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

Background and Aims: 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. Methods: We searched updated relevant information from PubMed, Google Scholar, and Scopus databases using Crimean-Congo hemorrhagic fever, tick-borne virus, and Nairovirus as keywords. Results: 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. Conclusion: 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.

ACCI could be a poor prognostic indicator for the in-hospital mortality of patients with SFTS.

This study aims to evaluate the predictive role of age-adjusted Charlson comorbidity index (ACCI) scores for in-hospital prognosis of severe fever in thrombocytopenia syndrome (SFTS) patients. A total of 192 patients diagnosed with SFTS were selected as the study subjects. Clinical data were retrospectively collected. Receiver operating characteristic curves were used to evaluate the diagnostic value of ACCI for the mortality of SFTS patients, and Cox regression models were used to assess the association between predictive factors and prognosis. The 192 SFTS patients were divided into two groups according to the clinical endpoints (survivors/non-survivors). The results showed that the mortality of the 192 hospitalized SFTS patients was 26.6%. The ACCI score of the survivor group was significantly lower than that of the non-survivor group. Multivariate Cox regression analysis showed that the increased ACCI score was a significant predictor of poor prognosis in SFTS. Kaplan-Meier survival analysis showed that SFTS patients with an ACCI >2.5 had shorter mean survival times, indicating a poor prognosis. Our findings suggest that ACCI, as an easy-to-use clinical indicator, may offer a simple and feasible approach for clinicians to determine the severity of SFTS.

Possible Transmission of Severe Fever with the Thrombocytopenia Syndrome Virus to an Individual Who Buried an Infected Cat.

Severe fever with thrombocytopenia syndrome (SFTS) is caused by the severe fever with thrombocytopenia syndrome virus (SFTSV). Although SFTS is a fatal tick-borne zoonosis, it can infect humans without tick bite exposure. Recently, direct transmission of SFTSV from companion pets to humans has become a major problem. We present a case of SFTSV transmission from a dead community cat to a woman who buried the cat in Miyazaki Prefecture, Japan. The community cat died without a diagnosis of SFTS, and the woman buried it without taking any precautions. She developed symptoms of SFTS 9 days later. The woman tested positive for SFTS viral RNA and anti-SFTSV antibodies. The cat's carcass was exhumed, and tissue samples were collected to confirm the viral infection. Numerous copies of viral RNA were detected. The SFTSV M segment sequences in the cat and the woman were 100% homologous. The woman claimed that she had touched blood that had leaked from the cat's body while burying it. However, she could have been infected while transporting the cat to the animal hospital. This study highlights the risk of SFTSV infection from contact with sick or dead community cats.

Bunyaviruses Affect Growth, Sporulation, and Elicitin Production in Phytophthora cactorum.

Phytophthora cactorum is an important oomycetous plant pathogen with numerous host plant species, including garden strawberry (Fragaria × ananassa) and silver birch (Betula pendula). P. cactorum also hosts mycoviruses, but their phenotypic effects on the host oomycete have not been studied earlier. In the present study, we tested polyethylene glycol (PEG)-induced water stress for virus curing and created an isogenic virus-free isolate for testing viral effects in pair with the original isolate. Phytophthora cactorum bunya-like viruses 1 and 2 (PcBV1 & 2) significantly reduced hyphal growth of the P. cactorum host isolate, as well as sporangia production and size. Transcriptomic and proteomic analyses revealed an increase in the production of elicitins due to bunyavirus infection. However, the presence of bunyaviruses did not seem to alter the pathogenicity of P. cactorum. Virus transmission through anastomosis was unsuccessful in vitro.

Infection of Severe Fever with Thrombocytopenia Syndrome Virus as a Cause of a Child's Fever of Unknown Origin: A Case Report.

Background: Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne disease resulted from SFTSV. It is found in Japan, South Korea, Central, and Eastern China. With the increasing prevalence of SFTS and the rapid spread of the SFTS virus (SFTSV) vector, it is obvious that this virus has pandemic potential and poses an imminent public health concern. Case Presentation: We depict SFTS in a child from Anhui Province and conduct a review of all reported pediatric cases in China, which is an endemic area for SFTS. From 2011 to 2021, ten SFTS pediatric cases confirmed by RT-PCR were reported, with no child dying. Although SFTS cases in adolescents and children are uncommon, the reported literature showed that clinical symptoms in adolescents and children were milder than in adults. Conclusion: To better understand this emerging disease, we described the clinical and epidemiological attributes of SFTS. We suggest that the possibility of SFTSV infection in children with seasonal and virus-related acute febrile diseases should be considered in major endemic areas.

Antiviral Treatment Options for Severe Fever with Thrombocytopenia Syndrome Infections.

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a tick-borne virus that produces severe fever with thrombocytopenia syndrome (SFTS). It is widespread in Japan, South Korea, and Central and Eastern China. The epidemic has developed rapidly through China in recent years. SFTS cases have been reported in 25 provinces in China, mainly distributed in rural areas in mountainous and hilly areas. The infection has a high case fatality rate and no specific treatments or vaccinations. Therefore, early diagnosis and treatment of SFTS infection is important to survival and disease control. In this article, we provide an overview on different aspects of SFTS with an emphasis on management, to explore the current treatment and prophylactic measures further.

The Diagnosis of Severe Fever with Thrombocytopenia Syndrome Using Metagenomic Next-Generation Sequencing: Case Report and Literature Review.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an infectious disease caused by a bunyaviridae virus. Its main clinical manifestation is fever with thrombocytopenia, which may be accompanied by other clinical symptoms. Here, we report a patient diagnosed with SFTS using metagenomic next­generation sequencing (mNGS). CASE PRESENTATION: A 56-year-old female patient was hospitalized with intermittent diarrhea and fever. She visited a local clinic for treatment, but instead of improving, the symptoms progressed to unconsciousness. DIAGNOSIS: Using mNGS, we isolated the bunyaviridae virus and several other pathogens from the patient's blood samples to confirm the diagnosis. INTERVENTIONS: The patient was treated with symptomatic and supportive therapy, including intravenous human γ-globulin (20 g/d), platelet transfusion, platelet elevation (subcutaneous injection of recombinant human thrombopoietin, 15,000 IU), white blood cell elevation (subcutaneous injection of recombinant human granulocyte colony-stimulating factor, 200 ug, qd); and antibiotic (cefoperazone sodium and tazobactam sodium, 2 g, q8h), antiviral (ganciclovir, 250 mg, q12h), and antifungal therapy (voriconazole for injection, 0.2 g, q12h). After ten days of treatment, the patient's condition gradually improved. CONCLUSION: Compared to traditional detection methods, mNGS has many advantages. It can quickly identify the pathogen when the patient's clinical manifestations are complex and difficult to diagnose, resulting in the formulation of an effective treatment.

Abnormal coagulation activity and the related clinical significance in patients with novel bunyavirus infection / 中华检验医学杂志

Objective:To explore the related indexes of coagulation and thrombosis and their clinical significance in patients with severe fever with thrombocytopenia symptoms (SFTS) during the onset and recovery period after novel bunyavirus infection.Methods:A total of 36 patients diagnosed with SFTS (SFTS onset group) and 18 convalescent SFTS patients, who were hospitalized in the First Affiliated Hospital of Anhui Medical University from April 12, 2020, to October 12, 2020 were recruited in this study. Thirty-six healthy controls were recruited from volunteers. Plasma was collected and prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), thrombin time(TT), antithrombin-Ⅲ (AT-Ⅲ), fibrin degradation product (FDP) and D-dimer (D-D) were determined by automatic blood coagulation analyzer. Thrombomodulin (TM), thrombin-antithrombin complex (TAT), plasminase-α2 plasminase inhibitor complex (PIC) and tissue plasminogen activator-plasminogen activator inhibitor 1 complex (t-PAIC) were determined by an automatic chemiluminescence analyzer.Results:Compared with the healthy control group, PT was significantly prolonged (12.5 [12.1, 13.6] s, vs 10.8 [10.5, 11.5] s, P<0.05) in SFTS onset group, but was still within the reference range (14.0-21.0 s), and APTT (49.1 [42.0, 58.2]s vs 28.5 [26.6, 30.4]s, P<0.05) was also significantly prolonged in SFTS onset group. Compared with healthy control group, FDP (6.07 [2.67, 8.64] μg/ml vs 1.00 [0.80, 1.87] μg/ml, P<0.001), D-D (2.27 [1.04, 2.98] μg/ml vs 0.30 [0.21, 0.47] μg/ml, P<0.001), TAT (16.05 [8.05, 26.58] ng/ml vs 3.55 [2.60, 4.85] ng/ml, P<0.001), PIC (4.44 [2.52, 5.54] μg/ml vs 0.84 [0.60, 1.35] μg/ml, P<0.001), TM ([19.41±8.29] TU/ml vs [9.33±1.89] TU/ml, P<0.001), and t-PAIC ([37.52±21.10] ng/ml vs [7.06±3.37] ng/ml, P<0.001) values were all significantly higher in the SFTS onset group (all P<0.001). The level of TAT in the SFTS recovery group (9.10 [3.95, 18.40] ng/ml) was still out of the reference range (<4 ng/ml), while the level of PIC in the SFTS recovery group was lower than in SFTS onset group (1.91 [1.45, 2.93] μg/ml vs 4.44 [2.52, 5.54] μg/ml, P<0.05). Compared with SFTS onset group, the levels of TM and t-PAIC were lower in the SFTS recovery group ( P<0.05). Conclusions:Coagulation system activation and vascular endothelial injury are evidenced in SFTS patients. In the convalescence period, the vascular endothelial injury is recovered, however, there is still a certain degree of coagulation dysfunction, therefore, it is necessary to monitor the coagulation indicator of discharged patients post SFTS.

Expert consensus on diagnosis and treatment of severe fever with thrombocytopenia syndrome / 中华临床感染病杂志

Since 2010, the incidence of severe fever with thrombocytopenia syndrome (SFTS) has been increased. Owing the progress in diagnosis and treatment, the overall mortality of SFTS in China has decreased, while the mortality in critical SFTS patients is still high. In order to provide guidance and working procedures for clinicians to diagnose and treat critical SFTS, the National Medical Center for Major Public Health Events invited experts to discuss and formulate this consensus based on their experience and up-to-date knowledge on SFTS.

The Cat Que Virus: a resurfacing orthobunyavirus could lead to epidemics.

The newly emerging and re-emerging of viral contagion in the present scenario are of more extensive health concern. After a long calm of many years, an unexpected eruption of the Cat Que Virus in China is a source of our concern. Cat Que Virus is an Arbovirus and belongs to the Simbu serogroup of the Orthobunyavirus genus of the Bunyaviridae family. The Simbu serogroup is an extremely diverse group of Arbovirus. The arboviruses are causing the infection in multiple hosts including humans and various livestock. They can cause mild to life-threatening infections. Arboviruses expand their spectrum and are more observable in recent times. Human actions have the most significant geophysical impact on the environment. Changes in rainfall patterns, floods, and the risk of extreme weather events are all consequences of climate change. These events may be connected to the extension of permissive vectors, geographic ranges, and therefore provide more chance of growth and spread of potential vector. Arboviruses are responsible for the health hazard to millions of people globally. It is critical to concentrate research and surveillance on these emerging and re-emerging viruses, particularly arthropod-borne viral infections. The appropriate research and surveillance on them will help us for the development of effective control and treatment strategies and also reduce health problems. The present review summarizes the current broad outline of discovery, evolution and dispersal of this unknown virus.

Outbreak of Oropouche Virus in French Guiana.

Oropouche fever is a zoonotic dengue-like syndrome caused by Oropouche virus. In August-September 2020, dengue-like syndrome developed in 41 patients in a remote rainforest village in French Guiana. By PCR or microneutralization, 23 (82.1%) of 28 tested patients were positive for Oropouche virus, documenting its emergence in French Guiana.

Screening and in vitro antiviral assessment of small molecules against fluorescent protein-expressing Bunyamwera virus in a cell-based assay using high-content imaging.

Many species of the order Bunyavirales contain potentially fatal viruses that lack effective medical countermeasures and are therefore collectively a major public health threat. Here, we describe a cell-based assay using Bunyamwera virus (BUNV)-mCherry to identify and characterize new antiviral molecules against bunyaviruses. BUNV is the type species for the genus Orthobunyavirus and has been reported to cause mild symptoms in humans, such as fever, joint pain, and rash. One major benefit of using our fluorescence-based assay over classical CPE-based assays is the fact that the antiviral effect of the tested compounds and their effect on the cell viability can be determined within the same assay well. For that reason, this type of assay could significantly advance our preclinical efforts towards finding new antiviral molecules against bunyaviruses.

Production, Quantitation, and Infection of Amazonian Icoaraci Phlebovirus (Bunyaviridae).

Phlebotomine vectors, sand flies of the order Diptera, are known to transmit Leishmania parasites as well as RNA viruses (arboviruses) to humans. The arbovirus, Icoaraci Phlebovirus (BeAN 24262 - ICOV), used in this study was isolated from Nectomys rodents, a mammalian species that is the same natural sylvatic reservoir of Leishmania (Leishmania) amazonensis. This Leishmania species is distributed in primary and secondary forests in Brazil and other countries in America and causes localized and diffuse anergic skin lesions. In our recent studies, we observed an aggravation of the protozoan infection by ICOV through the modulation of cytokine expression, such as IL-10 and IFN-ß, enhancing the parasite load and possibly the pathogenesis. Efficient viral production and quantitation had to be developed and standardized to ensure that immuno-molecular assays provide consistent and reproducible viral infection results. The standardization of these procedures becomes a particularly useful tool in research, with several applications in understanding the interaction between the host cell and Phlebovirus, as well as co-infections, allowing the study of intracellular signaling pathways. Here, we detail a protocol that allows the production and quantitation of the Icoaraci Phlebovirus using BHK-21 cells (baby hamster kidney cells) and subsequent infection of peritoneal macrophages from C57BL/6 mice.

Evidence of Oropouche Orthobunyavirus Infection, Colombia, 2017.

We describe an Oropouche orthobunyavirus infection in a women 28 years of age in Colombia. We confirmed the diagnosis by viral isolation, quantitative reverse transcription PCR, and phylogenetic analysis of the small, medium, and large genomic segments. The virus is related to a strain isolated in Ecuador in 2016.

Infection, Dissemination, and Transmission Potential of North American Culex quinquefasciatus, Culex tarsalis, and Culicoides sonorensis for Oropouche Virus.

Oropouche virus (OROV), a vector-borne Orthobunyavirus circulating in South and Central America, causes a febrile illness with high rates of morbidity but with no documented fatalities. Oropouche virus is transmitted by numerous vectors, including multiple genera of mosquitoes and Culicoides biting midges in South America. This study investigated the vector competence of three North American vectors, Culex tarsalis, Culex quinquefasciatus, and Culicoides sonorensis, for OROV. Cohorts of each species were fed an infectious blood meal containing 6.5 log10 PFU/mL OROV and incubated for 10 or 14 days. Culex tarsalis demonstrated infection (3.13%) but not dissemination or transmission potential at 10 days post infection (DPI). At 10 and 14 DPI, Cx. quinquefasciatus demonstrated 9.71% and 19.3% infection, 2.91% and 1.23% dissemination, and 0.97% and 0.82% transmission potential, respectively. Culicoides sonorensis demonstrated 86.63% infection, 83.14% dissemination, and 19.77% transmission potential at 14 DPI. Based on these data, Cx. tarsalis is unlikely to be a competent vector for OROV. Culex quinquefasciatus demonstrated infection, dissemination, and transmission potential, although at relatively low rates. Culicoides sonorensis demonstrated high infection and dissemination but may have a salivary gland barrier to the virus. These data have implications for the spread of OROV in the event of a North American introduction.

A clustering analysis based on clinical laboratory indications of patients with bunyavirus infection / 中国基层医药

Objective To execute a hierarchical cluster of clinical laboratory indicators in patients with bunyavirus infection.Methods From July 2015 to July 2017,14 patients with bunyavirus infection in Zhoushan Hospital were selected.The blood routine, coagulation function and biochemical indicators were detected.Cluster analysis and grouping were carried out by hierarchical clustering method.Results Hierarchical clustering classifica-tion was eventually divided into 2 cases of A category[with TT high and BNP high as the main characteristics (TThigh-BNPhigh)] and 12 cases of B category[with TT low and BNP low as the main characteristics (TTlowBNPlow)].The days of hormone drugs and dosage of hormone drugs in A category were (7.43 ±3.53)d,(489.19 ±173.02) mg, respectively,which were higher than those in B category [(5.20 ±1.03)d and (115.11 ±46.58)mg],the differences were statistically significant (t＝2.76,55.56,all P＜0.05).Conclusion It needs probably to pay more days and dose of hormonal drugs for patients with TThighBNPhigh.

A clustering analysis based on clinical laboratory indications of patients with bunyavirus infection / 中国基层医药

Objective@#To execute a hierarchical cluster of clinical laboratory indicators in patients with bunyavirus infection.@*Methods@#From July 2015 to July 2017, 14 patients with bunyavirus infection in Zhoushan Hospital were selected.The blood routine, coagulation function and biochemical indicators were detected.Cluster analysis and grouping were carried out by hierarchical clustering method.@*Results@#Hierarchical clustering classification was eventually divided into 2 cases of A category[with TT high and BNP high as the main characteristics(TThighBNPhigh)] and 12 cases of B category[with TT low and BNP low as the main characteristics (TTlowBNPlow)]. The days of hormone drugs and dosage of hormone drugs in A category were (7.43±3.53)d, (489.19±173.02)mg, respectively, which were higher than those in B category[(5.20±1.03)d and (115.11±46.58)mg], the differences were statistically significant(t=2.76, 55.56, all P<0.05).@*Conclusion@#It needs probably to pay more days and dose of hormonal drugs for patients with TThighBNPhigh.

Seroepidemiological survey of Crimean-Congo haemorrhagic fever among high-risk groups in the west of Iran.

Crimean-Congo haemorrhagic fever (CCHF) is a zoonotic viral haemorrhagic disease. This disease is more common in people who work with animals infected with CCHF virus. The aim of this study was to evaluate the CCHF exposure in high-risk occupational groups in Kurdistan Province in the west of Iran. This cross-sectional study was conducted in 2014 in three counties of Kurdistan Province, viz. Sanandaj, Marivan and Sarvabad. About 50 butchers and slaughterhouse workers, 50 hunters, 50 health care workers and 100 subjects referred to clinical laboratories were sampled and examined for the diagnosis of IgG antibodies against the CCHF using ELISA method. The serum sample of one of the butchers and slaughterhouse workers was positive for CCHF virus. No positive case was found in any other studied groups. The study findings indicate that although CCHF is an endemic disease in different parts of Iran, there is a low rate of seropositivity among high-risk occupations in the west of Iran. Therefore, it is not probably a serious public health problem in this area.

Epidemiological and Clinical Characteristics of Confirmed Cases of Severe Fever With Thrombocytopenia Syndrome in Jeju Province, Korea, 2014-2018.

OBJECTIVES: Jeju Province is well known as the region showing the highest incidence of severe fever with thrombocytopenia syndrome (SFTS) in South Korea. The aim of this study was to evaluate the epidemiological and clinical characteristics of SFTS patients in Jeju Province. METHODS: The primary data for this study were obtained from the Integrated Diseases and Health Control System of the Korea Centers for Disease Control and Prevention (KCDCIS). The selection criteria were confirmed cases of SFTS with a residence listed in Jeju Province at the time of diagnosis, reported to the KCDCIS between July 16, 2014 and November 30, 2018. RESULTS: Of 55 confirmed cases of SFTS, the case fatality rate was 10.9% (95% confidence interval [CI], 4.1 to 22.2). The most common presenting symptoms at diagnosis of severe fever, myalgia, and diarrhea had incidences of 83.6% (95% Cl, 71.2 to 92.2), 45.5% (95% Cl, 32.0 to 59.5), and 40.0% (95% CI, 27.0 to 54.1), respectively. CONCLUSIONS: Compared to SFTS patients nationwide in 2013-2015, the subjects of this study exhibited a lower case fatality rate and had a lower incidence of severe fever, myalgia, and confusion.

Prevalence of Severe Fever with Thrombocytopenia Syndrome Virus in Ticks Collected from National Parks in Korea.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging viral disease in East Asian countries, including China, Japan, and the Republic of Korea (ROK). The causative agent of SFTS is the SFTS virus (SFTSV), which is transmitted by ticks. To investigate the prevalence of SFTSV in the ROK, a total of 9744 ticks were collected from vegetation in five national parks between July and November 2015. Of the collected adult and nymph ticks, Haemaphysalis longicornis (68.44%) was the most abundant, followed by Haemaphysalis flava (29.66%), Ixodes nipponensis (1.56%), and Amblyomma testudinarium (0.34%). Collected larval ticks were of the genera Haemaphysalis (99.61%) and Ixodes (0.39%). One-step RT-PCR and nested PCR were used to detect SFTSV-specific genes from each individual adult and nymph tick and pooled larval ticks. SFTSV was detected in 4.77% (48/1006) in H. longicornis, 1.15% (5/436) in H. flava, 0% (0/23) in I. nipponensis, and 20% (1/5) in A. testudinarium. The infection rate of SFTSV in adult and nymph ticks was 3.61%. The prevalence of SFTSV in adult and nymph ticks was relatively high, compared with previous reports. In larval ticks, the minimum infection rate was 0.31%. SFTSV was detected in ticks collected from both trail and nontrail areas in the national parks, and up to 800 meters above sea level. The sequences obtained showed 99.4-99.7% homology with SFTS virus S segment sequences from Chinese and Japanese ticks.