SFTSKentaro Iwata, MD MSc FACP FIDSA

Division of Infectiuos DiseasesKobe University Hospital

Last Updated February 15, 2013

本スライドは教育目的に作られたもので、出自が明示されていれば転用自由です。著作権は主張しません。ただし、患者ケアにおけるアウトカムを保証するものではありませんので、診療時には慎重な活用をお願いします。

内容に関するご意見、お問い合わせは kiwata@med.kobe-u.ac.jpまでお願いします。

FTLS or SFTS• Fever, Thrombocytopenia and Leukopenia Syndrome

• Severe Fever with Thrombocytopenia Syndrome

• First reported in China in 2007

• First thought as Anaplasma or Tsutsugamushi? Later turned out to be viral illness.

• (1) acute onset with fever

• (2) low white blood cell and platelet counts

• (3) high AST/ALT

• (4) positive urine protein

• CFR 12.7%. 95 cases in 2007.

• CFR >30% in 2009

Xu B et al. PLoS Pathog [Internet]. 2011 Nov [cited 2013 Feb 14];7(11). Available from:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3219706/

Yu X-J et al. New England Journal of Medicine. 2011;364(16):1523–32.

Bunyaviridae

•a family of negative-stranded, enveloped RNA viruses.

•Mainly infected through arthropods.

•Hantavirus

•Rift Valley fever virus

•Crimean-Congo hemorrhagic fever virus

• Most phleboviruses (1 of 5 Bunyaviridae) are associated with sandflies

• The nonpathogenic Uukuniemi virus is a tickborne phlebovirus.

• Rift Valley fever is transmitted mainly by aedes species mosquitoes.

• Crimean-Congo hemorrhagic fever virus by tick bite

• Hantavirus by rat bite, feces, urines etc,,,

• 日本語では重症熱性血小板減少症候群

• SFTSV. ブニヤウイルス科フレボウイルス属

国立感染症研究所　http://www.nih.go.jp/niid/ja/sfts/sfts-iasrs/3142-pr3963.html

Geographic Distribution of SFTS in Mainland China.

Yu X et al. N Engl J Med 2011;364:1523-1532.

Xu B et al. PLoS Pathog [Internet]. 2011 Nov [cited 2013 Feb 14];7(11). Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3219706/

Clinical Symptoms of Hospitalized Patients with Laboratory-Confirmed SFTS.

Yu X et al. N Engl J Med 2011;364:1523-1532.

Xu B et al. PLoS Pathog [Internet]. 2011 Nov [cited 2013 Feb 14];7(11). Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3219706/

Laboratory Findings in Patients with SFTS.

Yu X et al. N Engl J Med 2011;364:1523-1532.

国内発生例• 2012 年秋、海外渡航歴のない成人患者• 発熱、嘔吐、下痢（黒色便）• 明らかなダニ咬傷なし• 白血球数（ 400/mm3 ）と血小板数（ 8.9×104/mm3 ） が著明に低下• AST 、 ALT 、 LDH 、 CK 高値• 血液凝固系の異常、フェリチンの著明な上昇• 血尿、 蛋白尿• 胸腹部単純 CT で右腋窩リンパ節腫大• 骨髄穿刺でマクロファージによる血球貪食像を伴う低形成髄の所見• その後に四肢脱力および肉眼的血尿と多量の黒色便を認め、全身状態が不良となり死亡• 血液からウイルスが分離され、 SFTSV と同定• ELISA 、 IF 法による SFTSV に対する抗体検査 陰性

国立感染症研究所　http://www.nih.go.jp/niid/ja/sfts/sfts-iasrs/3142-pr3963.html

Xu B et al. PLoS Pathog [Internet]. 2011 Nov [cited 2013 Feb 14];7(11). Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3219706/

Morphologic Features of SFTS Bunyavirus.

Yu X et al. N Engl J Med 2011;364:1523-1532.

Phylogenetic Analysis of SFTS Bunyavirus and Other Phleboviruses.

Yu X et al. N Engl J Med 2011;364:1523-1532.

DDxs

• Leptospirosis

• Hantavirus infection

• HUS

• TTP

• Anaplasma

• Tsutsugamushi disease

• Hemorrhagic fever syndromes of other types

ダニは、、、• 10 of 186 ticks (5.4%) of the species Haemaphysalis longicornis that

were collected from domestic animals in the areas where the patients lived contained SFTSV RNA.

• Regular hosts of H. longicornis include most mammals, including goats, cattle, sheep, yak, donkeys, pigs, deer, cats, rats, mice, hedgehogs, weasels, brushtail possums, and humans, along with some birds.

• H. longicornis ticks were dominant in regions of endemicity, while Rhipicephalus microplus is more abundant in regions of nonendemicity.

• H. longicornis is widely distributed in the Asia–Pacific region, including China, Korea, Japan, Australia, the Pacific Islands, and New Zealand.

• ライム、アナプラズマなども媒介

Ixodidae マダニ目マダニ科

Amblyomma – 130 species (includes some of Aponomma)•Anomalohimalaya – 3 species•Bothriocroton – 7 species•Cosmiomma – 1 species•Cornupalpatum – 1 species•Compluriscutula – 1 species•Dermacentor – 34 species (includes Anocentor)•Haemaphysalis – 166 species•Hyalomma – 27 species•Ixodes – 243 species•Margaropus – 3 species•Nosomma – 2 species•Rhipicentor – 2 species•Rhipicephalus – 82 species (includes Boophilus)

http://en.wikipedia.org/wiki/Ixodidae#cite_note-list-2

Zhang Y-Z et al. J. Virol. 2012 Mar;86(5):2864–8.

Journal of the New Zealand Medical Association, 29-July-2011, Vol 124 No 1339

Engorged female New Zealand cattle tick, Haemaphysalis longicornis フタトゲチマダニ

Wikipedia より。オウシマダニ（ Rhipicephalus microplus  ）

診断・治療

• 血液などからの SFTSV の分離・同定

• RT-PCR による SFTSV 遺伝子検出

• ペア血清 IgG 抗体価

• 国立感染症研究所ウイルス第一部で検査が可能である

• リバビリン使用の報告があるが、その有効性は確認されていない

• 有効なワクチンなし

国立感染症研究所　http://www.nih.go.jp/niid/ja/sfts/sfts-iasrs/3142-pr3963.html

http://www.yakuji.co.jp/entry30059.html

リバビリン？

•７２歳女性に免疫グロブリン、抗菌薬とともに使用

•元気になって退院

Li. BioScience Trends. 2012 Jan 11;5(6):273–6.

Li. BioScience Trends. 2012 Jan 11;5(6):273–6.

リバビリンとは、、• guanosine analog

• an unusually wide spectrum of antiviral activity in vitro

• against both DNA and RNA viruses

• first described in 1972

• approved by FDA in 1986 for aerosol treatment of children with severe RSV infection, although the efficacy remains controversial (American Academy of Pediatrics, 2006

• Oral ribavirin was approved by the US FDA in 1998 for treatment of chronic HCV infection in combination with interferon.

• 1-β-d-ribofuranosyl-1,2,4-triazole-3-carboxamide

• 日本では経口薬のみ（ HCV 用）

Grayson, M. Lindsay. Kucers' The Use of Antibiotics, 6th Edition. Hodder Arnold, 10/2010. <vbk:9781444120431#outline(252.1)>.

Grayson, M. Lindsay. Kucers' The Use of Antibiotics, 6th Edition. Hodder Arnold, 10/2010. <vbk:9781444120431#outline(252.1)>.

Grayson, M. Lindsay. Kucers' The Use of Antibiotics, 6th Edition. Hodder Arnold, 10/2010. <vbk:9781444120431#outline(252.1)>.

•ヒト−ヒト感染の可能性もあり

•血液との曝露？

•病院内感染も。 ICU医やエンゼルケア後に、、、

Gai Zet al.. Clin Infect Dis. 2012 Jan 15;54(2):249–52.

ヒト−ヒト感染？

Tang X et al. J Infect Dis. 2013 Mar 1;207(5):736–9.

Tang X et al. J Infect Dis. 2013 Mar 1;207(5):736–9.

Gai Zet al.. Clin Infect Dis. 2012 Jan 15;54(2):249–52.

Epidemic curve shows progression of the family cluster and timeline of key events during the index patient’s illness as well as pertinent exposure histories of secondary patients.

aExposure during period of providing bedside care may not have occurred continuously during the exposure period.

Bao C et al. Clin Infect Dis. 2011;53:1208-1214

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