47 results on '"Severe fever with thrombocytopenia syndrome"'
Search Results
2. High Seroprevalence of Severe Fever with Thrombocytopenia Syndrome Virus Infection among the Dog Population in Thailand.
- Author
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Ishijima, Keita, Phichitraslip, Thanmaporn, Naimon, Nattakarn, Ploypichai, Preeyaporn, Kriebkajon, Benyapa, Chinarak, Torntun, Sridaphan, Jirasin, Kritiyakan, Anamika, Prasertsincharoen, Noppadol, Jittapalapong, Sathaporn, Tangcham, Kanate, Rerkamnuaychoke, Worawut, Kuroda, Yudai, Taira, Masakatsu, Tatemoto, Kango, Park, Eunsil, Virhuez-Mendoza, Milagros, Inoue, Yusuke, Harada, Michiko, and Yamamoto, Tsukasa
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VIRUS diseases , *DOGS , *SYNDROMES , *ZOONOSES , *TICK-borne diseases - Abstract
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne zoonotic disease caused by the SFTS virus (SFTSV). In Thailand, three human cases of SFTS were reported in 2019 and 2020, but there was no report of SFTSV infection in animals. Our study revealed that at least 16.6% of dogs in Thailand were seropositive for SFTSV infection, and the SFTSV-positive dogs were found in several districts in Thailand. Additionally, more than 70% of the serum samples collected at one shelter possessed virus-neutralization antibodies against SFTSV and the near-complete genome sequences of the SFTSV were determined from one dog in the shelter. The dog SFTSV was genetically close to those from Thailand and Chinese patients and belonged to genotype J3. These results indicated that SFTSV has already spread among animals in Thailand. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
3. Clinical Characteristics and Diagnostic Prediction of Severe Fever with Thrombocytopenia Syndrome and Rickettsiosis in the Co-Endemic Wakayama Prefecture, Japan.
- Author
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Teramoto, Kan, Tamura, Shinobu, Yoshida, Kikuaki, Inada, Yukari, Yamashita, Yusuke, Morimoto, Masaya, Mushino, Toshiki, Koreeda, Daisuke, Miyamoto, Kyohei, Komiya, Nobuhiro, Nakano, Yoshio, Takagaki, Yusaku, and Koizumi, Yusuke
- Subjects
RICKETTSIAL diseases ,LEUCOPENIA ,TSUTSUGAMUSHI disease ,LEUCOCYTES ,VIRUS diseases ,SYNDROMES ,FEVER - Abstract
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. [ABSTRACT FROM AUTHOR]- Published
- 2023
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4. Emerging Tick-Borne Dabie bandavirus : Virology, Epidemiology, and Prevention.
- Author
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Kim, Eun-Ha and Park, Su-Jin
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EMERGING infectious diseases ,EPIDEMIOLOGY ,TICK infestations ,VIROLOGY ,VACCINE approval ,VACCINE development - Abstract
Severe Fever with Thrombocytopenia Syndrome (SFTS), caused by Dabie bandavirus (SFTSV), is an emerging infectious disease first identified in China. Since its discovery, infections have spread throughout East Asian countries primarily through tick bites but also via transmission between animals and humans. The expanding range of ticks, the primary vectors for SFTSV, combined with migration patterns of tick-carrying birds, sets the stage for the global spread of this virus. SFTSV rapidly evolves due to continuous mutation and reassortment; currently, no approved vaccines or antiviral drugs are available. Thus, the threat this virus poses to global health is unmistakable. This review consolidates the most recent research on SFTSV, including its molecular characteristics, transmission pathways through ticks and other animals, as well as the progress in antiviral drug and vaccine development, encompassing animal models and clinical trials. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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5. Genetic Diversity, Regional Distribution, and Clinical Characteristics of Severe Fever with Thrombocytopenia Syndrome Virus in Gangwon Province, Korea, a Highly Prevalent Region, 2019–2021.
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Moon, Mi-Young, Kim, Hyeon Kyu, Chung, Se-Jin, Byun, Jae Hwan, Kim, Ha-Na, Lee, Woan, Lee, Soon-Won, Monoldorova, Sezim, Lee, Sungkyeong, Jeon, Bo-Young, and Lim, Eun-Joo
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GENETIC variation ,FEVER ,THROMBOCYTOPENIA ,VIRUS diseases ,SYNDROMES - Abstract
Severe fever with thrombocytopenia syndrome (SFTS) is an arthropod-borne viral disease with a high mortality rate with high fever and thrombocytopenia. We investigated the clinical and epidemiological characteristics and viral genotypes from 2019 to 2021 in Gangwon Province, Korea. Of the 776 suspected cases, 62 were SFTS. The fatality rate was 11.5–28.6% (average rate, 19.4%), and the frequent clinical symptoms were high fever (95.2%), thrombocytopenia (95.2%), and leukopenia (90.3%). Hwacheon had the highest incidence rate per 100,000 persons at 8.03, followed by Inje and Yanggu (7.37 and 5.85, respectively). Goseong, Yangyang, and Hoengseong had rates of 2 or higher; Samcheok, Hongcheon, Jeongsen, and Yeonwol were 1.70–1.98, and Wonju, Gangneung, and Donghae were slightly lower, ranging from 0.31 to 0.74. Of the 57 cases with identified genotypes, eight genotypes (A, B1, B2, B3, C, D, E, and F) were detected, and the B2 genotype accounted for 54.4% (31 cases), followed by the A genotype at 22.8% (13 cases). The B2 and A genotypes were detected throughout Gangwon Province, and other genotypes, B1, B3, C, D, and F, were discovered in a few regions. In particular, genotype A could be further classified into subtypes. In conclusion, SFTS occurred throughout Gangwon Province, and Hwacheon had the highest incidence density. Multiple genotypes of SFTS were identified, with B2 and A being the most common. These findings provide important insights for the understanding and management of SFTS in this region. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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6. The Seroprevalence of Severe Fever with Thrombocytopenia Syndrome: An Epidemiological Study of Korean Veterinary Hospital Workers.
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Kim, Choon-Mee, Kim, Dong-Min, Bang, Mi-Seon, Seo, Jun-Won, Yun, Na-Ra, Kim, Da-Young, Han, Mi-Ah, Hwang, Ji-Hye, and Park, Sook-Kyung
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VETERINARY hospitals , *FEVER , *HOSPITAL personnel , *ENZYME-linked immunosorbent assay , *SEROPREVALENCE , *THROMBOCYTOPENIA - Abstract
Severe fever with thrombocytopenia syndrome (SFTS) is a zoonotic tick-borne infectious disease caused by the SFTS virus (SFTSV). Few studies have assessed SFTS seroprevalence among veterinary hospital staff and their awareness of SFTS. From January to May 2021, serum samples from 103 veterinary hospital staff were tested for SFTS using an enzyme-linked immunosorbent assay (ELISA), an immunofluorescence assay, and a 50% plaque reduction neutralization antibody test, which yielded positive results in four (3.9%), three (2.9%), and two (1.9%) participants, respectively. A questionnaire was used for an epidemiological investigation. ELISA positivity was higher among those who lacked awareness of possible animal-to-human SFTS transmission (p = 0.029). SFTS awareness was significantly lower among veterinary hospital staff than among the veterinarians (p < 0.001). Providing staff with training concerning standard precautions and the use of appropriate personal protective equipment is important. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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7. The First Nationwide Surveillance of Severe Fever with Thrombocytopenia Syndrome in Ruminants and Wildlife in Taiwan.
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Kuan, Chih-Ying, Lin, Tsai-Lu, Ou, Shan-Chia, Chuang, Shih-Te, Chan, Jacky Peng-Wen, Maeda, Ken, Mizutani, Tetsuya, Wu, Ming-Pin, Lee, Fan, Chan, Fang-Tse, Chang, Chao-Chin, Liang, Rui-Ling, Yang, Sue-Fung, Liu, Tsung-Ching, Tu, Wu-Chun, Tzeng, Hau-You, Lee, Chia-Jung, Lin, Chuen-Fu, Lee, Hsu-Hsun, and Wu, Jhih-Hua
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RUMINANTS , *REVERSE transcriptase polymerase chain reaction , *DOMESTIC animals , *THROMBOCYTOPENIA - Abstract
Since the first discovery of severe fever with thrombocytopenia syndrome virus (SFTSV) in China in 2009, SFTSV has rapidly spread through other Asian countries, including Japan, Korea, Vietnam and Pakistan, in chronological order. Taiwan reported its first discovery of SFTSV in sheep and humans in 2020. However, the prevalence of SFTSV in domestic and wildlife animals and the geographic distribution of the virus within the island remain unknown. A total of 1324 animal samples, including 803 domestic ruminants, 521 wildlife animals and 47 tick pools, were collected from March 2021 to December 2022 from 12 counties and one terrestrial island. The viral RNA was detected by a one-step real-time reverse transcription polymerase chain reaction (RT-PCR). Overall, 29.9% (240/803) of ruminants showed positive SFTSV RNA. Sheep had the highest viral RNA prevalence of 60% (30/50), followed by beef cattle at 28.4% (44/155), goats at 28.3% (47/166), and dairy cows at 27.5% (119/432). The bovine as a total of dairy cow and beef cattle was 27.8% (163/587). The viral RNA prevalence in ticks (predominantly Rhipicephalus microplus) was similar to those of ruminants at 27.7% (13/47), but wild animals exhibited a much lower prevalence at 1.3% (7/521). Geographically the distribution of positivity was quite even, being 33%, 29.1%, 27.5% and 37.5% for northern, central, southern and eastern Taiwan, respectively. Statistically, the positive rate of beef cattle in the central region (55.6%) and dairy cattle in the eastern region (40.6%) were significantly higher than the other regions; and the prevalence in Autumn (September–November) was significantly higher than in the other seasons (p < 0.001). The nationwide study herein revealed for the first time the wide distribution and high prevalence of SFTSV in both domestic animals and ticks in Taiwan. Considering the high mortality rate in humans, surveillance of other animal species, particularly those in close contact with humans, and instigation of protective measures for farmers, veterinarians, and especially older populations visiting or living near farms or rural areas should be prioritized. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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8. Clinical Differentiation of Severe Fever with Thrombocytopenia Syndrome from Japanese Spotted Fever.
- Author
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Nakada, Nana, Yamamoto, Kazuko, Tanaka, Moe, Ashizawa, Hiroki, Yoshida, Masataka, Umemura, Asuka, Fukuda, Yuichi, Katoh, Shungo, Sumiyoshi, Makoto, Mihara, Satoshi, Kobayashi, Tsutomu, Ito, Yuya, Ashizawa, Nobuyuki, Takeda, Kazuaki, Ide, Shotaro, Iwanaga, Naoki, Takazono, Takahiro, Tashiro, Masato, Tanaka, Takeshi, and Nakamichi, Seiko
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LEUCOCYTES , *EXANTHEMA , *THROMBOCYTOPENIA , *SYNDROMES , *DECISION making - Abstract
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]
- Published
- 2022
- Full Text
- View/download PDF
9. Development of a Scoring System to Differentiate Severe Fever with Thrombocytopenia Syndrome from Scrub Typhus.
- Author
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Sul, Hyoung, Yun, Na Ra, Kim, Dong-Min, Kim, Young Keun, Kim, Jieun, Hur, Jian, Jung, Sook In, Ryu, Seong Yeol, Lee, Ji Yeon, Huh, Kyungmin, Kwak, Yee Gyung, Jeong, Hye Won, Heo, Jung Yeon, Jung, Dong Sik, Lee, Sun Hee, Park, Sun Hee, Yeom, Joon-Sup, and Lee, Hyungdon
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TSUTSUGAMUSHI disease , *PARTIAL thromboplastin time , *SYSTEMS development , *CREATINE kinase , *THROMBOCYTOPENIA - Abstract
Severe fever with thrombocytopenia syndrome (SFTS) and scrub typhus are disorders with similar clinical features; therefore, differentiating between them is difficult. We retrospectively collected data from 183 SFTS and 178 scrub typhus patients and validated an existing scoring system to develop a more sensitive, specific, and objective scoring system. We first applied the scoring systems proposed by Kim et al. to differentiate SFTS from scrub typhus. Multivariable logistic regression revealed that altered mental status, leukopenia, prolonged activated partial thromboplastin time (aPTT), and normal C-reactive protein (CRP) level (≤1.0 mg/dL) were significantly associated with SFTS. We changed the normal CRP level from ≤1.0 mg/dL to ≤3.0 mg/dL and replaced altered mental status with the creatine kinase (CK) level. The modified scoring system showed 97% sensitivity and 96% specificity for SFTS (area under the curve (AUC): 0.983) and a higher accuracy than the original scoring system (p = 0.0308). This study's scoring system had 97% sensitivity and 98% specificity for SFTS (AUC: 0.992) and a higher accuracy than Kim et al.'s original scoring system (p = 0.0308). Our scoring system that incorporated leukopenia, prolonged aPTT, normal CRP level (≤3.0 mg/dL), and elevated CK level (>1000 IU/L) easily differentiated SFTS from scrub typhus in an endemic area. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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10. Difference in Intraspecies Transmissibility of Severe Fever with Thrombocytopenia Syndrome Virus Depending on Abrogating Type 1 Interferon Signaling in Mice.
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Oh B, Park SC, Yang MS, Yang D, Ham G, Tark D, You MJ, Oh SI, and Kim B
- Subjects
- Humans, Animals, Mice, Severe Fever with Thrombocytopenia Syndrome, Bunyaviridae Infections, Phlebovirus, Tick-Borne Diseases, Interferon Type I
- Abstract
Severe fever with thrombocytopenia syndrome (SFTS), a tick-borne zoonotic disease, is caused by infection with SFTS virus (SFTSV). A previous study reported that human-to-human direct transmission of SFTSV can occur. However, potential animal-to-animal transmission of SFTSV without ticks has not been fully clarified. Thus, the objective of this study was to investigate potential mice-to-mice transmission of SFTSV by co-housing three groups of mice [i.e., wild-type mice (WT), mice injected with an anti-type I interferon-α receptor-blocking antibody (IFNAR Ab), and mice with knockout of type I interferon-α receptor (IFNAR KO)] as spreaders or recipients with different immune competence. As a result, co-housed IFNAR Ab and IFNAR KO mice showed body weight loss with SFTS viral antigens detected in their sera, extracorporeal secretions, and various organs. Based on histopathology, white pulp atrophy in the spleen was observed in all co-housed mice except WT mice. These results obviously show that IFNAR Ab and IFNAR KO mice, as spreaders, exhibited higher transmissibility to co-housed mice than WT mice. Moreover, IFNAR KO mice, as recipients, were more susceptible to SFTSV infection than WT mice. These findings suggest that type I interferon signaling is a pivotal factor in mice intraspecies transmissibility of SFTSV in the absence of vectors such as ticks.
- Published
- 2024
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11. Current Progress of Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV) Vaccine Development.
- Author
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Kim D, Lai CJ, Cha I, and Jung JU
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- Aged, Animals, Humans, Vaccines, Attenuated, Disease Outbreaks, Models, Animal, Vaccine Development, Severe Fever with Thrombocytopenia Syndrome, Viral Vaccines
- Abstract
SFTSV is an emerging tick-borne virus causing hemorrhagic fever with a case fatality rate (CFR) that can reach up to 27%. With endemic infection in East Asia and the recent spread of the vector tick to more than 20 states in the United States, the SFTSV outbreak is a globally growing public health concern. However, there is currently no targeted antiviral therapy or licensed vaccine against SFTSV. Considering the age-dependent SFTS pathogenesis and disease outcome, a sophisticated vaccine development approach is required to safeguard the elderly population from lethal SFTSV infection. Given the recent emergence of SFTSV, the establishment of animal models to study immunogenicity and protection from SFTS symptoms has only occurred recently. The latest research efforts have applied diverse vaccine development approaches-including live-attenuated vaccine, DNA vaccine, whole inactivated virus vaccine, viral vector vaccine, protein subunit vaccine, and mRNA vaccine-in the quest to develop a safe and effective vaccine against SFTSV. This review aims to outline the current progress in SFTSV vaccine development and suggest future directions to enhance the safety and efficacy of these vaccines, ensuring their suitability for clinical application.
- Published
- 2024
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12. Time-Course Transcriptome Analysis Reveals Distinct Phases and Identifies Two Key Genes during Severe Fever with Thrombocytopenia Syndrome Virus Infection in PMA-Induced THP-1 Cells.
- Author
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Huang T, Wang X, Mi Y, Wu W, Xu X, Li C, Wen Y, Li B, Li Y, Sun L, Li J, Wang M, Liu T, Wang S, and Liang M
- Subjects
- Humans, THP-1 Cells, Gene Expression Profiling, Transcriptome, Cluster Analysis, Severe Fever with Thrombocytopenia Syndrome
- Abstract
In recent years, there have been significant advancements in the research of Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV). However, several limitations and challenges still exist. For instance, researchers face constraints regarding experimental conditions and the feasibility of sample acquisition for studying SFTSV. To enhance the quality and comprehensiveness of SFTSV research, we opted to employ PMA-induced THP-1 cells as a model for SFTSV infection. Multiple time points of SFTSV infection were designed to capture the dynamic nature of the virus-host interaction. Through a comprehensive analysis utilizing various bioinformatics approaches, including diverse clustering methods, MUfzz analysis, and LASSO/Cox machine learning, we performed dynamic analysis and identified key genes associated with SFTSV infection at the host cell transcriptomic level. Notably, successful clustering was achieved for samples infected at different time points, leading to the identification of two important genes, PHGDH and NLRP12. And these findings may provide valuable insights into the pathogenesis of SFTSV and contribute to our understanding of host-virus interactions.
- Published
- 2023
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13. Identification and Analysis of a Four-Gene Set for Diagnosing SFTS Virus Infection Based on Machine Learning Methods and Its Association with Immune Cell Infiltration.
- Author
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Huang T, Wang X, Mi Y, Liu T, Li Y, Zhang R, Qian Z, Wen Y, Li B, Sun L, Wu W, Li J, Wang S, and Liang M
- Subjects
- Humans, Cyclic N-Oxides, Ethylnitrosourea, Severe Fever with Thrombocytopenia Syndrome, Bunyaviridae Infections, Phlebovirus
- Abstract
Severe Fever with thrombocytopenia syndrome (SFTS) is a highly fatal viral infectious disease that poses a significant threat to public health. Currently, the phase and pathogenesis of SFTS are not well understood, and there are no specific vaccines or effective treatment available. Therefore, it is crucial to identify biomarkers for diagnosing acute SFTS, which has a high mortality rate. In this study, we conducted differentially expressed genes (DEGs) analysis and WGCNA module analysis on the GSE144358 dataset, comparing the acute phase of SFTSV-infected patients with healthy individuals. Through the LASSO-Cox and random forest algorithms, a total of 2128 genes were analyzed, leading to the identification of four genes: ADIPOR1, CENPO, E2F2, and H2AC17. The GSEA analysis of these four genes demonstrated a significant correlation with immune cell function and cell cycle, aligning with the functional enrichment findings of DEGs. Furthermore, we also utilized CIBERSORT to analyze the immune cell infiltration and its correlation with characteristic genes. The results indicate that the combination of ADIPOR1, CENPO, E2F2, and H2AC17 genes has the potential as characteristic genes for diagnosing and studying the acute phase of SFTS virus (SFTSV) infection.
- Published
- 2023
- Full Text
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14. Clinical Differentiation of Severe Fever with Thrombocytopenia Syndrome from Japanese Spotted Fever
- Abstract
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., Viruses, 14(8), art. no. 1807; 2022
- Published
- 2022
15. Associations between Chest CT Abnormalities and Clinical Features in Patients with the Severe Fever with Thrombocytopenia Syndrome
- Abstract
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by the SFTS virus. It involves multiple organ systems, including the lungs. However, the significance of the lung involvement in SFTS remains unclear. In the present study, we aimed to investigate the relationship between the clinical findings and abnormalities noted in the chest computed tomography (CT) of patients with SFTS. The medical records of 22 confirmed SFTS patients hospitalized in five hospitals in Nagasaki, Japan, between April 2013 and September 2019, were reviewed retrospectively. Interstitial septal thickening and ground-glass opacity (GGO) were the most common findings in 15 (68.1%) and 12 (54.5%) patients, respectively, and lung GGOs were associated with fatalities. The SFTS patients with a GGO pattern were elderly, had a disturbance of the conscious and tachycardia, and had higher c-reactive protein levels at admission (p = 0.009, 0.006, 0.002, and 0.038, respectively). These results suggested that the GGO pattern in patients with SFTS displayed disseminated inflammation in multiple organs and that cardiac stress was linked to higher mortality. Chest CT evaluations may be useful for hospitalized patients with SFTS to predict their severity and as early triage for the need of intensive care., Viruses, 14(2), art. no. 279; 2022
- Published
- 2022
16. Clinical Differentiation of Severe Fever with Thrombocytopenia Syndrome from Japanese Spotted Fever
- Abstract
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., Viruses, 14(8), art. no. 1807; 2022
- Published
- 2022
17. Non-Structural Protein-W61 as a Novel Target in Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV): An In-Vitro and In-Silico Study on Protein-Protein Interactions with Nucleoprotein and Viral Replication.
- Author
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Park JY, Sivasankar C, Kirthika P, Prabhu D, and Lee JH
- Subjects
- Humans, Nucleoproteins genetics, Nucleoproteins metabolism, HeLa Cells, Signal Transduction, Molecular Docking Simulation, Virus Replication, Serine metabolism, Viral Nonstructural Proteins genetics, Viral Nonstructural Proteins metabolism, Severe Fever with Thrombocytopenia Syndrome, Bunyaviridae Infections, Phlebovirus genetics
- Abstract
The non-structural protein (NSs) and nucleoprotein (NP) of the severe fever with thrombocytopenia syndrome virus (SFTSV) encoded by the S segment are crucial for viral pathogenesis. They reside in viroplasm-like structures (VLS), but their interaction and their significance in viral propagation remain unclear. Here, we investigated the significance of the association between NSs and NP during viral infection through in-silico and in-vitro analyses. Through in-silico analysis, three possible binding sites were predicted, at positions C6S (Cystein at 6th position to Serine), W61Y (Tryptophan 61st to Tyrosine), and S207T (Serine 207th to Threonine), three mutants of NSs were developed by site-directed mutagenesis and tested for NP interaction by co-immunoprecipitation. NSsW61Y failed to interact with the nucleoprotein, which was substantiated by the conformational changes observed in the structural analyses. Additionally, molecular docking analysis corroborated that the NSW61Y mutant protein does not interact well compared to wild-type NSs. Over-expression of wild-type NSs in HeLa cells increased the SFTSV replication by five folds, but NSsW61Y exhibited 1.9-folds less viral replication than wild-type. We demonstrated that the W61Y alteration was implicated in the reduction of NSs-NP interaction and viral replication. Thus, the present study identified a critical NSs site, which could be targeted for development of therapeutic regimens against SFTSV.
- Published
- 2023
- Full Text
- View/download PDF
18. Construction and Characterization of Severe Fever with Thrombocytopenia Syndrome Virus with a Fluorescent Reporter for Antiviral Drug Screening.
- Author
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Wang X, Xu M, Ke H, Ma L, Li L, Li J, Deng F, Wang M, Hu Z, and Liu J
- Subjects
- Chlorocebus aethiops, Animals, Mice, Antiviral Agents therapeutic use, Vero Cells, Drug Evaluation, Preclinical, Mice, Inbred C57BL, Severe Fever with Thrombocytopenia Syndrome, Phlebovirus, Bunyaviridae Infections
- Abstract
Severe fever with thrombocytopenia syndrome (SFTS) caused by a novel bunyavirus (SFTSV) is an emerging infectious disease with up to 30% case fatality. Currently, there are no specific antiviral drugs or vaccines for SFTS. Here, we constructed a reporter SFTSV in which the virulent factor nonstructural protein (NSs) was replaced by eGFP for drug screening. First, we developed a reverse genetics system based on the SFTSV HBMC5 strain. Then, the reporter virus SFTSV-delNSs-eGFP was constructed, rescued, and characterized in vitro. SFTSV-delNSs-eGFP showed similar growth kinetics with the wild-type virus in Vero cells. We further detected the antiviral efficacy of favipiravir and chloroquine against wild-type and recombinant SFTSV by the quantification of viral RNA, and compared the results with that of fluorescent assay using high-content screening. The results showed that SFTSV-delNSs-eGFP could be used as a reporter virus for antiviral drug screening in vitro. In addition, we analyzed the pathogenesis of SFTSV-delNSs-eGFP in interferon receptor-deficient (IFNAR
-/- ) C57BL/6J mice and found that unlike the fatal infection of the wild-type virus, no obvious pathological change or viral replication were observed in SFTSV-delNSs-eGFP-infected mice. Taken together, the green fluorescence and attenuated pathogenicity make SFTSV-delNSs-eGFP a potent tool for the future high-throughput screening of antiviral drugs.- Published
- 2023
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19. Severe Fever with Thrombocytopenia Syndrome with Necrotizing Lymphadenitis in a Patient who Underwent 18F-FDG PET/CT: A Case Report
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Taehwa Kim, A Reum Kim, Su Jin Lee, Seungjin Lim, and Dong Hoon Shin
- Subjects
medicine.medical_specialty ,Health, Toxicology and Mutagenesis ,Computed tomography ,Case Report ,hemic and lymphatic diseases ,lymphadenitis ,Medicine ,Infectious disease (athletes) ,Leukopenia ,medicine.diagnostic_test ,business.industry ,Public Health, Environmental and Occupational Health ,computed tomography ,medicine.disease ,Lymphoma ,Severe fever with thrombocytopenia syndrome ,Positron emission tomography ,Necrotizing lymphadenitis ,Radiology ,positron-emission tomography ,medicine.symptom ,business ,Generalized lymphadenopathy ,severe fever with thrombocytopenia syndrome - Abstract
Severe fever with thrombocytopenia syndrome (SFTS), also known as fever, thrombocytopenia, and leukopenia syndrome, is an emerging tick-borne infectious disease in Asian countries. SFTS should be suspected in patients presenting with fever, thrombocytopenia, and leukopenia and have a history of tick exposure in an endemic area. Since SFTS can be accompanied by lymphadenopathy, particularly generalized lymphadenopathy, it can be confused with a primary malignancy, such as lymphoma. The study reports a case of SFTS accompanied by multiple lymphadenopathies, which mimicked malignant lymphoma on F-18 fluorodeoxyglucose positron emission tomography/computed tomography.
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- 2021
20. In Silico Structure-Based Design of Antiviral Peptides Targeting the Severe Fever with Thrombocytopenia Syndrome Virus Glycoprotein Gn
- Author
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Mifang Liang, Shuofeng Yuan, Jasper Fuk-Woo Chan, Gang Lu, Jianli Cao, Kwok-Yung Yuen, Jian-Piao Cai, Dong-Yan Jin, Hin Chu, Feifei Yin, Kaiming Tang, Lei Wen, Zi-Wei Ye, Kenn Ka-Heng Chik, Jiang Du, Ronghui Liang, and Cuiting Luo
- Subjects
Phlebovirus ,Orthobunyavirus ,Severe Fever with Thrombocytopenia Syndrome ,In silico ,Peptide ,Favipiravir ,Biology ,bunyavirales ,Bunyaviridae Infections ,Microbiology ,Antiviral Agents ,Article ,Cell Line ,Viral Envelope Proteins ,Viral entry ,Virology ,Cell Line, Tumor ,Humans ,SFSTV ,Computer Simulation ,chemistry.chemical_classification ,treatment ,Virus Internalization ,antiviral ,Thrombocytopenia ,QR1-502 ,In vitro ,peptide ,tick ,Infectious Diseases ,chemistry ,RNA Polymerase Inhibitor ,Hong Kong ,Glycoprotein ,Peptides ,Severe fever with thrombocytopenia syndrome virus - Abstract
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.
- Published
- 2021
21. Solitary Fibrous Tumors of the Lung: A Clinicopathological Analysis of 52 Cases.
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Wang YX, Zhong Y, Fan SS, Zhu YS, Peng XR, and Zhang X
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- Aged, Middle Aged, Male, Female, Humans, Vimentin, Biomarkers, Tumor analysis, Lung pathology, Proto-Oncogene Proteins c-bcl-2, Severe Fever with Thrombocytopenia Syndrome, Solitary Fibrous Tumors genetics, Solitary Fibrous Tumors metabolism, Solitary Fibrous Tumors pathology
- Abstract
Objective: To explore the clinicopathological features of solitary fibrous tumors (SFTs) of the lung., Methods: We collected the clinical data of 52 patients with SFTs of the lung confirmed by pathology, and summarized the clinical, radiological, and morphological features, the immunophenotypes, and the prognosis of SFTs., Results: Fifty-two cases of SFTs of the lung were enrolled in this study, including 51 cases of borderline and 1 case of malignancy, 22 males and 30 females. The average onset age was 52.7 years. The lower lobe of the left lung was the preferred site of SFTs, accounting for 30.77% (16/52). Chest CT showed regular and well-demarcated soft tissue density mass, and the tumor size of most cases (46/52, 88.46%) was 1-10 cm. Morphological features: The distribution of tumor cells showed sparse and dense areas. Tumor cells were spindle-shaped, in whorls or hemangiopericytoma-like conformation. Atypia, mitotic figures, and necrosis were found. Immunohistochemistry showed positive expression of CD34, STAT6, Vimentin, BCL2, and CD99. Ki-67 was ≤ 5% in borderline SFTs and >20% in a malignant SFT., Conclusions: Solitary fibrous tumors of the lung occur more frequently in middle-aged and elderly people, and there is no significant difference in gender. The lower lobe of the left lung is the preferred site of SFTs. The size of most SFTs is 1-10 cm. Chest CT shows morphologically regular and well-demarcated soft tissue density mass. Pathologically, SFTs of the lung are mostly borderline and occasionally malignant. Immunohistochemistry shows the positive expression of CD34, STAT6, Vimentin, BCL2, and CD99.
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- 2023
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22. Severe Fever with Thrombocytopenia Syndrome Accompanied by Invasive Pulmonary Aspergillosis: An Autopsy Case
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S. Miyauchi, Motohiro Matsuda, Masatoshi Kimura, Takumi Kiwaki, Ichiro Takajo, Kunihiko Umekita, Kosho Iwao, Akihiko Okayama, Takeshi Kawaguchi, Tadaki Suzuki, Chihiro Iwao, Hiroaki Kataoka, Ayako Aizawa, Mao Rikitake, Yumi Kariya, and Tsuyoshi Fukushima
- Subjects
0301 basic medicine ,medicine.medical_specialty ,030106 microbiology ,Autopsy ,Case Report ,Microbiology ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,autopsy ,Leukocytopenia ,Virology ,Internal medicine ,medicine ,Blood test ,030212 general & internal medicine ,Mycosis ,medicine.diagnostic_test ,biology ,business.industry ,invasive pulmonary aspergillosis ,SFTS virus ,biology.organism_classification ,medicine.disease ,QR1-502 ,Severe fever with thrombocytopenia syndrome ,Infectious Diseases ,Respiratory failure ,Hemophagocytosis ,business ,severe fever with thrombocytopenia syndrome - 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.
- Published
- 2021
23. Development of an RT-LAMP Assay for the Rapid Detection of SFTS Virus
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Takeshi Kurosu, Yuka Hamada, Tomoki Yoshikawa, Souichi Yamada, Satoko Sugimoto, Hitomi Kinoshita, Yuki Takamatsu, Masayuki Shimojima, Naoki Fujisawa, Shizuko Harada, Takayuki Sugimoto, Masayuki Saijo, Shoichi Toda, Shuetsu Fukushi, and Shiori Sano
- Subjects
Phlebovirus ,0301 basic medicine ,Severe Fever with Thrombocytopenia Syndrome ,genetic structures ,030106 microbiology ,Loop-mediated isothermal amplification ,Biology ,Real-Time Polymerase Chain Reaction ,Microbiology ,Sensitivity and Specificity ,Virus ,Article ,03 medical and health sciences ,Virology ,Genotype ,medicine ,Humans ,RT-LAMP ,SFTS virus ,simplified method ,medicine.disease ,biology.organism_classification ,QR1-502 ,Reverse transcriptase ,eye diseases ,Severe fever with thrombocytopenia syndrome ,030104 developmental biology ,Infectious Diseases ,Molecular Diagnostic Techniques ,Nucleic acid ,RNA, Viral ,sense organs ,Primer (molecular biology) ,Nucleic Acid Amplification Techniques - Abstract
Detection of severe fever with thrombocytopenia syndrome (SFTS) virus (SFTSV) during the early phase of the disease is important for appropriate treatment, infection control, and prevention of further transmission. The reverse transcription loop-mediated isothermal amplification (RT-LAMP) is a nucleic acid amplification method that amplifies the target sequence under isothermal conditions. Here, we developed an RT-LAMP with a novel primer/probe set targeting a conserved region of the SFTSV L segment after extraction of viral RNA (standard RT-LAMP). Both the Chinese and Japanese SFTSV strains, including various genotypes, were detected by the standard RT-LAMP. We also performed RT-LAMP using the same primer/probe set but without the viral RNA extraction step (called simplified RT-LAMP) and evaluated the diagnostic efficacy. The sensitivity and specificity of the simplified RT-LAMP were 84.9% (45/53) and 89.5% (2/19), respectively. The simplified RT-LAMP can detect SFTSV in human sera containing >, 103.5 copies/mL viral RNA. The two RT-LAMP positive but quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) negative samples were positive in the conventional RT-PCR, suggesting that there was no false positive reaction in the RT-LAMP. Both the standard and simplified RT-LAMP are useful for detecting the SFTSV genome in patients during the early phase of the disease.
- Published
- 2021
24. Seroprevalence of Severe Fever with Thrombocytopenia Syndrome Virus in Small-Animal Veterinarians and Nurses in the Japanese Prefecture with the Highest Case Load
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Tamaki Okabayashi, Akatsuki Saito, Yumi Kirino, Hirohisa Mekata, Eugene Mazimpaka, Keita Ishijima, Taro Nomachi, Miho Miura, Atsushi Yamanaka, Putu Eka Sudaryatma, Takayuki Sugimoto, and Ken Maeda
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0301 basic medicine ,Male ,Phlebovirus ,medicine.medical_specialty ,dogs ,Severe Fever with Thrombocytopenia Syndrome ,Occupational risk ,Health Personnel ,030106 microbiology ,030231 tropical medicine ,lcsh:QR1-502 ,Disease ,Antibodies, Viral ,lcsh:Microbiology ,Article ,Veterinarians ,03 medical and health sciences ,0302 clinical medicine ,Japan ,Seroepidemiologic Studies ,Virology ,Small animal ,Internal medicine ,medicine ,Seroprevalence ,Animals ,Humans ,SFTS ,Transmission (medicine) ,business.industry ,Public health ,Bandavirus ,cats ,public health ,Infectious Diseases ,Enzootic ,Female ,business ,Severe fever with thrombocytopenia syndrome virus - Abstract
Severe fever with thrombocytopenia syndrome virus (SFTSV) is the causative agent of SFTS, an emerging tick-borne disease in East Asia, and is maintained in enzootic cycles involving ticks and a range of wild animal hosts. Direct transmission of SFTSV from cats and dogs to humans has been identified in Japan, suggesting that veterinarians and veterinary nurses involved in small-animal practice are at occupational risk of SFTSV infection. To characterize this risk, we performed a sero-epidemiological survey in small-animal-practice workers and healthy blood donors in Miyazaki prefecture, which is the prefecture with the highest per capita number of recorded cases of SFTS in Japan. Three small-animal-practice workers were identified as seropositive by ELISA, but one had a negative neutralization-test result and so was finally determined to be seronegative, giving a seropositive rate of 2.2% (2 of 90), which was significantly higher than that in healthy blood donors (0%, 0 of 1000, p <, 0.05). The seroprevalence identified here in small-animal-practice workers was slightly higher than that previously reported in other high-risk workers engaged in agriculture and forestry in Japan. Thus, enhancement of small-animal-practice workers’ awareness of biosafety at animal hospitals is necessary for control of SFTSV.
- Published
- 2021
25. Evaluation of Alternative Risk Stratification Systems in a Large Series of Solitary Fibrous Tumors with Molecular Findings and Ki-67 Index Data: Do They Improve Risk Assessment?
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Machado I, Blázquez Bujeda Á, Giner F, Nieto Morales MG, Cruz J, Lavernia J, Navarro S, Ferrandez A, Ruiz-Sauri A, and Llombart-Bosch A
- Subjects
- Humans, Ki-67 Antigen genetics, Risk Assessment, Mutation, Neoplasm Recurrence, Local pathology, Biomarkers, Tumor genetics, Severe Fever with Thrombocytopenia Syndrome, Solitary Fibrous Tumors pathology
- Abstract
The clinical evolution of solitary fibrous tumors (SFTs) is often uncertain and several risk stratification systems (RSS) have been proposed. The Demicco et al. RSS is the most frequently implemented. In this study we aim to validate two alternative RSS (Sugita et al. and G-Score) using results for the Demicco RSS from a previous study of 97 SFTs. In addition, we aim to determine whether reclassified cases had any distinctive molecular features. As the Sugita et al. system substitutes mitotic count with Ki-67 index we also investigated whether Ki-67 results for tissue microarrays are comparable to those obtained using whole tissue sections. In the present study we detected that many cases classified by Demicco RSS as low-risk were reclassified as intermediate risk using the new system (G-score RSS). Kaplan-Meier survival plots for G-Score RSS showed that the low-risk and intermediate-risk SFTs had a similar evolution that contrasted with the more aggressive high-risk group. Moreover, the similar evolution in both low and intermediate-risk groups occurred despite the G-score system being stricter in classifying low-risk tumors. We observed that Sugita RSS does not provide any better risk stratification in comparison with the Demicco RSS, and testing both RSS in our series produced similar Kaplan-Meier survival data. We found some discordant results when comparing whole sections and the corresponding tissue microarrays samples, finding the hotspot areas easier to locate in whole sections. Forty-one SFTs with initial low-risk assigned by the Demicco RSS were reclassified as intermediate-risk by G-score finding both TP53 and HTER mutations in four cases, only HTER mutation in 11 cases, and only TP53 mutation in 2 cases. All six cases of SFT classified as high-risk by both the Demicco and G-score RSS suffered recurrence/metastasis, and half showed both TP53 and HTER mutations. Five SFTs were categorized as low-risk by both Demicco and G-score, of which 4 cases revealed HTER mutation. Regarding the outcome of these 5 patients, two were lost to follow-up, and one of the remaining three patients suffered recurrence. We believe that although the presence of both TP53 and HTER mutations may confer or be related to poor evolution, the isolated presence of HTER mutation alone would not necessarily be related to poor outcome. The G-score RSS more accurately identified low-risk patients than the other two risk models evaluated in the present series. Late recurrence/metastasis may occasionally be observed even in low-risk SFTs categorized by stricter classification systems such as the G-score RSS. These findings support the possibility that additional, as yet unknown factors may influence the clinical evolution of SFTs. In conclusion, given the possibility of late recurrence, long-term follow-up is recommended for all SFT patients, even in cases classified as low risk by the stricter G-score system. An integration of clinical, radiological, pathological, and molecular findings may improve SFT risk stratification and better predict patient outcome.
- Published
- 2022
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26. Increased Risk of Infection with Severe Fever with Thrombocytopenia Virus among Animal Populations on Tsushima Island, Japan, Including an Endangered Species, Tsushima Leopard Cats.
- Author
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Matsuu A, Doi K, Ishijima K, Tatemoto K, Koshida Y, Yoshida A, Kiname K, Iwashita A, Hayama SI, and Maeda K
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- Humans, Animals, Cats, Dogs, Endangered Species, Japan epidemiology, Seroepidemiologic Studies, Deer, Phlebovirus, Severe Fever with Thrombocytopenia Syndrome, Panthera, Thrombocytopenia, Bunyaviridae Infections epidemiology, Bunyaviridae Infections veterinary
- Abstract
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.
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- 2022
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27. Serological Evidence of Severe Fever with Thrombocytopenia Syndrome Virus and IgM Positivity Were Identified in Healthy Residents in Vietnam.
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Tran XC, Kim SH, Lee JE, Kim SH, Kang SY, Binh ND, Duc PV, Phuong PTK, Thao NTP, Lee W, Bae JY, Park MS, Kim M, Yoo JR, Heo ST, An KH, Kim JM, Cho NH, Kee SH, and Lee KH
- Subjects
- Humans, Seroepidemiologic Studies, Vietnam epidemiology, Antibodies, Viral, Antibodies, Neutralizing, Immunoglobulin M, Immunoglobulin G, Severe Fever with Thrombocytopenia Syndrome, Bunyaviridae Infections, Phlebovirus, Tick-Borne Diseases
- Abstract
Severe fever with thrombocytopenia syndrome (SFTS), an emerging tick-borne viral disease, is prevalent in East Asia and has also been reported in Southeast Asia since 2019. SFTS patients in Vietnam were first reported in 2019. However, the seroprevalence of severe fever with thrombocytopenia syndrome virus (SFTSV) in Vietnam has not been reported. To investigate the seroprevalence of SFTSV in Vietnam, we collected serum samples from 714 healthy residents in Thua Thien Hue and Quang Nam Province, Vietnam, and the seroprevalence of SFTSV was assessed using immunofluorescence antibody assay (IFA), Enzyme-Linked Immunosorbent Assays (ELISAs) and the 50% focus reduction neutralization test (FRNT50) assay. The seroprevalence of anti-SFTSV IgM or IgG was observed to be 3.64% (26/714), high IgM positivity was >80 (0.28%, 2/714) and the titer of neutralizing antibodies against SFTSV ranged from 15.5 to 55.9. In Pakistan, SFTSV infection confirmed using a microneutralization test (MNT) assay (prevalence is 2.5%) and ELISAs showed a high seroprevalence (46.7%) of SFTSV. Hence, the seroprevalence rate in Vietnam is similar to that in Pakistan and the number of SFTS patients could increase in Vietnam.
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- 2022
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28. Neutralizing mAbs against SFTS Virus Gn Protein Show Strong Therapeutic Effects in an SFTS Animal Model.
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Shimojima M, Sugimoto S, Umekita K, Onodera T, Sano K, Tani H, Takamatsu Y, Yoshikawa T, Kurosu T, Suzuki T, Takahashi Y, Ebihara H, and Saijo M
- Subjects
- Animals, Antibodies, Monoclonal therapeutic use, Antibodies, Neutralizing therapeutic use, Antibodies, Viral therapeutic use, Disease Models, Animal, Humans, Mice, Viral Envelope Proteins metabolism, Phlebovirus, Severe Fever with Thrombocytopenia Syndrome
- Abstract
Severe fever with thrombocytopenia syndrome (SFTS) is an infectious disease with a high case fatality rate caused by the SFTS virus, and currently there are no approved specific treatments. Neutralizing monoclonal antibodies (mAbs) against the virus could be a therapeutic agent in SFTS treatment, but their development has not sufficiently been carried out. In the present study, mouse and human mAbs exposed to the viral envelope proteins Gn and Gc (16 clones each) were characterized in vitro and in vivo by using recombinant proteins, cell culture with viruses, and an SFTS animal model with IFNAR
-/- mice. Neutralization activities against the recombinant vesicular stomatitis virus bearing SFTS virus Gn/Gc as envelope proteins were observed with three anti-Gn and six anti-Gc mAbs. Therapeutic activities were observed among anti-Gn, but not anti-Gc mAbs with neutralizing activities. These results propose an effective strategy to obtain promising therapeutic mAb candidates for SFTS treatment, and a necessity to reveal precise roles of the SFTS virus Gn/Gc proteins.- Published
- 2022
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29. Associations between Chest CT Abnormalities and Clinical Features in Patients with the Severe Fever with Thrombocytopenia Syndrome.
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Ashizawa, Hiroki, Yamamoto, Kazuko, Ashizawa, Nobuyuki, Takeda, Kazuaki, Iwanaga, Naoki, Takazono, Takahiro, Sakamoto, Noriho, Sumiyoshi, Makoto, Ide, Shotaro, Umemura, Asuka, Yoshida, Masataka, Fukuda, Yuichi, Kobayashi, Tsutomu, Tashiro, Masato, Tanaka, Takeshi, Katoh, Shungo, Morimoto, Konosuke, Ariyoshi, Koya, Morimoto, Shimpei, and Tun, Mya Myat Ngwe
- Subjects
- *
COMPUTED tomography , *THROMBOCYTOPENIA , *FEVER , *C-reactive protein , *SYNDROMES , *OLDER patients - Abstract
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by the SFTS virus. It involves multiple organ systems, including the lungs. However, the significance of the lung involvement in SFTS remains unclear. In the present study, we aimed to investigate the relationship between the clinical findings and abnormalities noted in the chest computed tomography (CT) of patients with SFTS. The medical records of 22 confirmed SFTS patients hospitalized in five hospitals in Nagasaki, Japan, between April 2013 and September 2019, were reviewed retrospectively. Interstitial septal thickening and ground-glass opacity (GGO) were the most common findings in 15 (68.1%) and 12 (54.5%) patients, respectively, and lung GGOs were associated with fatalities. The SFTS patients with a GGO pattern were elderly, had a disturbance of the conscious and tachycardia, and had higher c-reactive protein levels at admission (p = 0.009, 0.006, 0.002, and 0.038, respectively). These results suggested that the GGO pattern in patients with SFTS displayed disseminated inflammation in multiple organs and that cardiac stress was linked to higher mortality. Chest CT evaluations may be useful for hospitalized patients with SFTS to predict their severity and as early triage for the need of intensive care. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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30. Suspected Transmission of Severe Fever with Thrombocytopenia Syndrome Virus from a Cat to a Veterinarian by a Single Contact: A Case Report.
- Author
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Miyauchi, Atsushi, Sada, Ken-Ei, Yamamoto, Hirotaka, Iriyoshi, Hiroki, Touyama, Yuji, Hashimoto, Daisuke, Nojima, Shigeru, Yamanaka, Shingo, Ishijima, Keita, Maeda, Ken, and Kawamura, Masafumi
- Subjects
- *
WHOLE genome sequencing , *THROMBOCYTOPENIA , *CATS , *SEROTHERAPY , *EYE protection - Abstract
A 67-year-old male veterinarian presented with fatigue, anorexia, and diarrhea. Although there were no tick bite marks, we suspected severe fever with thrombocytopenia syndrome (SFTS) due to bicytopenia, mild disturbance of consciousness, and a history of outdoor activities. Thus, we started immunoglobulin therapy immediately. A serum reverse transcription-polymerase chain reaction (RT-PCR) test for SFTS virus (SFTSV) was positive. The patient had treated a cat with thrombocytopenia 10 days prior to admission. The cat's serum SFTSV RT-PCR test result was positive, and the whole genome sequences of the patient's and cat's SFTSV were identical, suggesting the possibility of transmission from the cat to the patient. Other cases of direct cat-to-human SFTV transmission have been reported recently. Mucous membranes should be protected, including eye protection, in addition to standard precautions, when in contact with any cat with suspected SFTS. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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31. Infection Route Impacts the Pathogenesis of Severe Fever with Thrombocytopenia Syndrome Virus in Ferrets.
- Author
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Park SJ, Kim YI, Casel MA, Kim EH, Kim SM, Yu KM, Rollon R, Jang SG, Jeong HW, and Choi YK
- Subjects
- Aged, Animals, Ferrets, Humans, Bunyaviridae Infections, Phlebovirus, Severe Fever with Thrombocytopenia Syndrome, Ticks
- Abstract
The threat of severe fever with thrombocytopenia syndrome (SFTS) to public health has been increasing due to the rapid spread of the ticks that carry the causative viral agent. The SFTS virus (SFTSV) was first identified in China and subsequently detected in neighboring countries, including South Korea, Japan, and Vietnam. In addition to the tick-mediated infection, human-to-human transmission has been recently reported with a high mortality rate; however, differential study of the pathogen has been limited by the route of infection. In this study, we investigated the pathogenic potential of SFTSV based on the infection route in aged ferrets, which show clinical signs similar to that of human infections. Ferrets inoculated with SFTSV via the intramuscular and subcutaneous routes show clinical signs comparable to those of severe human infections, with a mortality rate of 100%. Contrastingly, intravascularly infected ferrets exhibit a comparatively lower mortality rate of 25%, although their early clinical signs are similar to those observed following infection via the other routes. These results indicate that the infection route could influence the onset of SFTS symptoms and the pathogenicity of SFTSV. Thus, infection route should be considered in future studies on the pathogenesis of SFTSV infection.
- Published
- 2022
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32. Viral Load as a Factor Affecting the Fatality of Patients Suffering from Severe Fever with Thrombocytopenia Syndrome.
- Author
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Jo HN, Kim J, Hwang SY, Seo JW, Kim DY, Yun NR, Kim DM, Kim CM, Jung SI, Kim UJ, Kim SE, Kim H, Kim ES, Hur J, Kim YK, Jeong HW, Heo JY, Jung DS, Lee H, Park SH, Kwak YG, Lee S, and Lim S
- Subjects
- Aged, Humans, RNA, Viral genetics, Viral Load, Bunyaviridae Infections, Phlebovirus, Severe Fever with Thrombocytopenia Syndrome
- Abstract
The clinical characteristics and the effect of viral RNA loads on fatality in 56 patients with severe fever with thrombocytopenia syndrome (SFTS) were analyzed. The non-survival group (12 patients) demonstrated a significantly higher mean age (77 years) than the survival group (44 patients, 65 years) (p = 0.003). The survival rates were 91.7% and 8.3% in patients with Ct values ≥30 and differed significantly (p = 0.001) in the survival and non-survival groups, respectively. The survival rates were 52.4% and 47.6% in patients with viral copy numbers ≥10,000 and 94.3% and 5.7% in patients with viral copy numbers <10,000 in the survival and non-survival groups, respectively (p = 0.001). In a multivariate analysis, viral copy numbers and initial Acute Psychologic Assessment and Chronic Health Evaluation II (APACHE II) scores were identified as the factors affecting fatality (p = 0.015 and 0.011, respectively). SFTS viral RNA loads can be useful markers for the clinical prediction of mortality and survival.
- Published
- 2022
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33. Clinical Presentation and Mortality of Severe Fever with Thrombocytopenia Syndrome in Japan: A Systematic Review of Case Reports.
- Author
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Yokomizo K, Tomozane M, Sano C, and Ohta R
- Subjects
- Aged, Animals, Humans, Japan epidemiology, Bunyaviridae Infections, Phlebovirus, Severe Fever with Thrombocytopenia Syndrome, Thrombocytopenia diagnosis, Ticks
- Abstract
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.
- Published
- 2022
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34. Severe Fever with Thrombocytopenia Syndrome with Necrotizing Lymphadenitis in a Patient who Underwent 18 F-FDG PET/CT: A Case Report.
- Author
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Kim AR, Kim T, Shin DH, Lee S, and Lim S
- Subjects
- Fluorodeoxyglucose F18, Humans, Positron Emission Tomography Computed Tomography, Lymphadenitis diagnostic imaging, Lymphadenitis etiology, Phlebovirus, Severe Fever with Thrombocytopenia Syndrome
- Abstract
Severe fever with thrombocytopenia syndrome (SFTS), also known as fever, thrombocytopenia, and leukopenia syndrome, is an emerging tick-borne infectious disease in Asian countries. SFTS should be suspected in patients presenting with fever, thrombocytopenia, and leukopenia and have a history of tick exposure in an endemic area. Since SFTS can be accompanied by lymphadenopathy, particularly generalized lymphadenopathy, it can be confused with a primary malignancy, such as lymphoma. The study reports a case of SFTS accompanied by multiple lymphadenopathies, which mimicked malignant lymphoma on F-18 fluorodeoxyglucose positron emission tomography/computed tomography.
- Published
- 2021
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35. Severe Fever with Thrombocytopenia Syndrome in Cats and Its Prevalence among Veterinarian Staff Members in Nagasaki, Japan.
- Author
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Ando, Tsuyoshi, Nabeshima, Takeshi, Inoue, Shingo, Tun, Mya Myat Ngwe, Obata, Miho, Hu, Weiyin, Shimoda, Hiroshi, Kurihara, Shintaro, Izumikawa, Koichi, Morita, Kouichi, and Hayasaka, Daisuke
- Subjects
- *
CATS , *THROMBOCYTOPENIA , *VETERINARIANS , *BODY fluids , *VIRAL antibodies , *CELL culture , *FEVER - Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
36. Severe Fever with Thrombocytopenia Syndrome Accompanied by Invasive Pulmonary Aspergillosis: An Autopsy Case.
- Author
-
Iwao, Kosho, Kawaguchi, Takeshi, Kimura, Masatoshi, Iwao, Chihiro, Rikitake, Mao, Aizawa, Ayako, Kariya, Yumi, Matsuda, Motohiro, Miyauchi, Syunichi, Takajo, Ichiro, Kiwaki, Takumi, Fukushima, Tsuyoshi, Kataoka, Hiroaki, Suzuki, Tadaki, Okayama, Akihiko, and Umekita, Kunihiko
- Subjects
- *
ASPERGILLOSIS , *PULMONARY aspergillosis , *EMERGING infectious diseases , *AUTOPSY , *THROMBOCYTOPENIA , *MULTIPLE organ failure , *SYNDROMES - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
37. Corticosteroids May Have Negative Effects on the Management of Patients with Severe Fever with Thrombocytopenia Syndrome: A Case–Control Study.
- Author
-
Kawaguchi, Takeshi, Umekita, Kunihiko, Yamanaka, Atsushi, Hara, Seiichiro, Yamaguchi, Tetsuro, Inoue, Eisuke, Okayama, Akihiko, and Saijo, Masayuki
- Subjects
- *
PULMONARY aspergillosis , *HEMORRHAGIC fever , *HEALTH facilities , *PROPENSITY score matching , *THROMBOCYTOPENIA , *FEVER - Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
38. Residual and Late Onset Symptoms Appeared in a Patient with Severe Fever with Thrombocytopenia in a Convalescence Stage.
- Author
-
Kanda, Kohei, Kinoshita, Noriko, Kutsuna, Satoshi, Nakamura, Keiji, Okuhama, Ayako, Shimomura, Akira, Inagaki, Takeshi, Yoshikawa, Tomoki, Kurosu, Takeshi, Shimojima, Masayuki, Saijo, Masayuki, Ohmagari, Norio, and Cosset, François-Loïc
- Subjects
- *
HEMORRHAGIC fever , *FEVER , *THROMBOCYTOPENIA , *SYMPTOMS , *CONVALESCENCE , *EMERGING infectious diseases - Abstract
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease caused by Dabie bandavirus (formerly SFTS virus, SFTSV). Its manifestations during the convalescent phase have not been widely described. We report a patient presenting with hematospermia, fatigue, myalgia, alopecia, insomnia, and depression during the recovery phase of SFTS. Since these symptoms are widely observed in patients with viral hemorrhagic fevers, there might be common mechanisms between SFTS and other viral hemorrhagic fevers. Close monitoring may be required during the recovery phase of SFTS. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
39. Vaccine Development for Severe Fever with Thrombocytopenia Syndrome.
- Author
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Yoshikawa, Tomoki and Kuhn, Jens H.
- Subjects
- *
VACCINE development , *LABORATORY mice , *VACCINE approval , *THROMBOCYTOPENIA , *FEVER - Abstract
Severe fever with thrombocytopenia syndrome (SFTS), which is caused by SFTS virus (SFTSV), is a tick-borne emerging zoonosis with a high case-fatality rate. At present, there is no approved SFTS vaccine, although the development of a vaccine would be one of the best strategies for preventing SFTS. This article focused on studies aimed at establishing small animal models of SFTS that are indispensable for evaluating vaccine candidates, developing these vaccine candidates, and establishing more practical animal models for evaluation. Innate immune-deficient mouse models, a hamster model, an immunocompetent ferret model and a cat model have been developed for SFTS. Several vaccine candidates for SFTS have been developed, and their efficacy has been confirmed using these animal models. The candidates consist of live-attenuated virus-based, viral vector-based, or DNA-based vaccines. SFTS vaccines are expected to be used for humans and companion dogs and cats. Hence for practical use, the vaccine candidates should be evaluated for efficacy using not only nonhuman primates but also dogs and cats. There is no practical nonhuman primate model of SFTS; however, the cat model is available to evaluate the efficacy of these candidate SFTS vaccines on domesticated animals. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
40. Pathological Characteristics of a Patient with Severe Fever with Thrombocytopenia Syndrome (SFTS) Infected with SFTS Virus through a Sick Cat's Bite.
- Author
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Tsuru, Masatoshi, Suzuki, Tadaki, Murakami, Tomoyuki, Matsui, Kumiko, Maeda, Yuuji, Yoshikawa, Tomoki, Kurosu, Takeshi, Shimojima, Masayuki, Shimada, Tomome, Hasegawa, Hideki, Maeda, Ken, Morikawa, Shigeru, Saijo, Masayuki, and Cosset, François-Loïc
- Subjects
- *
THROMBOCYTOPENIA , *FEVER , *CATS , *MULTIPLE organ failure , *APPETITE loss , *AUTOPSY - Abstract
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]
- Published
- 2021
- Full Text
- View/download PDF
41. Prognostic Factors of Severe Fever with Thrombocytopenia Syndrome in South Korea.
- Author
-
Kim, Misun, Heo, Sang Taek, Oh, Hyunjoo, Oh, Suhyun, Lee, Keun Hwa, Yoo, Jeong Rae, and Saijo, Masayuki
- Subjects
- *
PROGNOSIS , *REVERSE transcriptase polymerase chain reaction , *THROMBOCYTOPENIA , *SYNDROMES , *FEVER - Abstract
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 (2013–2019) 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 °C vs. 18.9 °C; 77.9% vs. 70.7%, all p < 0.001). In the multivariate analysis, poor oral intake (Odds ratio [OR] 5.87, 95% CI: 2.42–8.25), lymphadenopathy (OR 7.20, 95% CI: 6.24–11.76), mean ambient temperature ≥ 20 °C (OR 4.62, 95% CI: 1.46–10.28), absolute neutrophil count ≤ 2000 cells/μL (OR 8.95, 95% CI: 2.30–21.25), C-reactive protein level ≤ 1.2 mg/dL (OR 6.42, 95% CI: 4.02–24.21), and creatinine kinase level ≥ 200 IU/L (OR 5.94, 95% CI: 1.42–24.92) 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. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
42. M Segment-Based Minigenome System of Severe Fever with Thrombocytopenia Syndrome Virus as a Tool for Antiviral Drug Screening.
- Author
-
Yamada H, Taniguchi S, Shimojima M, Tan L, Kimura M, Morinaga Y, Fukuhara T, Matsuura Y, Komeno T, Furuta Y, Saijo M, and Tani H
- Subjects
- Cell Line, Drug Evaluation, Preclinical methods, HEK293 Cells, Humans, Severe Fever with Thrombocytopenia Syndrome, Antiviral Agents pharmacology, Genome, Viral, High-Throughput Screening Assays methods, Phlebovirus drug effects, Phlebovirus genetics
- Abstract
Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne bunyavirus that causes severe disease in humans with case fatality rates of approximately 30%. There are few treatment options for SFTSV infection. SFTSV RNA synthesis is conducted using a virus-encoded complex with RNA-dependent RNA polymerase activity that is required for viral propagation. This complex and its activities are, therefore, potential antiviral targets. A library of small molecule compounds was processed using a high-throughput screening (HTS) based on an SFTSV minigenome assay (MGA) in a 96-well microplate format to identify potential lead inhibitors of SFTSV RNA synthesis. The assay confirmed inhibitory activities of previously reported SFTSV inhibitors, favipiravir and ribavirin. A small-scale screening using MGA identified four candidate inhibitors that inhibited SFTSV minigenome activity by more than 80% while exhibiting less than 20% cell cytotoxicity with selectivity index (SI) values of more than 100. These included mycophenolate mofetil, methotrexate, clofarabine, and bleomycin. Overall, these data demonstrate that the SFTSV MGA is useful for anti-SFTSV drug development research.
- Published
- 2021
- Full Text
- View/download PDF
43. A Model for the Production of Regulatory Grade Viral Hemorrhagic Fever Exposure Stocks: From Field Surveillance to Advanced Characterization of SFTSV.
- Author
-
Perez-Sautu, Unai, Gu, Se Hun, Caviness, Katie, Song, Dong Hyun, Kim, Yu-Jin, Paola, Nicholas Di, Lee, Daesang, Klein, Terry A., Chitty, Joseph A., Nagle, Elyse, Kim, Heung-Chul, Chong, Sung-Tae, Beitzel, Brett, Reyes, Daniel S., Finch, Courtney, Byrum, Russ, Cooper, Kurt, Liang, Janie, Kuhn, Jens H., and Zeng, Xiankun
- Subjects
- *
HEMORRHAGIC fever , *BLUE chip stocks , *GOVERNMENT agencies - Abstract
Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging human pathogen, endemic in areas of China, Japan, and the Korea (KOR). It is primarily transmitted through infected ticks and can cause a severe hemorrhagic fever disease with case fatality rates as high as 30%. Despite its high virulence and increasing prevalence, molecular and functional studies in situ are scarce due to the limited availability of high-titer SFTSV exposure stocks. During the course of field virologic surveillance in 2017, we detected SFTSV in ticks and in a symptomatic soldier in a KOR Army training area. SFTSV was isolated from the ticks producing a high-titer viral exposure stock. Through the use of advanced genomic tools, we present here a complete, in-depth characterization of this viral stock, including a comparison with both the virus in its arthropod source and in the human case, and an in vivo study of its pathogenicity. Thanks to this detailed characterization, this SFTSV viral exposure stock constitutes a quality biological tool for the study of this viral agent and for the development of medical countermeasures, fulfilling the requirements of the main regulatory agencies. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
44. Vascular Leak and Hypercytokinemia Associated with Severe Fever with Thrombocytopenia Syndrome Virus Infection in Mice.
- Author
-
Westover, Jonna B., Hickerson, Brady T., Van Wettere, Arnaud J., Hurst, Brett L., Kurz, Jacqueline P., Dagley, Ashley, Wülfroth, Petra, Komeno, Takashi, Furuta, Yousuke, Steiner, Thomas, and Gowen, Brian B.
- Subjects
VIRUS diseases ,HEMORRHAGIC fever ,FIBRIN tissue adhesive ,FEVER ,SYNDROMES ,THROMBOCYTOPENIA - Abstract
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging viral hemorrhagic fever (VHF) endemic to China, South Korea, Japan, and Vietnam. Here we characterize the pathogenesis and natural history of disease in IFNAR
-/- mice challenged with the HB29 strain of SFTS virus (SFTSV) and demonstrate hallmark features of VHF such as vascular leak and high concentrations of proinflammatory cytokines in blood and tissues. Treatment with FX06, a natural plasmin digest product of fibrin in clinical development as a treatment for vascular leak, reduced vascular permeability associated with SFTSV infection but did not significantly improve survival outcome. Further studies are needed to assess the role of vascular compromise in the SFTS disease process modeled in IFNAR-/- mice. [ABSTRACT FROM AUTHOR]- Published
- 2019
- Full Text
- View/download PDF
45. Epidemiological Characteristics of Severe Fever with Thrombocytopenia Syndrome from 2010 to 2019 in Mainland China.
- Author
-
Huang X, Li J, Li A, Wang S, and Li D
- Subjects
- Adult, Aged, Aged, 80 and over, China epidemiology, Cities, Female, Humans, Male, Middle Aged, Bunyaviridae Infections epidemiology, Communicable Diseases, Emerging, Phlebovirus, Severe Fever with Thrombocytopenia Syndrome
- Abstract
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease and that is a severe threat to public health considering its high fatality and person-to-person transmission. In order to obtain an updated and deep understanding of the epidemiological characteristics of SFTS in mainland China, we used Pearson's chi-squared test to compare the fatality rate and demographic characteristics in different groups. Data were analyzed in R3.6.1 (R Development Core Team 2018), while the visualization was performed in ArcGIS 10 (ESRI, Redlands, CA, USA), and the statistical significance was set at p < 0.05. A total of 13,824 SFTS cases involving 8899 lab-confirmed cases and 4925 probable cases were reported and included in the epidemiological analysis. Our study found that the number of SFTS cases showed an increasing trend with a small decrease in the past three years. The laboratory-confirmed rate was about 64.4%, which varied between different years and areas. Although most cases (99.3%) were distributed in 7 provinces (Henan, Shandong, Anhui, Hubei, Liaoning, Zhejiang, and Jiangsu), the regional distribution of SFTS gradually expanded from 5 provinces in 2010 to 25 provinces by 2019, especially at the town level. The SFTS cases were mainly sporadic. A total of 96.5% occurred from April to October, and 93.3% of cases were concentrated in middle-aged and elderly people (40-84 years old). Farmers were the main high-risk population. Female cases were slightly more than male cases; however, there were differences between different provinces. The mortality rate showed an increasing trend with age. Overall, the SFTS cases were mainly middle-aged and elderly farmers that sporadically distributed throughout seven provinces with a spatially expanding trend. The laboratory-confirmed rate varied in different years and provinces, which implied that the diagnosis and report criteria for SFTS should be further updated and unified in order to get a better understanding of its epidemiological characteristics and provide scientific data for SFTS control.
- Published
- 2021
- Full Text
- View/download PDF
46. The Polarity of an Amino Acid at Position 1891 of Severe Fever with Thrombocytopenia Syndrome Virus L Protein Is Critical for the Polymerase Activity.
- Author
-
Noda K, Tsuda Y, Kozawa F, Igarashi M, Shimizu K, Arikawa J, and Yoshimatsu K
- Subjects
- Amino Acid Sequence, Amino Acid Substitution, Animals, Cell Line, DNA-Directed RNA Polymerases chemistry, DNA-Directed RNA Polymerases genetics, Fluorescent Antibody Technique, Humans, Models, Molecular, Protein Conformation, Severe Fever with Thrombocytopenia Syndrome, Viral Proteins chemistry, Viral Proteins genetics, Amino Acids chemistry, DNA-Directed RNA Polymerases metabolism, Phlebovirus physiology, Viral Proteins metabolism
- Abstract
Severe fever with thrombocytopenia syndrome virus subclone B7 shows strong plaque formation and cytopathic effect induction compared with other subclones and the parental strain YG1. Compared to YG1 and the other subclones, only B7 possesses a single substitution in the L protein at the amino acid position 1891, in which N is changed to K (N1891K). In this study, we evaluate the effects of this mutation on L protein activity via a cell-based minigenome assay. Substitutions of N with basic amino acids (K or R) enhanced polymerase activity, while substitutions with an acidic amino acid (E) decreased this activity. Mutation to other neutral amino acids showed no significant effect on activity. These results suggest that the characteristic of the amino acid at position 1891 of the L protein are critical for its function, especially with respect to the charge status. Our data indicate that this C-terminal domain of the L protein may be crucial to its functions in genome transcription and viral replication.
- Published
- 2020
- Full Text
- View/download PDF
47. Prognostic Factors of Severe Fever with Thrombocytopenia Syndrome in South Korea.
- Author
-
Kim M, Heo ST, Oh H, Oh S, Lee KH, and Yoo JR
- Subjects
- Aged, Female, Genetic Testing, Genome, Viral, Geography, Medical, Humans, Male, Middle Aged, Odds Ratio, Prognosis, Public Health Surveillance, ROC Curve, Republic of Korea epidemiology, Risk Factors, Severe Fever with Thrombocytopenia Syndrome diagnosis, Severe Fever with Thrombocytopenia Syndrome therapy, Severe Fever with Thrombocytopenia Syndrome virology, Socioeconomic Factors, Viral Load, Phlebovirus genetics, Severe Fever with Thrombocytopenia Syndrome epidemiology
- Abstract
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 (2013-2019) 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 °C vs. 18.9 °C; 77.9% vs. 70.7%, all p < 0.001). In the multivariate analysis, poor oral intake (Odds ratio [OR] 5.87, 95% CI: 2.42-8.25), lymphadenopathy (OR 7.20, 95% CI: 6.24-11.76), mean ambient temperature ≥ 20 °C (OR 4.62, 95% CI: 1.46-10.28), absolute neutrophil count ≤ 2000 cells/μL (OR 8.95, 95% CI: 2.30-21.25), C-reactive protein level ≤ 1.2 mg/dL (OR 6.42, 95% CI: 4.02-24.21), and creatinine kinase level ≥ 200 IU/L (OR 5.94, 95% CI: 1.42-24.92) 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.
- Published
- 2020
- Full Text
- View/download PDF
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