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The Topic of This Month Vol.35 No.2 (No.408)

Severe fever with thrombocytopenia syndrome (SFTS) in Japan, 2013

(IASR 35: 31-32, February 2014)

Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne systemic infectious disease.  It is caused by SFTS virus (SFTSV), a novel virus belonging to Genus Phlebovirus, Family Bunyaviridae (Fig. 1), which was first reported from China in 2011 (see p. 33 of this issue).  Latency is 6-13 days and the main symptoms are fever and gastrointestinal symptoms, such as nausea, vomiting, abdominal pain, diarrhea, and melena.  Hematuria and proteinuria are frequently observed.  Leukopenia and thrombocytopenia are usually seen in peripheral blood, and hemophagocytosis with cellular hypoplasia are also demonstrated in the bone marrow.  Blood biochemistry shows elevation of AST, ALT and LDH.  Neurological symptoms, such as disturbed consciousness, are often associated with poor prognosis.  SFTS has been reported from China since 2011 and from Japan and the Republic of Korea since 2013.

Natural history of SFTSV and transmission to humans: In nature, SFTSV is maintained through vertical transmission from adult ticks to their offspring through transovarial transmission (tick-tick cycle) and also by transmission from infected mammals to ticks and vice versa (tick-mammal cycle).  Two tick species, Haemaphysalis longicornis and Rhipicephalus microplus, frequently found in areas inhabited by humans in China, are considered to be the natural reservoir of SFTSV; 5.0% and 0.6% of these two species, respectively, were found to harbor SFTSV or its genome.  In Japan, the ticks responsible for SFTSV transmission to humans are probably H. longicornis and Amblyomma testudinarium (Fig. 2), because these ticks were found on the patients’ body surface.

The infection route to humans is mainly tick bite; transmission to family members or to medical providers, mediated by blood and other body fluids, have also been reported from China.  No air-borne or droplet-borne infection has been reported so far.

Identification of SFTS patient in Japan and retrospective clinical and epidemiological studies: An adult with no history of travel abroad developed fever, vomiting and bloody diarrhea in autumn of 2012, and died of systemic organ failure.  SFTSV was isolated from the patient’s blood and pathological examinations revealed SFTSV antigens in various affected organs.  This was the first patient diagnosed as having SFTS in Japan (IASR 34: 40-41, 2013).

The Ministry of Health, Labour and Welfare (MHLW) issued a case definition for the surveillance of SFTS on January 30, 2013 (http://www.niid.go.jp/niid/images/iasr/rapid/graph/pt39811.gif) so as to effectively collect information on SFTS patients in Japan.  Retrospective studies using the MHLW’s case definition identified 8 patients with severe SFTS in or before 2012 (including the first clinical case) (IASR 34: 110, 2013).  Subsequently, 3 additional severe or fatal cases before 2013 were also identified, bringing the total number to 11.  Among the 11 patients, 6 died and all the patients were reported from western Japan.  Among 5 patients in whom bone marrow was examined, all exhibited the findings characteristic to the hemophagocytic syndrome, and many of the patients suffered from blood coagulation abnormality and/or systemic organ failure.  SFTSV was isolated from 8 patients.  Phylogenetic analysis revealed that Japanese strains formed an independent cluster from those of the Chinese strains, indicating that Japanese strains are indigenous to Japan and evolved independently from Chinese strains (see p. 35 of this issue).

Japanese SFTS patients reported in 2013: On March 4, 2013, SFTS was designated as a category IV infectious disease, requiring notification to the designated public health center (see http://www.niid.go.jp/niid/images/iasr/35/408/de4081.pdf for notification criteria), and SFTSV as a biosafety level group 3 pathogen (IASR 34: 110-111, 2013) (see p. 34 & 37 of this issue).  Physicians, who have treated a patient diagnosed virologically as SFTS, must notify the information to the designated public health center within 24 hours.

The number of SFTS patients reported in compliance with the Infectious Diseases Control Law under the National Epidemiological Surveillance of Infectious Diseases was 48 until the end of 2013; 40 were developed in 2013 (see p. 38 of this issue), and 8 in or before 2012 (2 cases in 2005; 1 case in 2010; 5 cases in 2012; IASR 34: 110, 2013).  The seasonal peak was in May (Fig. 3).  Patients were reported from 13 prefectures in Kyushu, Shikoku and Chugoku regions (Fig. 4).  Twenty-two cases were males and 26 females. Patients’ ages ranged from 48 to 95 years (median 72 years) (Fig. 5).  Seventeen of 48 had died.

With increased recognition of SFTS, mild SFTS cases were discovered (see p. 39 of this issue; IASR 34: 207-208, 2013).  Tick-bites were not always found on the body surface of the patients.  It is, therefore, advised to conduct laboratory diagnosis if a patient is suspected of having SFTS, even if the clinical pictures, including presence of bites, do not fit perfectly to the previous case definitions (see p. 38 of this issue).

Laboratory diagnosis available in Japan: Virological diagnosis includes detection/isolation of SFTSV from acute phase patients’ blood and other body fluids (throat swab, urine), and/or the demonstration of a significant rise in IgG antibody titers in paired sera between acute and convalescent phases.  Diagnosis using RT-PCR detection of SFTSV genome is available within the network of prefectural and municipal public health institutes (PHIs).  Furthermore, indirect fluorescent antibody test using the SFTSV-infected cells and IgG-ELISA using the SFTSV antigen are also available in the National Institute of Infectious Disease (NIID), Department of Virology I (see p. 40 of this issue).  Methods for the detection of SFTSV genome in ticks inhabiting Japan and antibody detection methods in mammals have been developed and the surveillance of SFTSV genome prevalence in some species of ticks and antibody levels in wild animals are being conducted (IASR 34: 303-304, 2013).

Measures to be taken: An SFTS patient was first reported in January 2013 in Japan.  Subsequent retrospective and prospective surveillance has revealed the existence of SFTS in western Japan.  PHIs and NIID established a laboratory diagnosis system, which should be maintained and developed further.  In 2013, an MHLW-funded 3-year project “Comprehensive research on control of SFTS” (chief investigator T. Kurata) started.  The project includes 1) detailed epidemiological and clinical studies on SFTS to elucidate the clinical and pathological characteristics; 2) development of rapid SFTSV detection kit; 3) basic research for vaccine development; 4) assessment of risk of SFTSV infection and risk communication on SFTS; and 5) elucidation of SFTSV prevalence among ticks inhabiting Japan, geographical distribution of SFTSV-positive ticks, sero-epidemiology of wild animals, and geographical spread of SFTSV in Japan.

Copyright 1998 National Institute of Infectious Diseases, Japan