Severe fever with thrombocytopenia syndrome virus

Author:Myoung-don Oh, MDSection Editor:Martin S Hirsch, MDDeputy Editor:Nicole White, MD
Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Sep 2025.

This topic last updated: May 02, 2025.

INTRODUCTION

はじめに

重症発熱血小板減少症候群（SFTS）は、中国および東南アジア諸国で新興の感染症である[1]。原因体は一般にSFTSウイルス（SFTSV）と呼ばれ、ダニ（すなわち長角ヘマフィサリス）によって媒介されると思われる新規同定のブニアウイルスである。

ウイルス学

SFTSV（ダビー・バンダウイルス：Bandavirus davieense）は、ブニアウイルス目（Bunyavirales）フェヌイウイルス科（Phenuiviridae）バンダウイルス属（Bandavirus）に属する[2]。最も近縁なウイルスは、発熱性疾患や髄膜炎を引き起こすダニ媒介性ヒト病原性フレボウイルスであるバンジャウイルスである [3]。ブニアウイルスは主に球形で、直径80〜120nmのエンベロープを有する粒子である。粒子には大（L）、中（M）、小（S）と指定された3つのゲノムセグメントが存在する。

LセグメントはRNA依存性RNAポリメラーゼを、Mセグメントは糖タンパク質GnおよびGcを、Sセグメントは核タンパク質（N）と非構造タンパク質（NSs）を、アンビセンスコード戦略を用いてコードする[4]。Nタンパク質はゲノムRNAを封入し、この複合体はさらにLタンパク質と結合して活性型転写酵素/複製酵素複合体を形成する。GnおよびGc糖タンパク質はヘテロ二量体を形成し、ウイルス粒子表面のスパイク構造を形作る。これらの糖タンパク質は受容体結合とウイルス侵入を仲介し、中和性体液性免疫応答の標的となる[4]。

C型レクチンDC-SIGNは、SFTSVの細胞への付着および侵入に関与する因子の一つとして同定されている[5]。グルコシルセラミド（グルコース修飾脂質）は、SFTSVの効率的な細胞侵入に必須である[6]。NSsタンパク質はI型インターフェロン拮抗物質として機能し、IPS-1/IRF-3およびNF-κB経路を介した自然免疫応答の活性化を抑制する。SFTSVは、そのコードするNSsを介して、外因性インターフェロン-α誘導性Jak/STATシグナル伝達を阻害する[7]。

系統解析により、SFTSVは6つの遺伝子型に分類可能であることが示されている[8]。SFTSVは地理的分布と一致して中国系統と日本系統に分類され、さらにそれぞれ6つと4つの亜系統に分かれる[9]。少なくとも4つの異なるSFTSV遺伝子型が韓国で同時流行している[10]。

疫学

SFTSは2009年に中国で初めて報告された[11]。その後、日本、韓国、その他東アジア諸国で症例が発生している。公衆衛生当局によるSFTSの監視強化により、感染発生率に関する理解が深まっている[12]。

中国における症例 - 2009年、中国淮陽山山脈地域においてSFTSが新たな疾患として同定された[13-16]。患者血液からSFTSVと命名された新ウイルスが分離され、症例致死率は30％であった。遡及的に、SFTSは2006年にも中国で発生していたが、ヒト顆粒球性アナプラズマ症と誤診されていた。

新たな症例定義と高度な検査技術による監視強化により、SFTSVの流行地域は近隣省に拡大し、SFTSは中国東部農村部における主要な公衆衛生上の懸念事項と位置づけられた[13-19]。2009年以降、SFTS症例は中国中部の河南省、湖北省、山東省、安徽省、浙江省、 遼寧省で確認され、流行地域は27郷鎮から1500郷鎮以上に拡大した[13-15,20,21]。東台県の沿海平野部でも症例が報告されているが、中国国内の症例のほとんどは森林・灌木・農作地に覆われた丘陵地帯や山岳地帯で報告されている。

2009年から2019年にかけて、中国におけるヒトSFTS感染症の年間平均発生率は20倍以上増加し、検査室で確認されたSFTSV症例は合計7000例を超えた[13,14,21-24]。症例は主に5月から8月の間に報告され、この時期は中国におけるダニの活動と農作業のピーク時である。報告によれば、症例は通常、農地や茶畑のある農村地域に住む60歳以上の住民に発生している。健康な中国人におけるSFTSVの血清陽性率は約4％であるとの報告がある。

中国以外の国における症例

●日本 - 2014年には西日本でSFTS症例11例（うち6例が死亡）が報告された[25-28]。2019年8月までに434例（うち66例が死亡）が確認されている。全患者が西日本出身であり 患者年齢の中央値は74歳であった。ほとんどの症例は4月から8月の間に発生し、多くは農民であった。日本の流行地域に住む50歳以上の健康な個人における血清陽性率は0.14％であった。系統解析により、日本のSFTSV分離株は中国の株とは独立した遺伝子型を構成していることが示され、中国の系統群と日本の系統群が時間の経過とともに別々に進化した可能性が示唆された。

●韓国 - 韓国では2013年に初のSFTS症例が報告された[29,30]。2018年12月までに866例（うち174例が死亡）が確認された。ほとんどの症例は5月から10月の間に発生し、国内の農村地域で疾患が観察された。

●その他の国々 - ベトナムでは2017年、原因不明の急性発熱性疾患患者80名の血液検体を遡及的に分析した結果、ポリメラーゼ連鎖反応（PCR）によりSFTSV陽性反応を示した患者2名が同定された[31-34]。ミャンマーでは2018年、ツツガムシ病が疑われた患者152名中5名がPCR検査でSFTSV陽性であった。●台湾では2019年、海外渡航歴のない70歳男性でSFTS症例が確認された。パキスタンでは2016年と2017年の血清有病率調査で、1600人以上の畜産農家の2.5％がSFTSVに対する微量中和抗体を保有していた。タイでは 2018年10月から2021年3月にかけて調査した700人以上の入院患者のうち、3例がSFTSウイルスPCR陽性のSFTSであった[35]。

ダニ媒介と感染伝播

媒介ダニの特定 - SFTSVがヒトや他の動物に感染する主な経路は、アジア長角ダニ（H. longicornis）による咬傷であると考えられている[11,13,15,36-39]。多数のダニ種を対象とした有病率検査では、生ウイルスが分離されたのはH. longicornisのみであった。感染したH. longicornisマダニの研究では、マダニの唾液腺にウイルスが確認されており、このマダニ種がウイルスを媒介する能力をさらに裏付けている。

PCRなどの分子検査では、H. hystricus、H. flava、Amblyomma testudinarium、Ixodes nipponensis、Rhipicephalus microplus、Dermacentor nuttalli、Hyalomma asiaticumなど、他の複数のダニ種からもSFTSウイルスRNAが検出されている[11]。これらの他の種が媒介において果たす役割を評価するには、さらなる研究が必要である。

H. longicornisダニの地理的分布と生活環H. longicornisダニは東南アジア、オーストラリア、ニュージーランド、および西太平洋地域の複数の島嶼国に固有である（図1）[11,40-42]。2017年、米国ニュージャージー州の在来種羊から本マダニが発見され、その後米国東部広域の植生や動物から検出されている（図2）[43]。

H. longicornisが遠隔地へ拡散する経路は不明である [11,44]。地理空間的研究によれば、H. longicornis ダニに感染した渡り鳥がアジアの新地域へのウイルス導入に関与している可能性がある[45]。米国では、このダニ種はペット、馬、家畜の輸入、あるいは人への付着によって導入された可能性が高い。米国農務省は2017年の数年前、輸入検疫中の馬や家畜から初めてこのダニを検出した。

2018年以降、H. longicornisマダニは米国において侵入種に指定されている[44,46]。このダニ種は、新たな地域に導入された後、急速に大規模な個体群を形成するいくつかの特徴を有している。第一に、雌は雄と交尾せずに生存可能な卵を産むことができる。これにより、単一の雌ダニがダニの個体群全体を形成することが可能となる。さらに、このダニは幅広い環境温度に耐えられ、多様な哺乳類や鳥類の宿主から吸血することができる。

成虫の雌ダニは産卵前に動物宿主から吸血する必要がある[11,40,43,47]。米国では、オジロジカや鳥類などの野生動物、家畜や馬、ペットの犬猫、そして人間から本ダニが確認されている。本ダニは攻撃的に咬みつき、動物に大量寄生を引き起こすことがある。

ダニおよび動物におけるSFTSV - SFTSVは培養法およびPCR法により、東アジア全域および西太平洋諸島のH. longicornisダニから検出されている（上記の「媒介ダニの同定」参照）。2024年現在、米国におけるダニからのSFTSV検出例はない。

H. longicornisマダニは、感染宿主からの吸血、あるいは母体伝播によりSFTSVに感染する[38]。感染宿主からの吸血により、マダニ個体群へ感染が導入される。SFTSVを保有する保菌宿主（保菌宿主とは感染率が高く、マダニが好んで吸血する動物種を指す）が存在するかは不明である。感染ダニの研究では、ダニの卵巣や産卵した卵からSFTSウイルスRNAが検出されており、ウイルスがダニの子孫へ母体感染する可能性が示唆されている。

中国と韓国における動物血清調査では、牛、山羊、羊、犬、豚、鶏、ミンク、ハリネズミなど複数の種でSFTSV特異的抗体が確認されている[36,37,48-52]。さらに、猫はSFTSVに対して非常に感受性が高い。猫の血清、眼部スワブ、唾液から高濃度のウイルスRNAが検出されており[53]、SFTSV感染猫の尿からは感染性ウイルスが分離されている[54]。

韓国では渡り鳥が感染ダニを媒介していることが確認されており、渡り鳥が長距離移動する際に感染を拡散させる懸念が生じている[55]。

SFTSVの人への感染経路は？ SFTSVが主にヒトに感染する経路は、マダニ（H. longicornis）の咬傷によるものである。

感染した猫や犬から、その体液への曝露を介したヒトへの直接感染の可能性も報告されている[11,36,37,40,47-51,56-58]。ミンク農場の労働者間でヒト症例の集団発生が確認された[59]。また、屠殺時の血液への曝露による病弱なラクダからヒトへの感染も報告されている[59]。

血液や体液との密接な接触によるヒトからヒトへの感染も報告されている。例えば、家族が患者の介護中に感染したり、救急部門や集中治療室の状況で院内感染が発生したり、針刺し事故による感染が報告されている。さらに、血清から消失した後も精液からSFTSV RNAがPCRで検出されており、性感染の可能性が示唆されている[17,60-66]。

病態形成

SFTSV感染の病態形成における重要な要因としては、高ウイルス量、全身性炎症反応症候群（SIRS）に類似した炎症反応、凝固異常、多臓器不全が考えられる。複数のサイトカイン（ （インターロイキン[IL]-1RA、IL-6、IL-10、顆粒球コロニー刺激因子[G-CSF]、誘導性タンパク質[IP]-10、単球走化性タンパク質[MCP]-1など）の制御不能な上調は疾患重症度と相関し、SIRSが病態形成の重要な因子であることを示唆している[67-69]。SFTSV非構造タンパク質はサイトカイン/ケモカイン遺伝子の過剰誘導を促進する[70,71]。SFTSVはマクロファージに感染し複製可能である[72]。SFTSV感染B細胞は形質芽球への分化を誘導する因子を分泌し、SFTSV-B細胞軸が病態形成に重要な役割を果たす可能性を示唆している[73]。特定の共変異パターンを有するユニークなウイルス系統群（IV）は、他の3つの主要系統群（I系統：16.7％、II系統：13.8％、III系統：11.8％）と比較して高い致死率（32.9％）と関連しており、特定のウイルス系統群とSFTS死亡率の関連性を示唆している[74]。

剖検研究により、リンパ節構造が組織球、免疫芽球、核残骸、好酸球性ゴーストを含む大規模な壊死に置き換わることが示されている。SFTSV核タンパク質は肝臓、脾臓、副腎、骨髄、リンパ節で検出可能である[25,75,76]。リンパ節内のSFTSV感染細胞は、形質芽球と類似した免疫表現型を示すマクロファージおよびクラススイッチB細胞である[77]。

骨髄では好中球貪食細胞が頻繁に観察される [78]。生存患者では、フルデオキシグルコースF18陽電子放射断層撮影により、局所リンパ節および脾臓における代謝亢進が確認された[79]。

C57/BL6マウスおよびα/βインターフェロンノックアウトマウスを用いたSFTS動物モデルでは、ウイルス複製は脾臓および腸間膜リンパ節で最も活発である[80,81] 。リンパ節の組織学的特徴には広範な壊死と組織球増殖が含まれる[82]。SFTSVと血小板は脾臓マクロファージの細胞質内で共局在する。SFTSVはマウス血小板に付着し、その貪食を促進する。ウイルス結合型循環血小板の脾臓クリアランスは、SFTSにおける血小板減少症の病態形成に重要と考えられる[81]。

SFTSにおける血小板の一般的な機能変化には、血小板を介した好中球活性化、I型インターフェロン（IFN）シグナル伝達、およびウイルスライフサイクル調節が含まれる。SFTS患者の血小板は、フェロプトーシスではなく、ピロプトーシス、アポトーシス、ネクロプトーシス、オートファジーによって破壊される[83]。

臨床症状

7〜14日（平均9日）の潜伏期間を経て、SFTSは発熱、倦怠感、頭痛、筋肉痛、関節痛、めまいなどの非特異的前駆症状で始まり、約1週間持続する。悪心、嘔吐、下痢などの胃腸症状も一般的である[1,13-15,30,37,63,84-89]。SFTSVのウイルス量は発熱後7〜10日目にピークに達する[90]。

検査所見の異常としては、白血球減少（＜4,000/mm3）および血小板減少（＜100,000/mm3）、血清中のアラニン/アスパラギン酸アミノトランスフェラーゼ、アルカリホスファターゼ、乳酸脱水素酵素、クレアチンキナーゼの上昇、活性化部分トロンボプラスチン時間の延長が認められる。SFTSVは血清フェリチン値の上昇とも関連している[91] 発症後4〜8日で末梢血に異型のリンパ球が出現することがある[92]。

発症第2週には多臓器不全が進行し、急性腎障害や心筋炎・不整脈などの心血管系病変を伴うことがある[93]。髄膜脳炎も発生し得る[94]。出血傾向は粘膜出血および/または播種性血管内凝固（DIC）の形で観察されることがある。生存患者では、これらの症状は発症後8〜11日で改善し始める。

侵襲性肺アスペルギルス症（IPA）は、SFTSで入院した患者の20〜32％に認められている[95,96] （「侵襲性アスペルギルス症の疫学と臨床症状」の「肺アスペルギルス症」の項を参照）。

SFTSでは二次性好中球貪食性リンパ組織球症（HLH）が関連しており、高フェリチン血症と骨髄における好中球貪食の所見が認められる。活性化リンパ球およびマクロファージの髄膜・脳内浸潤を伴うHLHによる急速な精神状態悪化が報告されている[97]（「血球貪食性リンパ組織球症の臨床的特徴と診断」参照）。

致死率は6〜21％の範囲である[21,22,30,88]。症状発現から死亡までの期間は通常8〜10日である。

予後不良因子には、入院までの遅延期間の長期化[98]、高齢、意識レベルの低下、血清乳酸脱水素酵素（LDH）またはアスパラギン酸アミノトランスフェラーゼ（AST）値の上昇、リンパ球割合の低下、活性化部分トロンボプラスチン時間（aPTT）の延長が含まれる[30,88,99]。初診時の高レベルの細胞遊離DNA、IL-6およびIL-10レベル、不十分な抗体応答は重症化を予測する可能性がある[100-102]。中国の研究では、女性の致死率は男性より低かった（オッズ比0.73、95%信頼区間0.61-0.87）[103]。

診断

発熱、血小板減少、白血球減少を呈し、かつ流行地域（中国中部・東部、西日本、韓国農村部）でのダニ曝露歴がある患者では、SFTSV感染を疑うべきである。

発症後1週間以内に、逆転写ポリメラーゼ連鎖反応（RT-PCR）またはループ媒介等温増幅法による血清中のウイルスRNA検出によりSFTSV感染の検査診断が可能である[104-109]。

発症後2〜3週目には、不活化ウイルス粒子または組換え発現ウイルスタンパク質を抗原として用いた酵素免疫測定法（ELISA）による血清中のウイルス特異的免疫グロブリン（Ig）MおよびIgGの検出により、SFTSV感染の検査室診断が可能である[48,110,111] 。IgMおよびIgGの平均血清転換時間は、症状発現からそれぞれ10日および17日である[112]。

鑑別診断

SFTSの鑑別診断には以下が含まれる：

●デング熱 - デング出血熱の主要な特徴には、発熱、血管透過性の増加、出血症状、および著明な血小板減少（-100,000細胞/mm3）が含まれる 。ウイルスは世界的に広く分布するネッタイシマカによって媒介され、潜伏期間は4〜7日である。診断は血清学的検査によって確定される（「デングウイルス感染症：臨床症状と診断」を参照）。

●ツツガムシ病 - ツツガムシ病はオリエンティア・ツツガムシ（Orientia tsutsugamushi）による感染症で、発熱、頭痛、食欲不振、倦怠感が特徴。患者の一部に瘢痕（瘡痕）や発疹が生じることがある。アジア及びオーストラリア北部では幼虫期（チガー）のダニによって媒介される。潜伏期間は6〜20日。診断は、血清学検査またはポリメラーゼ連鎖反応（PCR）によって確定することができます。精神状態の変化、白血球減少、血小板減少、および正常な C 反応性タンパク質は、スクランブルチフスよりも SFTS を示唆しています [113、114]。（「スクランブルチフス」を参照してください）。「ツツガムシ病」を参照のこと）。

●Candidatus Rickettsia tarasevichiae (CRT) - CRT によるヒト感染は、2012 年に中国北東部で初めて報告され、SFTSV との重複感染も発生する可能性がある [115]。臨床症状には、発熱、倦怠感、筋肉痛、咳、胃腸症状などがあり、ごく一部の患者では痂皮が観察された。検査所見としては、血小板減少、白血球減少、乳酸脱水素酵素、アスパラギン酸アミノトランスフェラーゼ、アラニンアミノトランスフェラーゼの上昇などが認められる。CRT の診断は PCR によって確定できる。

●カヤスヌール森林病（KFD） - KFD は、発熱、頭痛、胃腸症状、出血を特徴とします。ダニや感染動物との接触によって感染します（潜伏期間は 3〜8 日）。インドで風土病として流行しており、中国でも症例が報告されています。診断は、PCR、血液からのウイルス分離、または酵素免疫測定法によって確定されます。

●斑点熱リケッチア - リケッチア感染症は、発熱、頭痛、筋肉痛を特徴とし、しばしば発疹や痂皮を伴う。通常、ダニによって感染し、潜伏期間は 2〜14 日で、地理的に広く分布している。診断は、血清学検査または PCR によって確定できる（「その他の斑点熱群リケッチア感染症」を参照）。

●腎症候群を伴う出血熱（HFRS） - HFRS はハンタウイルス感染によって引き起こされ、発熱、出血、低血圧、腎不全、血小板減少を特徴とします。齧歯動物の尿や糞便がエアロゾル化したものとの接触や吸入によって感染します。感染はアジア、ヨーロッパ、南北アメリカなど、世界中で発生しています。診断は血清学によって確定されます。（「ハンタウイルス感染症における腎臓病変」および「ハンタウイルス感染症の疫学と診断」を参照のこと）

●クリミア・コンゴ出血熱（CCHF） - CCHFは発熱と出血を特徴とする。ダニを介した感染（潜伏期間1〜9日）または感染したヒト・齧歯類との接触（潜伏期間3〜13日）により伝播し、南欧、中東、アフリカ、中国北西部の一部地域に風土病として存在する。診断は逆転写ポリメラーゼ連鎖反応（RT-PCR）または血清学検査により確定される。（「クリミア・コンゴ出血熱」参照） アフリカ、中国北西部の一部地域に流行している。診断は逆転写ポリメラーゼ連鎖反応（RT-PCR）または血清学検査により確定される（「クリミア・コンゴ出血熱」参照）。

●その他の出血熱 - エボラやマールブルグなどのその他の出血熱は、症状だけではSFTSVとの鑑別が困難な場合があるが、地理的要因（いずれもアフリカに流行）により除外できる。（「エボラ病の臨床症状と診断」および「マールブルグウイルス感染症」を参照）

●レプトスピラ症 - レプトスピラ症は発熱、悪寒、筋肉痛、結膜充血、頭痛を特徴とする。咳、吐き気、嘔吐、下痢、腹痛、黄疸などの症状は比較的まれである。動物の尿や汚染された水・土壌への曝露により感染し、世界的に発生するが、特に南アジア・東南アジア・南米で多い。診断は血清学検査により確定される。（「レプトスピラ症：疫学、微生物学、臨床症状、診断」を参照。）

●エールリキア症およびアナプラズマ症 - エールリキア症とアナプラズマ症の臨床症状には、発熱、悪寒、倦怠感、筋肉痛、頭痛が含まれる。検査所見には、白血球減少、血小板減少、血清アミノトランスフェラーゼ値の上昇が見られる。診断は間接蛍光抗体法により確定される。（「ヒトエリオコシスおよびアナプラズマ症」参照）

●ハートランドウイルス感染症 - ハートランドウイルス（ハートランドバンダウイルス）は、非特異的症状・徴候（発熱、食欲不振、頭痛、錯乱、悪心、筋痛および／または関節痛）を伴う可能性の高いダニ媒介性ウイルスである。主に米国中西部および南東部で観察されている。診断は血清学的検査および/またはリアルタイムRT-PCRにより確定可能である（「新興ウイルス」の『ハートランドウイルス感染症』の項を参照）。

●血球貪食性リンパ組織球症（HLH） - HLHは過剰な免疫活性化を特徴とする症候群であり、SFTSを含むウイルス感染症と関連することが多い。一般的な所見には発熱、肝脾腫、発疹、リンパ節腫脹、神経症状、血球減少、高フェリチン血症、肝機能異常が含まれる。診断は別途要約された診断基準により確定される。（「血球貪食性リンパ組織球症の臨床的特徴と診断」を参照。）

●ランヤ・ヘニパウイルス（LayV）感染症 - ランヤ・ヘニパウイルスは、中国の高熱患者から同定された新規人獣共通感染症ウイルスである。一般的な症状および検査異常には、発熱、倦怠感、咳嗽、食欲不振、筋肉痛、白血球減少、血小板減少が含まれる。LayV感染患者35例中6例はSFTSV感染も併発していた[116]。

●新規オルソナイロウイルス感染症（シュエチェンウイルス）- 中国では、マダニ咬傷歴のある発熱患者から、他のマダニ媒介感染症陰性でありながら、暫定的にシュエチェンウイルス（XCV）と命名されたオルソナイロウイルスが同定された [117]。臨床症状は非特異的な発熱性疾患から入院を要する重篤な疾患まで多岐にわたった。白血球減少症と肝機能検査値の上昇が一般的に観察された。感染患者が確認された地域から採取したHaemaphysalis concinnaダニの6％、H. japonicaダニの3.2％からXCVが検出された[117]。

治療

SFTSの治療に有効な抗ウイルス療法は存在せず、管理は支持療法が中心である。重症化や合併症の早期認識が重要である。

SFTS患者の治療にリバビリンが使用された事例は報告されているが、治療効果を裏付ける確固たる証拠はない[98,118]。ピラジン誘導体であるファビピラビルは、in vitroおよびマウスモデルにおいてリバビリンよりも強力な抗ウイルス活性を示す[119,120]。日本のSFTS患者23例を対象としたファビピラビル研究では、国内の他の症例シリーズと比較して死亡率が低かったが、肝酵素上昇を含む有害事象の発生頻度はより高かった [121]。中国で実施された研究者主導の単盲検ランダム化比較試験では、ファビピラビル治療群の9.5％（74例中7例）と対照群の18.3％（71例中13例）に致死的な転帰が認められた（オッズ比0.466、95％信頼区間0.17-1.25）。本試験におけるファビピラビルの投与量はエボラウイルス感染症治療時より低く、重篤な有害事象は認められなかった[122]。70歳以上の患者と比較し、70歳以下の患者においてファビピラビルの有益性がより高い可能性を示すデータもある[123]。ファビピラビルに関する予備データは有望であるが、厳密に管理された試験からのさらなるデータが必要である。

アナプラズマ症およびツツガムシ病が風土病である地域では、診断検査の結果が出るまで、ドキシサイクリンによるこれらの感染症に対する経験的治療が妥当である。SFTS とツツガムシ病またはリケッチア・ジャポニカ（Rickettsia japonica）の重複感染が起こる可能性がある [34、124-127]。（上記の「鑑別診断」を参照のこと。

出血合併症は、国際標準化比/プロトロンビン時間を指針として、新鮮凍結血漿または新鮮全血の輸血により管理すべきである [128]。一部の報告では、血漿交換が有益である可能性を示唆している [129-131]。限定的なデータによると、ステロイド治療は予後を改善しないようであり、侵襲性アスペルギルス症などの二次感染を含む合併症を増加させる可能性がある [132-134]。

侵襲性肺アスペルギルス症の早期診断と治療が重要である［96,135,136］（「侵襲性アスペルギルス症の診断」および「侵襲性アスペルギルス症の治療と予防」を参照）。


&note{:96 Xu Y, Shao M, Liu N, et al. Invasive pulmonary aspergillosis is a frequent complication in patients with severe fever with thrombocytopenia syndrome: A retrospective study. Int J Infect Dis 2021; 105:646.};&note{:135 Iwao K, Kawaguchi T, 木村真、他．侵襲性肺アスペルギルス症を伴う重症発熱血小板減少症候群：剖検例．Viruses 2021; 13.};&note{:136 左勇、王輝、黄建、他．重症発熱血小板減少症候群患者における肺感染症：多施設観察研究．J Med Virol 2023; 95:e28712.};

予防

SFTS予防のためのワクチンは存在しない。感染リスクのある地域では、ダニ咬傷を避ける対策が必要である（「節足動物咬傷の予防：忌避剤およびその他の対策」参照）。

SFTSが疑われる患者のケア時には標準予防策を実施すべきである。患者退室後は病室を消毒すべきである[137]（「感染予防：感染伝播防止のための予防策」参照）。

流行地域では、特に病状の重い猫の体液との直接接触を避けるべきである[53,56]。毛皮を剥ぐ作業を行う農場労働者は標準予防策を遵守すべきである[52,138]。

要約と推奨事項

●概要 - 重症発熱血小板減少症候群（SFTS）は、発熱・血小板減少・白血球減少症候群とも呼ばれる新興のダニ媒介感染症である。病原体はブニヤウイルスであり、一般にSFTSウイルス（SFTSV）と称される。（上記「序論」参照）

●疫学（上記「疫学」参照）

-ヒト症例 - 2009年以降、SFTSのヒト症例は中国、日本、韓国、その他東アジア諸国で報告されている（上記「中国における症例」および「中国以外の国における症例」参照）。

-ヒトへの感染経路 - SFTSVがヒトに感染する主な経路は、アジア長角ダニ（Haemaphysalis longicornis）の咬傷によるものである。感染した猫や犬からヒトへの直接感染の可能性が報告されているほか、血液や体液への密接な接触を介したヒトからヒトへの感染も報告されている（上記「SFTSVのヒトへの感染」参照）。

-ダニ媒介 - アジア長角ダニは東南アジア全域、西太平洋諸島、および米国に生息する。SFTSVは東アジア全域のアジア長角ダニから検出されている。2021年現在、米国におけるダニからのウイルス検出例はない。（上記「H. longicornisマダニの地理的分布と生活環」および「マダニ・動物におけるSFTSV」参照）

●臨床症状（上記「臨床症状」参照）

-臨床経過 - 7〜14日の潜伏期間後、発熱・頭痛・筋肉痛・関節痛が現れ、時に嘔吐や下痢を伴う。発症2週目には、粘膜出血、出血性発疹、髄膜脳炎を伴う／伴わない意識障害、多臓器不全を呈する症例もある。

-検査所見 - 検査所見には白血球減少症および血小板減少症が含まれる。一部の症例では肝酵素、乳酸脱水素酵素、クレアチンキナーゼの上昇、ならびに播種性血管内凝固症候群が認められる。

-合併症 - SFTS入院患者の20〜32％に侵襲性肺アスペルギルス症が認められる。二次性血球貪食性リンパ組織球症（HLH）の報告もある。

●診断 - 流行地域でのダニ曝露歴を伴う発熱、血小板減少、白血球減少を呈する患者ではSFTSV感染を疑う。検査診断は血清ポリメラーゼ連鎖反応（PCR；発症第1週）または抗体検出（発症第2〜3週）に基づく（上記「診断」参照）。

●治療と予防 - 治療は支持療法が中心である。SFTSVに対する抗ウイルス療法は存在せず、予防ワクチンも開発されていない。（上記「治療」参照）

●死亡率 - 症例致死率は6〜21％の範囲である。（上記「臨床症状」参照）








































Introduction

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious zoonosis in China and other countries in southeast Asia [1].The causative agent is commonly designated SFTS virus (SFTSV), a newly identified bunyavirus that appears to be carried by ticks (ie, Haemaphysalis longicornis).

VIROLOGY

SFTSV, or Dabie bandavirus (Bandavirus davieense), is a member of the genus Bandavirus in the family Phenuiviridae and in the order Bunyavirales [2]. The closest relative is Bhanja virus, a tickborne human pathogenic phlebovirus that causes febrile illness and meningitis [3]. Bunyaviruses are largely spherical, enveloped particles with a diameter of 80 to 120 nm. Particles carry three genomic segments designated large (L), medium (M), and small (S).

The L segment encodes the RNA-dependent RNA polymerase, the M segment the glycoproteins Gn and Gc, and the S segment the nucleoprotein (N) and a nonstructural protein (NSs) using an ambisense coding strategy [4]. The N protein encapsulates the genomic RNA; this complex is further associated with the L protein and forms the active transcriptase/replicase complex. The Gn and Gc glycoproteins form a heterodimer and shape the spikes on the surface of the virion. The glycoproteins mediate receptor binding and virus entry and are the target for neutralizing humoral immune responses [4].

The C-type lectin, DC-SIGN, has been identified as one of the factors for SFTSV attachment and entry into cells [5]. Glucosylceramide, the glucose-modified lipid, is required for efficient SFTSV entry into cells [6]. The NSs protein serves as a type-I interferon antagonist that suppresses activation of innate immune responses via the IPS-1/IRF-3 and NF-kappaB pathways. SFTSV inhibits exogenous interferon-alpha-induced Jak/STAT signaling through its encoded NSs [7].

Phylogenetic analysis shows SFTSV can be clustered into six genotypes [8]. SFTSV has been classified into Chinese and Japanese lineages, consistent with the geographical distribution; the two lineages are further divided into six and four sublineages, respectively [9]. At least four different genotypes of SFTSV are cocirculating in South Korea [10].

EPIDEMIOLOGY

SFTS was first reported in China in 2009 [11]. Since then, cases have emerged from Japan, South Korea, and other countries in eastern Asia. Increased surveillance for SFTS by public health authorities has improved understanding of the incidence of infection [12].

Cases in China - In 2009, SFTS was identified as a new disease in the Huaiyangshan mountain range in China [13-16]. A new virus, designated SFTSV, was isolated from patient blood; the case-fatality rate was 30 percent. In retrospect, SFTS occurred in China as early as 2006, but the cases were misdiagnosed as human granulocytic anaplasmosis.

Enhanced surveillance using a new case definition and advanced laboratory testing expanded the endemicity zone of SFTSV to neighboring provinces and designated SFTS as a major public health concern in rural eastern China [13-19]. Since 2009, SFTS cases have been identified in central China in the Henan, Hubei, Shandong, Anhui, Zhejiang, Jiangsu, and Liaoning provinces, and endemic areas have expanded from 27 to over 1500 townships [13-15,20,21]. The coastal plains of Dongtai County also have reported cases, but most cases in China are reported in hilly or mountainous areas covered by woods, shrubs, and crops.

Between 2009 and 2019, the average annual incidence of human SFTS infections in China increased over 20-fold with over 7000 laboratory-confirmed SFTSV cases in total [13,14,21-24]. Cases are reported predominantly between the months of May and August, the peak time of tick and farming activities in China. In reports, cases typically occur in residents -60 years of age in rural areas with crop fields and tea farms. Among healthy Chinese individuals, one report noted SFTSV seroprevalence of approximately 4 percent.

Cases in countries other than China

●Japan - In 2014, 11 cases of SFTS (including 6 fatalities) were reported in western Japan [25-28]. By August of 2019, 434 cases (including 66 fatalities) had been identified. All patients were from western Japan, and the median age of the patients was 74 years. Most cases occurred between April and August, and many were farmers. Among healthy individuals >50 years of age living in an endemic area in Japan, seroprevalence was 0.14 percent. Phylogenetic analyses indicated that the Japanese SFTSV isolates comprised a genotype independent from those in China, suggesting that the Chinese clade and the Japanese clade may have evolved separately over time.

●South Korea - In South Korea, the first case of SFTS was reported in 2013 [29,30]. By December 2018, 866 patients (including 174 fatal cases) had been confirmed. Most cases occurred between May and October, and the disease was observed in rural areas throughout the country.

●Other countries - In Vietnam in 2017, a retrospective analysis of blood samples from 80 patients with unexplained acute febrile illness identified two patients who were positive for SFTSV by polymerase chain reaction (PCR) [31-34]. In Myanmar in 2018, 5 of 152 patients suspected of having scrub typhus actually had SFTSV by PCR. In Taiwan in 2019, a case of SFTS was confirmed in a 70-year-old man who had not traveled outside the country. A seroprevalence study in Pakistan in 2016 and 2017 found that 2.5 percent of more than 1600 livestock farmers had micro-neutralizing antibodies against SFTSV. In Thailand, three of over 700 hospitalized patients studied from October 2018 to March 2021 had SFTS with a positive SFTS virus PCR [35].

Tick vector and transmission of infection

Identification of tick vector - The primary mode of spread of SFTSV to humans and other animals appears to be via tick bite from the Asian longhorned tick, H. longicornis [11,13,15,36-39]. In prevalence testing of numerous tick species, live virus has only been isolated from H. longicornis ticks. Studies of infected H. longicornis ticks reveal virus in the ticks' salivary glands, further supporting the capacity of this tick species to transmit the virus.

Molecular tests such as PCR have detected SFTS viral RNA in multiple other tick species, including H. hystricis, H. flava, Amblyomma testudinarium, Ixodes nipponensis, Rhipicephalus microplus, Dermacentor nuttalli, and Hyalomma asiaticum [11]. Further studies are needed to assess the role of these other species in transmission.

Geographic distribution and lifecycle of H. longicornis ticks - H. longicornis ticks are endemic in southeast Asia, Australia, New Zealand, and several island nations of the western Pacific Region (figure 1) [11,40-42]. In 2017 in the United States, the tick was found on a native sheep in New Jersey; since then it has been detected in vegetation and on animals in a wide area of the eastern United States (figure 2) [43].

It is unclear how H. longicornis ticks spread to distant locales [11,44]. Geospatial studies suggest that migratory birds infested with H. longicornis ticks may be responsible for introducing the virus into new regions of Asia [45]. In the United States, the tick species was more likely introduced via importation of domestic pets, horses, or livestock, or on people. The United States Department of Agriculture first detected the ticks on imported quarantined horses and livestock several years before 2017.

Since 2018, H. longicornis ticks have been designated an invasive species in the United States [44,46]. The tick species has several features that allow it to rapidly establish large populations following introduction to a new location. First, females can lay viable eggs without mating with males; this allows a single female tick to create an entire population of ticks. Additionally, the tick can tolerate a wide range of environmental temperatures and can feed on a wide range of mammalian and avian hosts.

Adult female ticks must feed on animal hosts before they can lay eggs [11,40,43,47]. In the United States, the tick has been found on wildlife including white-tailed deer and birds, domestic livestock and horses, companion dogs and cats, and humans. The tick is an aggressive biter and can cause massive infestations on animals.

SFTSV in ticks and animals - The SFTSV has been found by culture and by PCR in H. longicornis ticks throughout east Asia and the western Pacific islands (see 'Identification of tick vector' above). As of 2024, SFTSV has not been detected in ticks in the United States.

H. longicornis ticks become infected with SFTSV by feeding on infected hosts or possibly by maternal transmission [38]. Feeding on infected hosts introduces the infection into the tick population. It is unclear if there is a reservoir host that harbors SFTSV (reservoir hosts are animal species that have a high prevalence of infection and are typically favored meal sources for ticks). Maternal transmission of the virus to tick offspring is suggested by studies of infected ticks that show SFTS viral RNA in the ticks' ovaries and laid eggs.

Animal serosurveys in China and South Korea have demonstrated SFTSV-specific antibodies in multiple species such as cattle, goats, sheep, dogs, pigs, chickens, minks, and hedgehogs [36,37,48-52]. In addition, cats are highly susceptible to SFTSV. High levels of viral RNA have been detected in cats' serum, eye swabs, and saliva [53], and infectious virus has been isolated from urine of SFTSV-infected cats [54].

Migratory birds in South Korea have been found to carry infected ticks, raising concern that these birds could disperse the infection over long distances as they migrate [55].

Transmission of SFTSV to humans - The primary mode of SFTSV transmission to humans is via the bite of the H. longicornis tick.

Possible direct transmission from infected cats and dogs to humans via exposure to the animals' bodily fluids has been reported [11,36,37,40,47-51,56-58]. A cluster of human cases occurred among workers at a mink farm [59]. Transmission from sick camel to humans due to exposure to blood during slaughtering has also been reported [59].

Human-to-human transmission via close contact with blood and body secretions has also been reported. For example, family members may be infected during patient care, nosocomial transmission may occur at emergency department and intensive care unit settings, and transmission via needle-stick injury has been reported. In addition, SFTSV RNA has been detected by PCR in semen after disappearance from serum, raising the possibility of sexual transmission [17,60-66].

PATHOGENESIS

Important factors in the pathogenesis of SFTSV infections likely include high viral load, inflammatory responses similar to systemic inflammatory response syndrome (SIRS), coagulation abnormalities, and multiorgan dysfunction. Uncontrolled upregulation of several cytokines (including interleukin [IL]-1RA, IL-6, IL-10, granulocyte colony-stimulating factor [G-CSF], induced protein [IP]-10, and monocyte chemoattractant protein [MCP]-1) appears to correlate with disease severity, suggesting that SIRS is a significant factor in pathogenesis [67-69]. SFTSV nonstructural protein promotes the hyperinduction of cytokine/chemokine genes [70,71]. SFTSV can infect and replicate in macrophages [72]. SFTSV-infected B cells secrete factors that induce B-cell differentiation into plasmablasts, suggesting that the SFTSV-B cell axis may play an important role in pathogenesis [73]. A unique virus clade (IV) with a specific co-mutation pattern has been associated with a higher case fatality rate (32.9 percent), compared with other three common clades (I, 16.7 percent; II, 13.8 percent; and III, 11.8 percent), suggesting an association between specific viral clades and SFTS mortality [74].

Autopsy studies have demonstrated that lymph node architecture is replaced with massive necrosis containing histiocytes, immunoblasts, nuclear debris, and eosinophilic ghosts. SFTSV nuclear protein can be detected in the liver, spleen, adrenal, bone marrow, and lymph nodes [25,75,76]. SFTSV-infected cells in lymph nodes are macrophages and class-switched B cells with a similar immunophenotype to that of plasmablasts [77].

Hemophagocytes are commonly observed in the bone marrow [78]. In a surviving patient, fludeoxyglucose F 18 positron emission tomography imaging demonstrated hypermetabolism in regional lymph nodes and the spleen [79].

In animal models of SFTS using C57/BL6 mice and alpha/beta interferon knockout mice, viral replication is most active in the spleen and mesenteric lymph nodes [80,81]. The characteristic histologic findings of the lymph nodes include extensive necrosis and histiocytic proliferation [82]. SFTSV and platelets are colocalized in cytoplasm of macrophages in the spleen. SFTSV adheres to mouse platelets and facilitates their phagocytosis. Splenic clearance of virus-bound, circulating platelets may be important in the pathogenesis of thrombocytopenia in SFTS [81].

Common functional changes of platelets in SFTS include platelet-mediated neutrophil activation, type I interferon (IFN) signaling, and viral life cycle regulation. Platelets in patients with SFTS are destroyed by pyroptosis, apoptosis, necroptosis, and autophagy but not by ferroptosis [83].

CLINICAL MANIFESTATIONS

Following an incubation period of 7 to 14 days (average 9 days), SFTS begins with a nonspecific prodrome including fever, malaise, headache, myalgia, arthralgia, and dizziness, which persists for approximately a week. Gastrointestinal manifestations such as nausea, vomiting, and diarrhea are also common [1,13-15,30,37,63,84-89]. SFTSV viral loads peak on days 7 to 10 after fever onset [90].

Laboratory abnormalities may include leukopenia (<4,000/mm3) and thrombocytopenia (<100,000/mm3); elevated serum levels of alanine/aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase, and creatine kinase; and prolongation of activated partial thromboplastin time. SFTSV is also associated with elevated serum ferritin levels [91]. Atypical lymphocytes may appear in the peripheral blood four to eight days after onset of disease [92].

During the second week of illness, multiorgan dysfunction may develop, including acute kidney injury and cardiac involvement (myocarditis, arrhythmia) [93]. Meningoencephalitis may occur [94]. Bleeding tendency may be observed in the form of mucosal hemorrhage and/or disseminated intravascular coagulation. In surviving patients, these manifestations begin to resolve after 8 to 11 days of illness.

Invasive pulmonary aspergillosis (IPA) has been observed in 20 to 32 percent of patients hospitalized with SFTS [95,96]. (See "Epidemiology and clinical manifestations of invasive aspergillosis", section on 'Pulmonary aspergillosis'.)

Secondary hemophagocytic lymphohistiocytosis (HLH) has been associated with SFTS, with hyperferritinemia and evidence of hemophagocytosis in the bone marrow. Rapidly deteriorating mental status due to HLH with infiltration of activated lymphocytes and macrophages into the meninges and brain has been described [97]. (See "Clinical features and diagnosis of hemophagocytic lymphohistiocytosis".)

Case-fatality rates range from 6 to 21 percent [21,22,30,88]. The time from symptom onset to death is typically 8 to 10 days.

Poor prognostic factors include longer delay in admission [98], older age, decreased level of consciousness, elevated serum levels of lactate dehydrogenase or aspartate aminotransferase, low lymphocyte percentage, and prolonged activated partial thromboplastin times [30,88,99]. A high level of cell-free DNA at initial presentation, IL-6 and IL-10 levels, and inadequate antibody responses may predict severe illness [100-102]. In a study from China, females had a lower-case fatality rate than males (OR 0.73, 95% CI 0.61-0.87) [103].

DIAGNOSIS

The diagnosis of SFTSV infection should be suspected in patients with fever, thrombocytopenia, and leukopenia together with a history of tick exposure in an endemic area (central and eastern China, western Japan, and rural areas of South Korea).

During the first week of illness, a laboratory diagnosis of SFTSV infection may be established by detection of viral RNA in serum via reverse-transcriptase polymerase chain reaction (RT-PCR) or loop-mediated isothermal amplification [104-109].

During the second and third weeks of illness, a laboratory diagnosis of SFTSV infection may be established by detection of virus-specific immunoglobulin (Ig)M and IgG in serum via enzyme-linked immunosorbent assay using inactivated virus particles or recombinant expressed viral proteins as antigens [48,110,111]. The average time of seroconversion for IgM and IgG is 10 and 17 days, respectively, from symptom onset [112].

DIFFERENTIAL DIAGNOSIS

The differential diagnosis of SFTS includes:

●Dengue fever - The cardinal features of dengue hemorrhagic fever include fever, increased vascular permeability, hemorrhagic manifestations, and marked thrombocytopenia (-100,000 cells/mm3). The virus is transmitted by Aedes aegypti mosquitoes, which have broad global distribution; the incubation period is four to seven days. The diagnosis is established via serologic testing. (See "Dengue virus infection: Clinical manifestations and diagnosis".)

●Scrub typhus - Scrub typhus infection is caused by Orientia tsutsugamushi and characterized by fever, headache, anorexia, and malaise; an eschar or rash may develop in a subset of patients. It is transmitted by larval mites (chiggers) in Asia and northern Australia. The incubation period is 6 to 20 days. The diagnosis may be established via serology or polymerase chain reaction (PCR). Altered mental status, leukopenia, thrombocytopenia, and normal C-reactive protein favor SFTS rather than scrub typhus [113,114]. (See "Scrub typhus".)

●Candidatus Rickettsia tarasevichiae (CRT) - Human infection with CRT was initially described in northeastern China in 2012, and coinfection with SFTSV may occur [115]. Clinical manifestations include fever, malaise, myalgia, cough, and gastrointestinal symptoms; eschar was observed in a minority of patients. Laboratory manifestations include thrombocytopenia, leukopenia, and elevated levels of lactate dehydrogenase, aspartate aminotransferase, and alanine aminotransferase. The diagnosis of CRT may be established via PCR.

●Kyasanur forest disease (KFD) - KFD is characterized by fever, headache, gastrointestinal symptoms, and bleeding. It is transmitted by ticks or contact with infected animals (incubation period of three to eight days). Infection is endemic in India; cases have been reported in China. The diagnosis is established via PCR, virus isolation from blood, or enzyme-linked immunosorbent serologic assay.

●Spotted fever Rickettsia - Rickettsial infections are characterized by fever, headache, and myalgia, often in association with a rash and/or eschar. They are usually transmitted by ticks with an incubation period of 2 to 14 days and span a broad geographic distribution. The diagnosis may be established via serology or PCR. (See "Other spotted fever group rickettsial infections".)

●Hemorrhagic fever with renal syndrome (HFRS) - HFRS is caused by hantavirus infection; it is characterized by fever, hemorrhage, hypotension, renal failure, and thrombocytopenia. It is transmitted by contact with or inhalation of aerosolized rodent urine or feces. Infection occurs worldwide, including Asia, Europe, and the Americas. The diagnosis is established via serology. (See "Kidney involvement in hantavirus infections" and "Epidemiology and diagnosis of hantavirus infections".)

●Crimean-Congo hemorrhagic fever (CCHF) - CCHF is characterized by fever and hemorrhage. It is transmitted by ticks (incubation period of 1 to 9 days) or contact with infected humans or rodents (incubation period of 3 to 13 days) and is endemic in parts of southern Europe, the Middle East, Africa, and northwestern China. The diagnosis is established via reverse-transcriptase polymerase chain reaction (RT-PCR) or serology. (See "Crimean-Congo hemorrhagic fever".)

●Other hemorrhagic fevers - Other hemorrhagic fevers, such as Ebola and Marburg, may be difficult to distinguish from SFTSV based on symptoms but may be excluded by geography (both are endemic to Africa). (See "Clinical manifestations and diagnosis of Ebola disease" and "Marburg virus disease".)

●Leptospirosis - Leptospirosis is characterized by fever, rigors, myalgia, conjunctival suffusion, and headache. Less common symptoms and signs include cough, nausea, vomiting, diarrhea, abdominal pain, and jaundice. It is transmitted via exposure to animal urine or contaminated water or soil and occurs worldwide, particularly south and Southeast Asia and South America. The diagnosis is established via serology. (See "Leptospirosis: Epidemiology, microbiology, clinical manifestations, and diagnosis".)

●Ehrlichiosis and anaplasmosis - Clinical manifestations of ehrlichiosis and anaplasmosis include fever, chills, malaise, myalgia, and headache; laboratory manifestations include leukopenia, thrombocytopenia, and elevated serum aminotransferase levels. The diagnosis is established via indirect fluorescent antibody test. (See "Human ehrlichiosis and anaplasmosis".)

●Heartland virus disease - Heartland virus, or Heartland bandavirus, is a likely tickborne virus associated with nonspecific symptoms and signs (fever, anorexia, headache, confusion, nausea, and myalgias and/or arthralgias); it has been observed primarily in the midwestern and southeastern United States. The diagnosis may be established via serologic studies and/or real-time RT-PCR. (See "Emerging viruses", section on 'Heartland virus disease'.)

●Hemophagocytic lymphohistiocytosis (HLH) - HLH is syndrome of excessive immune activation; it is often associated with viral infections, including SFTS. Common findings include fever, hepatosplenomegaly, rash, lymphadenopathy, neurologic symptoms, cytopenias, high serum ferritin, and liver function abnormalities. The diagnosis is established by diagnostic criteria as summarized separately. (See "Clinical features and diagnosis of hemophagocytic lymphohistiocytosis".)

●Langya henipavirus (LayV) infection - Langya henipavirus is a novel zoonotic virus identified in febrile patients in China. Common symptoms and laboratory abnormalities include fever, fatigue, cough, anorexia, myalgia, leukopenia, and thrombocytopenia. Six of the 35 patients with LayV infection also had SFTSV infection [116].

●A novel orthonairovirus infection (Xue-Cheng virus) - In China, an orthonairovirus provisionally named Xue-Cheng virus (XCV) has been identified in febrile patients with recent tick bites who tested negative for other tickborne infections [117]. Clinical presentations ranged from nonspecific febrile illness to severe illness requiring hospitalization. Leukopenia and elevated liver function tests were commonly observed. XCV was detected in 6 percent of Haemaphysalis concinna ticks and 3.2 percent of H. japonica ticks from the region where infected patients had been identified [117].

TREATMENT

There is no antiviral therapy available for treatment of SFTS; management consists of supportive care. Early recognition of severe disease and complication is important.

Use of ribavirin for treatment of patients with SFTS has been described, but there is no convincing evidence for a therapeutic effect [98,118]. Favipiravir, a pyrazine derivative, has stronger antiviral activity than that of ribavirin in vitro and in a mouse model [119,120]. A study of favipiravir in 23 SFTS patients in Japan found lower mortality rates compared with other case series of SFTS patients in Japan, but adverse events, including elevated hepatic enzymes, were more frequent [121]. In an investigator-initiated, single-blind, randomized controlled trial in China, fatal outcomes occurred in 9.5 percent (7 of 74) of favipiravir-treated patients and 18.3 percent (13 of 71) of controls (OR 0.466, 95% CI 0.17-1.25). The dose of favipiravir in the trial was lower than that used for treating Ebola virus disease, and severe adverse events were not observed [122]. Some data suggest that favipiravir may more beneficial for patients -70 years of age compared with patients over 70 [123]. Although preliminary data with favipiravir are promising, more data from carefully controlled trials are necessary.

In areas where anaplasmosis and scrub typhus are endemic, empiric treatment with doxycycline for these infections may be reasonable until diagnostic test results are available. Coinfection of SFTS and scrub typhus or Rickettsia japonica may occur [34,124-127]. (See 'Differential diagnosis' above.)

Bleeding complications should be managed via transfusion of fresh frozen plasma or fresh whole blood, guided by international normalized ratio/prothrombin time [128]. Some reports suggest that plasma exchange may be beneficial [129-131]; controlled clinical trials are needed. Based on limited data, steroid treatment does not appear to improve prognosis and may increase complications, including secondary infections like invasive aspergillosis [132-134].

Early diagnosis and treatment of invasive pulmonary aspergillosis are important [96,135,136]. (See "Diagnosis of invasive aspergillosis" and "Treatment and prevention of invasive aspergillosis".)


&note{:96 Xu Y, Shao M, Liu N, et al. Invasive pulmonary aspergillosis is a frequent complication in patients with severe fever with thrombocytopenia syndrome: A retrospective study. Int J Infect Dis 2021; 105:646.};&note{:135 Iwao K, Kawaguchi T, Kimura M, et al. Severe Fever with Thrombocytopenia Syndrome Accompanied by Invasive Pulmonary Aspergillosis: An Autopsy Case. Viruses 2021; 13.};&note{:136 Zuo Y, Wang H, Huang J, et al. Pulmonary infection in patients with severe fever with thrombocytopenia syndrome: A multicentre observational study. J Med Virol 2023; 95:e28712.};

PREVENTION

There is no vaccine available for prevention of SFTS. Individuals in areas with risk for transmission should take measures to avoid tick bites. (See "Prevention of arthropod bites: Repellents and other measures".)

Standard precautions should be implemented while taking care of patients with suspected SFTS. Patient rooms should be disinfected after discharge [137]. (See "Infection prevention: Precautions for preventing transmission of infection".)

In endemic areas, direct contact with bodily fluids of cats, particularly those that are sick, should be avoided [53,56]. Farm workers should use standard precaution while skinning furred animals [52,138].

SUMMARY AND RECOMMENDATIONS

●Overview - Severe fever with thrombocytopenia syndrome (SFTS), also known as fever, thrombocytopenia, and leukopenia syndrome, is an emerging tickborne infection. The causative agent is a bunyavirus, commonly designated SFTS virus (SFTSV). (See 'Introduction' above.)

●Epidemiology (see 'Epidemiology' above)

-Human cases - Since 2009, human cases of SFTS have been reported in China, Japan, South Korea, and other countries in eastern Asia. (See 'Cases in China' above and 'Cases in countries other than China' above.)

-Transmission to humans - The primary mode of spread of SFTSV to humans is via a bite from the Asian longhorned tick, Haemaphysalis longicornis. Possible direct transmission from infected cats and dogs to humans has been reported, as has human-to-human spread via close contact to blood and body secretions. (See 'Transmission of SFTSV to humans' above.)

-Tick vector - The H. longicornis tick is found throughout southeast Asia and the islands of the western Pacific, as well as in the United States. SFTSV has been detected in H. longicornis ticks throughout eastern Asia. As of 2021, the virus has not been detected in ticks in the United States. (See 'Geographic distribution and lifecycle of H. longicornis ticks' above and 'SFTSV in ticks and animals' above.)

●Clinical manifestations (see 'Clinical manifestations' above)

-Clinical presentation - Following an incubation period of 7 to 14 days, patients develop fever, headache, myalgia, and arthralgia, sometimes accompanied by vomiting and diarrhea. During the second week of illness, some individuals develop mucosal hemorrhage, hemorrhagic rash, altered mental status with or without meningoencephalitis, and multiorgan failure.

-Laboratory findings - Laboratory findings include leukopenia and thrombocytopenia. Some cases have elevated liver enzymes, lactate dehydrogenase, and creatine kinase, as well as disseminated intravascular coagulopathy.

-Complications - Invasive pulmonary aspergillosis has been observed in 20 to 32 percent of hospitalized patients with SFTS. Secondary hemophagocytic lymphohistiocytosis (HLH) has also been reported.

●Diagnosis - SFTSV infection should be suspected in patients with fever, thrombocytopenia, and leukopenia together with a history of tick exposure in an endemic area. Laboratory diagnosis is based on serum polymerase chain reaction (PCR; during the first week of illness) or antibody detection (during the second or third week of illness). (See 'Diagnosis' above.)

●Treatment and prevention - Treatment consists of supportive care. There is no antiviral therapy available for treatment of SFTSV, and no vaccine is available for prevention of SFTSV. (See 'Treatment' above.)

●Mortality - Case-fatality rates range from 6 to 21 percent. (See 'Clinical manifestations' above.)


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