69 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
-
Keita Ishijima, Thanmaporn Phichitraslip, Nattakarn Naimon, Preeyaporn Ploypichai, Benyapa Kriebkajon, Torntun Chinarak, Jirasin Sridaphan, Anamika Kritiyakan, Noppadol Prasertsincharoen, Sathaporn Jittapalapong, Kanate Tangcham, Worawut Rerkamnuaychoke, Yudai Kuroda, Masakatsu Taira, Kango Tatemoto, Eunsil Park, Milagros Virhuez-Mendoza, Yusuke Inoue, Michiko Harada, Tsukasa Yamamoto, Ayano Nishino, Aya Matsuu, and Ken Maeda
- Subjects
severe fever with thrombocytopenia syndrome ,companion animal ,dogs ,zoonosis ,RT-PCR ,ELISA ,Microbiology ,QR1-502 - 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.
- Published
- 2023
- Full Text
- View/download PDF
3. The Seroprevalence of Severe Fever with Thrombocytopenia Syndrome: An Epidemiological Study of Korean Veterinary Hospital Workers
- Author
-
Choon-Mee Kim, Dong-Min Kim, Mi-Seon Bang, Jun-Won Seo, Na-Ra Yun, Da-Young Kim, Mi-Ah Han, Ji-Hye Hwang, and Sook-Kyung Park
- Subjects
epidemiology ,seroprevalence ,severe fever with thrombocytopenia syndrome virus ,severe fever with thrombocytopenia syndrome ,veterinary hospital ,Microbiology ,QR1-502 - 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.
- Published
- 2023
- Full Text
- View/download PDF
4. The First Nationwide Surveillance of Severe Fever with Thrombocytopenia Syndrome in Ruminants and Wildlife in Taiwan
- Author
-
Chih-Ying Kuan, Tsai-Lu Lin, Shan-Chia Ou, Shih-Te Chuang, Jacky Peng-Wen Chan, Ken Maeda, Tetsuya Mizutani, Ming-Pin Wu, Fan Lee, Fang-Tse Chan, Chao-Chin Chang, Rui-Ling Liang, Sue-Fung Yang, Tsung-Ching Liu, Wu-Chun Tu, Hau-You Tzeng, Chia-Jung Lee, Chuen-Fu Lin, Hsu-Hsun Lee, Jhih-Hua Wu, Hsiao-Chien Lo, Kuan-Chieh Tseng, Wei-Li Hsu, and Chi-Chung Chou
- Subjects
severe fever with thrombocytopenia syndrome ,ruminant ,wildlife ,Taiwan ,Microbiology ,QR1-502 - 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.
- Published
- 2023
- Full Text
- View/download PDF
5. Correlation between the Cycle Threshold Values in Detection of Severe Fever with Thrombocytopenia Syndrome Virus Using PowerChek TM SFTSV Real-Time PCR Kit and Viral Load: Prognostic Implications.
- Author
-
Kim M, Heo ST, Kim HC, Kang MJ, Kim S, Lee KH, and Yoo JR
- Subjects
- Humans, Male, Female, Prognosis, Retrospective Studies, Aged, Middle Aged, Aged, 80 and over, Adult, RNA, Viral genetics, Viral Load, Phlebovirus genetics, Phlebovirus isolation & purification, Severe Fever with Thrombocytopenia Syndrome diagnosis, Severe Fever with Thrombocytopenia Syndrome virology, Real-Time Polymerase Chain Reaction methods
- Abstract
Background: This study aimed to analyze the correlation between the cycle threshold (Ct) values of severe fever with thrombocytopenia syndrome (SFTS) virus small (S) and middle (M) segments and the SFTS viral load, aiming to estimate the initial viral load and predict prognosis in the early clinical course., Method: A retrospective study was conducted with confirmed SFTS patients at Jeju National University Hospital (2016-2022). Patients were categorized into non-fatal and fatal groups., Results: This study included 49 patients with confirmed SFTS (non-fatal group, n = 42; fatal group, n = 7). A significant negative correlation (-0.783) was observed between the log SFTS viral load and Ct values ( p < 0.001). This negative correlation was notably stronger in the fatal group (correlation coefficient -0.940) than in the non-fatal group (correlation coefficient -0.345)., Conclusion: In this study, we established a correlation between SFTS viral load and Ct values for estimating the initial viral load and early predicting prognosis. These results are expected to offer valuable insights for SFTS patient treatment and prognosis prediction.
- Published
- 2024
- Full Text
- View/download PDF
6. Clinical Differentiation of Severe Fever with Thrombocytopenia Syndrome from Japanese Spotted Fever
- Author
-
Nana Nakada, Kazuko Yamamoto, Moe Tanaka, Hiroki Ashizawa, Masataka Yoshida, Asuka Umemura, Yuichi Fukuda, Shungo Katoh, Makoto Sumiyoshi, Satoshi Mihara, Tsutomu Kobayashi, Yuya Ito, Nobuyuki Ashizawa, Kazuaki Takeda, Shotaro Ide, Naoki Iwanaga, Takahiro Takazono, Masato Tashiro, Takeshi Tanaka, Seiko Nakamichi, Konosuke Morimoto, Koya Ariyoshi, Kouichi Morita, Shintaro Kurihara, Katsunori Yanagihara, Akitsugu Furumoto, Koichi Izumikawa, and Hiroshi Mukae
- Subjects
severe fever with thrombocytopenia syndrome ,Japanese spotted fever ,clinical differentiation ,white blood cell ,Microbiology ,QR1-502 - 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.
- Published
- 2022
- Full Text
- View/download PDF
7. Development of a Scoring System to Differentiate Severe Fever with Thrombocytopenia Syndrome from Scrub Typhus
- Author
-
Hyoung Sul, Na Ra Yun, Dong-Min Kim, Young Keun Kim, Jieun Kim, Jian Hur, Sook In Jung, Seong Yeol Ryu, Ji Yeon Lee, Kyungmin Huh, Yee Gyung Kwak, Hye Won Jeong, Jung Yeon Heo, Dong Sik Jung, Sun Hee Lee, Sun Hee Park, Joon-Sup Yeom, and Hyungdon Lee
- Subjects
severe fever with thrombocytopenia syndrome ,scrub typhus ,tsutsugamushi ,differential diagnosis ,scoring system ,Microbiology ,QR1-502 - 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.
- Published
- 2022
- Full Text
- View/download PDF
8. Suspected Transmission of Severe Fever with Thrombocytopenia Syndrome Virus from a Cat to a Veterinarian by a Single Contact: A Case Report
- Author
-
Atsushi Miyauchi, Ken-Ei Sada, Hirotaka Yamamoto, Hiroki Iriyoshi, Yuji Touyama, Daisuke Hashimoto, Shigeru Nojima, Shingo Yamanaka, Keita Ishijima, Ken Maeda, and Masafumi Kawamura
- Subjects
severe fever with thrombocytopenia syndrome ,cat-to-human transmission ,human ,cats ,polymerase chain reaction ,Microbiology ,QR1-502 - 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.
- Published
- 2022
- Full Text
- View/download PDF
9. Associations between Chest CT Abnormalities and Clinical Features in Patients with the Severe Fever with Thrombocytopenia Syndrome
- Author
-
Hiroki Ashizawa, Kazuko Yamamoto, Nobuyuki Ashizawa, Kazuaki Takeda, Naoki Iwanaga, Takahiro Takazono, Noriho Sakamoto, Makoto Sumiyoshi, Shotaro Ide, Asuka Umemura, Masataka Yoshida, Yuichi Fukuda, Tsutomu Kobayashi, Masato Tashiro, Takeshi Tanaka, Shungo Katoh, Konosuke Morimoto, Koya Ariyoshi, Shimpei Morimoto, Mya Myat Ngwe Tun, Shingo Inoue, Kouichi Morita, Shintaro Kurihara, Koichi Izumikawa, Katzunori Yanagihara, and Hiroshi Mukae
- Subjects
severe fever with thrombocytopenia syndrome ,lung abnormalities ,chest computed tomography ,ground-glass opacity ,Microbiology ,QR1-502 - 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.
- Published
- 2022
- Full Text
- View/download PDF
10. Difference in Intraspecies Transmissibility of Severe Fever with Thrombocytopenia Syndrome Virus Depending on Abrogating Type 1 Interferon Signaling in Mice.
- Author
-
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
- Full Text
- View/download PDF
11. Current Progress of Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV) Vaccine Development.
- Author
-
Kim D, Lai CJ, Cha I, and Jung JU
- Subjects
- 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
- Full Text
- View/download PDF
12. Severe Fever with Thrombocytopenia Syndrome Accompanied by Invasive Pulmonary Aspergillosis: An Autopsy Case
- Author
-
Kosho Iwao, Takeshi Kawaguchi, Masatoshi Kimura, Chihiro Iwao, Mao Rikitake, Ayako Aizawa, Yumi Kariya, Motohiro Matsuda, Syunichi Miyauchi, Ichiro Takajo, Takumi Kiwaki, Tsuyoshi Fukushima, Hiroaki Kataoka, Tadaki Suzuki, Akihiko Okayama, and Kunihiko Umekita
- Subjects
severe fever with thrombocytopenia syndrome ,invasive pulmonary aspergillosis ,autopsy ,Microbiology ,QR1-502 - 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
- Full Text
- View/download PDF
13. Severe Fever with Thrombocytopenia Syndrome in Cats and Its Prevalence among Veterinarian Staff Members in Nagasaki, Japan
- Author
-
Tsuyoshi Ando, Takeshi Nabeshima, Shingo Inoue, Mya Myat Ngwe Tun, Miho Obata, Weiyin Hu, Hiroshi Shimoda, Shintaro Kurihara, Koichi Izumikawa, Kouichi Morita, and Daisuke Hayasaka
- Subjects
severe fever with thrombocytopenia syndrome ,cats ,veterinarians ,Microbiology ,QR1-502 - 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.
- Published
- 2021
- Full Text
- View/download PDF
14. Vaccine Development for Severe Fever with Thrombocytopenia Syndrome
- Author
-
Tomoki Yoshikawa
- Subjects
severe fever with thrombocytopenia syndrome ,vaccine ,animal model ,Microbiology ,QR1-502 - 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.
- Published
- 2021
- Full Text
- View/download PDF
15. Residual and Late Onset Symptoms Appeared in a Patient with Severe Fever with Thrombocytopenia in a Convalescence Stage
- Author
-
Kohei Kanda, Noriko Kinoshita, Satoshi Kutsuna, Keiji Nakamura, Ayako Okuhama, Akira Shimomura, Takeshi Inagaki, Tomoki Yoshikawa, Takeshi Kurosu, Masayuki Shimojima, Masayuki Saijo, and Norio Ohmagari
- Subjects
severe fever with thrombocytopenia syndrome ,convalescence ,viral hemorrhagic fevers ,Microbiology ,QR1-502 - 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.
- Published
- 2021
- Full Text
- View/download PDF
16. Corticosteroids May Have Negative Effects on the Management of Patients with Severe Fever with Thrombocytopenia Syndrome: A Case–Control Study
- Author
-
Takeshi Kawaguchi, Kunihiko Umekita, Atsushi Yamanaka, Seiichiro Hara, Tetsuro Yamaguchi, Eisuke Inoue, and Akihiko Okayama
- Subjects
severe fever with thrombocytopenia syndrome ,viral hemorrhagic fever ,prognostic factor ,corticosteroid ,Microbiology ,QR1-502 - 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.
- Published
- 2021
- Full Text
- View/download PDF
17. 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
-
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
- Full Text
- View/download PDF
18. High Seroprevalence of Severe Fever with Thrombocytopenia Syndrome Virus Infection among the Dog Population in Thailand.
- Author
-
Ishijima K, Phichitraslip T, Naimon N, Ploypichai P, Kriebkajon B, Chinarak T, Sridaphan J, Kritiyakan A, Prasertsincharoen N, Jittapalapong S, Tangcham K, Rerkamnuaychoke W, Kuroda Y, Taira M, Tatemoto K, Park E, Virhuez-Mendoza M, Inoue Y, Harada M, Yamamoto T, Nishino A, Matsuu A, and Maeda K
- Subjects
- Animals, Humans, Dogs, Seroepidemiologic Studies, Thailand epidemiology, Antibodies, Viral, Severe Fever with Thrombocytopenia Syndrome epidemiology, Severe Fever with Thrombocytopenia Syndrome veterinary, Bunyaviridae Infections epidemiology, Bunyaviridae Infections veterinary, Phlebovirus genetics, 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.
- Published
- 2023
- Full Text
- View/download PDF
19. 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
-
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
- View/download PDF
20. Pathological Characteristics of a Patient with Severe Fever with Thrombocytopenia Syndrome (SFTS) Infected with SFTS Virus through a Sick Cat’s Bite
- Author
-
Masatoshi Tsuru, Tadaki Suzuki, Tomoyuki Murakami, Kumiko Matsui, Yuuji Maeda, Tomoki Yoshikawa, Takeshi Kurosu, Masayuki Shimojima, Tomome Shimada, Hideki Hasegawa, Ken Maeda, Shigeru Morikawa, and Masayuki Saijo
- Subjects
severe fever with thrombocytopenia syndrome ,cat ,companion animals ,viral hemorrhagic fever ,pathology ,Microbiology ,QR1-502 - 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.
- Published
- 2021
- Full Text
- View/download PDF
21. Prognostic Factors of Severe Fever with Thrombocytopenia Syndrome in South Korea
- Author
-
Misun Kim, Sang Taek Heo, Hyunjoo Oh, Suhyun Oh, Keun Hwa Lee, and Jeong Rae Yoo
- Subjects
severe fever with thrombocytopenia syndrome ,ambient temperature ,clinical characteristics ,Microbiology ,QR1-502 - 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
22. 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
-
Aya Matsuu, Kandai Doi, Keita Ishijima, Kango Tatemoto, Yushi Koshida, Ayako Yoshida, Kohei Kiname, Akio Iwashita, Shin-ichi Hayama, and Ken Maeda
- Subjects
Phlebovirus ,Severe Fever with Thrombocytopenia Syndrome ,Deer ,Endangered Species ,Bunyaviridae Infections ,Thrombocytopenia ,Infectious Diseases ,Dogs ,Japan ,Seroepidemiologic Studies ,Virology ,Cats ,Humans ,Animals ,Panthera ,SFTS ,Tsushima leopard cat ,wildlife ,zoonosis - 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.
- Published
- 2022
23. 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
-
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
24. Construction and Characterization of Severe Fever with Thrombocytopenia Syndrome Virus with a Fluorescent Reporter for Antiviral Drug Screening.
- Author
-
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
- Full Text
- View/download PDF
25. Associations between Chest CT Abnormalities and Clinical Features in Patients with the Severe Fever with Thrombocytopenia Syndrome
- Author
-
Hiroki Ashizawa, Kazuko Yamamoto, Nobuyuki Ashizawa, Kazuaki Takeda, Naoki Iwanaga, Takahiro Takazono, Noriho Sakamoto, Makoto Sumiyoshi, Shotaro Ide, Asuka Umemura, Masataka Yoshida, Yuichi Fukuda, Tsutomu Kobayashi, Masato Tashiro, Takeshi Tanaka, Shungo Katoh, Konosuke Morimoto, Koya Ariyoshi, Shimpei Morimoto, Mya Myat Ngwe Tun, Shingo Inoue, Kouichi Morita, Shintaro Kurihara, Koichi Izumikawa, Katzunori Yanagihara, and Hiroshi Mukae
- Subjects
Inflammation ,Male ,Severe Fever with Thrombocytopenia Syndrome ,Patient Acuity ,chest computed tomography ,ground-glass opacity ,Infectious Diseases ,C-Reactive Protein ,Virology ,Tachycardia ,lung abnormalities ,Humans ,Female ,severe fever with thrombocytopenia syndrome ,Tomography, X-Ray Computed ,Lung ,Aged ,Retrospective Studies - 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
- 2021
26. Kinetics of Serological Response in Patients with Severe Fever with Thrombocytopenia Syndrome
- Author
-
Seong Yeon Park, Sang-Ho Choi, Min Jae Kim, Se Yoon Park, Keun Hwa Lee, Sung-Han Kim, Yong Pil Chong, Sang-Oh Lee, Sang Hyun Ra, Sun Ho Kee, Yang Soo Kim, and Min-Chul Kim
- Subjects
0301 basic medicine ,Male ,Phlebovirus ,medicine.medical_specialty ,Severe Fever with Thrombocytopenia Syndrome ,030231 tropical medicine ,lcsh:QR1-502 ,Enzyme-Linked Immunosorbent Assay ,Immunofluorescence ,Antibodies, Viral ,Gastroenterology ,lcsh:Microbiology ,Serology ,03 medical and health sciences ,0302 clinical medicine ,Virology ,Internal medicine ,medicine ,Humans ,In patient ,Viremia ,immunofluorescence assay (IFA) ,enzyme-linked immunosorbent assay (ELISA) ,severe fever with thrombocytopenia syndrome (SFTS) ,immunoglobulin G (IgG) ,Aged ,medicine.diagnostic_test ,biology ,business.industry ,Brief Report ,SFTS virus ,Middle Aged ,medicine.disease ,biology.organism_classification ,viral load ,Reverse transcription polymerase chain reaction ,Titer ,Severe fever with thrombocytopenia syndrome ,030104 developmental biology ,Infectious Diseases ,immunoglobulin M (IgM) ,Immunoglobulin M ,Tick-Borne Diseases ,Immunoglobulin G ,Female ,business ,Viral load - Abstract
Severe fever with thrombocytopenia syndrome (SFTS) is caused by SFTS virus (SFTSV). We investigated the detailed kinetics of serologic response in patients with SFTS. Twenty-eight patients aged ≥18 years were enrolled between July 2015 and October 2018. SFTS was confirmed by detecting SFTSV RNA in their plasma using reverse transcription polymerase chain reaction. SFTSV-specific IgG and IgM were measured using immunofluorescence assay (IFA) and enzyme-linked immunosorbent assay (ELISA). We found that SFTSV-specific IgG was detected at days 5–9 after symptom onset, and its titer was rising during the course of disease. SFTSV-specific IgM titer peaked at around week 2–3 from symptom onset. The SFTSV-specific seropositive rates for days 5–9, 10–14, 15–19, and 20–24 from symptom onset using IFA and ELISA were 63%, 76%, 90%, and 100%, and 58%, 86%, 100%, and 100%, respectively, for IgG, whereas they were 32%, 62%, 80%, and 100%, and 53%, 62%, 70%, and 100%, respectively, for IgM. The delayed IgM response could be attributed to the low sensitivity of SFTSV-specific IgM IFA or ELISA and/or impaired immune responses. The IgM test using IFA or ELISA that we used in this study is, therefore, insufficient for the early diagnosis of SFTS.
- Published
- 2021
27. Prognostic Factors of Severe Fever with Thrombocytopenia Syndrome in South Korea
- Author
-
Suhyun Oh, Keun Hwa Lee, Hyunjoo Oh, Jeong Rae Yoo, Misun Kim, and Sang Taek Heo
- Subjects
Male ,Phlebovirus ,0301 basic medicine ,medicine.medical_specialty ,Multivariate analysis ,030106 microbiology ,030231 tropical medicine ,ambient temperature ,lcsh:QR1-502 ,Genome, Viral ,Gastroenterology ,Article ,lcsh:Microbiology ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Virology ,Internal medicine ,parasitic diseases ,Republic of Korea ,Odds Ratio ,medicine ,Humans ,Public Health Surveillance ,Genetic Testing ,Geography, Medical ,clinical characteristics ,Aged ,Univariate analysis ,biology ,business.industry ,SFTS virus ,Retrospective cohort study ,Odds ratio ,Middle Aged ,Viral Load ,Prognosis ,biology.organism_classification ,medicine.disease ,Severe fever with thrombocytopenia syndrome ,Infectious Diseases ,ROC Curve ,Socioeconomic Factors ,Absolute neutrophil count ,biology.protein ,Female ,Creatine kinase ,business ,severe fever with thrombocytopenia syndrome - 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&ndash, 2019) demonstrated the role of climatic factors as predictors of SFTS and developed a clinical scoring system for SFTS using climate variables and clinical characteristics. The presence of the SFTS virus was confirmed using reverse transcription polymerase chain reaction (RT-PCR) tests. In the univariate analysis, the SFTS-positive group was significantly associated with higher mean ambient temperature and humidity compared with the SFTS-negative group (22.5 °, 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&ndash, 8.25), lymphadenopathy (OR 7.20, 95% CI: 6.24&ndash, 11.76), mean ambient temperature &ge, 20 °, C (OR 4.62, 95% CI: 1.46&ndash, 10.28), absolute neutrophil count &le, 2000 cells/&mu, L (OR 8.95, 95% CI: 2.30&ndash, 21.25), C-reactive protein level &le, 1.2 mg/dL (OR 6.42, 95% CI: 4.02&ndash, 24.21), and creatinine kinase level &ge, 200 IU/L (OR 5.94, 95% CI: 1.42&ndash, 24.92) were significantly associated with the SFTS-positive group. This study presents the risk factors, including ambient temperature and clinical characteristics, that physicians should consider when suspecting SFTS.
- Published
- 2021
28. Viral and Immunologic Factors Associated with Fatal Outcome of Patients with Severe Fever with Thrombocytopenia Syndrome in Korea
- Author
-
Se-Yoon Park, Keun-Hwa Lee, Dasarang Kim, Min Chul Kim, Ji-Yeun Kim, Ji-Soo Kwon, Hyunjung Lee, Seong-Yeon Park, Sang-Oh Lee, Sung-Han Kim, Hye-Hee Cha, Yang-Soo Kim, Sang-Hyun Ra, Min Jae Kim, Sun-Ho Kee, Sol Jin, Yong-Pil Chong, Sang-Ho Choi, and Tae Eun Kim
- Subjects
Male ,Phlebovirus ,medicine.medical_specialty ,Fatal outcome ,Severe Fever with Thrombocytopenia Syndrome ,Immunologic Factors ,fatal outcome ,Inflammation ,chemokines ,Antibodies, Viral ,Gastroenterology ,Microbiology ,Virus ,Article ,Virology ,Internal medicine ,humoral immunity ,Republic of Korea ,SFTS phlebovirus ,medicine ,Humans ,Prospective Studies ,Aged ,business.industry ,Middle Aged ,Viral Load ,medicine.disease ,Pathophysiology ,humanities ,cytokines ,QR1-502 ,Severe fever with thrombocytopenia syndrome ,Infectious Diseases ,Humoral immunity ,Disease Progression ,Female ,medicine.symptom ,business ,Viral load - Abstract
Significant progress has been made on the molecular biology of the severe fever with thrombopenia virus (SFTSV); however, many parts of the pathophysiological mechanisms of mortality in SFTS remain unclear. In this study, we investigated virologic and immunologic factors for fatal outcomes of patients with SFTS. We prospectively enrolled SFTS patients admitted from July 2015 to October 2020. Plasma samples were subjected to SFTSV RNA RT-PCR, multiplex microbead immunoassay for 17 cytokines, and IFA assay. A total of 44 SFTS patients were enrolled, including 37 (84.1%) survivors and 7 (15.9%) non-survivors. Non-survivors had a 2.5 times higher plasma SFTSV load than survivors at admission (p < 0.001), and the viral load in non-survivors increased progressively during hospitalization. In addition, non-survivors did not develop adequate anti-SFTSV IgG, whereas survivors exhibited anti-SFTSV IgG during hospitalization. IFN-α, IL-10, IP-10, IFN-γ, IL-6, IL-8, MCP-1, MIP-1α, and G-CSF were significantly elevated in non-survivors compared to survivors and did not revert to normal ranges during hospitalization (p < 0.05). Severe signs of inflammation such as a high plasma concentration of IFN-α, IL-10, IP-10, IFN-γ, IL-6, IL-8, MCP-1, MIP-1α, and G-CSF, poor viral control, and inadequate antibody response during the disease course were associated with mortality in SFTS patients.
- Published
- 2021
29. In Silico Structure-Based Design of Antiviral Peptides Targeting the Severe Fever with Thrombocytopenia Syndrome Virus Glycoprotein Gn
- Author
-
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
30. Serological Evidence of Severe Fever with Thrombocytopenia Syndrome Virus and IgM Positivity Were Identified in Healthy Residents in Vietnam
- Author
-
Xuan Chuong Tran, Sung Hye Kim, Jeong-Eun Lee, So-Hee Kim, Su Yeon Kang, Nguyen D. Binh, Pham V. Duc, Phan T. K. Phuong, Nguyen T. P. Thao, Wonwoo Lee, Joon-Yong Bae, Man-Seong Park, Misun Kim, Jeong Rae Yoo, Sang Taek Heo, Kyeong Ho An, Jung Mogg Kim, Nam-Hyuk Cho, Sun-Ho Kee, and Keun Hwa Lee
- Subjects
Phlebovirus ,Severe Fever with Thrombocytopenia Syndrome ,Bunyaviridae Infections ,Antibodies, Viral ,severe fever with thrombocytopenia syndrome virus (SFTSV) ,serological evidence ,IgM positivity ,healthy residents ,Vietnam ,Antibodies, Neutralizing ,Infectious Diseases ,Immunoglobulin M ,Seroepidemiologic Studies ,Tick-Borne Diseases ,Immunoglobulin G ,Virology ,Humans - 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.
- Published
- 2022
31. The Seroprevalence of Severe Fever with Thrombocytopenia Syndrome: An Epidemiological Study of Korean Veterinary Hospital Workers.
- Author
-
Kim CM, Kim DM, Bang MS, Seo JW, Yun NR, Kim DY, Han MA, Hwang JH, and Park SK
- Subjects
- Animals, Humans, Seroepidemiologic Studies, Hospitals, Animal, Antibodies, Viral, Personnel, Hospital, Republic of Korea epidemiology, Severe Fever with Thrombocytopenia Syndrome epidemiology
- 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.
- Published
- 2023
- Full Text
- View/download PDF
32. The First Nationwide Surveillance of Severe Fever with Thrombocytopenia Syndrome in Ruminants and Wildlife in Taiwan.
- Author
-
Kuan CY, Lin TL, Ou SC, Chuang ST, Chan JP, Maeda K, Mizutani T, Wu MP, Lee F, Chan FT, Chang CC, Liang RL, Yang SF, Liu TC, Tu WC, Tzeng HY, Lee CJ, Lin CF, Lee HH, Wu JH, Lo HC, Tseng KC, Hsu WL, and Chou CC
- Subjects
- Female, Humans, Animals, Cattle, Sheep, Taiwan epidemiology, Ruminants, Goats, Pakistan, RNA, Viral genetics, Animals, Wild, Severe Fever with Thrombocytopenia Syndrome
- 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.
- Published
- 2023
- Full Text
- View/download PDF
33. Lethal Disease in Dogs Naturally Infected with Severe Fever with Thrombocytopenia Syndrome Virus
- Author
-
Keita Ishijima, Kango Tatemoto, Eunsil Park, Masanobu Kimura, Osamu Fujita, Masakatsu Taira, Yudai Kuroda, Milagros Virhuez Mendoza, Yusuke Inoue, Michiko Harada, Aya Matsuu, Hiroshi Shimoda, Ryusei Kuwata, Shigeru Morikawa, and Ken Maeda
- Subjects
Phlebovirus ,Dogs ,Infectious Diseases ,Immunoglobulin M ,Severe Fever with Thrombocytopenia Syndrome ,Immunoglobulin G ,Virology ,Animals ,Humans ,Leukopenia ,Bunyaviridae Infections ,Thrombocytopenia ,severe fever with thrombocytopenia syndrome virus ,dog ,zoonosis ,RT-PCR ,ELISA ,animal hospital in Japan - Abstract
Severe fever with the thrombocytopenia syndrome virus (SFTSV) causes fatal disease in humans, cats, and cheetahs. In this study, the information on seven dogs with SFTS was summarized. All dogs showed anorexia, high fever, leukopenia, and thrombocytopenia, two dogs showed vomiting and loose stool, and five dogs had tick parasites. All dogs also had a history of outdoor activity. The SFTSV gene was detected in all dogs. Remarkably, three dogs (43%) died. SFTSV was isolated from six dogs and the complete genomes were determined. A significant increase in anti-SFTSV-IgG antibodies was observed in two dogs after recovery, and anti-SFTSV-IgM antibodies were detected in four dogs in the acute phase. Using an ELISA cut-off value of 0.410 to discriminate between SFTSV-negative and positive dogs, the detection of anti-SFTSV-IgM antibodies was useful for the diagnosis of dogs with acute-phase SFTS. Four out of the ninety-eight SFTSV-negative dogs possessed high anti-SFTSV IgG antibody titers, indicating that some dogs can recover from SFTSV infection. In conclusion, SFTSV is lethal in some dogs, but many dogs recover from SFTSV infection.
- Published
- 2022
34. Neutralizing mAbs against SFTS Virus Gn Protein Show Strong Therapeutic Effects in an SFTS Animal Model
- Author
-
Masayuki Shimojima, Satoko Sugimoto, Kunihiko Umekita, Taishi Onodera, Kaori Sano, Hideki Tani, Yuki Takamatsu, Tomoki Yoshikawa, Takeshi Kurosu, Tadaki Suzuki, Yoshimasa Takahashi, Hideki Ebihara, and Masayuki Saijo
- Subjects
Phlebovirus ,Disease Models, Animal ,Mice ,Infectious Diseases ,Severe Fever with Thrombocytopenia Syndrome ,Viral Envelope Proteins ,Virology ,Animals ,Antibodies, Monoclonal ,Humans ,Antibodies, Viral ,Antibodies, Neutralizing ,severe fever with thrombocytopenia syndrome (SFTS) ,SFTS virus ,therapeutic monoclonal antibody ,neutralization ,animal model - 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
35. M Segment-Based Minigenome System of Severe Fever with Thrombocytopenia Syndrome Virus as a Tool for Antiviral Drug Screening
- Author
-
Miyuki Kimura, Masayuki Shimojima, Yoshitomo Morinaga, Takashi Komeno, Yoshiharu Matsuura, Takasuke Fukuhara, Hideki Tani, Satoshi Taniguchi, Long Tan, Masayuki Saijo, Hiroshi Yamada, and Yousuke Furuta
- Subjects
0301 basic medicine ,Phlebovirus ,Severe Fever with Thrombocytopenia Syndrome ,medicine.drug_class ,ribavirin ,030106 microbiology ,Drug Evaluation, Preclinical ,Genome, Viral ,Favipiravir ,favipiravir ,Mycophenolate ,Antiviral Agents ,Microbiology ,Article ,Cell Line ,03 medical and health sciences ,chemistry.chemical_compound ,antivirals ,Virology ,RNA polymerase ,medicine ,Clofarabine ,Humans ,antiviral screening ,business.industry ,allergology ,Ribavirin ,QR1-502 ,High-Throughput Screening Assays ,030104 developmental biology ,Infectious Diseases ,HEK293 Cells ,chemistry ,minigenome assay ,Methotrexate ,Antiviral drug ,SFTSV ,business ,medicine.drug ,Severe fever with thrombocytopenia syndrome virus - 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
36. Severe Fever with Thrombocytopenia Syndrome Accompanied by Invasive Pulmonary Aspergillosis: An Autopsy Case
- Author
-
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
37. Development of an RT-LAMP Assay for the Rapid Detection of SFTS Virus
- Author
-
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
38. Seroprevalence of Severe Fever with Thrombocytopenia Syndrome Virus in Small-Animal Veterinarians and Nurses in the Japanese Prefecture with the Highest Case Load
- Author
-
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
- Subjects
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
39. Pathological Characteristics of a Patient with Severe Fever with Thrombocytopenia Syndrome (SFTS) Infected with SFTS Virus through a Sick Cat’s Bite
- Author
-
Tomoki Yoshikawa, Shigeru Morikawa, Tomoyuki Murakami, Kumiko Matsui, Tadaki Suzuki, Masatoshi Tsuru, Yuuji Maeda, Hideki Hasegawa, Masayuki Shimojima, Takeshi Kurosu, Ken Maeda, Tomome Shimada, and Masayuki Saijo
- Subjects
0301 basic medicine ,Phlebovirus ,medicine.medical_specialty ,030106 microbiology ,lcsh:QR1-502 ,cat ,Autopsy ,Article ,lcsh:Microbiology ,Viral hemorrhagic fever ,03 medical and health sciences ,Virology ,Cause of Death ,companion animals ,Medicine ,Animals ,Humans ,Bites and Stings ,viral hemorrhagic fever ,Retrospective Studies ,biology ,business.industry ,SFTS virus ,Middle Aged ,biology.organism_classification ,medicine.disease ,Dermatology ,Severe fever with thrombocytopenia syndrome ,030104 developmental biology ,Infectious Diseases ,Vomiting ,Etiology ,Cats ,Female ,pathology ,Differential diagnosis ,Hemophagocytosis ,medicine.symptom ,business ,severe fever with thrombocytopenia syndrome - 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&rsquo, 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.
- Published
- 2021
- Full Text
- View/download PDF
40. Two Different Strains of Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV) in North and South Osaka by Phylogenetic Analysis of Evolutionary Lineage: Evidence for Independent SFTSV Transmission
- Author
-
Kazuyoshi Ikuta, Hirono Takabayashi, Tadahiro Sasaki, Ryo Ikemori, Kazutoshi Morisada, Takahiro Yumisashi, Masaru Kinoshita, Kazushi Motomura, and Ikuko Aoyama
- Subjects
0301 basic medicine ,Phlebovirus ,Lineage (genetic) ,Severe Fever with Thrombocytopenia Syndrome ,genotype ,030231 tropical medicine ,Reassortment ,lcsh:QR1-502 ,Genome, Viral ,lcsh:Microbiology ,Evolution, Molecular ,03 medical and health sciences ,0302 clinical medicine ,Japan ,Virology ,Genotype ,medicine ,Humans ,Phylogeny ,biology ,Phylogenetic tree ,SFTS ,whole genome ,Brief Report ,SFTS virus ,biology.organism_classification ,medicine.disease ,Severe fever with thrombocytopenia syndrome ,030104 developmental biology ,Infectious Diseases ,Infectious disease (medical specialty) ,RNA, Viral ,Severe fever with thrombocytopenia syndrome virus - Abstract
Severe fever with thrombocytopenia syndrome (SFTS) is a novel tick-borne infectious disease, therefore, the information on the whole genome of the SFTS virus (SFTSV) is still limited. This study demonstrates a nearly whole genome of the SFTSV identified in Osaka in 2017 and 2018 by next-generation sequencing (NGS). The evolutionary lineage of two genotypes, C5 and J1, was identified in Osaka. The first case in Osaka belongs to suspect reassortment (L:C5, M:C5, S:C4), the other is genotype J1 (L: J1, M: J1, S: J1) according to the classification by a Japanese group. C5 was identified in China, indicating that C5 identified in this study may be transmitted by birds between China and Japan. This study revealed that different SFTSV genotypes were distributed in two local areas, suggesting the separate or focal transmission patterns in Osaka.
- Published
- 2021
41. 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
-
Matsuu A, Doi K, Ishijima K, Tatemoto K, Koshida Y, Yoshida A, Kiname K, Iwashita A, Hayama SI, and Maeda K
- Subjects
- 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.
- Published
- 2022
- Full Text
- View/download PDF
42. Serological Evidence of Severe Fever with Thrombocytopenia Syndrome Virus and IgM Positivity Were Identified in Healthy Residents in Vietnam.
- Author
-
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.
- Published
- 2022
- Full Text
- View/download PDF
43. 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
-
Yoshimi Tsuda, Jiro Arikawa, Kumiko Yoshimatsu, Manabu Igarashi, Fumiya Kozawa, Kisho Noda, and Kenta Shimizu
- Subjects
Models, Molecular ,Phlebovirus ,0301 basic medicine ,Severe Fever with Thrombocytopenia Syndrome ,Protein Conformation ,030106 microbiology ,Cell ,lcsh:QR1-502 ,Fluorescent Antibody Technique ,bunyavirus ,Genome ,Article ,lcsh:Microbiology ,Cell Line ,Viral Proteins ,03 medical and health sciences ,Transcription (biology) ,Virology ,medicine ,Animals ,Humans ,Amino Acid Sequence ,Amino Acids ,Polymerase ,Cytopathic effect ,chemistry.chemical_classification ,biology ,Chemistry ,DNA-Directed RNA Polymerases ,Molecular biology ,polymerase activity ,Amino acid ,030104 developmental biology ,Infectious Diseases ,medicine.anatomical_structure ,Amino Acid Substitution ,Viral replication ,biology.protein ,L protein ,SFTSV ,Severe fever with thrombocytopenia syndrome virus - 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
44. Clinical Differentiation of Severe Fever with Thrombocytopenia Syndrome from Japanese Spotted Fever.
- Author
-
Nakada N, Yamamoto K, Tanaka M, Ashizawa H, Yoshida M, Umemura A, Fukuda Y, Katoh S, Sumiyoshi M, Mihara S, Kobayashi T, Ito Y, Ashizawa N, Takeda K, Ide S, Iwanaga N, Takazono T, Tashiro M, Tanaka T, Nakamichi S, Morimoto K, Ariyoshi K, Morita K, Kurihara S, Yanagihara K, Furumoto A, Izumikawa K, and Mukae H
- Subjects
- Animals, Humans, Japan epidemiology, Retrospective Studies, Exanthema, Leukopenia diagnosis, Phlebovirus, Severe Fever with Thrombocytopenia Syndrome diagnosis, Spotted Fever Group Rickettsiosis diagnosis
- 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.
- Published
- 2022
- Full Text
- View/download PDF
45. Neutralizing mAbs against SFTS Virus Gn Protein Show Strong Therapeutic Effects in an SFTS Animal Model.
- Author
-
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
- Full Text
- View/download PDF
46. Infection Route Impacts the Pathogenesis of Severe Fever with Thrombocytopenia Syndrome Virus in Ferrets.
- Author
-
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
- Full Text
- View/download PDF
47. Development of a Scoring System to Differentiate Severe Fever with Thrombocytopenia Syndrome from Scrub Typhus.
- Author
-
Sul H, Yun NR, Kim DM, Kim YK, Kim J, Hur J, Jung SI, Ryu SY, Lee JY, Huh K, Kwak YG, Jeong HW, Heo JY, Jung DS, Lee SH, Park SH, Yeom JS, and Lee H
- Subjects
- Humans, Retrospective Studies, Leukopenia diagnosis, Phlebovirus, Scrub Typhus diagnosis, Scrub Typhus epidemiology, Severe Fever with Thrombocytopenia Syndrome diagnosis, Thrombocytopenia diagnosis
- 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.
- Published
- 2022
- Full Text
- View/download PDF
48. Viral Load as a Factor Affecting the Fatality of Patients Suffering from Severe Fever with Thrombocytopenia Syndrome.
- Author
-
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
- Full Text
- View/download PDF
49. Clinical Update of Severe Fever with Thrombocytopenia Syndrome
- Author
-
Na-Ra Yun, Da-young Kim, Dong-Min Kim, and Jun-Won Seo
- Subjects
Phlebovirus ,0301 basic medicine ,Pediatrics ,medicine.medical_specialty ,Severe Fever with Thrombocytopenia Syndrome ,030106 microbiology ,Review ,Antiviral Agents ,Microbiology ,03 medical and health sciences ,Ticks ,Virology ,parasitic diseases ,Case fatality rate ,Animals ,Humans ,Medicine ,severe fever with thrombocytopenia ,Leukopenia ,treatment ,biology ,business.industry ,Mortality rate ,SFTS virus ,biology.organism_classification ,medicine.disease ,QR1-502 ,Severe fever with thrombocytopenia syndrome ,Diarrhea ,030104 developmental biology ,Infectious Diseases ,Vomiting ,Haemaphysalis longicornis ,medicine.symptom ,business - Abstract
Severe fever with thrombocytopenia syndrome (SFTS) is an acute febrile illness characterized by fever, leukopenia, thrombocytopenia, and gastrointestinal symptoms such as diarrhea, nausea, and vomiting resulting from infection with the SFTS virus (SFTSV). The SFTSV is transmitted to humans by tick bites, primarily from Haemaphysalis longicornis, Amblyomma testudinarium, Ixodes nipponensis, and Rhipicephalus microplus. Human-to-human transmission has also been reported. Since the first report of an SFTS patient in China, the number of patients has also been increasing. The mortality rate of patients with SFTS remains high because the disease can quickly lead to death through multiple organ failure. In particular, an average fatality rate of approximately 20% has been reported for SFTS patients, and no treatment strategy has been established. Therefore, effective antiviral agents and vaccines are required. Here, we aim to review the epidemiology, clinical manifestations, laboratory diagnosis, and various specific treatments (i.e., antiviral agents, steroids, intravenous immunoglobulin, and plasma exchange) that have been tested to help to cope with the disease.
- Published
- 2021
50. Severe Fever with Thrombocytopenia Syndrome in Cats and Its Prevalence among Veterinarian Staff Members in Nagasaki, Japan
- Author
-
Kouichi Morita, Shingo Inoue, Shintaro Kurihara, Takeshi Nabeshima, Daisuke Hayasaka, Mya Myat Ngwe Tun, Miho Obata, Tsuyoshi Ando, Hiroshi Shimoda, Weiyin Hu, and Koichi Izumikawa
- Subjects
Phlebovirus ,0301 basic medicine ,Severe Fever with Thrombocytopenia Syndrome ,030106 microbiology ,Genome, Viral ,Antibodies, Viral ,Cat Diseases ,Microbiology ,Article ,Virus ,Veterinarians ,03 medical and health sciences ,Japan ,Virology ,Genotype ,Animals ,Medicine ,Seroprevalence ,Sentinel Animals ,Phylogeny ,CATS ,biology ,business.industry ,High-Throughput Nucleotide Sequencing ,medicine.disease ,QR1-502 ,Severe fever with thrombocytopenia syndrome ,030104 developmental biology ,Infectious Diseases ,Immunoglobulin G ,Cats ,biology.protein ,RNA, Viral ,Antibody ,business - 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.
- Published
- 2021
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.