Skip to main content

Clinical Aspects of SFTS

  • Chapter
  • First Online:

Abstract

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-born disease. The incubation period after tick-bite is generally 6–14 days. The typical course of SFTS has three clinical stages, the “fever stage”, the “multiple organ failure stage”, and the “convalescent stage”. The clinical symptoms include sudden onset of high fever, chills, headache, myalgia, gastrointestinal symptoms, lymphadenopathy, hemorrhagic tendency, and central nervous system (CNS) manifestations. SFTS frequently accompanies with hemophagocytic lymphohistiocytosis. Common laboratory findings include leukocytopenia, thrombocytopenia, elevated levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactic acid dehydrogenase (LDH), and creatine kinase (CK). Blood coagulation times are prolonged. Notably, the level of C-reactive protein remains normal range. The levels of inflammatory cytokines are associated with clinical severity of SFTS. Diagnosis of SFTS is confirmed by reverse transcriptase polymerase chain reaction for SFTS virus genome. SFTS should be differentially diagnosed with human granulocytic anaplasmosis, hemorrhagic fever with renal syndrome, spotted fever group rickettsioses, dengue fever, and leptospirosis. Prognostic risk factors of SFTS include older age, high SFTS virus load, CNS manifestations, elevated levels of AST, ALT, LDH, and CK, abnormal values of coagulation factors, disseminated intravascular coagulation, renal failure, elevated levels of inflammatory cytokines, and delay in making diagnosis.

This is a preview of subscription content, log in via an institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  • Aguero-Rosenfeld ME, Donnarumma L, Zentmaier L et al (2002) Seroprevalence of antibodies that react with Anaplasma phagocytophila, the agent of human granulocytic ehrlichiosis, in different populations in Westchester County, New York. J Clin Microbiol 40:2612–2615

    Article  PubMed  PubMed Central  Google Scholar 

  • Azuma T, Suemori K, Murakami Y, Yasukawa M (2015) Severe fever with thrombocytopenia syndrome mimicking intravascular lymphoma. Rinsho Ketsueki 56:491–495. Japanese

    PubMed  Google Scholar 

  • Bakken JS, Aguero-Rosenfeld ME, Tilden RL et al (2001) Serial measurements of hematologic counts during the active phase of human granulocytic ehrlichiosis. Clin Infect Dis 32:862–870

    Article  CAS  PubMed  Google Scholar 

  • Brisse E, Matthys P, Wouters CH (2016) Understanding the spectrum of haemophagocytic lymphohistiocytosis: update on diagnostic challenges and therapeutic options. Br J Haematol 174:175–187

    Article  PubMed  Google Scholar 

  • Chen JP, Cosgriff TM (2000) Hemorrhagic fever virus-induced changes in hemostasis and vascular biology. Blood Coagul Fibrinolysis 11:461–483

    Article  CAS  PubMed  Google Scholar 

  • Chen Y, Jia B, Liu Y, Huang R, Chen J, Wu C (2017) Risk factors associated with fatality of severe fever with thrombocytopenia syndrome: a meta-analysis. Oncotarget 8:89119–89129

    PubMed  PubMed Central  Google Scholar 

  • Choi SJ, Park SW, Bae IG, Kim SH, Ryu SY, Kim HA, Jang HC, Hur J, Jun JB, Jung Y, Chang HH, Kim YK, Yi J, Kim KH, Hwang JH, Kim YS, Jeong HW, Song KH, Park WB, Kim ES, Oh MD, for Korea SFTS Clinical Network (2016) Severe fever with thrombocytopenia syndrome in South Korea, 2013–2015. PLoS Negl Trop Dis 10:e0005264

    Article  PubMed  PubMed Central  Google Scholar 

  • Crum-Cianflone NF (2008) Bacterial, fungal, parasitic, and viral myositis. Clin Microbiol Rev 21:473–494

    Article  PubMed  PubMed Central  Google Scholar 

  • Cui N, Liu R, Lu QB, Wang LY, Qin SL, Yang ZD, Zhuang L, Liu K, Li H, Zhang XA, Hu JG, Wang JY, Liu W, Cao WC (2015) Severe fever with thrombocytopenia syndrome bunyavirus-related human encephalitis. J Infect 70:52–59

    Article  PubMed  Google Scholar 

  • Deng B, Cui W, Wen Y, Zhou Y, Wang W, Liu P (2012a) A case of a male presenting with fever, myalgia, leucopenia, thrombocytopenia and acute kidney injury. J Clin Virol 55:285–288

    Article  PubMed  Google Scholar 

  • Deng B, Zhang S, Geng Y, Zhang Y, Wang Y, Yao W, Wen Y, Cui W, Zhou Y, Gu Q, Wang W, Wang Y, Shao Z, Wang Y, Li C, Wang D, Zhao Y, Liu P (2012b) Cytokine and chemokine levels in patients with severe fever with thrombocytopenia syndrome virus. PLoS One 7:e41365

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Deng B, Zhou B, Zhang S, Zhu Y, Han L, Geng Y, Jin Z, Liu H, Wang D, Zhao Y, Wen Y, Cui W, Zhou Y, Gu Q, Sun C, Lu X, Wang W, Wang Y, Li C, Wang Y, Yao W, Liu P (2013) Clinical features and factors associated with severity and fatality among patients with severe fever with thrombocytopenia syndrome Bunyavirus infection in Northeast China. PLoS One 8:e80802

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ding S, Niu G, Xu X, Li J, Zhang X, Yin H, Zhang N, Jiang X, Wang S, Liang M, Wang X, Yu XJ (2014) Age is a critical risk factor for severe fever with thrombocytopenia syndrome. PLoS One 9:e111736

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Gai ZT, Zhang Y, Liang MF, Jin C, Zhang S, Zhu CB, Li C, Li XY, Zhang QF, Bian PF, Zhang LH, Wang B, Zhou N, Liu JX, Song XG, Xu A, Bi ZQ, Chen SJ, Li DX (2012) Clinical progress and risk factors for death in severe fever with thrombocytopenia syndrome patients. J Infect Dis 206:1095–1102

    Article  CAS  PubMed  Google Scholar 

  • Hiraki T, Yoshimitsu M, Suzuki T, Goto Y, Higashi M, Yokoyama S, Tabuchi T, Futatsuki T, Nakamura K, Hasegawa H, Saijo M, Kakihana Y, Arima N, Yonezawa S (2014) Two autopsy cases of severe fever with thrombocytopenia syndrome (SFTS) in Japan: a pathognomonic histological feature and unique complication of SFTS. Pathol Int 64:569–575

    Article  PubMed  PubMed Central  Google Scholar 

  • Hu C, Guo C, Yang Z, Wang L, Hu J, Qin S, Cui N, Peng W, Liu K, Liu W, Cao W (2015) The severe fever with thrombocytopenia syndrome bunyavirus (SFTSV) antibody in a highly endemic region from 2011 to 2013: a comparative serological study. Am J Trop Med Hyg 92:479–481

    Article  PubMed  PubMed Central  Google Scholar 

  • Ishii E, Ohga S, Imashuku S, Yasukawa M, Tsuda H, Miura I, Yamamoto K, Horiuchi H, Takada K, Ohshima K, Nakamura S, Kinukawa N, Oshimi K, Kawa K (2007) Nationwide survey of hemophagocytic lymphohistiocytosis in Japan. Int J Hematol 86:58–65

    Article  PubMed  Google Scholar 

  • Jia B, Yan X, Chen Y, Wang G, Liu Y, Xu B, Song P, Li Y, Xiong Y, Wu W, Hao Y, Xia J, Zhang Z, Huang R, Wu C (2017) A scoring model for predicting prognosis of patients with severe fever with thrombocytopenia syndrome. PLoS Negl Trop Dis 11:e0005909

    Article  PubMed  PubMed Central  Google Scholar 

  • Jiang H, Du H, Wang LM, Wang PZ, Bai XF (2016) Hemorrhagic fever with renal syndrome: pathogenesis and clinical picture. Front Cell Infect Microbiol 6:1

    CAS  PubMed  PubMed Central  Google Scholar 

  • Jordan MB, Allen CE, Weitzman S, Filipovich AH, McClain KL (2011) How I treat hemophagocytic lymphohistiocytosis. Blood 118:4041–4052

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kaneyuki S, Yoshikawa T, Tani H, Fukushi S, Taniguchi S, Fukuma A, Shimojima M, Kurosu T, Morikawa S, Saijo M (2016) Ulcerative lesions with hemorrhage in a patient with severe fever with thrombocytopenia syndrome observed via upper gastrointestinal endoscopy. Jpn J Infect Dis 69:525–527

    Article  PubMed  Google Scholar 

  • Kato H, Yamagishi T, Shimada T, Matsui T, Shimojima M, Saijo M, Oishi K (2016) SFTS epidemiological research group-Japan. Epidemiological and clinical features of severe fever with thrombocytopenia syndrome in Japan, 2013–2014. PLoS One 11:e0165207

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kawaguchi T, Matsuda M, Takajo I, Kawano A, Kariya Y, Kubo K, Miyauchi S, Umekita K, Nagatomo Y, Yano T, Yano K, Okayama A (2016) Severe fever with thrombocytopenia syndrome with myocardial dysfunction and encephalopathy: a case report. J Infect Chemother 22:633–637

    Article  PubMed  Google Scholar 

  • Kim KH, Yi J, Kim G, Choi SJ, Jun KI, Kim NH, Choe PG, Kim NJ, Lee JK, Oh MD (2013) Severe fever with thrombocytopenia syndrome, South Korea, 2012. Emerg Infect Dis 19:1892–1894

    Article  PubMed  PubMed Central  Google Scholar 

  • Kim KH, Ko MK, Kim N, Kim HH, Yi J (2017a) Seroprevalence of severe fever with thrombocytopenia syndrome in southeastern Korea, 2015. J Korean Med Sci 32:29–32

    Article  CAS  PubMed  Google Scholar 

  • Kim MG, Jung J, Hong SB, Lee SO, Choi SH, Kim YS, Woo JH, Kim SH (2017b) Severe fever with thrombocytopenia syndrome presenting with rhabdomyolysis. Infect Chemother 49:68–71

    Article  PubMed  PubMed Central  Google Scholar 

  • Kitao A, Ieki R, Takatsu H, Tachibana Y, Nagae M, Hino T, Nakaji H, Shimojima M, Saijo M, Okayama M, Kenzaka T (2016) Severe fever with thrombocytopenia syndrome presenting as hemophagocytic syndrome: two case reports. Springerplus 5:361

    Article  PubMed  PubMed Central  Google Scholar 

  • Lee J, Jeong G, Lim JH, Kim H, Park SW, Lee WJ, Jun JB (2016) Severe fever with thrombocytopenia syndrome presenting with hemophagocytic lymphohistiocytosis. Infect Chemother 48:338–341

    Article  PubMed  PubMed Central  Google Scholar 

  • Li P, Tong ZD, Li KF, Tang A, Dai YX, Yan JB (2017) Seroprevalence of severe fever with thrombocytopenia syndrome virus in China: A systematic review and meta-analysis. PLoS One 12:e0175592

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Liu W, Lu QB, Cui N, Li H, Wang LY, Liu K, Yang ZD, Wang BJ, Wang HY, Zhang YY, Zhuang L, Hu CY, Yuan C, Fan XJ, Wang Z, Zhang L, Zhang XA, Walker DH, Cao WC (2013) Case-fatality ratio and effectiveness of ribavirin therapy among hospitalized patients in china who had severe fever with thrombocytopenia syndrome. Clin Infect Dis 57:1292–1299

    Article  CAS  PubMed  Google Scholar 

  • Liu Q, He B, Huang SY, Wei F, Zhu XQ (2014) Severe fever with thrombocytopenia syndrome, an emerging tick-borne zoonosis. Lancet Infect Dis 14:763–772

    Article  CAS  PubMed  Google Scholar 

  • Liu MM, Lei XY, Yu H, Zhang JZ, Yu XJ (2017a) Correlation of cytokine level with the severity of severe fever with thrombocytopenia syndrome. Virol J 14:6

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Liu J, Wang L, Feng Z, Geng D, Sun Y, Yuan G (2017b) Dynamic changes of laboratory parameters and peripheral blood lymphocyte subsets in severe fever with thrombocytopenia syndrome patients. Int J Infect Dis 58:45–51

    Article  CAS  PubMed  Google Scholar 

  • Ma T, Sun JM, Chen LF, Shi XG, Liu K, Gong ZY, Chen J, Zhang R, Ren JP, Jiang JM (2015) A pediatric case of severe fever with thrombocytopenia syndrome in Zhejiang Province, China. J Clin Virol 72:85–87

    Article  CAS  PubMed  Google Scholar 

  • Mahara F (1997) Japanese spotted fever: report of 31 cases and review of the literature. Emerg Infect Dis 3:105–111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kaneko M, Shikata H, Matsukage S, Maruta M, Shinomiya H, Suzuki T, Hasegawa H, Shimojima M, Saijo M (2017) A patient with severe fever with thrombocytopenia syndrome and hemophagocytic lymphohistiocytosis-associated involvement of the central nervous system. J Infect Chemother 24:292–297

    Article  PubMed  Google Scholar 

  • Massung RF, Slater KG (2003) Comparison of PCR assays for detection of the agent of human granulocytic ehrlichiosis, Anaplasma phagocytophilum. J Clin Microbiol 41:717–722

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nakano A, Ogawa H, Nakanishi Y, Fujita H, Mahara F, Shiogama K, Tsutsumi Y, Takeichi T (2017) Hemophagocytic lymphohistiocytosis in a fatal case of severe fever with thrombocytopenia syndrome. Intern Med 56:1597–1602

    Article  PubMed  PubMed Central  Google Scholar 

  • Oh HS, Kim M, Lee JO, Kim H, Kim ES, Park KU, Kim HB, Song KH (2016) Hemophagocytic lymphohistiocytosis associated with SFTS virus infection: A case report with literature review. Medicine (Baltimore) 95:e4476

    Article  Google Scholar 

  • Ozsurekci Y, Arasli M, Karadag Oncel E, Caglayik DY, Kaya A, Icagasioglu FD, Engin A, Korukluoglu G, Elaldi N, Ceyhan M (2013) Can the mild clinical course of crimean-congo hemorrhagic fever in children be explained by cytokine responses? J Med Virol 85:1955–1959

    Article  CAS  PubMed  Google Scholar 

  • Park JG (2015) Severe fever with thrombocytopenia syndrome presenting as acute hepatic failure. Clin Exp Emerg Med 2:137–140

    Article  PubMed  PubMed Central  Google Scholar 

  • Peter JV, Sudarsan TI, Prakash JA, Varghese GM (2015) Severe scrub typhus infection: clinical features, diagnostic challenges and management. World J Crit Care Med 4:244–250

    Article  PubMed  PubMed Central  Google Scholar 

  • Rand JV, Tarasen AJ, Kumar J, Homan SM, Tobin E (2014) Intracytoplasmic granulocytic morulae counts on confirmed cases of ehrlichiosis/anaplasmosis in the Northeast. Am J Clin Pathol 141:683–686

    Article  PubMed  Google Scholar 

  • Shin J, Kwon D, Youn SK, Park JH (2015) Characteristics and factors associated with death among patients hospitalized for severe fever with thrombocytopenia syndrome, South Korea, 2013. Emerg Infect Dis 21:1704–1710

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shin SY, Cho OH, Bae IG (2016) Bone marrow suppression and hemophagocytic histiocytes are common findings in Korean severe fever with thrombocytopenia syndrome patients. Yonsei Med J 57:1286–1289

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Song TY, Yang EM, Kim CJ (2017) A pediatric case of severe fever with thrombocytopenia syndrome in Korea. J Korean Med Sci 32:704–707

    Article  PubMed  PubMed Central  Google Scholar 

  • Sun Y, Jin C, Zhan F, Wang X, Liang M, Zhang Q, Ding S, Guan X, Huo X, Li C, Qu J, Wang Q, Zhang S, Zhang Y, Wang S, Xu A, Bi Z, Li D (2012) Host cytokine storm is associated with disease severity of severe fever with thrombocytopenia syndrome. J Infect Dis 206:1085–1094

    Article  CAS  PubMed  Google Scholar 

  • Sun J, Tang Y, Ling F, Chang Y, Ye X, Shi W, Zhang L, Chen Z, Lin H, Qiu Z, Zhang Y, Zhang R, Mao H, Chen E, Lin J, Jiang J, Xia S, Gong Z (2015) Genetic susceptibility Is one of the determinants for severe fever with thrombocytopenia syndrome virus infection and fatal outcome: an epidemiological investigation. PLoS One 10:e0132968

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Sun J, Gong Z, Ling F, Zhang R, Tong Z, Chang Y, Chen E, Liu Q, Lin J, Chen Z, Jiang J (2016) Factors associated with severe fever with thrombocytopenia syndrome infection and fatal outcome. Sci Rep 6:33175

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Takahashi T, Maeda K, Suzuki T, Ishido A, Shigeoka T, Tominaga T, Kamei T, Honda M, Ninomiya D, Sakai T, Senba T, Kaneyuki S, Sakaguchi S, Satoh A, Hosokawa T, Kawabe Y, Kurihara S, Izumikawa K, Kohno S, Azuma T, Suemori K, Yasukawa M, Mizutani T, Omatsu T, Katayama Y, Miyahara M, Ijuin M, Doi K, Okuda M, Umeki K, Saito T, Fukushima K, Nakajima K, Yoshikawa T, Tani H, Fukushi S, Fukuma A, Ogata M, Shimojima M, Nakajima N, Nagata N, Katano H, Fukumoto H, Sato Y, Hasegawa H, Yamagishi T, Oishi K, Kurane I, Morikawa S, Saijo M (2014) The first identification and retrospective study of Severe Fever with Thrombocytopenia Syndrome in Japan. J Infect Dis 209:816–827

    Article  CAS  PubMed  Google Scholar 

  • Uchida Y, Kanekura T (2017) Two cases of severe fever with thrombocytopenia syndrome virus infection. J Dermatol 45:e106-e107

    Article  PubMed  Google Scholar 

  • Uehara N, Yano T, Ishihara A, Saijou M, Suzuki T (2016) Fatal severe fever with thrombocytopenia syndrome: an autopsy case report. Intern Med 55:831–838

    Article  CAS  PubMed  Google Scholar 

  • Wada T, Iwata Y, Kamikawa Y, Wada T, Yachie A (2017) Peripheral blood plasmacytosis in severe fever with thrombocytopenia syndrome. Jpn J Infect Dis 70:470–471

    Article  PubMed  Google Scholar 

  • Wang LY, Cui N, Lu QB, Wo Y, Wang HY, Liu W, Cao WC (2014) Severe fever with thrombocytopenia syndrome in children: a case report. BMC Infect Dis 14:366

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Weng Y, Chen N, Han Y, Xing Y, Li J (2014) Clinical and laboratory characteristics of severe fever with thrombocytopenia syndrome in Chinese patients. Braz J Infect Dis 18:88–91

    Article  PubMed  Google Scholar 

  • Xiong S, Zhang W, Li M, Xiong Y, Li M, Wang H, Yang D, Peng C, Zheng X (2016) A simple and practical score model for predicting the mortality of severe fever with thrombocytopenia syndrome patients. Medicine (Baltimore) 95:e5708

    Article  Google Scholar 

  • Yoo J, Oh JW, Jang CG, Moon JH, Kim EH, Chang JH, Kim SH, Kang SG (2017) Spontaneous acute subdural hemorrhage in a patient with a tick borne Bunyavirus-Induced severe fever with thrombocytopenia syndrome. Korean J Neurotrauma 13:57–60

    Article  PubMed  PubMed Central  Google Scholar 

  • Yu XJ, Liang MF, Zhang SY, Liu Y, Li JD, Sun YL, Zhang L, Zhang QF, Popov VL, Li C, Qu J, Li Q, Zhang YP, Hai R, Wu W, Wang Q, Zhan FX, Wang XJ, Kan B, Wang SW, Wan KL, Jing HQ, Lu JX, Yin WW, Zhou H, Guan XH, Liu JF, Bi ZQ, Liu GH, Ren J, Wang H, Zhao Z, Song JD, He JR, Wan T, Zhang JS, Fu XP, Sun LN, Dong XP, Feng ZJ, Yang WZ, Hong T, Zhang Y, Walker DH, Wang Y, Li DX (2011) Fever with thrombocytopenia associated with a novel bunyavirus in China. N Engl J Med 364:1523–1532

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zeng P, Ma L, Gao Z, Wang J, Liu J, Huang X, Yang Q, Cao R, Wen X, Zhu L, Ma H, Yang Z, Lee TH, Brambilla D, Yuan M, Glynn S, Ness P, Kleinman S, Busch M, Shan H (2015) International Component of the NHLBI Recipient Epidemiology and Donor Evaluation Study-III (REDS-III). A study of seroprevalence and rates of asymptomatic viremia of severe fever with thrombocytopenia syndrome virus among Chinese blood donors. Transfusion 55:965–971

    Article  CAS  PubMed  Google Scholar 

  • Zhang YZ, He YW, Dai YA, Xiong Y, Zheng H, Zhou DJ, Li J, Sun Q, Luo XL, Cheng YL, Qin XC, Tian JH, Chen XP, Yu B, Jin D, Guo WP, Li W, Wang W, Peng JS, Zhang GB, Zhang S, Chen XM, Wang Y, Li MH, Li Z, Lu S, Ye C, de Jong MD, Xu J (2012) Hemorrhagic fever caused by a novel Bunyavirus in China: pathogenesis and correlates of fatal outcome. Clin Infect Dis 54:527–533

    Article  CAS  PubMed  Google Scholar 

  • Zhang XA, Guo CT, Lu QB, Hu JG, Cui N, Yang ZD, Peng W, Liu R, Hu CY, Qin SL, Wang XJ, Ding SJ, Huang DD, Liu W, Cao WC (2016) The platelet derived growth factor-B polymorphism is associated with risk of severe fever with thrombocytopenia syndrome in Chinese individuals. Oncotarget 7:33340–33349

    PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Masaki Yasukawa .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Yasukawa, M., Azuma, T. (2019). Clinical Aspects of SFTS. In: Saijo, M. (eds) Severe Fever with Thrombocytopenia Syndrome. Springer, Singapore. https://doi.org/10.1007/978-981-13-9562-8_11

Download citation

Publish with us

Policies and ethics