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Background Severe fever with thrombocytopenia syndrome (SFTS) is a life-threatening infectious disease for which no effective treatment strategy has been established. Although corticosteroids (CSs) are widely administered to patients with SFTS, their efficacy remains uncertain. This study aimed to assess the impact of CS therapy on the in-hospital mortality of patients with SFTS. Methods In this nationwide observational study using the Japanese Diagnosis Procedure Combination database, patients hospitalized for SFTS from April 2013 to March 2021 were reviewed. We compared patients who were treated with CSs to those who were treated without them after propensity score matching to adjust for their background, disease severity, and combination therapy. Results We included 494 patients with SFTS, and 144 pairs of them were analyzed after propensity score matching. No significant difference in the 30-day mortality (19% vs 15%, P =.272) and the number of survival days (log-rank test, P =.392) was found between the CS treatment group and the non-CS treatment group. However, in subgroup analyses, the CS treatment group tended to have better survival among patients with impaired consciousness on admission and/or shock status within 7 days after admission. Conclusions CS therapy does not seem effective for all patients with SFTS; however, the impact might be altered by disease severity assessed by the consciousness level and shock status. A large-scale interventional study is required to determine its efficacy, especially for critically ill patients with SFTS. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia syndrome (SFTS) and Japanese spotted fever (JSF; a spotted fever group rickettsiosis) are tick-borne zoonoses that are becoming a significant public health threat in Japan and East Asia. Strategies for treatment and infection control differ between the two; therefore, initial differential diagnosis is important. We aimed to compare the clinical characteristics of SFTS and JSF based on symptomology, physical examination, laboratory data, and radiography findings at admission. This retrospective study included patients with SFTS and JSF treated at five hospitals in Nagasaki Prefecture, western Japan, between 2013 and 2020. Data from 23 patients with SFTS and 38 patients with JSF were examined for differentiating factors and were divided by 7:3 into a training cohort and a validation cohort. Decision tree analysis revealed leukopenia (white blood cell [WBC] < 4000/μL) and altered mental status as the best differentiating factors (AUC 1.000) with 100% sensitivity and 100% specificity. Using only physical examination factors, absence of skin rash and altered mental status resulted in the best differentiating factors with AUC 0.871, 71.4% sensitivity, and 90.0% specificity. When treating patients with suspected tick-borne infection, WBC < 4000/µL, absence of skin rash, and altered mental status are very useful to differentiate SFTS from JSF. [ABSTRACT FROM AUTHOR]

Background: Miyazaki Prefecture is one of the hotspots of severe fever with thrombocytopenia syndrome (SFTS) cases and related deaths in Japan since 2013 and other pathogens of tick‐borne diseases (TBDs). Japanese spotted fever and scrub typhus are also endemic in this region. Objectives: A total of 105 wild boars, hunted in 2009, were serologically examined as sentinels for TBDs to indirectly demonstrate the potential hazard of ticks transmitting pathogens to humans in the studied area. Methods: The collected blood and spleens of the wild boars underwent serological and molecular tests for SFTSV, Rickettsia japonica (Rj) [antibody to spotted fever group rickettsiae (SFGR) were tested by using species‐common antigen], and Orientia tsutsugamushi (Ot). Results: Seroprevalences of SFTSV, SFGR, and Ot were 41.9%, 29.5%, and 33.3%, respectively. SFTS viral RNA was identified in 7.6% of the sera, whereas DNA of Rj or Ot was not detected in any sample. In total, 43.8% of the boars possessed an infection history with SFTSV (viral gene and/or antibody). Of these, 23.8% had multiple‐infection history with SFGR and/or Ot. Conclusions: The high prevalence of SFTSV in wild boars might reflect the high risk of exposure to the virus in the studied areas. In addition, SFTSV infection was significantly correlated with Ot infection, and so were SFGR infection and Ot infection, indicating that these pathogens have common factors for infection or transmission. These data caution of the higher risk of SFTSV infection in areas with reported cases of other TBDs. [ABSTRACT FROM AUTHOR]

Introduction: Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne infectious disease caused by the SFTS virus (SFTSV). The Miyazaki Prefecture has the highest number of SFTS cases in Japan and requires countermeasures for prevention. In this study, we aimed to conduct an epidemiological survey in Miyazaki Prefecture to determine the exposure conditions of SFTSV by measuring the seroprevalence among residents of Miyazaki and to evaluate the factors that influence the endemicity of SFTS., Methods: The survey was conducted between June 2014 and April 2019 in all 26 municipalities in Miyazaki Prefecture. SFTSV antibodies were detected using an enzyme-linked immunosorbent assay in the blood samples of 6013 residents (3184 men and 2829 women). A questionnaire-based survey of the living environment was also conducted., Results: Multiple logistic regression analysis revealed that age and occupation were significant factors related to the proportion of participants with an optical density (OD) value > 0.2 and a seroprevalence of 0.9 % (54/6013). Seven seropositive individuals (0.1 %) with an OD value of >0.4 were identified (three men and four women, aged 54-69 years), and all were asymptomatic. One participant had a higher OD than the positive control., Conclusion: Although SFTS is endemic in Miyazaki Prefecture, Japan, its seroprevalence is relatively low. Since some risk areas in Miyazaki prefecture have been identified, it is important to enhance awareness of SFTS in residences and reduce contact with ticks, especially in high-risk areas., Competing Interests: Declarations of competing interest None of declare., (Copyright © 2023 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

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. [ABSTRACT FROM AUTHOR]

Background Severe fever with thrombocytopenia syndrome (SFTS) is an emerging viral hemorrhagic fever in China, Korea, and Japan. Japanese spotted fever (JSF), which belongs to spotted fever group rickettsioses, is also endemic to Western Japan. Patients with SFTS and those with JSF display many of the same clinical manifestations. Sudden fever, rash, tick bite, and neurological and gastrointestinal symptoms may be seen in both infections, but the frequency and severity of each disease have not been compared and studied. Because laboratory confirmation of pathogens takes time, it is important to predict diagnosis of SFTS vs JSF based on the features of the clinical characteristics at the initial presentation, particularly in primary care settings. Methods We conducted a case series review at 4 medical facilities in Miyazaki, Japan. Based on the medical records, clinical and laboratory characteristics were compared between patients with SFTS and those with JSF. Results Eighty-one patients were enrolled in this study, including 41 with SFTS and 40 with JSF. The absence of rash (P  < .001), leukopenia (P  < .001), and normal C-reactive protein (CRP) levels (P  < .001) were the variables distinguishing SFTS from JSF. Normal CRP levels (≤1.0 mg/dL) had a 95% sensitivity (84%–99%) and 97% specificity (87%–100%) for SFTS, with a positive likelihood ratio of 37.1 (5.35–257). Conclusions Normal serum CRP levels were shown to differentiate SFTS from JSF with a very high probability. [ABSTRACT FROM AUTHOR]

We conducted an epidemiologic study of severe fever with thrombocytopenia syndrome (SFTS) in Japan during 2013-2017. Of 303 cases reported during that period, 133 (44%) were included in this study. The median time between onset of illness and diagnosis of SFTS shortened, from 11.5 to 3.0 days, but the case-fatality rate remained high, at 27%. In 64 patients (48%), a close contact with companion animals was reported within 2 weeks of disease onset. Of these 64 patients, 40 were surveyed further, and we confirmed that 3 had direct contact with body fluids of ill companion animals; 2 had direct contact with the saliva of an ill feral cat or pet dog. These patients reported no history of tick bite, suggesting that ill companion animals might be a source of SFTS virus transmission. Direct contact with the body fluids of ill companion animals should be avoided. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background and Objectives : The Wakayama prefecture is endemic for two types of tick-borne rickettsioses: Japanese spotted fever (JFS) and scrub typhus (ST). Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne hemorrhagic viral disease with a high mortality rate and is often difficult to differentiate from such rickettsioses. SFTS cases have recently increased in Wakayama prefecture. For early diagnosis, this study aimed to evaluate the clinical characterization of such tick-borne infections in the co-endemic area. Materials and Methods : The study included 64 febrile patients diagnosed with tick-borne infection in Wakayama prefecture between January 2013 and May 2022. Medical records of 19 patients with SFTS and 45 with rickettsiosis (JSF, n = 26; ST, n = 19) were retrospectively examined. The receiver operating curve (ROC) and area under the curve (AUC) were calculated to evaluate potential factors for differentiating SFTS from rickettsiosis. Results : Adults aged ≥70 years were most vulnerable to tick-borne infections (median, 75.5 years; interquartile range, 68.5-84 years). SFTS and rickettsiosis occurred mostly between summer and autumn. However, no significant between-group differences were found in age, sex, and comorbidities; 17 (89%) patients with SFTS, but none of those with rickettsiosis, experienced gastrointestinal symptoms such as vomiting, abdominal pain, and diarrhea. Meanwhile, 43 (96%) patients with rickettsiosis, but none of those with SFTS, developed a skin rash. The AUCs of white blood cells (0.97) and C-reactive protein (CRP) levels (0.98) were very high. Furthermore, the differential diagnosis of SFTS was significantly associated with the presence of gastrointestinal symptoms (AUC 0.95), the absence of a skin rash (AUC 0.98), leukopenia <3.7 × 10 9 /L (AUC 0.95), and low CRP levels < 1.66 mg/dL (AUC 0.98) ( p < 0.001 for each factor). Conclusions : Clinical characteristics and standard laboratory parameters can verify the early diagnosis of SFTS in areas where tick-borne infections are endemic.

Atypical lymphocytes in the peripheral blood in patients with severe fever with thrombocytopenia syndrome (SFTS) have not been well examined. In this study, we analyzed counts and characteristics of atypical lymphocytes in 7 patients with SFTS. Atypical lymphocytes resembled plasma cells morphologically and appeared in the peripheral blood of all patients 4-8 days after onset of disease. Among these lymphocytes flow cytometry showed a CD19+CD38+CD138-/+ phenotype, and immunohistochemical staining revealed a CD79a+CD38+CD138-/+CD27+ phenotype. From our observations, atypical lymphocytes transiently that appeared in the peripheral blood during the acute phase of SFTS were considered to be plasmablasts. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia syndrome (SFTS) was first identified as an emerging tick-borne infectious disease caused by the SFTS virus (SFTSV) in China and has also been found to be endemic to Japan and South Korea, indicating that SFTS is of great concern in East Asia. The aim of the present study was to determine the seroprevalence of SFTSV antibodies in humans and animals in SFTS-endemic regions of Japan. One of 694 (0.14%) healthy persons over 50 years of age and 20 of 107 (18.7%) wild and domestic animals in Ehime prefecture of western Japan were determined to be seropositive for SFTSV antibodies by virus neutralization test and ELISA, respectively. The seropositive person, a healthy 74-year-old woman, was a resident of the southwest part of Ehime prefecture engaged in citriculture and field work. This woman's sample exhibited neutralizing activity against SFTSV although she had neither a clear experience with tick bites nor SFTS-like clinical illness. These findings indicate that most people living in the endemic regions are not infected with SFTSV and suggest that most of the SFTS patients reported so far do not reflect the tip of an iceberg of people infected with SFTSV, but at the same time, that SFTSV infection does not always induce severe SFTS-associated symptoms. These findings also suggested that SFTSV has been maintained in nature within animal species and ticks. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease caused by the SFTS virus (SFTSV). The aim of this study was to clarify whether SFTS is potentially mis-diagnosed as rickettsioses, including spotted fever, typhus fever, and scrub typhus, which are also tick-borne disease. A total of 464 serum samples collected from 222 patients with clinically suspected rickettsiosis between 1999 and 2012 were tested for antibodies against the SFTSV. Of the 464 serum samples, one was positive for antibodies against the virus in an enzyme-linked immunosorbent assay and indirect immunofluorescence assay. The patient of SFTSV antibody-positive sample (15 days after disease onset) was positive for SFTSV genome in the acute phase sample (3 days after disease onset) as determined via reverse transcription-quantitative polymerase chain reaction. This patient, who was a resident of the Yamaguchi prefecture in Western Japan, was in his 40s when he showed symptoms in 2011. As the result, 1 of 222 patients, who was clinically suspected of rickettsiosis, was retrospectively diagnosed with SFTS. In this case, both the C-reactive protein and white blood cell count levels were lower than the ranges of these parameters for patients diagnosed with rickettsiosis. Therefore, SFTS should be considered in the differential diagnosis for rickettsiosis in Japan. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia syndrome (SFTS), a tickborne viral disease, has been identified in China, South Korea, and Japan since 2009. We found retrospective evidence of SFTS virus (SFTSV) infection in Vietnam, which suggests that SFTSV infections also occur in Vietnam, where the virus has not been known to be endemic. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia syndrome (SFTS) is a fatal emerging tick-borne zoonotic disease caused by the SFTS virus (SFTSV). SFTSV infection in humans and companion animals is a matter of concern in endemic areas. Various wild animals are involved in the transmission cycle of SFTSV with vector ticks. Because the home range of medium-sized wild mammals commonly overlaps with humans' living spheres, this study aimed to reveal the endemicity of SFTSV in such mammals. This study investigated the prevalence of antibodies against SFTSV and viral RNA in medium-sized wild mammals in Miyazaki Prefecture, Japan where human cases have been most frequently reported in Japan and performed a phylogenetic analysis to compare the detected SFTSV with those previously reported. Forty-three of 63 (68%) Japanese badgers (Meles anakuma) and 12 of 53 (23%) Japanese raccoon dogs (Nyctereutes procyonoides viverrinus) had antibodies against SFTSV. Japanese marten (n = 1), weasels (n = 4), and Japanese red fox (n = 1) were negative. Two of 63 (3%) badgers tested positive for SFTSV RNA, whereas the other species were negative. Phylogenetic analysis of the partial nucleotide sequence of SFTSV revealed that viral RNA detected from badgers exhibited 99.8% to 100% similarity to SFTSV, as previously reported in humans, cat, and ticks in the study area. This study demonstrated high seropositivity of antibodies in medium-sized wild mammals and suggested that SFTSV could be shared among these mammals, humans, and companion animals in endemic areas., (Copyright © 2022. Published by Elsevier GmbH.)

In Japan, 2 cats that underwent surgery in a room where a sick dog had been euthanized became ill within 9 days of surgery. Severe fever with thrombocytopenia syndrome virus was detected in all 3 animals; nucleotide sequence identity was 100%. Suspected cause was an uncleaned pulse oximeter probe used for all patients.

We have shown that human alveolar lining fluid (ALF) contains homeostatic hydrolases capable of altering the Mycobacterium tuberculosis cell wall and subsequently its interaction with human macrophages. Neutrophils are also an integral part of the host immune response to M. tuberculosis infection. Here we show that the human lung mucosa influences M. tuberculosis interaction with neutrophils, enhancing the intracellular killing of ALFexposed M. tuberculosis and up-regulating the expression of tumor necrosis factor and interleukin 8. In contrast, ALF-exposed M. tuberculosis does not induce neutrophil apoptosis or necrosis, degranulation, or release of extracellular traps, and it decreases the oxidative response. These results suggest an important role for the human alveolar mucosa: increasing the innate capacity of the neutrophil to recognize and kill M. tuberculosis by favoring the use of intracellular mechanisms, while at the same time limiting neutrophil extracellular inflammatory responses to minimize their associated tissue damage. [ABSTRACT FROM AUTHOR]

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.

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.

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.

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.

Severe fever with thrombocytopenia syndrome virus (SFTSV) can be transmitted between humans. We describe a case of severe fever with thrombocytopenia syndrome in which SFTSV RNA was detected in semen after its disappearance from serum. Our findings indicate possible sexual transmission of this emerging virus. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia syndrome (SFTS) is an infection mediated by ticks and has been reported to have a high mortality rate in Japan. At our hospital, we reported three cases of SFTS with relatively positive outcomes. We reviewed reports of SFTS cases in Japan to clarify the current state of the disease in Japan, the treatment provided, and its outcome. The Ichushi Web was searched for literature using the following terms as keywords: "SFTS" or "severe fever with thrombocytopenia syndrome". Overall, 174 cases were collected and reviewed. The mean age of patients was 70.69 years old, and the mortality rate was 35%. The dead group was significantly older ( p < 0.001) than the alive group, had a significantly shorter period from symptom onset to hospital admission, and experienced significantly more hemorrhage-related and neurological symptoms. Further, the most frequently provided treatment methods were adrenocorticosteroids, antibiotics, and conservative treatment. The low recognition rate of SFTS in Japan might lead to a misdiagnosis or delay in diagnosis and treatment, especially in mild to moderate cases. Medical professionals and citizens who live in areas inhabited by ticks need to be informed about SFTS to appropriately diagnose and manage SFTS cases in Japan in the future.

In Okinawa prefecture, Japan, the first case of severe fever with thrombocytopenia syndrome (SFTS) was confirmed in August 2016, and this case remains to be the only reported case of SFTS in Okinawa. The epidemiological investigation indicated that the patient had been infected on the main island of Okinawa, but source and route of infection were unknown. Therefore, to understand the possible source and route of SFTS virus (SFTSV) infection in Okinawa, we performed a seroepidemiological study of SFTSV among animals and dwellers in Okinawa and conducted a questionnaire survey to investigate risk factors for tick bites in Okinawa. Among the 1,035 serum samples from four different animal species, anti-SFTSV antibodies were detected in only 4.2% wild mongoose (Herpestes auropunctatus) serum samples. To our knowledge, this is the first study to report the detection of anti-SFTSV antibodies in wild mongooses. Meanwhile, all 1,104 human inhabitants tested negative for anti-SFTSV antibodies, suggesting that the frequency of SFTSV exposure is low in Okinawa. Logistic regression analysis of the questionnaire results showed that outdoor activity was associated with an increased risk of tick bite among Okinawa residents. Despite the current low frequency of SFTSV infection in animals and humans, endemic circulation of the virus in Okinawa should be carefully monitored in the area for preventing future infections., (Copyright © 2021 Elsevier GmbH. All rights reserved.)

We conducted a seroprevalence investigation of the healthy population of animals in Kagoshima Prefecture, an area in which severe fever with thrombocytopenia syndrome (SFTS) is endemic. Of 104 domestic cat and 114 dog samples, 2 (1.9%) and 11 (9.6%) were positive for anti-SFTS virus (SFTSV) IgG by indirect ELISA, respectively. Viral RNA was detected in one dog (0.9%) by RT-PCR. Of the 102 wild boar (Sus scrofa) and 107 deer (Cervus nippon) samples tested, 55 (53.9%) and 37 (34.7%) were positive for anti-SFTSV IgG, respectively. Only one wild boar (1.0%) was positive for viral RNA. Although symptomatic SFTSV infections in domestic cats have increased in this area, the seroprevalence of the healthy population of domestic cats tends to be lower than those of other animals. We developed a Gaussia luciferase immunoprecipitation system (GLIPS) using mammalian cells expressing a recombinant SFTSV nucleoprotein (SFTSV-rNP) for the detection of SFTSV-specific antibodies in samples from various animal species. The sensitivity of the assay was highly consistent with that of indirect ELISA, indicating that it could serve as a useful tool for a large-scale surveillance of SFTSV across multiple species of animals., (Copyright © 2021 Elsevier GmbH. All rights reserved.)

A woman in her fifties showed symptoms of fever, loss of appetite, vomiting, and general fatigue 2 days after she was bitten by a sick cat, which had later died, in Yamaguchi prefecture, western Japan, in June 2016. She subsequently died of multiorgan failure, and an autopsy was performed to determine the cause of death. However, the etiological pathogens were not quickly identified. The pathological features of the patient were retrospectively re-examined, and the pathology of the regional lymph node at the site of the cat bite was found to show necrotizing lymphadenitis with hemophagocytosis. The pathological features were noted to be similar to those of patients reported to have severe fever with thrombocytopenia syndrome (SFTS). Therefore, the lymph node section was retrospectively tested immunohistochemically, revealing the presence of the SFTS virus (SFTSV) antigen. The sick cat showed similar symptoms and laboratory findings similar to those shown in human SFTS cases. The patient had no history of tick bites, and did not have skin lesions suggestive of these. She had not undertaken any outdoor activities. It is highly possible that the patient was infected with SFTSV through the sick cat's bite. If a patient gets sick in an SFTS-endemic region after being bitten by a cat, SFTS should be considered in the differential diagnosis. [ABSTRACT FROM AUTHOR]

In this study, we investigated severe fever with thrombocytopenia syndrome (SFTS) virus (SFTSV) infection in cats in Nagasaki, Japan. In total, 44 of 133 (33.1%) cats with suspected SFTS were confirmed to be infected with SFTSV. Phylogenetic analyses of SFTSV isolates from cats indicated that the main genotype in Nagasaki was J1 and that unique reassortant strains with J2 (S segment) and unclassified genotypes (M and L segments) were also present. There were no significant differences in virus growth in cell cultures or fatality in SFTSV-infected mice between the SFTSV strains that were isolated from recovered and fatal cat cases. Remarkably, SFTSV RNAs were detected in the swabs from cats, indicating that the body fluids contain SFTSV. To evaluate the risk of SFTSV infection when providing animal care, we further examined the seroprevalence of SFTSV infection in veterinarian staff members; 3 of 71 (4.2%) were seropositive for SFTSV-specific antibodies. Our results provide useful information on the possibility of using cats as sentinel animals and raised concerns of the zoonotic risk of catching SFTSV from animals.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging viral hemorrhagic fever in China, Korea, and Japan. To date, no standardized treatment protocol for SFTS has been established. Corticosteroids (CS) may be administered to patients with SFTS and hemophagocytic syndrome, but its effectiveness and safety are still debatable. We conducted a retrospective case series review at four medical facilities in Miyazaki, Japan. Based on the medical records, clinical data, including the patients background, symptoms, physical findings, laboratory data at initial presentation, treatment, and outcome, were compared between the CS-treated and the non-CS-treated group. A total of 47 patients with confirmed SFTS in each hospital were enrolled in this study; there were 14 fatal cases and 33 nonfatal cases. The case fatality ratio was 29.8%. After adjusting patients' background by propensity score matching, the case fatality ratio was higher ( p = 0.04) and complications of secondary infections, including invasive pulmonary aspergillosis, tended to be more frequent ( p = 0.07) in the CS-treated group than in the non-CS-treated group. These data suggested that administration of CS to patients with SFTS should be carefully considered.

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) 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.

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.

We conducted an epidemiologic study of severe fever with thrombocytopenia syndrome (SFTS) in Japan during 2013-2017. Of 303 cases reported during that period, 133 (44%) were included in this study. The median time between onset of illness and diagnosis of SFTS shortened, from 11.5 to 3.0 days, but the case-fatality rate remained high, at 27%. In 64 patients (48%), a close contact with companion animals was reported within 2 weeks of disease onset. Of these 64 patients, 40 were surveyed further, and we confirmed that 3 had direct contact with body fluids of ill companion animals; 2 had direct contact with the saliva of an ill feral cat or pet dog. These patients reported no history of tick bite, suggesting that ill companion animals might be a source of SFTS virus transmission. Direct contact with the body fluids of ill companion animals should be avoided.

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.

• SFTSV infection in cats was characterized by an acute onset and high mortality. • Cats infected with SFTSV showed fever, icterus, thrombocytopenia, and leukopenia frequently. • Outdoor cats were commonly at risk of SFTSV infection in the endemic area. • The almost cat SFTSV was genetically close to human SFTSV. • SFTS in cats is a public health issue, affecting pet owners and animal hospitals. Severe fever with thrombocytopenia syndrome (SFTS) is a recently discovered emerging infectious disease. A zoonotic disease with a high fatality rate in human beings, clinical information on SFTS virus (SFTSV) infection in animals is important. Since 2017, we have diagnosed 24 client-owned cats living in western Japan with SFTS, by genetic and serological testing. In this study, we characterized the clinical features of SFTS in cats and their associated risk factors, by evaluating the clinical parameters retrospectively. A phylogenetic analysis on SFTSV was also conducted. There were no obvious tendencies in age or sex, outdoor cats were commonly at risk of SFTSV infection. All infected cats showed acute onset of clinical signs including anorexia and lethargy, while 68.2% of the cats showed fever and 41.7% showed vomiting. The case fatality rate was 62.5%. Thrombocytopenia, leukopenia, and elevated serum total bilirubin, serum amyloid A, and creatinine phosphokinase concentration were the characteristic findings in the first clinical blood examination. Phylogenic analysis revealed that regional clustered viruses infect both humans and cats. For pet owners and animal hospitals, SFTS in small animals could be an important public health issue. [ABSTRACT FROM AUTHOR]

Background: Cases of severe fever with thrombocytopenia syndrome (SFTS) have increasingly been observed in Miyazaki, southwest Japan. It is critical to identify and elucidate the risk factors of infection at community level. In the present study, we aimed to identify areas with a high risk of SFTS virus infection using a geospatial dataset of SFTS cases in Miyazaki., Methods: Using 10 × 10-km mesh data and a geographically weighted logistic regression (GWLR) model, we examined the statistical associations between environmental variables and spatial variation in the risk of SFTS. We collected geospatial and population census data as well as forest and agriculture mesh information. Altitude and farmland were selected as two specific variables for predicting the presence of SFTS cases in a given mesh area., Results: Using GWLR, the area under the receiver operating characteristic curve (AUC) was estimated at 73.9%, outperforming the classical logistic regression model (72.4%). The sensitivity and specificity of the GWLR model were estimated at 90.9 and 58.7%, respectively. We identified altitude (odds ratio (OR) = 0.996, 95% confidence interval (CI): 0.994-0.999 per one-meter elevation) and farmland (OR = 0.999, 95% CI: 0.998-1.000 per % increase) as useful negative predictors of SFTS cases in Miyazaki., Conclusions: Our study findings revealed that the risk of SFTS is high in geographic areas where farmland area begins to diminish and at mid-level altitudes. Our findings can help to improve the efficiency of ecological and animal surveillance in high-risk areas. Using finer geographic resolution, such surveillance can help raise awareness among local residents in areas with a high risk of SFTS.

Severe fever with thrombocytopenia syndrome (SFTS) caused by SFTS virus (SFTSV), a novel phlebovirus, was reported to be endemic to central and northeastern PR China and was also to be endemic to South Korea and western Japan. SFTS is an emerging viral infection, which should be categorized as a viral hemorrhagic fever disease as Crimean-Congo hemorrhagic fever (CCHF) is caused by CCHF virus. SFTS is a tick-borne viral infection. SFTSV is maintained between several species of ticks and wild and domestic animals in nature. Patients with SFTS show symptoms of fever, general fatigue, and gastrointestinal symptoms such as bloody diarrhea. The severely ill SFTS patients usually show gastrointestinal hemorrhage and deteriorated consciousness. The case fatality rate of SFTS ranges from 5 to 40%. Pathological studies on SFTS have revealed that the mechanisms behind the high case fatality rate are virus infection-related hemophagocytic syndrome associated with cytokine storm, coagulopathy due to disseminated intravascular coagulation causing bleeding tendency, and multi-organ failure. Favipiravir was reported to show efficacy in the prevention and treatment of SFTSV infections in an animal model. A clinical study to evaluate the efficacy of favipiravir in the treatment of SFTS patients has been initiated in Japan. SFTSV is circulating in nature in PR China, Korea, and Japan, indicating that we cannot escape from the risk being infected with SFTSV. The development of specific therapy and preventive measures is a pressing issue requiring resolution to reduce the morbidity and mortality of SFTS patients., (Copyright © 2018 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Severe fever with thrombocytopenia syndrome (SFTS) was first reported in 2011 as an emerging virus infection caused by a novel Phlebovirus in the Bunyaviridae family [SFTS virus (SFTSV)]. In addition, it was reported to be endemic to Hubei, Henan, Shandong, and Heilongjiang provinces in China. The primary symptoms of SFTS are gastrointestinal symptoms such as fever, general fatigue, nausea, vomiting, and diarrhea. The total blood cell counts in patients with SFTS reveal thrombocytopenia and leukopenia. A woman in her 50s died due to multiorgan failure, intestinal hemorrhage, and hemophagocytosis in the autumn of 2012. She was retrospectively diagnosed with SFTS, suggesting that SFTS was endemic not only to China but also to Japan. Subsequently, SFTS was reported to be endemic to South Korea as well. Approximately 5 years have passed since the discovery of SFTS endemicity in Japan. To date, 40-100 patients with SFTS from the western part of Japan have been reported annually to the National Institute of Infectious Diseases. The case-fatality rate of SFTS is approximately 20%. This high case-fatality rate could be attributed to multiorgan failure, coagulopathy, and hemophagocytosis, which are induced in most patients with SFTS. Reportedly, an antiviral drug, favipiravir, was effective in treating SFTSV infection in an animal infection model. SFTSV has been found to circulate between wild animals and several species of ticks in nature, suggesting that we cannot escape the risk of infection with SFTSV and that SFTS will continue to occur in endemic areas. Hence, the development of specific treatment and preventive measures with SFTS vaccines is imperative.

Background: Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne acute infectious disease caused by the SFTS virus (SFTSV). SFTS has been reported in China, South Korea, and Japan as a novel Bunyavirus. Although several molecular epidemiology and phylogenetic studies have been performed, the information obtained was limited, because the analyses included no or only a small number of SFTSV strains from Japan., Methods: The nucleotide sequences of 75 SFTSV samples in Japan were newly determined directly from the patients' serum samples. In addition, the sequences of 7 strains isolated in vitro were determined and compared with those in the patients' serum samples. More than 90 strains that were identified in China, 1 strain in South Korea, and 50 strains in Japan were phylogenetically analyzed., Results: The viruses were clustered into 2 clades, which were consistent with the geographic distribution. Three strains identified in Japan were clustered in the Chinese clade, and 4 strains identified in China and 26 in South Korea were clustered in the Japanese clade., Conclusions: Two clades of SFTSV may have evolved separately over time. On rare occasions, the viruses were transmitted overseas to the region in which viruses of the other clade were prevalent., (© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: Severe fever with thrombocytopenia syndrome (SFTS) is caused by SFTS virus (SFTSV), a novel bunyavirus reported to be endemic in central and northeastern China. This article describes the first identified patient with SFTS and a retrospective study on SFTS in Japan., Methods:  Virologic and pathologic examinations were performed on the patient's samples. Laboratory diagnosis of SFTS was made by isolation/genome amplification and/or the detection of anti-SFTSV immunoglobulin G antibody in sera. Physicians were alerted to the initial diagnosis and asked whether they had previously treated patients with symptoms similar to those of SFTS., Results: A female patient who died in 2012 received a diagnosis of SFTS. Ten additional patients with SFTS were then retrospectively identified. All patients were aged ≥50 years and lived in western Japan. Six cases were fatal. The ratio of males to females was 8:3. SFTSV was isolated from 8 patients. Phylogenetic analyses indicated that all of the Japanese SFTSV isolates formed a genotype independent to those from China. Most patients showed symptoms due to hemorrhage, possibly because of disseminated intravascular coagulation and/or hemophagocytosis., Conclusions: SFTS has been endemic to Japan, and SFTSV has been circulating naturally within the country.