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Severe fever with thrombocytopenia syndrome virus (SFTSV) is a tickborne bandavirus mainly transmitted by Haemaphysalis longicornis ticks in East Asia, mostly in rural areas. As of April 2022, the amplifying host involved in the natural transmission of SFTSV remained unidentified. Our epidemiologic field survey conducted in endemic areas in China showed that hedgehogs were widely distributed, had heavy tick infestations, and had high SFTSV seroprevalence and RNA prevalence. After experimental infection of Erinaceus amurensis and Atelerix albiventris hedgehogs with SFTSV, we detected robust but transitory viremias that lasted for 9-11 days. We completed the SFTSV transmission cycle between hedgehogs and nymph and adult H. longicornis ticks under laboratory conditions with 100% efficiency. Furthermore, naive H. longicornis ticks could be infected by SFTSV-positive ticks co-feeding on naive hedgehogs; we confirmed transstadial transmission of SFTSV. Our study suggests that the hedgehogs are a notable wildlife amplifying host of SFTSV in China.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease with a high case fatality rate. Key gaps remained as to the assessment of the clinical picture in fatal cases.A retrospective study was performed on 496 patients with fatal SFTS. The dynamic pattern of clinical manifestations and laboratory indicators were delineated.The mean age of the fatal cases was 69.0 years (standard deviation: 9.3), and 52.8% were male. The median clinical course from disease onset to death was 11 (interquartile range: 10-13) days. A total of 11 laboratory indicators (neutrophil %, platelet, aspartate aminotransferase, aspartate aminotransferase/alanine transaminase, lactate dehydrogenase, creatine kinase, cystatin C, D-dimer, activated partial thromboplastin time, thrombin time, glucose) persistently deviated from normality across hospitalization. The critical time points when the rapid worsening of the indicators was at 6-9 days after disease onset. Alanine transaminase, AST, lactate dehydrogenase, total bile acid, gamma-glutamyl transpeptidase, and glucose were all elevated to a more pronounced level in fatal cases of those aged ≤70 years.The fatal outcome was developed in rather a short course after the disease onset of SFTS. High vigilance should be put on the key time points when the severe worsening and severe complications occur.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging zoonotic tick-borne disease caused by SFTS virus (SFTSV). SFTSV has a wide spectrum of animal hosts and is considered to circulate in an enzootic tick-vertebrate-tick cycle. A previous seroepidemiological study showed the presence of anti-SFTSV antibodies in wild mongooses (Herpestes auropunctatus) and indicated that outdoor activity was associated with an increased risk of tick bites among Okinawa residents. However, the association of SFTSV with wild mongooses and ticks remains unclear. To understand the association between ticks and mongooses with respect to the SFTSV enzootic cycle, we investigated the presence of SFTSV RNA in ticks collected from wild mongooses on the Okinawa Island. A total of 638 ticks belonging to 2 genera and 3 species (Haemaphysalis hystricis, Haemaphysalis formosensis, and Ixodes granulatus) were collected from 22 wild mongooses from 2016 to 2021. SFTSV RNA was detected in two pools of H. hystricis larvae collected from a wild mongoose in the central area of the main island of Okinawa in 2017. Although the prevalence of SFTSV in ticks from wild mongooses is low, endemic circulation of the virus in Okinawa should be carefully monitored to prevent future infections.

Selenium deficiency can be associated with increased susceptibility to some viral infections and even more severe diseases. In this study, we aimed to examine whether this association applies to severe fever with thrombocytopenia syndrome (SFTS).An observational study was conducted based on the data of 13,305 human SFTS cases reported in mainland China from 2010 to 2020. The associations among incidence, case fatality rate of SFTS, and crop selenium concentration at the county level were explored. The selenium level in a cohort of patients with SFTS was tested, and its relationship with clinical outcomes was evaluated.The association between selenium-deficient crops and the incidence rate of SFTS was confirmed by multivariate Poisson analysis, with an estimated incidence rate ratio (IRR, 95% confidence interval [CI]) of 4.549 (4.215-4.916) for moderate selenium-deficient counties and 16.002 (14.706-17.431) for severe selenium-deficient counties. In addition, a higher mortality rate was also observed in severe selenium-deficient counties with an IRR of 1.409 (95% CI: 1.061-1.909). A clinical study on 120 patients with SFTS showed an association between serum selenium deficiency and severe SFTS (odds ratio, OR: 2.94; 95% CI: 1.00-8.67) or fatal SFTS (OR: 7.55; 95% CI: 1.14-50.16).Selenium deficiency is associated with increased susceptibility to SFTS and poor clinical outcomes.

To evaluate the effect and safety of corticosteroid (CS) treatment in patients with severe fever with thrombocytopenia syndrome (SFTS).Patients with and without CS were retrospectively compared by Cox regression and 1:1 propensity score matching analysis to evaluate the effects of CS on mortality and secondary infections in patients with SFTS.A total of 467 patients with SFTS were enrolled in the cohort study, there were 52 fatal cases and 415 nonfatal cases, the overall fatality rate was 11.1%. The mortality was observed in 36/144 (25%) and 16/323 (5%) patients in the CS-treated and non-CS-treated groups, respectively (P0.001). Multi variate Cox regression analysis showed that the difference was not statistically significant for CS treatment in fatality (P0.05, aHR 0.767, 95% CI 0.360-1.634). Difference in survival time between the CS-treated and non-CS-treated groups after propensity score matching had no statistical significance (Log-rank test P = 0.390), whereas there was a significant difference in secondary infections between the CS-treated and non-CS-treated groups (P = 0.007).Although the CS treatment had no impact on fatality in patients with SFTS, it increased the risk of secondary infections. Administration of CS in patients with SFTS should be carefully considered and evaluated the balance between therapeutic efficacy and adverse effects.

Infection with severe fever with thrombocytopenia syndrome (SFTS) virus, which can cause hemorrhagic febrile illness, is often transmitted by ticks. We identified 3 patients with SFTS in or near Bangkok, Thailand. Our results underscore a need for heightened awareness by clinicians of possible SFTS virus, even in urban centers.

Severe fever with thrombocytopenia syndrome (SFTS) is a zoonotic disease with a high mortality rate for humans and cats. The clinical course and prognosis of SFTS in dogs remains unclear. In the present study, we investigated the clinical and epidemiological characteristics of SFTS virus (SFTSV) infection in dogs. All evaluated dogs exhibited an acute course and symptoms including fever (57.1%), anorexia (57.1%), depression (42.9%), and vomiting (35.7%). Thrombocytopenia was present in 45.5% of dogs, while jaundice was not observed. C-reactive protein, alanine transaminase, and alkaline phosphatase were elevated in some cases. Viral clearance occurred within 6 to 26 days. Phylogenetic analysis revealed that the SFTSV sequences were consistent with viruses circulating in the Republic of Korea. As dogs often live in close contact with humans, awareness of the clinical and epidemiological features of SFTS in dogs is crucial. Further large-scale studies are necessary to investigate SFTSV infection in dogs.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging hemorrhagic fever with high mortality. Severe cases progressed rapidly, with deaths occurring within 2 weeks. Therefore, constructing a model to predict disease progression among hospitalized patients plays an important role in clinical practice. The development cohort included 121 patients with SFTS, 25 with severe SFTS, and 96 with mild SFTS. Two of the 64 variables were independent risk factors, including neurological symptoms (odds ratio [OR], 12.915; 95% confidence interval [CI], 3.342-49.916; P0.001) and aspartate aminotransferase/alanine aminotransferase levels (OR, 1.891; 95% CI, 1.272-2.813; P = 0.002). The model's area under the curve (AUC) was 0.882 (95% CI: 0.808-0.956). The mean AUC value obtained from the internal validation was 0.883 (95% CI: 0.809-0.957). The AUC in the external validation cohort was 0.873 (95% CI: 0.775-0.972). This model can be used to identify severely ill patients as early as possible with high predictive value, stability, and repeatability. This model can help clinicians with their treatment plans.

Severe fever with thrombocytopenia syndrome (SFTS) caused by Dabie bandavirus (formerly SFTS virus, SFTSV), which belongs to the Bandavirus genus (formerly Phlebovirus genus) of the Phenuiviridae family (formerly Bunyaviridae family), is a tick-borne novel bunyavirus infection with high rates of mortality. SFTSV infection was diagnosed virologically in a 4-year-old dog with symptoms of lethargy and anorexia in western Japan in June 2017. The dog's owner, a man in his 40s, had taken care of the sick dog and became sick 10 days after disease onset in the dog, showing symptoms, such as fever, arthralgia, headache, nausea, and vomiting. Total blood cell counts revealed leukocytopenia and thrombocytopenia. He was treated as an outpatient. He had no scars suggesting that he had not been bitten by ticks. He was diagnosed as having SFTS via the detection of IgM and neutralizing antibodies to SFTSV. The patient was directly infected with SFTSV from the SFTSV-infected dog. In conclusion, humans can be at a risk of SFTSV infection through direct contact with sick dogs infected with SFTSV.

A 67-year-old man, hospitalized with fever and pancytopenia, experienced cardiogenic shock on the 3rd day of hospitalization. He complained of chest pain and exhibited cardiac dysfunction, upregulated serum troponin levels, and an ST elevation on electrocardiogram. Severe fever with thrombocytopenia syndrome (SFTS) was suspected based on the symptom course after a tick bite and was definitively diagnosed using the serum polymerase chain reaction (PCR) test. An endomyocardial biopsy performed in the convalescent phase revealed a sign of myocardial inflammation with increases in CD3- and CD68-positive cells. We herein report the first case of acute myocarditis complicated with SFTS.

Severe fever with thrombocytopenia syndrome (SFTS), a novel infectious disease caused by a novel bunyavirus and with a high case fatality rate (CFR), was reported by Chinese scientists in 2011. The causative virus, Dabie bandavirus also known as the SFTS virus (SFTSV), belongs to the genus Bandavirus (formerly named Phlebovirus) of the family Phenuiviridae (formerly named Bunyaviridae). SFTS was also reported to be endemic in South Korea and Japan in 2013. SFTSV circulates between some species of ticks and animals in nature. Humans are infected with SFTSV through bites from ticks such as Haemaphysalis longicornis and Amblyomma testidinarium. Domesticated animals, such as cats and dogs, are also infected with SFTSV and shown SFTS-like symptoms with a high CFR, likely having been infected through tick bites in the living environment. Furthermore, there have been cases of patients with SFTS who were infected with SFTSV through close contact with sick cats or dogs. The CFR in patients with SFTS is approximately 30% in Japan. There is always a risk of SFTSV infection in human populations living in endemic areas. Therefore, the development of specific therapies and vaccines is urgently needed to reduce the number of fatal SFTS cases.

Seasonal activity of ticks, including disease vectors of fatal severe fever with thrombocytopenia syndrome (SFTS) virus, was monitored using CO

Report of a human death and exposure of white-tailed deer to Heartland virus (HRTV) in Georgia, USA, prompted the sampling of questing ticks during 2018-2019 in 26 sites near where seropositive deer were captured and the residence of the human case-patient. We processed 9,294 Amblyomma americanum ticks in pools by virus isolation in Vero E6 cells and reverse transcription PCR. Positive pools underwent whole-genome sequencing. Three pools were positive for HRTV (minimum infection rate 0.46/1,000 ticks) and none for Bourbon virus. Cell cultures confirmed HRTV presence in 2 pools. Genome sequencing, achieved for the 3 HRTV isolates, showed high similarity among samples but marked differences with previously sequenced HRTV isolates. The isolation and genomic characterization of HRTV from A. americanum ticks in Georgia confirm virus presence in the state. Clinicians and public health professionals should be aware of this emerging tickborne pathogen.

Severe fever with thrombocytopenia syndrome (SFTS) caused by Dabie bandavirus (SFTSV) is a serious public health concern in endemic areas, particularly in Asian and Southeast Asian countries. SFTSV is transmitted by direct contact with body fluids from infected humans and animals. Therefore, environmental hygiene in hospitals and veterinary clinics in SFTSV-endemic areas is highly important. This study assessed the effects of continuous and intermittent irradiation with deep-ultraviolet light-emitting diode (DUV-LED) on SFTSV. Evaluation was performed by conducting plaque assay in which SFTSV irradiated with deep-ultraviolet (DUV; 280 ± 5 nm) was inoculated onto Vero cells. The results showed that continuous and intermittent irradiation for 5 s, resulting in 18.75 mJ/cm

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a zoonotic, tick-borne RNA virus of the genus Bandavirus (Family Phenuiviridae), mainly reported in China, Japan, and the Republic of Korea (Korea). For the purpose of this study, a total of 3,898 adult and nymphal ticks of species Haemaphysalis longicornis (94.2%), Haemaphysalis flava (5.0%), Ixodes nipponensis (0.8%), and 1 specimen of Ixodes ovatus, were collected from the Deogyusan National Park, Korea, between April 2016 and June 2018. A single-step reverse transcriptase–nested PCR was performed, targeting the S segment of the SFTSV RNA. Total infection rate (IR) of SFTSV in individual ticks was found to be 6.0%. Based on developmental stages, IR was 5.3% in adults and 6.0% in nymphs. The S segment sequences obtained from PCR were divided into 17 haplotypes. All haplotypes were phylogenetically clustered into clades B-2 and B-3, with 92.7% sequences in B-2 and 7.3% in B-3. These observations indicate that the Korean SFTSV strains were closer to the Japanese than the Chinese strains. Further epidemiological studies are necessary to better understand the characteristics of the Korean SFTSV and its transmission cycle in the ecosystem.

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a newly emerging tick-borne virus with a case fatality rate between 12% and 50%. Currently, effective vaccines or antiviral drugs are not available, and a diagnostic method for detecting SFTSV is urgently needed. The monoclonal (MAb) and polyclonal antibodies (PAb) against SFTSV were prepared by immunizing animals with SFTSV nucleocapsid protein (NP), and using both monoclonal and polyclonal antibodies as capture antibodies against NP, we developed two different double-antibody sandwich enzyme-linked immunosorbent assays (DAS-ELISAs) for detecting the NP of SFTSV. Both methods were applicable for the diagnosis of SFTSV-infected patients, as confirmed by quantitative polymerase chain reaction. Furthermore, the sensitivity and specificity of two assays for diagnosing SFTS were both 100%, and had no reaction to recombinant Dabieshan NP or recombinant Dengue virus NS1 subtype 1 and 2 proteins. In addition, two standard curves were established for quantitative detection of the NP, and the monoclonal antibody-based ELISA (MAb-based ELISA) test had a lower limit of detection than the polyclonal-based ELISA (PAb-based ELISA) test. Therefore, the MAb-based ELISA could be employed for detecting SFTSV in a convenient and effective way.

Since the Dabie bandavirus (DBV; former SFTS virus, SFTSV) was identified, the epidemics of severe fever with thrombocytopenic syndrome (SFTS) caused by this virus have occurred in several countries in East Asia. The rapid increase in incidence indicates that this infectious agent has a pandemic potential and poses an imminent global public health threat.The analysis of molecular evolution of SFTS agent that includes its variants isolated in China, Japan and South Korea was performed in this review. The evolution rate of DBV and the estimated dates of existence of the common ancestor were ascertained, and the possibility of reassortation was demonstrated.The evolutionary rates of DBV genome segments were estimated to be 2.28 × 10-4 nucleotides/site/year for S-segment, 2.42 × 10-4 for M-segment, and 1.19 × 10-4 for L-segment. The positions of positive selection were detected in the viral genome.Phylogenetic analyses showed that virus may be divided into two clades, containing six different genotypes. The structures of phylogenetic trees for S-, M- and L-segments showed that all genotypes originate from the common ancestor.Data of sequence analysis suggest that DBV use several mechanisms to maintain the high level of its genetic diversity. Understanding the phylogenetic factors that determine the virus transmission is important for assessing the epidemiological characteristics of the disease and predicting its possible outbreaks.

Rift Valley fever phlebovirus (RVFV) is a mosquito-transmitted phlebovirus (Family: Phenuiviridae, Order: Bunyavirales) causing severe neonatal mortality and abortion primarily in domestic ruminants. The susceptibility of young domestic swine to RVFV and this species’ role in geographic expansion and establishment of viral endemicity is unclear. Six commercially bred Landrace-cross piglets were inoculated subcutaneously with 105 plaque-forming units of RVFV ZH501 strain and two piglets received a sham inoculum. All animals were monitored for clinical signs, viremia, viral shedding, and antibody response for 14 days. Piglets did not develop evidence of clinical disease, become febrile, or experience decreased weight gain during the study period. A brief lymphopenia followed by progressive lymphocytosis was observed following inoculation in all piglets. Four piglets developed a brief viremia for 2 days post-inoculation and three of these had detectable virus in oronasal secretions three days post-inoculation. Primary inoculated piglets seroconverted and those that developed detectable viremias had the highest titers assessed by serum neutralization (1:64–1:256). Two viremic piglets had a lymphoplasmacytic encephalitis with glial nodules; RVFV was not detected by immunohistochemistry in these sections. While young piglets do not appear to readily develop clinical disease following RVFV infection, results suggest swine could be subclinically infected with RVFV.

In Japan, the first patient with severe fever with thrombocytopenia syndrome was reported in Yamaguchi in 2012. To understand the severe fever with thrombocytopenia syndrome virus (SFTSV) infection in this region, a retrospective surveillance in sika deer and wild boars in Yamaguchi was conducted using a virus-neutralizing (VN) test. The result revealed that 510 of the 789 sika deer and 199 of the 517 wild boars were positive for anti-SFTSV antibodies. Interestingly, seroprevalence in sika deer increased significantly from 2010-2013 to 2015-2020. The SFTSV gene was detected in one of the 229 serum samples collected from sika deer, but not from wild boars. In conclusion, SFTSV had spread among wild animals before 2012 and expanded gradually around 2013-2015 in Yamaguchi.

During 2018, Heartland virus RNA was detected in an Amblyomma americanum tick removed from a resident of Suffolk County, New York, USA. The persons showed seroconversion. Tick surveillance and white-tailed deer (Odocoileus virginianus) serosurveys showed widespread distribution in Suffolk County, emphasizing a need for disease surveillance anywhere A. americanum ticks are established or emerging.

An older man from the mid-Southeastern USA presented with acute onset of fever, fatigue, and non-bloody diarrhoea. There was high suspicion for tick-borne illness given exposure history, clinical presentation and laboratory abnormalities. Despite prompt treatment with doxycycline, the patient clinically worsened. He was diagnosed with secondary hemophagocytic lymphohistiocytosis (HLH) due to Heartland virus (HRTV). This is the second documented case of secondary HLH due to HRTV, and the first in a relatively immunocompetent patient. Furthermore, though HRTV has been primarily concentrated in the Central USA, our case provides evidence of further geographic expansion of HRTV, mirroring the increased range of the Lone Star tick. Clinicians should consider HRTV when a patient with a clinical presentation consistent with tick-borne illness fails to respond to doxycycline. Furthermore, healthcare providers should be aware of the geographic expansion of HRTV and the potential of HRTV to lead to secondary HLH.

To analyze the epidemiological distribution, clinical characteristics, and prognostic risk factors of patients having severe fever with thrombocytopenia syndrome (SFTS).We enrolled 790 patients with SFTS divided into the ordinary group and the severe group, analyzed the clinical characteristics, and screened the risk factors of severious patients by univariate logistic regression analysis.Most of the 790 patients (SFTS) are farmers (84.56%). The proportion of patients with fieldwork history was 72.41%, of which 21.27% had a clear history of a tick bite and 98.61% were sporadic cases. The annual peak season is from April to November. 16.33% patients were not accompanied by fever. The incidence of severe thrombocytopenia was 47.59%. They were statistically significant between the 2 groups in indicators such as age, hypertension, coronary heart disease, diabetes mellitus, bunyavirus nucleic acid load and mean platelet count (P .05). Multivariate non conditional Logistic regression analysis showed that the risk factors of the mild patients deteriorating severe disease were age (OR = 1.985, P ≤ .003), diabetes mellitus (OR = 1.702, P ≤ .001), coronary heart disease (OR = 1.381, P ≤ .003), platelet count (OR = 2.592, P ≤ .001), viral nucleic acid loading (OR = 3.908, P ≤ .001).The incidence population and seasonal distribution characteristics of patients with SFTS are obvious. The risk factors for poor prognosis of severe patients are old age, multiple basic medical histories, high viral load, a serious decrease of mean platelet count, and delay of treatment time.

Severe fever with thrombocytopenia syndrome (SFTS) is caused by infection with Dabie bandavirus [formerly SFTS virus (SFTSV)] and is an emerging zoonotic disease. Dogs can be infected with SFTSV, but its pathogenicity and transmissibility have not been fully elucidated. In experiment 1, immunocompetent dogs were intramuscularly inoculated with SFTSV. In experiment 2, immunosuppressed dogs (immunosuppressed group; oral azathioprine 5 mg/kg/day for 30 days) were intramuscularly inoculated with SFTSV. Both immunosuppressed and immunocompetent contact dogs were co-housed with the SFTSV-inoculated dogs that had been immunosuppressed. Immunocompetent SFTSV-infected dogs did not show any clinical symptom. However, immunosuppressed SFTSV-infected dogs showed high fever and weight loss without lethality. In all SFTSV-infected dogs, viral RNA could be measured in the serum only after 3 days post infection (DPI) and neutralizing antibodies were detected in the serum beginning 9 DPI. SFTSV shedding in the urine and faeces of some infected dogs occurred between 4 and 6 DPI. The immunocompromised SFTSV-infected dogs showed thrombocytopenia beginning 3 DPI to the end of the experiment (24 DPI). We confirmed SFTSV transmission to one of three immunocompetent co-housed dogs. This dog showed a high fever, weight loss, and shed viral RNA by urine. Viral RNA and neutralizing antibodies were also detected in the serum. These results demonstrated that intramuscular inoculation with SFTSV induced minor clinical symptoms in dogs, and intraspecies SFTSV transmission in dogs can occur by contact.

Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging negatively stranded enveloped RNA bunyavirus that causes SFTS with a high case fatality rate of up to 30%. Macroautophagy/autophagy is an evolutionarily conserved process involved in the maintenance of host homeostasis, which exhibits anti-viral or pro-viral responses in reaction to different viral challenges. However, the interaction between the bunyavirus SFTSV and the autophagic process is still largely unclear. By establishing various autophagy-deficient cell lines, we found that SFTSV triggered RB1CC1/FIP200-BECN1-ATG5-dependent classical autophagy flux. SFTSV nucleoprotein induced BECN1-dependent autophagy by disrupting the BECN1-BCL2 association. Importantly, SFTSV utilized autophagy for the viral life cycle, which not only assembled in autophagosomes derived from the ERGIC and Golgi complex, but also utilized autophagic vesicles for exocytosis. Taken together, our results suggest a novel virus-autophagy interaction model in which bunyavirus SFTSV induces classical autophagy flux for viral assembly and egress processes, suggesting that autophagy inhibition may be a novel therapy for treating or releasing SFTS.

Severe fever with thrombocytopenia syndrome (SFTS), caused by SFTS virus (SFTSV) is an emerging tick-borne infectious disease. Few studies have assessed the clinical usefulness of nested reverse-transcription polymerase chain reaction (RT-PCR) for diagnosing SFTS. We performed conventional RT-PCR targeting the M segment, nested RT-PCR targeting M and S segments, and real-time RT-PCR targeting the S segment of SFTSV for four patients with suspected SFTS. Although conventional RT-PCR results for the first two patients were negative at admission, nested RT-PCR using the S or M targets was positive for the same samples. Likewise, in the other two patients, initial samples were confirmed positive in all three tests, but follow-up testing demonstrated negative conventional RT-PCR and positive nested RT-PCR results. Thus, delayed testing using conventional RT-PCR or real-time RT-PCR in symptomatic patients with SFTS may result in missed diagnoses, and compared with these methods, nested RT-PCR may increase the window for obtaining positive SFTSV PCR results. Meanwhile, the indirect immunofluorescence assay showed seroconversion to SFTSV antibodies in all four patients. Nested RT-PCR for SFTSV M and S segments could help diagnose SFTS in patients testing negative by conventional RT-PCR.

Abstract Tick-borne diseases (TBDs) are bacterial, viral, and parasitic diseases transmitted by ticks. Viral TBDs have increased in prevalence over the last decade with many new pathogenic viruses being discovered. Doxycycline is often empirically prescribed by clinicians to treat symptomatic patients following tick bites due to suspicions of bacterial TBDs such as Rocky Mountain spotted fever, anaplasmosis, and ehrlichiosis. However, viral TBDs are included in the differential diagnosis if patients do not clinically improve following antibiotic therapy. Several viral TBDs present with dermatological manifestations. Recognizing the differences in clinical presentations of TBDs, particularly of newly emerging viral TBDs in the United States, can help physicians identify the viral TBD, and possibly rule out viral illnesses with different clinical presentations. Therefore, this review discusses clinical manifestations, with an emphasis on dermatologic manifestations of Heartland Virus, Bourbon Virus, Powassan Virus, Deer Tick Virus and Colorado Tick Fever Virus. Key points Viral tick-borne diseases have increased in prevalence over the last decade and often have similar clinical manifestations to other tick-borne diseases, including bacterial infections. Here, we review the dermatologic manifestations of Heartland Virus (HRTV), Bourbon Virus (BRBV), Powassan Virus (POWV), Deer Tick Virus (DTV) and Colorado Tick Fever Virus (CTFV) that are important for clinicians.

In Yangquan County, the sandfly-transmitted virus (Wuxiang virus) was first isolated from sandflies in 2018. However, relationships between the abundance and seasonal fluctuations of local sandflies and sandfly-transmitted viruses are unknown. Herein, we report that sandfly specimens were collected in three villages in Yangquan County, from June to August, 2019. A total of 8363 sandflies were collected (June, 7927; July, 428; August, 8). Eighteen virus strains (June, 18; July, 0; August, 0) were isolated in pools of Phlebotomus chinensis. The genome sequence of the newly isolated virus strain was highly similar to that of the Wuxiang virus (WUXV), isolated from sandflies in Yangquan County in 2018. Our results suggested that the sandfly-transmitted viruses, and the local sandfly population, are stable in Yangquan County, and that June is the peak period for the virus carried by sandflies in this area.

To investigate the seroprevalence of severe fever with thrombocytopenia syndrome (SFTS) among wild and companion animals on Tsushima Island, Japan, SFTS virus (SFTSV)-specific ELISA and virus-neutralizing tests were conducted on 50 wild boars, 71 Sika deer, 84 dogs, 323 domestic cats, and 6 Tsushima leopard cats. In total, 1 wild boar (1.8%), 2 dogs (2.4%), 7 domestic cats (2.2%), and 1 Tsushima leopard cat (16.7%) were positive for anti-SFTSV antibodies. Among the 11 positive animals, 10 were collected after 2019, and all were found on the southern part of the island. SFTSV, thus far, seems to be circulating within a limited area of Tsushima Island. To protect humans and animals, including endangered Tsushima leopard cats, from SFTSV infection, countermeasures are needed to prevent the spread of SFTSV on Tsushima Island.

Blood-sucking ticks are obligate parasites and vectors of a variety of human and animal viruses. Some tick-borne viruses have been identified as pathogens of infectious diseases in humans or animals, potentially imposing significant public health burdens and threats to the husbandry industry. Therefore, identifying the profiles of tick-borne viruses will provide valuable information about the evolution and pathogen ecology of tick-borne viruses. In this study, we investigated the viromes of parasitic ticks collected from the body surfaces of herbivores in Xinjiang Uyghur Autonomous Region and Inner Mongolia Autonomous Region of China, two regions in northwest China. By using a metatranscriptomic approach, 17 RNA viruses with high diversity in genomic organization and evolution were identified. Among them, nine are proposed to be novel species. The classified viruses belonged to six viral families, including

Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne viral hemorrhagic fever caused by the SFTS virus (SFTSV). Approximately 80 patients are infected annually, mainly in western Japan, and the case fatality rate is20%. The clinical presentation of SFTS typically includes fever, thrombocytopenia, leukocytopenia, and gastrointestinal symptoms. Localized lymphadenopathy, coagulopathy associated with prolonged activated partial thromboplastin time, muscular symptoms, and neurological abnormalities referred to as SFTS encephalopathy are often observed. Besides tick-borne spread, SFTSV infection is increasingly being transmitted via SFTS-infected cats. Clinicians should remain mindful of this emerging viral infection.

Severe fever with thrombocytopenia syndrome (SFTS) is an acute infectious disease caused by novel bunyavirus (SFTSV), with a mortality rate of 6.3% ~ 30%. To date, there is no specific treatment for SFTS. Previously, we demonstrated that SFTSV surface glycoprotein (Glycoprotein N, Gn) was a potential target for the development of SFTS vaccine or therapeutic antibodies, and anti-Gn neutralizing antibodies played a protective role in SFTS infection. Compared with traditional antibodies, nanobodies from camelids have various advantages, including small molecular weight, high affinity, low immunogenicity, convenient production by gene engineering, etc. In this study, we combined next-generation sequencing (NGS) with proteomics technology based on affinity purification-mass spectrometry (AP-MS) and bioinformatics analysis to high-throughput screen monoclonal anti-Gn nanobodies from camel immunized with Gn protein. We identified 19 anti-Gn monoclonal nanobody sequences, of which six sequences were selected for recombinant protein expression and purification. Among these six anti-Gn nanobodies, nanobody 57,493 was validated to be highly specific for Gn. The innovative high-throughput technical route developed in this study could also be expanded to the production of nanobodies specific for other viruses like SARS-CoV-2.

Wuxiang virus (WUXV) is a newly discovered Bunyavirales transmitted by sandflies. It is found to infect humans and chickens and can cause neurological symptoms and even death in mice. However, the susceptibility of different hosts and tissue-derived cells to this virus is unclear. In this study, we examined cells derived from murine (BHK-21, N2A), human (HEK-293T, SH-SY5Y), dog (MDCK), pig (PK-15), monkey (Vero), and chicken (DF1), which were inoculated with WUXV at 0.05 MOI, and monitored for monolayer cytopathic effect (CPE). Culture supernatants and cells were collected from 0 to 96 h post-infection, cell viability was determined by trypan blue staining, numbers of infectious virus particles were quantified using plaque tests, and viral nucleic acid contents were determined by RT-qPCR. The presence of WUXV N antigen in infected cells was detected by Western blotting (WB). In response to virus infection, BHK-21, MDCK, and PK-15 cells were characterized by a clear CPE, and we observed reductions in the proportion of viable cells after 96 h. By contrast, no significant CPEs were observed in the other cell lines. We detected increases in viral titers, viral nucleic acid content, and N antigen expression in BHK-21, MDCK, PK-15, HEK-293T, N2A, SH-SY5Y, and DF1 cells post-infection. Vero cells showed no CPE, and the findings for other tests were negative. In conclusion, we tested the susceptibility of different cell lines to WUXV, enhanced our current understanding of WUXV biology at the cellular level, and laid the foundations for further investigation of the underlying virus infection mechanisms.

Background The transmission and fatal risk of severe fever with thrombocytopenia syndrome (SFTS), an emerging infectious disease first discovered in China in 2009, still needed further quantification. This research aimed to analyze the SFTS clusters and assess the transmission and mortality risk for SFTS. Methods Both epidemiological investigation and case reports regarding SFTS clusters in China during 2011–2021 were obtained from the Public Health Emergency Information Management System of the Chinese Center for Disease Control and Prevention Information System. The transmission risk was evaluated by using the secondary attack rate (SAR) and relative risk (RR). Mortality risk factors were analyzed using a logistic regression model. Results There were 35 SFTS clusters during 2011–2021 involving 118 patients with a fatality rate of 22.0%. The number of clusters annually increased seasonally from April to September. The clusters mainly occurred in Anhui (16 clusters) and Shandong provinces (8 clusters). The SAR through contact with blood or bloody fluids was much higher than that through contact with non-bloody fluids (50.6% vs 3.0%; χ2 = 210.97, P RR of 16.61 [95% confidence interval (CI): 10.23–26.97]. There was a statistically significant difference in the SAR between exposure to the blood of a deceased person during burial preparation and exposure to the living patients’ blood (66.7% vs 34.5%; χ2 = 6.40, P RR of 1.93 (95% CI: 1.11–3.37). The mortality risk factors were a long interval from onset to diagnosis [odds ratio (OR) = 1.385), 95% CI: 1.083–1.772, P = 0.009) and advanced age (OR: 1.095, 95% CI: 1.031–1.163, P = 0.01). Conclusions The SFTS clusters showed a high mortality rate and resulted in a high SAR. Contact with a bleeding corpse was associated with a higher infection risk, compared with contacting the blood from living patients. It is important to promote early detection and appropriate case management of patients with SFTS, as well as improved handling of their corpses, to prevent further transmission and mortality. Graphical abstract

This study aimed to characterize the seasonal abundance of hard ticks that transmit severe fever with thrombocytopenia syndrome virus from April to November 2019 and 2020 on Ganghwa-do, Incheon Metropolitan City, Korea. The ticks were collected at grassland, grave site, copse and mountain road using a collection trap method. The ixodid hard ticks comprising three species (Haemaphysalis longicornis, H. flava, and Ixodes nipponensis) collected were 6,622 in 2019 and 3,811 in 2020. H. longicornis was the most frequent (97.9% in 2019 and 96.0% in 2020), followed by H. flava (2.0% and 3.0% in 2019 and 2020, respectively) and I. nipponensis (less than 0.1%). Our study demonstrated that seasonal patterns of the tick populations examined for two years were totally unsimilar. The hard ticks tested using RT-qPCR were all negative for severe fever with thrombocytopenia syndrome virus.

In this study, we isolated a group of viruses that can cause a cytopathic effect in BHK-21 cells from sandfly specimens collected in Yangquan County, Shanxi Province, central China. The representative virus strain is SXYQ1860 and, with increased viral injection, the suckling mice became ill and died, with viral titers continually increasing. The results of molecular genetic evolution analysis of the three gene segments of the virus, L, M, and S, indicate that the newly isolated viruses from Yangquan County are the same as the Wuxiang virus (WUXV) previously isolated from sandflies collected in Wuxiang county, China. This is the first time that the WUXV was also isolated outside Wuxiang County. Therefore, strengthening the surveillance of neglected sandflies and the viruses they transmit to help prevent and control arboviruses and the associated diseases is essential for public health.

An emerging infectious disease first identified in central China in 2009, severe fever with thrombocytopenia syndrome (SFTS) was found to be caused by a novel phlebovirus. Since SFTSV was first identified, epidemics have occurred in several East Asian countries. With the escalating incidence of SFTS and the rapid, worldwide spread of SFTSV vector, it is clear this virus has pandemic potential and presents an impending global public health threat. In this review, we concisely summarize the latest findings regarding SFTSV, including vector and virus transmission, genotype diversity and epidemiology, probable pathogenic mechanism, and clinical presentation of human SFTS. Ticks most likely transmit SFTSV to animals including humans; however, human-to-human transmission has been reported. The majority of arbovirus transmission cycle includes vertebrate hosts, and potential reservoirs include a variety of both domestic and wild animals. Reports of the seroprevalence of SFTSV in both wild and domestic animals raises the probability that domestic animals act as amplifying hosts for the virus. Major clinical manifestation of human SFTS infection is high fever, thrombocytopenia, leukocytopenia, gastrointestinal symptoms, and a high case-fatality rate. Several animal models were developed to further understand the pathogenesis of the virus and aid in the discovery of therapeutics and preventive measures., Virology: An emerging tick-borne disease Severe fever with thrombocytopenia syndrome (SFTS), a tick-borne infectious disease caused by a novel phlebovirus, is a growing global health concern. The main symptoms are high fever, low platelet and white blood cell levels, and gastrointestinal problems. The disease was first identified in China in 2009, and several SFTS epidemics have occurred in East Asia, with mortality rates of between 6 and 27 per cent. Researchers in South Korea led by Young Ki Choi at Chungbuk National University, Cheongju, review the latest research into SFTS virus and disease, including transmission, genetic diversity, epidemiology, pathology and clinical features, and pandemic potential. Animal models are helping researchers understand the virus and disease and develop treatments and vaccines.

Knowledge of the clinical progress of severe fever with thrombocytopenia syndrome (SFTS) and the associated predictors of mortality is important for providing appropriate treatment in severe cases. A multihospital retrospective study was conducted in three SFTS-endemic cities, in 2018. Of the 208 SFTS-confirmed cases, there were 189 survivors and 19 deaths. The median age was 64 years; 104 (50.0%) patients were men, and 188 (90.4%) were farmers. Furthermore, 203 (97.6%) patients reported fever and 70 (33.7%) reported fatigue. Most fatal cases had complications including multiple-organ failure, central nervous syndrome (CNS) abnormalities, and disseminated intravascular coagulation. During the fever phase, alanine transaminase, aspartate aminotransferase (AST), blood urea nitrogen (BUN), creatinine, D-dimer, glucose, hydroxybutyrate dehydrogenase, lactate dehydrogenase (LDH), procalcitonin, prothrombin time, and uric acid levels were higher in fatal than in nonfatal cases (P < 0.05). Creatine kinase (CK), CK-MB (CKMB), AST, and LDH levels were significantly lower in nonfatal than in fatal cases (P < 0.05). Central nervous syndrome abnormalities (odds ratio [OR] = 20.9, 95% CI: 4.3, 100), body temperature ≥ 38.5°C (OR = 23.2, 95% CI: 3.4, 158), BUN levels ≥ 6.4 mmol/L (OR = 9.9, 95% CI: 2.2, 44), CKMB levels ≥ 100 U/L (OR = 33.2, 95% CI: 5.8, 192), and LDH levels ≥ 1,000 U/L (OR = 8.3, 95% CI: 1.9, 37) were predictors of mortality. Our findings reveal that the presence of specific complications and laboratory parameters may serve as predictors of mortality and aid in early identification of severe SFTS cases in clinical practice.

Background: Wuxiang virus was isolated from sandfly specimens collected in Wuxiang County, Shanxi Province, China in 2018, representing the first reported isolation of sandfly-borne virus from sandflies collected in a natural environment in China. The local sandfly density, seasonal fluctuations, and temporal and spatial distributions of the virus in Wuxiang County remain unclear. Materials and Methods: Four fixed sandfly collection sites were set up in Wuxiang County and sandfly specimens were collected continuously from June to August 2019. All sandfly specimens were subjected to viral isolation and molecular biological analysis. Results: The data on sandfly specimens collected in Wuxiang County from June to August 2019 showed a significant difference in the density of sandflies between June 26 and August 16 (p 0.05). A total of 33 virus isolates causing cytopathic effects in mammalian (BHK-21) cells were obtained from 7466 sandflies (91 pools) collected from June to August 2019. The results of molecular genetic evolution analysis of the nucleotide sequence of these isolates showed that the L and S genes (encoding NS and N proteins) of the 33 viruses isolated in 2019 are in the same evolutionary branch as the previously isolated Wuxiang virus. No significant difference was found in the virus isolation rate (the pool isolation rate of virus) among sandflies collected at different times from June to August (p > 0.05). The virus isolation rate of sandflies collected at different collection sites showed a statistically significant difference (p

The heartland virus (HRTV) is a novel phlebovirus that causes severe infections in the USA and closely related to the severe fever thrombocytopenia syndrome virus (SFTSV), a causative agent for SFTS in Asia. The entry mechanisms of HRTV remain unclear. Here, we developed the pseudotyped vesicular stomatitis virus bearing the HRTV glycoprotein (GP) (HRTVpv), and the antigenicity and the entry mechanisms of HRTV were analyzed. HRTVpv was neutralized by anti-SFTSV Gc antibody, but not the anti-SFTSV Gn antibodies. Entry of HRTVpv to cells was inhibited by bafilomycin A1 and dynasore, and but it was enhanced in cells overexpressed with C-type lectins. Production of infectious HRTVpv and SFTSVpv was reduced by Nn-DNJ, α-glucosidase inhibitor. The entry of HRTV occurs via pH- and dynamin-dependent endocytosis. Furthermore, Nn-DNJ may be a possible therapeutic agent against HRTV and SFTSV.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tickborne infectious disease caused by SFTS virus (SFTSV). We report 7 cases of spontaneous fatal SFTS in felines. Necropsies revealed characteristic lesions, including necrotizing lymphadenitis in 5 cases and necrotizing splenitis and SFTSV-positive blastic lymphocytes in all cases. We detected hemorrhagic lesions in the gastrointestinal tract in 6 cases and lungs in 3 cases, suggesting a more severe clinical course of SFTS in felids than in humans. We noted necrotic or ulcerative foci in the gastrointestinal tract in 3 cases, the lung in 2 cases, and the liver in 4 cases. We clarified that blastic lymphocytes are predominant targets of SFTSV and involved in induction of necrotic foci. We also found that thymic epithelial cells were additional targets of SFTSV. These results provide insights for diagnosing feline SFTS during pathological examination and demonstrate the similarity of feline and human SFTS cases.

Phleboviruses transmitted by sandflies are among emerging public health threats. A novel Phlebovirus named Ntepes virus (NTPV) was recently described and found to infect humans from a wide geographic area in Kenya. However, the entomologic risk factors of this virus such as the potential vectors and the transmission cycles remain poorly defined. This study assessed the ability of the colonized sandfly Phlebotomus duboscqi to transmit NTPV and determined the bloodmeal host sources of field-collected sandflies from the area where NTPV was found in Baringo County, Kenya. Five-day old laboratory-reared P. duboscqi were orally challenged with an infectious dose of NTPV (≈106.0 pfu/ml) and incubated for up to 15 days postinfection. Individual sandflies were dissected into abdomens, legs, and salivary glands and screened for the virus infection by cell culture. Of the 205 virus-exposed sandflies, 19.5% developed non-disseminated infections in the midgut, with no evidence of virus dissemination or transmission in legs and salivary glands, respectively. The midgut infection rates decreased with increasing extrinsic incubation period (Spearman’s correlation, ρ = − 0.71 ). Blood-fed specimens analyzed by polymerase chain reaction (PCR) and sequencing of a region of the mitochondrial 12S rRNA, revealed almost exclusive feeding on humans (98%) represented by the sandflies Sergentomyia schwetzi, S. clydei, S. antennata, S. squamipleuris, S. africana, and Phlebotomus martini. One specimen of S. clydei had fed on cattle (2%). These findings suggest P. duboscqi is an incompetent laboratory vector of NTPV. The high human-feeding rate by diverse sandfly species increases the likelihood of human exposure to pathogens associated with these sandflies. Assessment of the susceptibility of Sergentomyia species to NTPV is recommended given their high human-feeding tendency.

Severe fever with thrombocytopenia syndrome (SFTS) virus (SFTSV) is an emerging tick-borne phlebovirus with a high fatality rate of 12–30%, which has an expanding endemic and caused thousands of infections every year. Central nervous system (CNS) manifestations are an important risk factor of SFTS outcome death. Further understanding of the process of how SFTSV invades the brain is critical for developing effective anti-SFTS encephalitis therapeutics. We obeserved changes of viral load in the brain at different time points after intraperitoneal infection of SFTSV in newborn C57/BL6 mice. The virus invaded the brain at 3 h post-infection (hpi). Notably, the viral load increased exponentially after 24 hpi. In addition, it was found that in addition to macrophages, SFTSV infected neurons and replicated in the brain. These findings provide insights into the CNS manifestations of severe SFTS, which may lead to drug development and encephalitis therapeutics.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease with a high case fatality rate. Few studies have been performed on bacterial or fungal coinfections or the effect of antibiotic therapy. A retrospective, observational study was performed to assess the prevalence of bacterial and fungal coinfections in patients hospitalized for SFTSV infection. The most commonly involved microorganisms and the effect of antimicrobial therapy were determined by the site and source of infection. A total of 1201 patients hospitalized with SFTSV infection were included; 359 (29.9%) had microbiologically confirmed infections, comprised of 292 with community-acquired infections (CAIs) and 67 with healthcare-associated infections (HAIs). Death was independently associated with HAIs, with a more significant effect than that observed for CAIs. For bacterial infections, only those acquired in hospitals were associated with fatal outcomes, while fungal infection, whether acquired in hospital or community, was related to an increased risk of fatal outcomes. The infections in the respiratory tract and bloodstream were associated with a higher risk of death than that in the urinary tract. Both antibiotic and antifungal treatments were associated with improved survival for CAIs, while for HAIs, only antibiotic therapy was related to improved survival, and no effect from antifungal therapy was observed. Early administration of glucocorticoids was associated with an increased risk of HAIs. The study provided novel clinical and epidemiological data and revealed risk factors, such as bacterial coinfections, fungal coinfections, infection sources, and treatment strategies associated with SFTS deaths/survival. This report might be helpful in curing SFTS and reducing fatal SFTS.

The purpose of this study is to assess the incidence and management of co-infections in hospitalized severe fever with thrombocytopenia syndrome bunyavirus (SFTSV) patients. We retrospectively evaluated the microbiological database records of the SFTS patients in the first affiliated hospital of Anhui Medical University from January 1, 2018, to December 1, 2021. According to the obtained results, co-infections including pulmonary infection, bloodstream infection, biliary tract infection, urinary tract infection, and abdominal infection were observed in SFTS patients. The incidence rate of fungal infections was found to be high in SFTS patients. Furthermore, we suggest that old age people should be evaluated for the risk of fungal infection. In comparison to the non-infection group, patients in the co-infection group were more likely to get mechanical ventilation, antibacterial treatment, antifungal treatment, and blood product therapy (p 0.001), with a significantly longer length of stay (p 0.05). In SFTS patients, the most prevalent strains were Aspergillus fumigatus, Aspergillus flavus, Candida, Klebsiella pneumonia, and Escherichia coli. In this investigation, 66.2% (106/160) of patients were given antibiotics, most often Piperacillin/tazobactam or minocycline. 15.6% (25/160) of patients were treated with antifungal drugs: 13.1% (21/160) with voriconazole. Patients with SFTS Associated Pulmonary Aspergillosis (SAPA) received active antifungal treatment, but the mortality rate was still 23.5% (8/34). Only 6 of the 11 patients with SFTS Associated Candidiasis were treated with antifungal drugs with no mortality. Due to the high frequency of fungal pulmonary infection in SFTS patients, more standardized fungal detection program should be strengthened.

In the last decade, several phleboviruses transmitted by sand flies were detected in the Mediterranean countries, with the health impact of some of them being unknown. From September to October 2020, a total of 3351 sand flies were captured in Kherrata (Bejaia, northern Algeria) and identified by sex, grouped in 62 pools, which were tested for the presence of phlebovirus RNA using endpoint RT-PCR. Two pools (male and female, respectively) were positive. The genome sequencing and phylogenetic analysis showed that the two phleboviruses detected were closely related to the Punique virus (PUNV) isolated in Tunisia and detected in Algeria. Both PUNV strains were isolated on VERO cells from positive pools. Morphological identification of 300 sand flies randomly selected, showed a clear dominance of Phlebotomus perniciosus (98.67%). The dominance of this species in the study area was confirmed by PCR targeting the mitochondrial DNA. Our result represents the first isolation of PUNV and the second report in Algeria from two distinct regions which confirm its large circulation in the country and more broadly in North Africa. Further studies are needed to measure the impact on public health through seroprevalence studies in humans as well as animals and to investigate its potential involvement in neurological viral diseases. This work was financed by a scholarship from the Algerian Ministry of Higher Education and Scientific Research (scholarship N° 210) of the national exceptional program 2019/2020 for 7 months in the laboratory (National Center of Microbiology, Instituto de Salud Carlos III, Spain). Sí

Severe fever with thrombocytopenia syndrome (SFTS), which is caused by SFTS virus (SFTSV), poses a serious threat to global public health, with high fatalities and an increasing prevalence. As effective therapies and prevention strategies are limited, there is an urgent need to elucidate the pathogenesis of SFTS. SFTSV has evolved several mechanisms to escape from host immunity. In this review, we summarize the mechanisms through which SFTSV escapes host immune responses, including the inhibition of innate immunity and evasion of adaptive immunity. Understanding the pathogenesis of SFTS will aid in the development of new strategies for the treatment of this disease.

Since the intricate and complex steps in pathogenesis and host-viral interactions of arthropod-borne viruses or arboviruses are not completely understood, the multi-omics approaches, which encompass proteomics, transcriptomics, genomics and metabolomics network analysis, are of great importance. We have reviewed the omics studies on mosquito-borne viruses of the Togaviridae, Peribuyaviridae and Phenuiviridae families, specifically for Chikungunya, Mayaro, Oropouche and Rift Valley Fever viruses. Omics studies can potentially provide a new perspective on the pathophysiology of arboviruses, contributing to a better comprehension of these diseases and their effects and, hence, provide novel insights for the development of new antiviral drugs or therapies.

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