A rapid and visual detection method for Crimean-Congo hemorrhagic fever virus by targeting S gene

Crimean-Congo hemorrhagic fever(CCHF)is a zoonotic disease caused by the CCHF virus(CCHFV),which is primarily transmitted by ticks(Lorenzo Juanes et al.2023).It is an emerging disease that occurs sporadically in Africa,Asia,and Europe,with a high morbidity and mortality rate,as high as 30%in humans(Ceylan et al.2013).CCHFV,belonging to genus Nairovirus,family Bunyaviridae,was first identified in the Congo in the 1960s.

Crimean-Congo hemorrhagic fever from the immunopathogenesis, clinical, diagnostic, and therapeutic perspective: A scoping review

Crimean-Congo hemorrhagic fever virus(CCHFV) is responsible for widespread tick-borne zoonotic viral disease CCHF in African, Middle Eastern, Asian, and European countries. CCHFV can be spread to humans through tick bites or contact with infected animals or humans, and it often progresses from asymptomatic to severe/lethal illness, with fatality rates ranging from 10% to 40% in humans. Today, CCHF is growing into a significant public health concern due to its very high prevalence, severity of the condition, and lack of available vaccines and specific treatments. Recent research has been drawn towards a more accurate study of CCHFV characteristics, including the structure, genetic diversity, mechanisms involved in pathogenesis and immunopathogenesis, and clinical features. In addition, the use of animal models(mouse and non-human primates) and advanced diagnostic tools in recent years has resulted in a significant advance in CCHF related studies. In this context, we summarized the latest findings about CCHF research, its health complications, animal models, current diagnosis, vaccination, and CCHF treatments, and therapeutic strategies. Furthermore, we discussed existing deficiencies and problems in CCHFV analysis, as well as areas that still need to yield conclusive answers.

Significance of IL-1Ra and IL-6 gene variants in Turkish patients with Crimean-Congo hemorrhagic fever

Objective: To investigate the association between IL-1 Ra variable number of tandem repeat(rs2234663), IL-6-597 GA(rs1800797), IL-6-572 GC(rs1800796) and the risk of CrimeanCongo hemorrhagic fever(CCHF) in the Turkish patients. Methods: This study included 50 patients infected with CCHF and 50 healthy controls. These variants were genotyped using polymerase chain reaction and/or restriction fragment length polymorphism method. Results: The distribution of the IL-6-572 GC genotypes and alleles varied significantly between the patients and the controls. The subjects carrying IL-6-572 GC GG genotype and G allele had increased risk of developing CCHF compared to the control group(P=0.006, P=0.014, respectively). IL-6-572 GC GC genotype was higher in the controls than the patients(P=0.006). For the triple genotype combinations, the 1/2-GC-GG genotype combination was detected more frequently in the control group than CCHF patients(P=0.016). IL-6(-572/-597) GG-GG genotype was significantly higher in the patient group(P=0.015), while the GC-GG genotype was significantly lower in the patient group(P=0.005). Additionally, the G-G haplotype was significantly higher in the patient group(P=0.042), whereas C-G was found to be significantly lower in the patients than the control group(P=0.037). Conclusions: The results of this study suggest the IL-6-572 GC variant might be genetic markers of sensitivity to CCHF in the Turkish population and may facilitate greater protection against the disease.

Crimean-Congo Hemorrhagic Fever: An Overview

Crimean-Congo hemorrhagic fever (CCHF) is a zoonotic viral infection that is a serious threat to humans. The disease is widely distributed in Africa, Asia, and Europe and has developed into a serious public health concern. Humans become infected through the bites of ticks, by contact with a patient with CCHF, or by contact with blood or tissues from viremic livestock. Microvascular instability and impaired hemostasis are the hallmarks of the infection. Infection in human begins with nonspecific febrile symptoms, but may progress to a serious hemorrhagic syndrome with high mortality rates. Enzyme-linked immunoassay (ELISA) and polymerase chain reaction (PCR) are the most used and specific tests for the diagnosis. The mainstay of treatment is supportive. Although definitive studies are not available, ribavirin is suggested to be effective especially at the earlier phase of the infection. Uses of universal protective measures are the best way to avoid the infection. In this review, all aspects of CCHF are overviewed in light of the current literature.

Knowledge, attitude and practice of healthcare workers concerning Crimean-Congo hemorrhagic fever in Western Iran

Objective: To determine the knowledge, attitude and practice of healthcare workers in Kermanshah Province about Crimean-Congo hemorrhagic fever(CCHF).Methods: This study was conducted in 2014 on healthcare personnel in different job categories including physicians, nurses, midwives, laboratory staff and network health staff of Kermanshah Province by direct interview.Results: A total of 367 respondents who had more than 5 years of experience in their jobs were interviewed. Among them 91% of physicians and nurses, 97% of midwives and health workers and 96% of laboratory staff stated that they had not been confronted with CCHF patients so far. Regarding knowledge, 76% of physicians, 78% of nurses, 77% of midwives and 58% of laboratory staff believed that the disease is remediable. Most of the interviewed participants stated that the disease pertains to people who are in close contact with domestic animals, but they did not consider their own occupations as one of the risk factors. More than 70% of the respondents believed that the disease may exist in the province or their work field. Generally, the knowledge about CCHF was inadequate, with nurses having the lowest level of knowledge.Conclusions: Knowledge of Kermanshah healthcare staff about CCHF was poor,especially nurses in a high risk job category. Therefore, it is necessary to conduct specific training programs for the disease identification, transmission, prevention, and treatment as well as the use of personal protection and safety devices.

Crimean-Congo hemorrhagic fever virus in Central,Eastern,and South-eastern Asia

Crimean-Congo hemorrhagic fever(CCHF),caused by Crimean-Congo hemorrhagic fever virus(CCHFV),is endemic in Africa,Asia,and Europe,but CCHF epidemiology and epizootiology is only rudimentarily defined for most regions.Here we summarize what is known about CCHF in Central,Eastern,and South-eastern Asia.Searching multiple international and country-specific databases using a One Health approach,we defined disease risk and burden through identification of CCHF cases,anti-CCHFV antibody prevalence,and CCHFV isolation from vector ticks.We identified 2313 CCHF cases that occurred in 1944–2021 in the three examined regions.Central Asian countries reported the majority of cases(2,026).In Eastern Asia,China was the only country that reported CCHF cases(287).In South-eastern Asia,no cases were reported.Next,we leveraged our previously established classification scheme to assign countries to five CCHF evidence levels.Six countries(China,Kazakhstan,Kyrgyzstan,Tajikistan,Turkmenistan,and Uzbekistan)were assigned to level 1 or level 2 based on CCHF case reports and the maturity of the countries’surveillance systems.Two countries(Mongolia and Myanmar)were assigned to level 3 due to evidence of CCHFV circulation in the absence of reported CCHF cases.Thirteen countries in Eastern and South-eastern Asia were categorized in levels 4 and 5 based on prevalence of CCHFV vector ticks.Collectively,this paper describes the past and present status of CCHF reporting to inform international and local public-health agencies to strengthen or establish CCHFV surveillance systems and address shortcomings.

Transcriptome profiling highlights regulated biological processes and type III interferon antiviral responses upon Crimean-Congo hemorrhagic fever virus infection

Crimean-Congo hemorrhagic fever virus(CCHFV)is a biosafety level-4(BSL-4)pathogen that causes Crimean-Congo hemorrhagic fever(CCHF)characterized by hemorrhagic manifestation,multiple organ failure and high mortality rate,posing great threat to public health.Despite the recently increasing research efforts on CCHFV,host cell responses associated with CCHFV infection remain to be further characterized.Here,to better understand the cellular response to CCHFV infection,we performed a transcriptomic analysis in human kidney HEK293 cells by high-throughput RNA sequencing(RNA-seq)technology.In total,496 differentially expressed genes(DEGs),including 361 up-regulated and 135 down-regulated genes,were identified in CCHFV-infected cells.These regulated genes were mainly involved in host processes including defense response to virus,response to stress,regulation of viral process,immune response,metabolism,stimulus,apoptosis and protein catabolic process.Therein,a significant up-regulation of type III interferon(IFN)signaling pathway as well as endoplasmic reticulum(ER)stress response was especially remarkable.Subsequently,representative DEGs from these processes were well validated by RT-qPCR,confirming the RNA-seq results and the typical regulation of IFN responses and ER stress by CCHFV.Furthermore,we demonstrate that not only type I but also type III IFNs(even at low dosages)have substantial anti-CCHFV activities.Collectively,the data may provide new and comprehensive insights into the virus-host interactions and particularly highlights the potential role of type III IFNs in restricting CCHFV,which may help inform further mechanistic delineation of the viral infection and development of anti-CCHFV strategies.

Cryo-EM structure of glycoprotein C from Crimean-Congo hemorrhagic fever virus

Crimean-Congo hemorrhagic fever virus(CCHFV)is a causative agent of serious hemorrhagic diseases in humans with high mortality rates.CCHFV glycoprotein Gc plays critical roles in mediating virus-host membrane fusion and has been studied extensively as an immunogen.However,the molecular mechanisms involved in membrane fusion and Gc-specific antibody-antigen interactions remain unresolved largely because structural information of this glycoprotein is missing.We designed a trimeric protein including most of the ectodomain region of Gc from the prototype CCHFV strain,Ib Ar10200,which enabled the cryo-electron microscopy structure to be solved at a resolution of 2.8Å.The structure confirms that CCHFV Gc is a class Ⅱ fusion protein.Unexpectedly,structural comparisons with other solved Gc trimers in the postfusion conformation revealed that CCHFV Gc adopted hybrid architectural features of the fusion loops from hantaviruses and domain Ⅲ from phenuiviruses,suggesting a complex evolutionary pathway among these bunyaviruses.Antigenic sites on CCHFV Gc that protective neutralizing antibodies target were mapped onto the CCHFV Gc structure,providing valuable information that improved our understanding of potential neutralization mechanisms of various antibodies.

Prevalence of Crimean-Congo hemorrhagic fever in Pakistan and its new research progress

Crimean-Congo hemorrhagic fever is a deadly and life-threatening viral sickness spreading throughout the world with high mortality rate of 10%–40%.The causative agents are ticks which show diversity in their strains and thus it is difficult to make vaccine,however some strains are conserved which is the positive point in vaccines development.From 2012 to 2015,a total of 161 cases were confirmed for Crimean-Congo hemorrhagic fever virus in Pakistan.And from 2012 to July 2014,45 deaths were reported in the country.It is spreading sporadically in Pakistan.Mapping of endemic areas and cross-border veterinary surveillance should be developed in high risk areas and workshops should be arranged to increase public awareness about the disease.Control measures must be taken to avoid spreading of the disease to new areas.

Prevalence and Phylogenetic Analysis of Crimean-Congo Hemorrhagic Fever Virus in Ticks from Different Ecosystems in Xinjiang,China

The Crimean-Congo hemorrhagic fever virus(CCHFV),a member of the genus Orthonairovirus and family Nairoviridae,is transmitted by ticks and causes severe hemorrhagic disease in humans.To study the epidemiology of CCHFV in different ecosystems in Xinjiang,China,a total of 58,932 ticks were collected from Tarim Basin,Junggar Basin,Tianshan Mountain,and Altai Mountain from 2014 to 2017.Hyalomma asiaticum asiaticum was the dominant tick species in Tarim and Junggar basins,whereas Dermacentor nuttalli and Hyalomma detritum were found in Tianshan Mountain and Altai Mountain,respectively.Reverse transcription-polymerase chain reaction of the CCHFV small(S)genome segment was used for the molecular detection.The CCHFV-positive percentage was 5.26%,6.85%,1.94%,and 5.56% in Tarim Basin,Junggar Basin,Tianshan Mountain,and Altai Mountain,respectively.Sequences of the S segment were used for phylogenetic analysis and the results showed that the newly identified CCHFV strains belonged to two clades.Our study confirms that H.asiaticum asiaticum is the major vector of CCHFV in desert habitats which is consistent with previous studies,and also suggests that H.detritum and D.nuttalli are emerging vectors for CCHFV in Xinjiang.Moreover,this study reports the presence of CCHFV in the mountain habitat of Xinjiang for the first time,suggesting that future surveillance of CCHFV should also include mountainous areas.

A new strain of Crimean-Congo hemorrhagic fever virus isolated from Xinjiang, China

Crimean-Congo hemorrhagic fever virus(CCHFV) is a highly pathogenic tick-borne virus with a fatality rate of up to 50% in humans. CCHFV is widely distributed in countries around the world.Outbreaks of CCHFV infection in humans have occurred in prior years in Xinjiang Province, China.Epidemiological surveys have detected CCHFV RNA in ticks and animals; however, few isolates were identified. In this study, we identified and isolated a new CCHFV strain from Hyalomma asiaticum asiaticum ticks collected from north of Tarim Basin in Xinjiang, China. A preliminary investigation of infection and antigens expression of CCHFV was performed in newborn mice. The target tissues for CCHFV replication in newborn mice were identified. The analysis of the phylogenetic relationships with other Chinese strains suggested that diverse genotypes of CCHFV have circulated in Xinjiang for years. These findings provide important insights into our understanding of CCHFV infection and evolution as well as disease prevention and control for local residents.

Isolation,Characterization,and Phylogenetic Analysis of Two New Crimean-Congo Hemorrhagic Fever Virus Strains from the Northern Region of Xinjiang Province,China

Crimean-Congo hemorrhagic fever(CCHF)caused by the CCHF virus(CCHFV)is a tick-borne natural focal disease with a mortality rate of approximately 50%.CCHFV is widely prevalent in Africa,southern Asia,the Middle East,and southeast Europe.CCHF outbreaks have been reported previously in Xinjiang province,China,especially in its southern region.Epidemiological surveys conducted on ticks and animals have revealed the presence of CCHFV strains in ticks,rodents,and infected individuals from cities and counties in southern Xinjiang.Phylogenetic analyses revealed that the Chinese CCHFV strains belong to one genotype,based on complete sequences of the S segments of its negative-stranded RNA genome.The present study reports two new CCHFV strains isolated from Hyalomma asiaticum asiaticum ticks collected from Fukang City and Wujiaqu City in the northern region of Xinjiang.Viral characteristics and their evolutionary relationships were analyzed through metagenomic and reverse-transcription PCR analyses;these analyses indicated that the genotype of both strains was different from that of other Chinese strains.Furthermore,previous reports of CCHFV in Xinjiang were reviewed and phylogenetic analyses were performed.CCHFV was found to prevail in Fukang City in Junggar Basin for more than 20 years,and that Fukang City and Wujiaqu City are considered natural reservoirs of different genotypes of CCHFV strains.Our findings facilitate the understanding of CCHFV distribution in Xinjiang province and provide insights into the evolutionary relationships among Chinese CCHFV strains.

The structure of Crimean-Congo hemorrhagic fever virus Gc is revealed;many more still need an answer

Crimean-Congo hemorrhagic fever virus(CCHFV)is regarded as one of the most deadly viruses,with mortality of up to 40%.Currently,no licensed vaccine with validated efficacy against CCHFV is available.CCHFV uses Gn and Gc glycoproteins to bind and penetrate the cell,like other bunyaviruses(Hulswit et al.,2021).Thus,the desired vaccines are needed,to elicit a potent neutralizing antibody(NAb)response to counteract this process.

Predictors of hemorrhagic manifestations in dengue:A prospective observational study from the Hadoti region of Rajasthan

Objective:To study the laboratory and clinical predictors of hemorrhagic manifestations in dengue virus-infected patients.Methods:This was a single-center hospital-based prospective observational study.200 Dengue seropositive patients were included in the study.A detailed clinical examination was done and comprehensive laboratory investigations were done.These parameters were compared between patients with and without hemorrhagic manifestations.Results:Out of the 200 patients,47(23.5%)had bleeding.64.5%Patients were males and 76.0%were under the age of 40 years.The most common presenting symptoms were fever(100.0%)followed by myalgia(77.0%),nausea and vomiting(56.0%).Leukocytosis,neutrophilia,thrombocytopenia,hyperbilirubinemia,transaminitis,decreased serum albumins,and raised D-dimer can serve as hematological,biochemical,and coagulation predictors of hemorrhagic manifestations for dengue.Conclusions:Dengue is a tropical infection with various complications.Bleeding complications are one of them.Laboratory parameters like white blood cells,platelets,bilirubin level,liver enzymes,and D-dimer can help to identify patients at risk for bleeding.Early identification and appropriate management can save a lot of resources and lives.

DETERMINATION OF URINE TUMOR NECROSIS FACTOR, IL-6, IL-8 AND SERUM IL-6 IN PATIENTS WITH HEMORRHAGIC FEVERS WITH RENAL SYNDROME

Objective To explore the roles of cytokines in the pathogenesis of hemorrhagic fever with renal syndrome(HFRS). Methods Double-antibody sandwich ELISA was used to determine serum interleukin (IL)-6, urine tumor necrosis factor (TNF), IL-6 and IL-8 levels in 56 patients with HFRS. Results Serum IL-6, urine TNF, IL-6 and IL-8 concentrations in HFRS patients were significantly higher than those in control group, respectively (P<0.001). The concentrations increased at fever stage, then continued to increase during hypotension stage and peaked at oliguria stage. The concentrations of serum IL-6, urine TNF, IL-6 and IL-8 increased in accord with the severity of the disease and differed greatly among different types of the disease. Serum IL-6 had remarkable relationships with serum specific antibodies. It was positively related to serum β_2-microglobulin (β_2-MG), blood ureanitrogen (BUN) and creatinine (Cr). Significant positive relationships were also found both between urine IL-6 and TNF, and between IL-6 and IL-8 (r=0.5768, P<0.05; r=0.3760, P<0.01). Conclusion TNF, IL-6 and IL-8 activated during the course of the disease. IL-6 is associated with the immunopathological lesions caused by the hyperfunction of humoral immune response. IL-6, IL-8 and TNF are involved in the renal immune impairment. Determining them might, in certain extent, be used in predicting the prognosis and outcome of patients with HFRS.

Dengue fever leading to acute dengue hemorrhagic leukoencephalitis:A case report

Rationale:Dengue fever is a prevalent tropical infectious disease that has a broad panorama of presentations from mild febrile illness to life-threatening manifestations in the form of dengue hemorrhagic fever and dengue shock syndrome.Patient’s concerns:A 20-year-old male presented with a 2-day history of fever,multiple episodes of vomiting,and altered sensorium.Diagnosis:Dengue fever leading to acute hemorrhagic leukoencephalitis.Interventions:Multiple transfusions of single donor platelets,intravenous methylprednisolone,intravenous immunoglobulin,anti-seizure prophylaxis,and broad-spectrum antibiotics.Outcomes:Repeat brain magnetic resonance imaging showed resolution of lesions.The patient was subsequently discharged from the hospital in a healthy state.Lessons:This report helps us to gain a better understanding of the patient’s presentation,which will help to improve the timely recognition and prevention of this rare devastating presentation.

A Retrospective Study of Continuous Renal Therapy and Anticoagulation in Patients with Hemorrhagic Fever with Renal Syndrome

Objective To observe the application of continuous renal replacement therapy(CRRT) and heparin anticoagulation in patients with HFRS, and to explore a more suitable anticoagulant strategy. Methods Eighty-five severe-type patients(severe group) and 71 critical-type patients(critical group) were enrolled in this study. The frequency of CRRT was compared between the two groups; the frequency of CRRT treated with and without heparin anticoagulation and the frequency of hemorrhage and channel blood clotting induced by the two anticoagulant strategies were observed. Results The frequency of CRRT in the critical group was higher than that in the severe group(P < 0.001). The frequency of CRRT initiated during the overlapping phases in the critical group was significantly higher than that of the severe group(P = 0.032). The total times of CRRT was 103, and 70 of them were treated with heparin anticoagulation. The frequencies of hemorrhage induced by heparin anticoagulation and no heparinization were 16 and 0, respectively, and the frequencies of channel blood clotting were 2 and 4, respectively. Conclusions CRRT has been used extensively in the critical-type patients with HFRS. The heparin anticoagulation and no anticoagulant strategies should be used more rationally in patients treated with CRRT, according to the clinical characteristics of the disease.

Hemorrhagic fever with renal syndrome complicated with aortic dissection:A case report

BACKGROUND Hemorrhagic fever with renal syndrome is caused by hantaviruses presenting with high fever,hemorrhage,and acute kidney injury.Microvascular injury and hemorrhage in mucus were often observed in patients with hantavirus infection.Infection with bacterial and virus related aortic aneurysm or dissection occurs sporadically.Here,we report a previously unreported case of hemorrhagic fever with concurrent aortic dissection.CASE SUMMARY A 56-year-old man complained of high fever and generalized body ache,with decreased platelet counts of 10×10^9/L and acute kidney injury.The enzymelinked immunosorbent assays test for immunoglobulin M and immunoglobulin G hantavirus-specific antibodies were both positive.During the convalescent period,he complained sudden onset acute chest pain radiating to the back,and the computed tomography angiography revealed an aortic dissection of the descending aorta extending to iliac artery.He was diagnosed with hemorrhagic fever with renal syndrome and Stanford B aortic dissection.The patient recovered completely after surgery with other support treatments.CONCLUSION Hemorrhagic fever with renal syndrome complicated with aortic dissection is rare and a difficult clinical condition.Hantavirus infection not only causes microvascular damage presenting with hemorrhage but may be risk factor for acute macrovascular detriment.A causal relationship has yet to be confirmed.

Hemorrhagic Fever with Renal Syndrome Associated with Acute Pancreatitis

Hemorrhagic fever with renal syndrome (HFRS) is a systemic infectious disease caused by Hantaviruses and characterized by fevers, bleeding tendencies, gastrointestinal symptoms and renal failure. It encompasses a broad spectrum of clinical presentations, ranging from unapparent or mild illnesses to fulminant hemorrhagic processes. Among the various complications of HFRS, acute pancreatitis is a rare find. In this report, based on clinical data, laboratory and radiologic examination findings, we describe a clinical case, with HFRS from Dobrava virus, associated with acute pancreatitis. The patient was successfully treated by supportive management. Clinicians should be alert to the possibility of HFRS when examining patients with epidemiological data and symptoms of acute pancreatitis.

Unilateral massive hemothorax in Dengue hemorrhagic fever:A unique presentation

Dengue hemorrhagic fever is a more serious form of disease characterised by plasma leakage syndrome,thrombocytopenia and disseminated intravascular coagulation.We present a 51 year old male who presented with fever,petechiae and acute onset of breathlessness.Emergency chest rhoentogram showed a massive riglit sided pleural effusion.On insertion of intercostal drain,there was a sudden gush of blood tinged fluid suggestive of hemothorax.There was no history of trauma or bleeding tendencies.Laboratory investigations revealed a raised hematocrit and severe thrombocytopenia.Dengue IgM was surprisingly positive.After aggressive supportive management the patient gradually improved and was discharged.While bilateral pleural effusion is a known occurrence in dengue hemorrhagic fever,massive hemothorax is unheard of.We report the first case in literature ol dengue hemorrhagic fever presenting as unilateral massive hemothorax.A suspicion of dengue must also be borne in mind in cases of non-traumatic hemothorax especially in endemic areas.