and gamma-glutamyl transferase to platelet ratio index (GPRI) scores (0.783, 0.773, and 0.769 respectively) in the estimation of intensive care requirements for up to ten days. S-index and KING index emerged as early predictors of ten-day survival, while KING, GUCI, and GPRI indices demonstrated predictive capabilities for ICU admission on the first day. The identified indices have the potential to assist healthcare providers in making timely and informed decisions regarding patient management and treatment strategies. Further research and validation are warranted to solidify the role of these hepatic fibrosis indices in the clinical setting and enhance their broader applicability in the management of CCHF.

Risk factors associated with exposure to Crimean-Congo haemorrhagic fever virus in animal workers and cattle, and molecular detection in ticks, South Africa.

Crimean-Congo haemorrhagic fever (CCHF) is a severe tick-borne viral zoonosis endemic to parts of Africa, Europe, the Middle East and Central Asia. Human cases are reported annually in South Africa, with a 25% case fatality rate since the first case was recognized in 1981. We investigated CCHF virus (CCHFV) seroprevalence and risk factors associated with infection in cattle and humans, and the presence of CCHFV in Hyalomma spp. ticks in central South Africa in 2017-18. CCHFV IgG seroprevalence was 74.2% (95%CI: 64.2-82.1%) in 700 cattle and 3.9% (95%CI: 2.6-5.8%) in 541 farm and wildlife workers. No veterinary personnel (117) or abattoir workers (382) were seropositive. The prevalence of CCHFV RNA was significantly higher in Hyalomma truncatum (1.6%) than in H. rufipes (0.2%) (P = 0.002). Seroprevalence in cattle increased with age and was greater in animals on which ticks were found. Seroprevalence in cattle also showed significant geographic variation. Seroprevalence in humans increased with age and was greater in workers who handled livestock for injection and collection of samples. Our findings support previous evidence of widespread high CCHFV seroprevalence in cattle and show significant occupational exposure amongst farm and wildlife workers. Our seroprevalence estimate suggests that CCHFV infections are five times more frequent than the 215 confirmed CCHF cases diagnosed in South Africa in the last four decades (1981-2019). With many cases undiagnosed, the potential seriousness of CCHF in people, and the lack of an effective vaccine or treatment, there is a need to improve public health awareness, prevention and disease control.

Mapping the environmental suitability of etiological agent and tick vectors of Crimean-Congo hemorrhagic fever.

Crimean-Congo hemorrhagic fever (CCHF) is one of the most important public health threats in many regions across Africa, Europe, and Asia. This study used ecological niche modeling analyses to map the environmental suitability of both CCHF virus (CCHFV), and its tick vectors (Amblyomma variegatum, Dermacentor marginatus, Hyalomma marginatum, Hyalomma rufipes, Hyalomma truncatum, Rhipicephalus appendiculatus, and Rhipicephalus evertsi evertsi) in the Old World countries. The CCHFV was anticipated to occur with high environmental suitability across southern and central Europe, northwestern Africa, central Asia, and western Mediterranean region. Ecological niche models of tick vectors anticipated diverse patterns based on the tick species in question; D. marginatus and H. marginatum showed high environmental suitability in southern and central Europe, and North Africa. The remaining vector species were anticipated to occur in Africa. All models were statistically robust and performed better than random (P < 0.001). Finally, we tested the niche similarities between CCHFV and diverse tick vectors and could not reject the null hypotheses of niche similarity in all vector-virus combinations (P > 0.05) except the combinations of CCHFV with A. variegatum, R. evertsi evertsi and R. appendiculatus (P < 0.05).

Risk Factors for and Seroprevalence of Tickborne Zoonotic Diseases among Livestock Owners, Kazakhstan.

Crimean-Congo hemorrhagic fever (CCHF), Q fever, and Lyme disease are endemic to southern Kazakhstan, but population-based serosurveys are lacking. We assessed risk factors and seroprevalence of these zoonoses and conducted surveys for CCHF-related knowledge, attitudes, and practices in the Zhambyl region of Kazakhstan. Weighted seroprevalence for CCHF among all participants was 1.2%, increasing to 3.4% in villages with a known history of CCHF circulation. Weighted seroprevalence was 2.4% for Lyme disease and 1.3% for Q fever. We found evidence of CCHF virus circulation in areas not known to harbor the virus. We noted that activities that put persons at high risk for zoonotic or tickborne disease also were risk factors for seropositivity. However, recognition of the role of livestock in disease transmission and use of personal protective equipment when performing high-risk activities were low among participants.

Crimean Congo Hemorrhagic Fever in Eastern Turkey: Epidemiological and Clinical Evaluation

Objective: The present study aimed to evaluate Crimean-Congo Haemorrhagic Fever (CCHF) in patients hospitalized in our hospital. Methods: A total of 61 adult patients who were diagnosed as having CCHF between January 2011 and August 2018, in whom the diagnosis was confirmed by detecting virus-specific IgM by ELISA and/or by showing viral RNA by RT-PCR and who were managed at our clinic were evaluated retrospectively for their epidemiological and clinical findings, treatment and prognosis. Results: Of the 61 cases, 41 (67.2%) were male and 20 (32.8%) female. The mean age of the patients was 45.31±2.12 years. Sixty (98.4%) patients were living in rural area. Forty four patients (72.1 %) had a tick-bite history. According to months, most of the cases were seen in June, July and May, respectively. Fever, weakness and loss of appetite were the most common complaints of the patients. Treatment of ribavirin was started on the day of admission in all patients. One patient who was admitted in the late period died. The other 60 patients were discharged after being healed. Conclusions: Especially during summers when the disease is seen frequently, the history of tick contact should be questioned and tick should be searched in the examination in the patients with suspected clinical findings. A significant number of the patients do not have a known tick contact. Therefore, training meetings should be organized about the symptoms and findings of the disease in the endemic areas and awareness should be raised among the community and the doctors working in emergency services and primary care.

Crimean Congo hemorrhagic fever serosurvey in humans for identifying high-risk populations and high-risk areas in the endemic state of Gujarat, India.

BACKGROUND: Crimean Congo Hemorrhagic Fever (CCHF) is a highly infectious zoonotic disease of humans transmitted by Hyalomma ticks. Earlier studies have shown CCHF seroprevalence in livestock throughout India, yet sporadic outbreaks have been recorded mostly from the Gujarat state of India since 2011. Occupational vulnerability to CCHF for animal handlers, veterinarians, abattoir workers, and healthcare workers has been documented. The current study was planned to determine the seroprevalence of CCHF with an intention to identify the high -risk population and high -risk areas from Gujarat state, India. METHODS: Based on the socio-clinical data, the human population of Gujarat was divided into eight categories viz. A: CCHF affected person/house/close contact, B: Neighborhood contacts, C: Animal handlers, D: General population, E: Farmers, F: Abattoir workers, G: Veterinarian, H: Healthcare workers. A total of 4978 human serum samples were collected from 33 districts of Gujarat during year 2015, 2016 and 2017. All the samples were screened for the presence of anti-CCHFV IgG using indigenously developed anti-CCHFV IgG ELISA. Univariate regression analysis was performed to recognize significant risk factors for CCHF seropositivity. RESULTS: Twenty-five serum samples were found to be positive with an overall CCHF human seropositivity of 0.5% (95% CI 0.30-0.74%). Gender predisposition to CCHF prevalence was observed in males (OR: 2.80; p-value: 0.020). The risk for seropositivity increased sevenfold when a person was in contact or neighbor with a CCHF case (OR 7.02; p-value: < 0.0001). No significant difference in seropositivity was observed within different age groups. Veterinarians, healthcare workers, and control group were found to be seronegative for CCHF. CONCLUSIONS: In-spite of CCHF sporadic outbreaks reported in Gujarat, the seropositivity for CCHF in the state was low as compared to other endemic countries. Males, close contacts and neighbors were identified as a high-risk population for CCHF infection. To recognize the high-risk area, tick screening and animal serosurvey would be a wiser choice. The study also suggests circulation and under diagnoses of CCHFV in the naïve regions of Gujarat.

Recent advances in understanding Crimean-Congo hemorrhagic fever virus.

Crimean-Congo hemorrhagic fever virus (CCHFV) is a widely distributed hemorrhagic fever virus and the cause of hemorrhagic disease in Africa, Southern and Eastern Europe, the Middle East, India and Asia. Recent emergence of CCHFV into Spain indicates that the geographic range of this virus is expanding and the presence of its tick vector in several countries without reported disease suggest that CCHFV will continue to spread. Research into CCHFV was historically limited by a lack of suitable animal models and tools to study viral pathogenesis. However, in the past few years the toolset for studying CCHFV has expanded with small animal and non-human primate models for CCHFV being developed along with a reverse genetics system that allows for investigation of viral determinants of disease. These tools have been utilized to understand how CCHFV antagonizes host restriction factors and to develop novel vaccine candidates that may help limit the substantial morbidity and mortality in humans caused by CCHFV.

An Unexpected Fatal CCHF Case and Management of Exposed Health Care Workers.

Crimean-Congo hemorrhagic fever (CCHF) is a tick borne viral disease which can also be transmitted by direct contact with blood or tissue specimens of infected animals or humans. We present a fatal case of CCHF, who was diagnosed after death, and describe the post-exposure management plan for the health care workers (HCWs) involved in her care. In total of 52 HCWs were involved in the patient's care and they were stratified into risk groups. Overall, 20 HCWs were grouped in high and intermediate risk groups, including the HCW with needle stick injury. High and intermediate risk groups were offered post exposure prophlaxis (PEP) with ribavirin. Fourteen of 20 HCWs started PEP, however 10 ceased after negative CCHF-PCR results. Negative CCHF-PCR results were reported for all HCWs at the 5th day of exposure. Side effects with PEP developed in 5 of HCWs and were mainly gastrointestinal complaints which reversed after drug discontinuation. All HCWs were followed for 14 days both clinically and with laboratory tests. None of the HCWs developed CCHF. PEP with ribavirin can be considered as a safe option in protection.

Prognostic factors, pathophysiology and novel biomarkers in Crimean-Congo hemorrhagic fever.

Crimean-Congo hemorrhagic fever (CCHF) is a geographically widespread tick-borne zoonosis. The clinical spectrum of the illness varies from mild infection to severe disease and death. In severe cases, hemorrhagic manifestations develop, with fatality rates of 4-20%, depending on the geographic region and quality of the health care. Although vast majority of the CCHF cases were reported from Turkey, mortality rate is lower than the other regions, which is 5% on average. Prediction of the clinical course of the disease enables appropriate management planning by the physician and prompt transportation, if needed, of the patient to a tertiary care hospital for an intensive therapy. Thus, predicting the outcome of the disease may avert potential mortality. There are numerous studies investigating the prognostic factors of CCHF in the literature. Majority of them were reported from Turkey and included investigations on clinical and biochemical parameters, severity scoring systems and some novel biomarkers. Somnolence, bleeding, thrombocytopenia, elevated liver enzymes and prolonged bleeding times are the most frequently reported prognostic factors to predict the clinical course of the disease earlier. High viral load seems to be the strongest predictor to make a clinical decision about the patient outcome. The severity scoring systems based on clinically important mortality-related parameters are especially useful for clinicians working in the field to predict the course of the disease and to decide which patient should be referred to a tertiary care hospital for intensive care. In the light of the pathophysiological characteristics of CCHF, some new biomarkers of prognosis including cytokines, soluble adhesion molecules, genetic polymorphisms and coagulopathy parameters were also investigated. However most of these tests are not available to clinicians and they were obtained mostly for research purposes. In spite of the various studies about prognostic factors, they have several inherent limitations, including large variability in the results and confusing data that are not useful for clinicians in routine practice. In this paper, the results of diverse studies of the prediction of the prognosis in CCHF based on epidemiological, clinical and laboratory findings of the disease were summarized and suggestions for future studies are provided.

Analysis of the entry mechanism of Crimean-Congo hemorrhagic fever virus, using a vesicular stomatitis virus pseudotyping system.

Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne disease causing severe hemorrhagic symptoms with a nearly 30 % case-fatality rate in humans. The experimental use of CCHF virus (CCHFV), which causes CCHF, requires high-biosafety-level (BSL) containment. In contrast, pseudotyping of various viral glycoproteins (GPs) onto vesicular stomatitis virus (VSV) can be used in facilities with lower BSL containment, and this has facilitated studies on the viral entry mechanism and the measurement of neutralizing activity, especially for highly pathogenic viruses. In the present study, we generated high titers of pseudotyped VSV bearing the CCHFV envelope GP and analyzed the mechanisms involved in CCHFV infection. A partial deletion of the CCHFV GP cytoplasmic domain increased the titer of the pseudotyped VSV, the entry mechanism of which was dependent on the CCHFV envelope GP. Using the pseudotype virus, DC-SIGN (a calcium-dependent [C-type] lectin cell-surface molecule) was revealed to enhance viral infection and act as an entry factor for CCHFV.

Predicting CCHF incidence and its related factors using time-series analysis in the southeast of Iran: comparison of SARIMA and Markov switching models.

Crimean-Congo haemorrhagic fever (CCHF) is endemic in the southeast of Iran. This study aimed to predict the incidence of CCHF and its related factors and explore the possibility of developing an empirical forecast system using time-series analysis of 13 years' data. Data from 2000 to 2012 were obtained from the Health Centre of Zahedan University of Medical Sciences, Climate Organization and the Veterinary Organization in the southeast of Iran. Seasonal autoregressive integrated moving average (SARIMA) and Markov switching models (MSM) were performed to examine the potential related factors of CCHF outbreaks. These models showed that the mean temperature (°C), accumulated rainfall (mm), maximum relative humidity (%) and legal livestock importation from Pakistan (LIP) were significantly correlated with monthly incidence of CCHF in different lags (P < 0·05). The modelling fitness was checked with data from 2013. Model assessments indicated that the MSM had better predictive ability than the SARIMA model [MSM: root mean square error (RMSE) 0·625, Akaike's Information Criterion (AIC) 266·33; SARIMA: RMSE 0·725, AIC 278·8]. This study shows the potential of climate indicators and LIP as predictive factors in modelling the occurrence of CCHF. Our results suggest that MSM provides more information on outbreak detection and can be a better predictive model compared to a SARIMA model for evaluation of the relationship between explanatory variables and the incidence of CCHF.

Crimean-Congo hemorrhagic fever, Kazakhstan, 2009-2010.

We evaluated Crimean-Congo hemorrhagic fever (CCHF) surveillance data from southern Kazakhstan during 2009-2010 and found both spatial and temporal association between reported tick bites and CCHF cases. Public health measures should center on preventing tick bites, increasing awareness of CCHF signs and symptoms, and adopting hospital infection control practices.

Interacting roles of immune mechanisms and viral load in the pathogenesis of crimean-congo hemorrhagic fever.

Until now, the pathogenesis of Crimean-Congo hemorrhagic fever (CCHF) has not been well described. However, it has been hypothesized that it could be a result of the direct injury of virus-infected tissues in combination with the indirect effects of host immune responses, including cytokines. To shed more light on the role of viral load and cytokines, differential influences of CCHF virus (CCHFV) RNA load, antibody response, and cytokine production on severity and outcome of the disease were studied in sera of 46 patients with confirmed acute CCHF from Kosovo. In this study, viral load proved to be strongly related to the severity and outcome of the disease, with higher viral loads detected in patients with fatal outcomes than in surviving patients. Also, patients with fatal outcome had on average a weaker antibody response, if one was present at all. High levels of interleukin-10 (IL-10), gamma interferon (IFN-gamma), and tumor necrosis factor alpha (TNF-alpha) were associated with poor outcome, since detected concentrations were highest in patients with fatal outcome and lowest in patients with moderate disease course. Additionally, a positive linear dependence between viral load and these cytokines was observed. Interestingly, reduced levels of IL-12 were detected in all CCHF patients. Our study favors the hypothesis that CCHF could be a result of a delayed and downregulated immune response caused by IL-10, which leads to an increased replication and spread of CCHFV throughout the body. This consequently triggers increased production of IFN-gamma and TNF-alpha, cytokines mediating vascular dysfunction, disseminated intravascular coagulation, organ failure, and shock.

[An overlooked disease of tick bites: Lyme disease]. / Kene isiriklarinda gözden kaçan bir hastalik: Lyme hastaligi.

The exact prevalence of Lyme disease caused by Borrelia burgdorferi is unknown in Turkey. However, B. burgdorferi seropositivity ranges between 6-44% among high risk groups. B. burgdorferi is transmitted to humans by the bite of infected ticks belonging to the genus Ixodes, which may be seen throughout our country. Since the Crimean-Congo Hemorrhagic Fever (CCHF) is attracting attentions to tick bites more than ever in Turkey, the patients with tick bites are followed up more cautiously and have been referred to central hospitals. In this study 4 patients who were referred to our center with prediagnosis of CCHF but later appeared to be Lyme cases, were presented. All of the cases were women, age ranging between 25-67 years old. The patients were from areas where there is high risk of CCHF. CCHF were ruled out in these patients by agent specific polymerase chain reaction and IgM results. All of the patients were clinically diagnosed as Lyme disease since they had lesions compatible with erythema migrans. B. burgdorferi total antibodies investigated by ELISA (Zeus Scientific Inc., USA) were found positive in all patients. Since Western blot method could not be performed, positive serologic results have not be confirmed. However, the diagnosis of Lyme disease was done according to Centers for Disease Control and Prevention (CDC) criteria and all of the cases have recovered following treatment with antibiotics (cefuroxime axetil or sulbactam ampicillin or amoxicillin clavulanic acid). When the increase in the incidence of arthropod-borne infections in our country is considered, it should be noted that tick-bite cases should also be evaluated in terms of Lyme disease besides CCHF. Differential diagnosis of these infections is of critical value since early appropriate therapy is important to prevent the development of serious complications in both of the disease settings.

[Crimean hemorrhagic fever in the Rostov region: epidemiological zoning and the activity of natural foci]. / Krymskaia gemorragicheskaia likhoradka v Rostovskoi oblasti: épidemiologicheskoe raionirovanie i aktivnost' prirodnogo ochaga.

The epidemiological zoning of the territory of the Rostov region has been made with the use of the epidemic process patterns and the data indicating the links between the landscape and the natural focus of infection. The spread of infected ticks has been established. The participation of several carrier species in the circulation of Crimean-Congo haemorrhagic fever virus has been confirmed. The mosaic character of their distribution and different levels of their contamination is of great prognostic importance. These data will be used for the improvement of epidemiological surveillance in working out the tactics of epizootological surveys and organization of prophylactic measures.

[The laboratory diagnosis of an outbreak of hemorrhagic fever at Oblivskaya village, Rostov Province: proof of the etiological role of the Crimean-Congo hemorrhagic fever virus]. / Laboratornaia diagnostike vspyshki gemorragicheskoi likhoradki v stanitse Oblivskoi Rostovskoi oblasti: dokazatel'stva étiologicheskoi roli virusa krymskoi-kongo gemorragicheskoi likhoradki.

The results of the molecular biological detection of the etiologic agent of hemorrhagic fever in Rostov Province are presented. The role of the causative agents of Astrakhan rickettsial fever, hemorrhagic fever with the renal syndrome, Q fever, leptospirosis and listeriosis has been excluded by means of such immunochemical reactions as the direct and indirect immunofluorescent tests, the solid-phase immunoenzyme assay, the complement fixation test and the agglutination test. The relationship between the cases of hemorrhagic fever in the focus of the outbreak and Crimean-Congo hemorrhagic fever virus has been demonstrated due to the use of the polymerase chain reaction with preliminary reverse transcription.

[Crimean-Congo hemorrhagic fever in Rostov Province: the epidemiological characteristics of an outbreak]. / Krymskaia-Kongo gemorragicheskaia likhoradka v Rostovskoi oblasti: épidemiologicheskie osobennosti vspyshki.

The results of the epidemiological analysis of the outbreak of hemorrhagic fever which was caused by Crimean-Congo hemorrhagic fever virus and occurred during the period of July 3-19, 1999, in the Oblivskaya district of Rostov Province are presented. The specific epidemiological features of the outbreak have been determined. The possible versions of the appearance of the focus of infection and the role of Ixodes ticks in the circulation of the infective agent are discussed.