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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.

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.

Severe fever with thrombocytopenia syndrome (SFTS) was first detected in China in 2009. The incidence of SFTS increases year by year, and there is no effective treatment. Considering that the reported prevalence of SFTSV infection varies from region to region, we aimed to quantitatively evaluate the epidemic characteristics of SFTSV infection in China from 2010 to 2020, including the distribution differences in infectious season, sex, age, occupation, and region. A meta-analysis framework was used to search for the related published data with keywords in electronic databases (CNKI, Wanfang, CBM, and PubMed). According to the PRISMA statement, the studies that included SFTS diagnosed in China were analyzed. Furthermore, we used Revman and Stata to merge statistical effects, and used I2 and P-values for heterogeneity test and quality assessment. Eleven studies containing 4,932 cases confirmed by SFTSV infection were included in this meta-analysis. The ratio of male-to-female is 1.04 to 1. Cases were concentrated between 40 and 80 years of age (MD = 92%, 95%CI: 91%–93%). Farmers are at the highest risk of SFTSV infection (MD = 84%, 95%CI: 77%–90%). The risk of infection for consecutive period of April-August was significantly higher than the sum of the remaining months (MD = 82%, 95%CI: 78%–85%). In addition, the patient has an extensive history of exposure, including living in the mountains, exposure to ticks, livestock, mouse and the patient. We came to the conclusion that SFTSV is transmitted primarily through tick bites in China, so middle-aged and older adults living in mountains regions are at the highest risk for SFTSV infection in April through August each year.

Relevance. Severe fever with thrombocytopenia syndrome is a viral disease characterized by acute fever, accompanied by progressive thrombocytopenia, leucopenia. The mortality is up to 30%. The disease was first identified in 2009 in rural areas of central China, Hubei and Henan. The causative agent of the disease is a new Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV). The SFTSV is mainly transmitted through tick bites, especially Haemaphysalis longicornis which is the dominant tick species in East Asia.The aim of the review is to analyze relevant information about Severe Fever with Thrombocytopenia Syndrome, including the molecular genetics features of the pathogen, clinical manifestations, geographical distribution, epidemiological features, as well as the possibility of drift and spread of infection in the Russian Federation.Conclusions. SFTS is a serious health threat as it relates to new and re-emerging infections. The further spread of SFTS in China may complicate the epidemiological situation in the country. SFTSV may have a much wider global distribution in Southeast Asia than is currently known. The risk of H. longicornis ticks spreading is predicted in the north-east United States, New Zealand, parts of Australia and several Pacific islands. The presence of the H. longicornis in the Primorsky Territory on the Far East indicates a possible risk of the natural focus formation in the event of the introduction of the pathogen.

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.

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.

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.

SFTS virus (SFTSV) is a novel bunyavirus, which was discovered as the etiological agent of severe fever with thrombocytopenia syndrome (SFTS) in China in 2009, and was now prevalent in at least 25 provinces in China. SFTS was subsequently identified in South Korea and Japan in 2012. To explore the molecular evolution and genetic characteristics of this newly identified pathogen, we reported 72 whole genome sequences of SFTSV, and built a dataset of SFTSV genome sequences containing 292 L-segment, 302 M-segment and 502 S-segment. We clearly divided SFTSV into six genotypes, Genotype A-F. It was found that genotype F was the dominant epidemic genotype of Japan, South Korea, and Zhejiang province of China. The coalescent analysis supported that SFTSV originated in the early 18th century from Zhejiang province, and Genotype F was the most primitive one. Henan, Hubei, and Anhui provinces which are located in Dabie Mountain area were mainly epidemic of Genotype A, which emerged relatively late but distributed widely. A total of 37 recombination events were identified, making SFTSV with a high recombination frequency (L segment 5.1%, M segment 3.6%, S segment 0.8%) among negative-strand segmented RNA viruses. It was identified that 19 reassortant strains belonged to 12 reassortment forms of SFTSV genome containing 6 newly identified forms. The reassortment virus and recombination in tick were both found for the first time. We also found many of genotype-specific mutation sites, 7 of which could be considered as potential molecular marker for genotype classification. This study promoted a more comprehensive understanding of the phylogeny and origin, and the genetic diversity of SFTSV, and it could help the studies of other newly discovered tick-borne bunyavirus as reference data and research ideas.

Severe fever with thrombocytopenia syndrome (SFTS) has a high fatality rate and is caused by SFTS virus (SFTSV). Currently, SFTS is endemic to some areas in western Japan, and wild animals are considered to play important roles in the circulation of SFTSV in the environment. Previous retrospective surveys using samples mainly obtained between 2006 and 2015 revealed serological evidence of SFTSV infection in wild animals; however, seroprevalence before 2006 remains unclear. In this study, we investigated the presence of anti‐SFTSV antibodies in a total of 521 serum samples from nine wild animal species collected from 11 prefectures in central and eastern Japan between 1980 and 2000. All samples yielded negative results for antibodies to SFTSV, suggesting that there had been few or no SFTSV infections before 2000 in the sampled areas., In this study, we investigated the presence of anti‐SFTSV antibodies in a total of 521 serum samples from nine wild animal species collected from 11 prefectures in central and eastern Japan between 1980 and 2000. All samples yielded negative results for antibodies to SFTSV, suggesting that there had been few or no SFTSV infections before 2000 in the sampled areas.

Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne zoonosis in China, the Republic of Korea (ROK), and Japan. The presence of the SFTS virus (SFTSV) in compani...

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease caused by the SFTS virus (SFTSV) of family Phenuiviridae. Since the virus was first identified in 2009, it has been rapidly spread in many Asian countries including Myanmar, Korea, Japan, and central China. In this study, we investigated the epidemiological characteristics of SFTS patients in Hefei from 2011 to 2018. In addition, we conducted a serological survey of SFTSV-specific antibody among healthy residents of five counties. We performed a retrospective observational study of SFTS cases reported to Hefei Center for Disease Control and Prevention (CDC) during Jan 2011 to Dec 2018. Almost every patient completed a structure questionnaire including clinical examination, course of disease, and history of epidemiology. A total of 754 serum specimens were collected and tested for IgG antibody with double-antigen sandwich ELISA method. Of 257 cases reported during that period, 33 died, with a case fatality rate of 13.0%. We found no significant difference between 30 non-survivors and 198 survivors except for age. The overall rate of seropositivity for SFTSV antibodies among healthy residents were 20.16%. We demonstrated that living in hilly areas, direct contact with domestic livestock and knowledge of tick-borne disease were significantly associated with positive serology result. SFTSV infection was prevalent among farming-related populations. Our study identified a relatively high seroprevalence of SFTSV-specific antibody in healthy residents, which provided the basis for asymptomatic SFTSV infections. More attention should be given to susceptible population and prevent SFTSV outbreak in high-endemic areas.

We used unbiased next-generation sequencing (NGS) to detect unknown viruses in cats. Serum or plasma samples were obtained from clinically ill cats with suspected acute viral infections. Nucleic acid was extracted from serum or plasma samples to construct a complementary DNA library for NGS. Comprehensive nucleotide sequencing analyses enabled detection of the genomes of various viruses, including the severe fever with thrombocytopenia syndrome virus, feline immunodeficiency virus, feline morbillivirus, parvovirus, and Torque teno felis virus. Our findings indicate that comprehensive nucleotide analyses of serum or plasma samples can be used to detect infections with unknown viruses in cats.

We report a case of an 8-year-old Korean girl diagnosed with severe fever with thrombocytopenia syndrome with Q fever coinfection after playing with a dog and being bitten by a tick in a suburb in South Korea. The clinical findings and treatment were summarized. To the best of our knowledge, this case is the youngest patient reported to have been diagnosed with severe fever with thrombocytopenia syndrome and Q fever from South Korea.

Severe fever with thrombocytopenia syndrome was diagnosed in a febrile woman in Japan after a tick bite. However, Rickettsia japonica DNA was retrospectively detected in the eschar specimen, suggesting co-infection from the bite. Establishment of the severe fever with thrombocytopenia syndrome virus infection might have overpowered the R. japonica infection.

Severe fever with thrombocytopenia syndrome (SFTS) virus is an emerging zoonotic virus in East Asia. However, SFTS virus (SFTSV) has not been reported to cause clinical infection in companion dogs to date. We report the case of a 4‐year‐old companion dog that presented with fever, vomiting, leukocytopenia and thrombocytopenia at a veterinary hospital in the Republic of Korea. It was diagnosed with SFTS, which was confirmed using real‐time reverse transcription PCR, sequencing and an indirect immunofluorescence assay, and recovered after supportive care. Further studies are required to investigate SFTSV infection in companion animals, living in close contact with humans, as well as animal‐to‐human transmission., A 4‐year‐old companion dog presented with fever, vomiting, leukocytopenia, and thrombocytopenia at a veterinary hospital in Republic of Korea. It was diagnosed with severe fever with thrombocytopenia syndrome (SFTS) and recovered after supportive care. To our knowledge, this is the first report of SFTSV infection with clinical manifestations in a companion dog.

This study focuses on the comparative and quantitative analysis of the epidemiologic trends and aspects of severe fever with thrombocytopenia syndrome (SFTS) outbreaks between Korea and Japan from 2013 to 2017. The following factors were analyzed; cumulative incidence rate (CIR), cases-fatality rate (CFR), and the epidemic aspects, including cases related to gender, male-to-female morbidity ratio (MFMR), age, seasonal, and geographical distributions. We observed 607 SFTS cases with CIR in Korea during the period 2013 to 2017 were as 0.24 per 100,000 populations and with a 127 fatal-cases (F.C.s), corresponding to a CFR of 20.9%, respectively. During the same period in Japan, 319 SFTS cases with a CIR of 0.05 and with 60 F.C.s to a CFR of 18.8% observed. When compared, the CIR of SFTS in Korea was significantly higher than in Japan (P

Serologic and molecular surveillance of serum collected from 152 suspected scrub typhus patients in Myanmar revealed Orientia tsutsugamushi of genotypic heterogeneity. In addition, potential co-infection with severe fever with thrombocytopenia syndrome virus was observed in 5 (3.3%) patients. Both scrub typhus and severe fever with thrombocytopenia syndrome are endemic in Myanmar.

The recent increase in severe fever with thrombocytopenia syndrome (SFTS) cases has led to the development of the SFTS-QS kit (MiCoBioMed, Seongnam, Korea) for detecting the SFTS virus (SFTSV, now renamed Huaiyangshan banyangvirus). SFTS-QS is a qualitative real-time reverse transcription PCR assay based on lab-on-a-chip technology. We evaluated the performance of the SFTS-QS kit and compared it with that of the PowerChek SFTSV Real-time PCR kit (PowerChek; Kogene Biotech, Seoul, Korea). A total of 117 serum samples were simultaneously assayed using the SFTS-QS and PowerChek kits. Sanger sequencing targeting the S and M segments of SFTSV was performed as the reference method. The total turnaround time of the two kits was compared. The SFTS-QS results agreed with those of PowerChek with a kappa value of 0.92. The diagnostic sensitivity and specificity of the SFTS-QS kit were both 100% (14/14 and 103/103, respectively), whereas those of the PowerChek kit were 100% (14/14) and 98.1% (101/103), respectively. The results of SFTS-QS and PowerChek were comparable; however, the SFTS-QS kit required a shorter total turnaround time. The SFTS-QS kit produced accurate and fast results and thus could serve as a useful tool for detecting SFTSV.

A sporadic but autochthonous dengue fever outbreak occurred in Tokyo in 2014, although the dengue virus is not in general circulation in Japan. Another lethal infectious disease, known as severe fever with thrombocytopenia syndrome (SFTS), was discovered to be endemic to Japan in January 2013. More than 400 patients with SFTS have been reported so far. The fatality rate of SFTS is approximately 30%. Also in 2014, a large outbreak of mosquito-borne Zika virus infections occurred in the South and Central parts of the American continent. Transplacental infection of a fetus with Zika virus occurs when pregnant women are infected. We cannot escape the risk of being infected with these viruses. Thus, preparedness for these emerging and reemerging virus infections is required.

The study examined the seasonal pattern of larvae, nymph, and adult life stages for Haemaphysalis longicornis and the rate of infection with severe fever from the thrombocytopenia syndrome virus in ticks collected from 12 sections (Jichukdong), 14 sections (Uldaeri), and 18 sections (Howondong) in Bukhansan dullegil for April–October 2019. Haemaphysalis longicornis ticks have been considered the main vector for severe fever with thrombocytopenia syndrome (SFTS). Haemaphysalis flava and Ixodes nipponensis were collected using the dragging and flagging method. The ratios of Haemaphysalis longicornis of the collected ticks were 91% (Jichukdong), 94% (Uldaeri), and 98% (Howondong). Monthly distributional studies of Haemaphysalis longicornis based on the developmental stage showed that the adults peaked in September while nymphs were collected more frequently from April through June. The larvae peaked in September and October. SFTS virus detection was performed using 2 × OneStep RT-PCR and nested PCR. On the other hand, no SFTS virus-specific gene was detected in 1,158 ticks of Haemaphysalis longicornis. This result provides estimates of the population densities for the life stages of Haemaphysalis longicornis and the associated disease risk in Bukhansan dullegil, where many people have visited since opening in 2010.

Severe fever with thrombocytopenia syndrome (SFTS) is being reported annually in South Korea since its first detection there in 2010. The causal agent is a negative-strand RNA virus 80–100 nm in diameter. It causes fever, thrombocytopenia, leukocytopenia, gastrointestinal symptoms, and neural symptoms. The mortality rate of SFTS was 32.6% among 172 cases reported from 2012 to 2015 in South Korea. Thus, is necessary to develop an effective diagnostic method that selectively identifies the isolates circulating in South Korea. The real-time reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay is a simple, rapid, and sensitive approach for molecular diagnosis. Here, we designed novel primers for this assay and found that the technique had very high specificity, sensitivity, and efficiency. This real-time RT-LAMP approach using the novel primers developed herein can be applied for early diagnosis of SFTSV strains in South Korea to reduce the mortality rate of SFTS.

Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease. SFTS is caused by the SFTS virus, a novel phlebovirus, and is spread by ticks. Methods: A 50-year-old man was admitted to our hospital with the chief complaint of fever and was diagnosed with confirmed SFTS. An epidemiological investigation was conducted, and immunofluorescent antibody assays (IFAs) were performed to determine the role of the patient's three dogs in the transmission. PCR assays were performed using ticks that were collected with the dragging and flagging method from the patient's dogs and home. Results: PCR results were positive, and IFA confirmed an increased antibody titer. Although the reverse transcription PCR results of the three dogs were negative for SFTS virus, one dog had an elevated SFTS IFA immunoglobulin G (IgG) titer of 1:1,024. Moreover, a number of ticks were observed in the area surrounding the dog cages. Based on the findings of the patient interview, the patient was likely to have acquired SFTS by blood splash because he removed or burst ticks from the dogs with his bare hands. Although no tick bites were reported, tick transmission could not be ruled out. Studies have shown that only one in three individuals with a diagnosis of SFTS recalls a tick bite; thus, a definite exclusion of tick transmission in this case was not possible. Conclusions: The epidemiological findings of our case suggest a possible relationship between tick infestation in domestic dogs and SFTS virus transmission to humans. However, there is no direct evidence supporting this viral transmission route. Future studies are needed to further investigate a potential route of SFTS transmission by exposure to engorged tick blood or pet dogs.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with increasing spread. Currently SFTS transmission has expanded beyond Asian countries, however, with definitive global extents and risk patterns remained obscure. Here we established an exhaustive database that included globally reported locations of human SFTS cases and the competent vector, Haemaphysalis longicornis (H. longicornis), as well as the explanatory environmental variables, based on which, the potential geographic range of H. longicornis and risk areas for SFTS were mapped by applying two machine learning methods. Ten predictors were identified contributing to global distribution for H. longicornis with relative contribution ≥1%. Outside contemporary known distribution, we predict high receptivity to H. longicornis across two continents, including northeastern USA, New Zealand, parts of Australia, and several Pacific islands. Eight key drivers of SFTS cases occurrence were identified, including elevation, predicted probability of H. longicornis presence, two temperature-related factors, two precipitation-related factors, the richness of mammals and percentage coverage of water bodies. The globally model-predicted risk map of human SFTS occurrence was created and validated effective for discriminating the actual affected and unaffected areas (median predictive probability 0.74 vs. 0.04, P

Summary Severe fever with thrombocytopenia syndrome (SFTS), a tick-borne infectious disease with high mortality, is diagnosed by the serological testing of serum samples from patients in the acute and convalescent phases and/or by direct detection of the SFTS virus (SFTSV). Conventionally, heat and UV treatments have been used to inactivate the viruses present in serum samples before performing the serological assays. Here, we examined the inactivation conditions optimal for SFTSV-containing serum samples to ensure the safety of laboratory workers while maintaining the accuracy of serological assay results simultaneously. Heating human serum samples spiked with SFTSV to 60 °C for 30 min or exposing them to UV irradiation for 30 min, reduced the infectious virus titer below the limit of detection. SFTSV in sera from patients in the acute phase of SFTS was completely inactivated by heating to 60 °C for 30 min, followed by UV irradiation for 10 min. This inactivation procedure had minimal impact on the performance of SFTSV antibody detection tests. The data provided herein can serve as a guide for laboratory workers and researchers working with SFTS serological tests.

The genus Phlebovirus contains about 70 named viruses, distributed widely in Europe, Africa, Central Asia, and the Americas. These viruses are currently classified into 10 species by the International Committee on Taxonomy of Viruses (ICTV): Bujaru phlebovirus, Candiru phlebovirus, Chilibre phlebovirus, Frijoles phlebovirus, Punta Torro phlebovirus, Rift Valley fever phlebovirus, Salehabad phlebovirus, Sandfly fever Naples phlebovirus, Mukawa phlebovirus, and Uukuniemi phlebovirus. In addition, at least 32 unclassified strains are associated with this genus.1 Phleboviruses have a genome comprising three segments of negative sense, single-stranded RNA. The large segment (L) encodes the viral RNA-dependent RNA polymerase, the medium segment (M) encodes the structural glycopolyproteins, and the small segment (S) has an ambisense strategy encoding the nucleoprotein (NP) in the negative sense and the nonstructural small (NSs) protein in the positive sense.2 Phleboviruses are largely transmitted by sand flies; Phlebotomus species in the Old World or Nyssomyia (previously Lutzomyia) species in the New World.3 However, some viruses in this genus are transmitted by mosquitoes, Culicoides, and ticks. Many phleboviruses have been associated with human and animal disease. Pathogenic strains include Rift Valley fever, Toscana, Candiru, Sandfly fever Naples, Sandfly fever Sicilian, and severe fever with thrombocytopenia syndrome viruses.4 Recent discoveries of Sandfly fever Turkey,5 Heartland,6 Hunter Island Group,7 Fermo,8 and Malsoor9 viruses highlight the extent to which the diversity and public or animal health impact of phleboviruses are still unknown and likely underestimated. Despite their public health impact, some phlebovirus species remain characterized solely by serological techniques. Given the many recent discoveries, genetic characterization of historically identified phleboviruses is important for the development of diagnostic and surveillance tools, and evolutionary insights into the ever-growing breadth of recognized phleboviruses. Here, we describe the complete sequences of two phlebovirus species complexes, and three previously unclassified phleboviruses isolated in the Americas.

Two veterinary personnel in Japan were infected with severe fever with thrombocytopenia syndrome virus (SFTSV) while handling a sick cat. Whole-genome sequences of SFTSV isolated from the personnel and the cat were 100% identical. These results identified a nosocomial outbreak of SFTSV infection in an animal hospital without a tick as a vector.

Encephalitis is an infrequent manifestation in the various spectrums caused by severe fever with thrombocytopenia syndrome virus (SFTSV) infection. There are few data about the possible pathogenic mechanisms of SFTSV-associated encephalitis. Here, two SFTSV-infected patients with onset of encephalitis were enrolled. The whole genome of two SFTSV strains isolated from cerebrospinal fluid (CSF) was deeply sequenced by next-generation sequencing (NGS) and phylogenetic analysis was conducted. The specific mutations of M fragment were P98L and T665S respectively. The three-dimensional structure of glycoprotein Gn which was encoded by M fragment, an important virulence factor of SFTSV, was constructed by SWISS-MODEL. There was no significant variation in glycoprotein Gn of the two isolates comparing to other strains without encephalitis. Phylogenetic trees based on the complete sequences of M segment showed the two strains were highly identical to other local strains without encephalitis. Our study demonstrates that the virulence factors of SFTSV with encephalitis are not different from those without encephalitis. SFTSV itself is a neurotropic virus.

Most prevalent infectious diseases worldwide are caused by mediators such as insects and characterized by high mortality and morbidity, thereby creating a global public health concern. Therefore, a sensitive, selective detection platform for diagnosing diseases in the early stages of infection is needed to prevent disease spread and to protect public health. Here, we developed novel DNA aptamers specific to the nucleocapsid protein (NP) of the severe fever with thrombocytopenia syndrome (SFTS) virus and synthesized ssDNA-binding protein-conjugated liposomes encapsulated with horseradish peroxidase (HRP) for application in a simple and universal platform. This platform achieved highly sensitive detection of the NP by measuring the colorimetric signal following lysis of the HRP encapsulated liposomes, mediated by a mixture of 3,3',5,5'-tetramethylbenzidine and H2O2 solution. The limit of detection was 0.009 ng·mL-1, and NP was successfully detected in diluted human serum with a high recovery rate. Moreover, this method was specific and did not exhibit cross-reactivity among NPs of other virus types. These results demonstrated the efficacy of the proposed method as a highly sensitive, specific, and universal diagnostic tool for potential application in monitoring of the early stages of infectious diseases.

Severe fever with thrombocytopenia syndrome (SFTS) is caused by SFTS virus (SFTSV). We investigated the detailed kinetics of serologic response in patients with SFTS. Twenty-eight patients aged ≥18 years were enrolled between July 2015 and October 2018. SFTS was confirmed by detecting SFTSV RNA in their plasma using reverse transcription polymerase chain reaction. SFTSV-specific IgG and IgM were measured using immunofluorescence assay (IFA) and enzyme-linked immunosorbent assay (ELISA). We found that SFTSV-specific IgG was detected at days 5–9 after symptom onset, and its titer was rising during the course of disease. SFTSV-specific IgM titer peaked at around week 2–3 from symptom onset. The SFTSV-specific seropositive rates for days 5–9, 10–14, 15–19, and 20–24 from symptom onset using IFA and ELISA were 63%, 76%, 90%, and 100%, and 58%, 86%, 100%, and 100%, respectively, for IgG, whereas they were 32%, 62%, 80%, and 100%, and 53%, 62%, 70%, and 100%, respectively, for IgM. The delayed IgM response could be attributed to the low sensitivity of SFTSV-specific IgM IFA or ELISA and/or impaired immune responses. The IgM test using IFA or ELISA that we used in this study is, therefore, insufficient for the early diagnosis of SFTS.

Disease vectors such as mosquitoes and ticks play a major role in the emergence and re-emergence of human and animal viral pathogens. Compared to mosquitoes, however, much less is known about the antiviral responses of ticks. Here we showed that Asian longhorned ticks (Haemaphysalis longicornis) produced predominantly 22-nucleotide virus-derived siRNAs (vsiRNAs) in response to severe fever with thrombocytopenia syndrome virus (SFTSV, an emerging tick-borne virus), Nodamura virus (NoV), or Sindbis virus (SINV) acquired by blood feeding. Notably, experimental acquisition of NoV and SINV by intrathoracic injection also initiated viral replication and triggered the production of vsiRNAs in H. longicornis. We demonstrated that a mutant NoV deficient in expressing its viral suppressor of RNAi (VSR) replicated to significantly lower levels than wildtype NoV in H. longicornis, but accumulated to higher levels after knockdown of the tick Dicer2-like protein identified by phylogeny comparison. Moreover, the expression of a panel of known animal VSRs in cis from the genome of SINV drastically enhanced the accumulation of the recombinant viruses. This study establishes a novel model for virus-vector-mouse experiments with longhorned ticks and provides the first in vivo evidence for an antiviral function of the RNAi response in ticks. Interestingly, comparing the accumulation levels of SINV recombinants expressing green fluorescent protein or SFTSV proteins identified the viral non-structural protein as a putative VSR. Elucidating the function of ticks’ antiviral RNAi pathway in vivo is critical to understand the virus-host interaction and the control of tick-borne viral pathogens., Author summary Tick-borne diseases (TBDs) are the most common illnesses transmitted by ticks, and the annual number of reported TBD cases continues to increase. The Asian longhorned tick, a vector associated with at least 30 human pathogens, is native to eastern Asia and recently reached the USA as an emerging disease threat. Newly identified tick-transmitted pathogens continue to be reported, raising concerns about how TBDs occur. Interestingly, tick can harbor pathogens without being affected themselves. For viral infections, ticks have their own immune systems that protect them from infection. Meanwhile, tick-borne viruses have evolved to avoid these defenses as they establish themselves within the vector. Here, we show in detail that infecting longhorned ticks with distinct arthropod-borne RNA viruses through two approaches natural blood feeding and injection, all induce the production of vsiRNAs. Dicer2-like homolog plays a role in regulating antiviral RNAi responses as knocking down of this gene enhanced viral replication. Furthermore, we demonstrate that tick antiviral RNAi responses are inhibited through expression heterologous VSR proteins in recombinant SINV. We identify both the virus and tick factors are critical components to understanding TBDs. Importantly, our study introduces a novel, in vivo virus-vector-mouse model system for exploring TBDs in the future.

Severe fever with thrombocytopenia syndrome (SFTS), a tick-borne infectious disease, is difficult to differentiate from other common febrile diseases. Clinically distinctive features and climate variates associated with tick growth can be useful predictors for SFTS. This retrospective study (2013&ndash, 2019) demonstrated the role of climatic factors as predictors of SFTS and developed a clinical scoring system for SFTS using climate variables and clinical characteristics. The presence of the SFTS virus was confirmed using reverse transcription polymerase chain reaction (RT-PCR) tests. In the univariate analysis, the SFTS-positive group was significantly associated with higher mean ambient temperature and humidity compared with the SFTS-negative group (22.5 &deg, C vs. 18.9 &deg, C, 77.9% vs. 70.7%, all p &lt, 0.001). In the multivariate analysis, poor oral intake (Odds ratio [OR] 5.87, 95% CI: 2.42&ndash, 8.25), lymphadenopathy (OR 7.20, 95% CI: 6.24&ndash, 11.76), mean ambient temperature &ge, 20 &deg, C (OR 4.62, 95% CI: 1.46&ndash, 10.28), absolute neutrophil count &le, 2000 cells/&mu, L (OR 8.95, 95% CI: 2.30&ndash, 21.25), C-reactive protein level &le, 1.2 mg/dL (OR 6.42, 95% CI: 4.02&ndash, 24.21), and creatinine kinase level &ge, 200 IU/L (OR 5.94, 95% CI: 1.42&ndash, 24.92) were significantly associated with the SFTS-positive group. This study presents the risk factors, including ambient temperature and clinical characteristics, that physicians should consider when suspecting SFTS.

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a recently emerged tickborne virus in east Asia with over 8,000 confirmed cases. With a high case fatality ratio, SFTSV has been designated a high priority pathogen by the WHO and the NIAID. Despite this, there are currently no approved therapies or vaccines to treat or prevent SFTS. Vesicular stomatitis virus (VSV) represents an FDA-approved vaccine platform that has been considered for numerous viruses due to its low sero-prevalence in humans, ease in genetic manipulation and promiscuity in incorporating foreign glycoproteins into its virions. In this study, we developed a recombinant VSV (rVSV) expressing the SFTSV glycoproteins Gn/Gc (rVSV-SFTSV) and assessed its safety, immunogenicity and efficacy in mice. We demonstrate that rVSV-SFTSV is safe when given to immunocompromised animals and is not neuropathogenic when injected intracranially into young immunocompetent mice. Immunization of Ifnar-/- mice with rVSV-SFTSV resulted in high levels of neutralizing antibodies and protection against lethal SFTSV challenge. Additionally, passive transfer of sera from immunized Ifnar-/- mice into naïve animals was protective when given pre- or post-exposure. Finally, we demonstrate that immunization with rVSV-SFTSV cross protects mice against challenge with the closely related Heartland virus despite low neutralizing titers to the virus. Taken together, these data suggest that rVSV-SFTSV is a promising vaccine candidate.ImportanceTick borne diseases are a growing threat to human health. Severe fever with thrombocytopenia syndrome (SFTS) and Heartland viruses are recently recognized, highly-pathogenic, tick-transmitted viruses. The fatality rates for individuals infected with SFTSV or HRTV are high and there are no therapeutics or vaccines available. The recent introduction of the tick vector for SFTSV (Haemaphysalis longicornis) to the eastern half of the United States and Austrailia raises concerns for SFTSV outbreaks outside East Asia. Here we report the development of a potential vaccine for SFTSV and HRTV based on the viral vector platform that has been successfully used for an Ebola vaccine. We demonstrate that the rVSV-SFTSV protects from lethal SFTSV or HRTV challenge when given as a single dose. We evaluated possible pathogenic effects of the vaccine and show that it is safe in immune compromised animlas and when introduced into the central nervous system.

Severe fever with thrombocytopenia syndrome (SFTS) is a zoonotic disease caused by the SFTS virus (SFTSV). SFTS can be considered a life-threatening notifiable infectious disease. The unavailability of specific therapeutics encourages the investigation of potential efficacy of existing drugs against this infection. Drug repurposing was done by performing virtual screening of already established drug molecules followed by 100 ns molecular dynamics simulations and molecular mechanics Poisson–Boltzmann surface area–based binding-energy calculation by targeting the SFTS L protein. On the basis of binding energy and protein–ligand interactions, top 10 promising hits were identified, showing stable binding with SFTS L protein. Further 100 ns atomistic MD simulation refined the hits from top 10 to top 4 with docking-based binding energy lesser than −8.0 kcal/mol toward the SFTS L protein and engaged in π–π interactions with pivotal amino acid residues. Various parameters and binding affinity of top 4 ligands towards L protein was computed. Ligand zaltoprofen exhibited best binding energy −220.095 kJ/mol. The present work is the first in silico study to assess bromfenac, cinchophen, elliptinium, and zaltoprofen; four promising hits against SFTS. Nonetheless, further proper biological evaluation is necessary to determine their efficacy against SFTS.

Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne bunyavirus in Asia that causes severe disease. Despite its clinical importance, treatment options for SFTSV infection remains limited. The SFTSV glycoprotein Gn plays a major role in mediating virus entry into host cells and is therefore a potential antiviral target. In this study, we employed an in silico structure-based strategy to design novel cyclic antiviral peptides that target the SFTSV glycoprotein Gn. Among the cyclic peptides, HKU-P1 potently neutralizes the SFTSV virion. Combinatorial treatment with HKU-P1 and the broad-spectrum viral RNA-dependent RNA polymerase inhibitor favipiravir exhibited synergistic antiviral effects in vitro. The in silico peptide design platform in this study may facilitate the generation of novel antiviral peptides for other emerging viruses.

Severe fever with thrombocytopenia syndrome (SFTS) is a novel tick-borne infectious disease caused by a new type of SFTS virus (SFTSV). Here, a longitudinal sampling study is conducted to explore the differences in transcript levels after SFTSV infection, and to characterize the transcriptomic and epigenetic profiles of hospitalized patients. The results reveal significant changes in the mRNA expression of certain genes from onset to recovery. Moreover, m6A-seq reveals that certain genes related with immune regulation may be regulated by m6A. Besides the routine tests such as platelet counts, serum ALT and AST levels testing, distinct changes in myocardial enzymes, coagulation function, and inflammation are well correlated with the clinical data and sequencing data, suggesting that clinical practitioners should monitor the above indicators to track disease progression and guide personalized treatment. In this study, the transcript changes and RNA modification may lend a fresh perspective to our understanding of the SFTSV and play a significant role in the discovery of drugs for effective treatment of this disease., Severe fever with thrombocytopenia syndrome (SFTS) is an emerging hemorrhagic fever caused by tick-borne SFTS virus. Here, Wang et al. characterize transcriptomic and epigenetic changes in infected patients and correlate them with clinical parameters to improve the understanding of disease progression.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging hemorrhagic fever, and the causative pathogen, the SFTS virus (SFTSV), was first discovered in China in 2010. In this study, a retrospective analysis of 86 patients that diagnosed with SFTS from two five-year periods (2011-2015 and 2016-2020) that was performed to explore the changes in epidemiology, clinical characteristics, laboratory parameters and prognosis between those two periods. The results showed that there were significant differences in age, the proportion of farmers, geographical distribution, the incidence of multiple organ dysfunction, the decrease in thrombocyte count, and the elevations of serum AST and lipase levels between the two groups (p

Severe fever with thrombocytopenia syndrome (SFTS) is a hemorrhagic fever. Patients mainly develop fever, thrombocytopenia, and leukopenia. A high case fatality rate of 16.2–47% has been reported. Vaccines and antivirals that are effective against SFTS virus (SFTSV) are not yet available in clinical practice. We previously showed that o-dihydroxybenzene is the important chemical core structure for anti-SFTSV activity. In this study, we evaluated the anti-SFTSV efficacy of 3-Hydroxy-L-tyrosine (L-DOPA), a treatment for Parkinson's disease and its enantiomer, 3-hydroxy-D-tyrosine (D-DOPA), both of which have an o-dihydroxybenzene backbone. SFTSV was preincubated with L- or D-DOPA and then inhibition of viral infection as well as viral attachment to host cells were evaluated by viral quantification. Both L- and D-DOPA inhibited SFTSV infection in a dose-dependent manner, mainly by blocking viral attachment to host cells. The half-maximal inhibitory concentration (IC50) of L-DOPA was 4.46–5.09 μM. IC50 of D-DOPA was 4.23–6.72 μM. IC50 of L-DOPA is very close to its maximum blood concentration after oral administration as a therapy for Parkinson's disease. D-DOPA, which IC50 was almost the same as that of L-DOPA, might not cause side effect. Thus, our present study demonstrated that L- and D-DOPA are potentially useful candidates for anti-SFTSV drugs.

Background We report a mononucleosis-like illnesses case due to co-infection with severe fever with thrombocytopenia syndrome virus (SFTSV) and spotted fever group rickettsia (SFGR), which to the best of our knowledge, has never been reported . Case presentation A 64-year-old male with an 11-day history of fever, sore throat, malaise, nausea, and non-pruritic rash was admitted to our emergency department. Prior to admission, he was bitten by ticks. Laboratory tests revealed a white blood cell count of 24,460 cells/μL with 25% atypical lymphocytes and 20% mononucleosis, thrombocytopenia. Test results were positive for SFTSV RNA, SFTSV-specific IgM antibody, and SFGR-specific IgM antibody. He was diagnosed with mononucleosis-like illnesses due to co-infection with SFTSV and SFGR. After administration of doxycycline, he recovered completely. Conclusions The clinical presentation may be atypical in co-infection with SFTSV and SFGR. This finding highlighted the importance of considering SFGR infection, as well as a SFSTV and SFGR co-infection for the differential diagnosis of patients bitten by ticks in SFTSV-endemic areas.

Severe fever with thrombocytopenia syndrome (SFTS) is a disease caused by infection with the SFTS virus (SFTSV). SFTS has become a crucial public health concern because of the heavy burden, lack of vaccines, effective therapies, and high-fatality rate. Evidence suggests that SFTSV circulates between ticks and animals in nature and is transmitted to humans by tick bites. In particular, ticks have been implicated as vectors of SFTSV, where domestic or wild animals may play as the amplifying hosts. Many studies have identified antigens and antibodies against SFTSV in various animals such as sheep, goats, cattle, and rodents. Besides, person-to-person transmission through contact with blood or mucous of an infected person has also been reported. In this study, we reviewed the literature and summarized the vectors and hosts associated with SFTS and the possible risk factors.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease caused by the SFTS virus (SFTSV). There is no specific treatment for SFTS, although several reports have indicated that plasma exchange (PE) can be an effective therapy for severe SFTS. However, whether or not PE can reduce the viral load is unclear. We herein report a woman with SFTS who had her SFTSV viral load measured just before and after PE. While the patient recovered, there was no significant difference in the SFTSV viral load after PE. Our results confirmed that PE itself does not reduce the SFTSV viral load.

With global warming and lush forest change, vector-borne infections are expected to increase in the number and diversity of agents. Since the first report of severe fever with thrombocytopenia syndrome (SFTS) in 2013, the number of reported cases has increased annually in South Korea. However, although tick-borne encephalitis virus (TBEV) was detected from ticks and wild rodents, there is no human TBE case report in South Korea. This study aimed to determine the seroprevalence of TBEV and SFTS virus (SFTSV) among forest and field workers in South Korea. From January 2017 to August 2018, a total 583 sera were obtained from the forest and field workers in South Korea. IgG enzyme-linked immunosorbent assay (ELISA) and neutralization assay were conducted for TBEV, and indirect immunofluorescence assay (IFA) and neutralization assay were performed for SFTSV. Seroprevalence of TBEV was 0.9% (5/583) by IgG ELISA, and 0.3% (2/583) by neutralization assay. Neutralizing antibody against TBEV was detected in a forest worker in Jeju (1:113) and Hongcheon (1:10). Only 1 (0.2%) forest worker in Yeongju was seropositive for SFTSV by IFA (1:2,048) and neutralizing antibody was detected also. In conclusion, this study shows that it is necessary to raise the awareness of physicians about TBEV infection and to make efforts to survey and diagnose vector-borne diseases in South Korea., Author summary With global warming and lush forest change, vector-borne infections are expected to increase in the number and diversity of agents. Since the first report of severe fever with thrombocytopenia syndrome (SFTS) in 2013, the number of reported cases has increased annually in South Korea. However, although tick-borne encephalitis virus (TBEV) was detected from ticks and wild rodents, there is no human TBE case report in South Korea. This study aimed to determine the seroprevalence of TBEV and SFTS virus (SFTSV) among forest and field workers in South Korea. Among 583 forest/field workers, the seroprevalence of neutralizing antibodies against TBEV and SFTSV were 0.3% (2/583) and 0.2% (1/583), respectively. This study shows that it is necessary to raise the awareness of physicians about TBEV infection and to make efforts to survey and diagnose vector-borne diseases in South Korea.

Severe fever with thrombocytopenia syndrome (SFTS) is a new tick-borne viral disease, and most SFTS virus (SFTSV) infections occur via bites from the tick Haemaphysalis longicornis; however, SFTSV transmission can also occur through close contact with an infected patient. SFTS is characterized by acute high fever, thrombocytopenia, leukopenia, elevated serum hepatic enzyme levels, gastrointestinal symptoms, and multiorgan failure and has a 16.2 to 30% mortality rate. In this study, we found that age, dyspnea rates, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase, multiorgan dysfunction score (MODS), viral load, IL-6 levels, and IL-10 levels were higher in patients with fatal disease than in patients with nonfatal disease during the initial clinical course of SFTS. In addition, we found that IL-6 and IL-10 levels, rather than viral load and neutralizing antibody titers, in patients with an SFTSV infection strongly correlated with outcomes (for severe disease with an ultimate outcome of recovery or death).

Objectives: The objective was to describe the changes of severe fever with thrombocytopenia syndrome virus (SFTSV) and antibody in the disease course and explore the relationship between antibody titers and patients’ prognosis.Methods: The levels of SFTSV, virus-specific immunoglobulin M (IgM), immunoglobulin G (IgG) titers, and cytokines in 37 patients with severe fever with thrombocytopenia syndrome (SFTS) were measured dynamically by real-time PCR and ELISA during the disease course; IgG titers were followed up in 53 cases. The correlation analysis of antibody titers with individual serum cytokines was calculated using the Spearman test.Results: The average time of SFTSV duration in individual serum was 22.45 ± 7.6 days from onset. We found SFTSV turned negative within the 10th day from the onset in two patients. SFTSV-specific IgM seroconversion occurred as early as within 3 days from the onset, increased gradually within the first 2 months, decreased gradually 3 months later, and disappeared after 6 months in all the patients. The average time of SFTSV-specific IgG antibody seroconversion was at 17 days from onset in the patients; the time was later in severe cases than in mild cases (23 ± 1.4 vs. 14.3 ± 1.0 days, p < 0.0001). IgG titers were maintained at the peak levels during the periods from 6 months to 1 year and decreased from the second year gradually. Severe cases had higher IgG levels than mild cases and also had a slower decreasing trend. During follow-up, only one lost IgG antibody 7 years later; no chronic infection and sequela were found among the 53 patients. None of the patients had SFTSV reinfection even if they were bitten by ticks again. The correlation analysis showed a positive relationship between inflammatory factors and IgG antibody levels.Conclusion: IgM antibody has important value in early diagnosis of SFTS. A moderate inflammatory response is beneficial for production and duration of IgG antibodies.

Background An emerging infectious zoonosis known as Severe Fever with Thrombocytopenia Syndrome (SFTS) is discovered mainly in Japan, South Korea and China. SFTS virus (SFTSV) which is recently recognised as bunyavirus is borne by ticks such as Haemaphysalis longicornis. It has the capabilities to spread as develop clusters and become a considerable public health threat as this virus could experience rapid evolution via gene mutation. Case fatality rate has been reported up to higher than 30%. The aim of this review is to determine the associated risk factors of SFTS and its outcome. Materials and methods Literature search was conducted using online databases PubMed, ScienceDirect, and Scopus. A total of 517 records were identified from searches in PubMed, ScienceDirect, and Scopus. From the final exclusions, a total of 26 studies were included for final analysis. Results Associated risk factors to getting SFTS infection include occupation, history of bite from a tick, biological susceptibility, and owning of domestic animal. Fatality rates apart from single case reports range from 15.1% to 50% and are contributed by various factors including delay in hospital admission, high viral load, older age group and presence of comorbid and complication. Conclusion A seroprevalence study can be conducted amongst the high-risk occupation group such as farmers and agricultural workers, as well as testing cases where viral fever is suspected but available tests for other diseases turns out negative., Highlights • SFTSV is a bunyavirus borne by ticks such as Haemaphysalis longicornis. • Public health threat if progress into rapid evolution via gene mutation. • Case fatality rate has been reported up to higher than 30%. • SFTS infection risk factors include occupation, tick bite history, biological susceptibility, and owning domestic animal. • Fatality rates ranges from 15.1% - 50%. • Fatality associated with delay admission, viral load, older age and comorbidity.

Background Severe fever with thrombocytopenia syndrome (SFTS), an emerging tickborne infectious disease caused by a novel banyangvirus (SFTS virus, SFTSV), was endemic in several Asian countries with a high mortality up to 30%. Until recently, SFTSV-associated re-infection have not been reported and investigated. Case presentation A 42-year-old female patient was identified as a case of SFTS with re-infection, with two episodes of SFTSV infection on June 2018 and May 2020. The diagnosis of SFTS was confirmed by detection of SFTSV RNA in the blood samples using real-time reverse-transcription polymerase chain reaction and antibodies specific for SFTSV using enzyme linked immunosorbent assay. The changes of viremia and antibody response differed between the two episodes. Phylogenetic analysis showed the two viral genome sequences were in the same clade, but showing 0.6% dissimilarity of the nearly whole nucleotide sequence. Analysis of clinical data revealed that the second episode showed milder illness than that of the first episode. Conclusions Epidemiological and clinical findings, viral whole genomic sequences, and serological evidence, provided evidence for the re-infection of SFTSV rather than prolonged viral shedding or relapse of the original infection. The patients with re-infection of SFTSV may be at high odds of clinically inapparent or mildly symptomatic. More attention should be directed towards the long-term follow up of the recovered patients in the future, to explicitly acquire the decay profile of their immunity response. Graphic abstract

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tickborne infectious disease in China, Korea, and Japan caused by the SFTS virus (SFTSV). SFTS has a high mortality rate due to multiorgan failure. Recently, there are several reports on SFTS patients with mycosis. Here, we report a middle-aged Japanese SFTS patient with invasive pulmonary aspergillosis (IPA) revealed by an autopsy. A 61-year-old man with hypertension working in forestry was bitten by a tick and developed fever, diarrhea, and anorexia in 2 days. On day 4, consciousness disorder was appearing, and the patient was transferred to the University of Miyazaki Hospital. A blood test showed leukocytopenia, thrombocytopenia, as well as elevated levels of alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, and creatine kinase. The SFTSV gene was detected in serum using a reverse-transcription polymerase chain reaction. On day 5, respiratory failure appeared and progressed rapidly, and on day 7, the patient died. An autopsy was performed that revealed hemophagocytosis in the bone marrow and bleeding of several organs. IPA was observed in lung specimens. SFTSV infection may be a risk factor for developing IPA. Early diagnosis and treatment of IPA may be important in patients with SFTS.

Aspergillus-related disease was confirmed to be associated with immune disorders in patients, severe patients with severe fever with thrombocytopenia syndrome (SFTS) infected by novel phlebovirus were confirmed to have severe immune damage including cellular immunosuppression and cytokine storms. Secondary invasive pulmonary aspergillosis (IPA) in severe SFTS patients can increase fatality rate. This study investigated early-warning predictive factors of secondary IPA in severe SFTS patients. Receiver operating characteristic analysis was used to assess the value of immune parameters to predict IPA in SFTS patients. The cut-off values of CD4+ and CD8+ T-cell counts to predict IPA were 68 and 111 cells/mm3, with sensitivities of 82.6% and 72%, and specificities of 56.7% and 83.3%, respectively. Cut-off values of IL-6, TNF-α, IL-8, and IL-10 to predict IPA incidence in critically ill SFTS patients were 99 pg/mL, 63 pg/mL, 120 pg/mL, and 111 pg/mL, with sensitivities of 90.0%, 86.7%, 83.3% and 90.0% and specificities of 80.4%, 71.7%, 82.6% and 65.2%, respectively. Lower CD4+ and CD8+ T-cells counts, higher levels of IL-6, TNF-α, IL-8 and IL-10, higher incidence of pancreatic and renal damage, early antibacterial therapy of carbapenems, and intensive care unit admission were risk factors of IPA in SFTS patients. Multivariate logistic regression analysis indicated counts of CD4+ T-cells 3 combined with CD8+ T-cells 3 (odds ratio [OR] 0.218, 95% confidence interval [CI] 0.059–0.803, p=0.022), IL-6 >99 pg/ml combined with IL-10 >111 pg/ml (OR 17.614, 95% CI 2.319–133.769, p=0.006), and brain natriuretic peptide level >500 pg/ml (OR 13.681, 95% CI 1.994–93.871, p=0.008) were independent risk factors for IPA in SFTS patients. The mortality in the IPA group was significantly higher than in the non-IPA group (p=0.001). Early antifungal treatment of IPA patients was significantly associated with improved survival (log-rank, p=0.022). Early diagnosis of IPA and antifungal treatment can improve the prognosis of SFTS patients. Besides, we speculate SFTS may be as a host factor for IPA.