Relapsing fever

Japanese: 回帰熱

Relapsing fever, a condition characterized by repeated episodes of fever and fever reduction, is an extremely rare infectious disease in Japan and is classified as a Class 4 infectious disease under the Infectious Diseases Control Law.
The causative agent of the disease is Borrelia, a spirochete, and at least a dozen species have been identified (Table 4-8-1). The bacteria are carried by small rodents and birds, and are transmitted by lice (louse-borne relapsing fever) and ticks (tick-borne relapsing fever). The distribution areas of vector mites and areas where tick-borne relapsing fever occurs are roughly the same.
During the fever phase, the number of bacterial cells in the bloodstream increases to 100,000 cells/μL. The immune response then removes the bacterial cells from the bloodstream, leading to the subpyretic phase. The bacteria evade the immune system (specific antibodies) by mutating their antigenicity, and the number of bacterial cells in the bloodstream increases again, leading to the fever phase.
Epidemiology: It had not been reported in Japan for several decades, but in 2010, a case (B. persica) was reported in a 20-year-old woman who had returned to Japan after a week of volunteer work in Uzbekistan (Kutsuna et al., 2010). B. recurrentis is transmitted from person to person by lice, so outbreaks occur in times of war or famine when people are crowded together in unsanitary conditions. It is estimated that 50,000 people died in North Africa and Europe during World War II. Even now, cases have been reported in the Americas, Africa, the Middle East, and Europe. Tick-borne relapsing fever is thought to be a zoonotic disease.
Clinical symptomsThe clinical symptoms are similar whether the disease is transmitted by lice or ticks (Table 4-8-2). Symptoms begin with a sudden onset of fever, accompanied by severe headache, joint pain, muscle pain, and sometimes neck stiffness, cough, lung noise, and swollen lymph nodes. The initial fever suddenly subsides within 3-6 days. A skin rash may be present when the initial fever subsides. After a 7-10 day period of subsidence, the fever reappears. Lice transmission usually results in a single recurrence, whereas tick transmission occurs several times. In rare cases, myocarditis, cerebral hemorrhage, liver failure, and acute respiratory distress syndrome (ARDS) may occur, which may be the cause of death.
Myocarditis may also occur, but is more common in severe cases. Tick-borne infections often involve direct invasion of the bacteria into the central nervous system, causing meningitis or meningoencephalitis and may leave patients with aftereffects such as paralysis. Test results show no characteristic changes.
Definitive diagnosis is made by staining blood during the fever phase (with Giemsa or Wright staining) and identifying the bacteria, which is possible in 70% of cases (if there are 100,000 bacteria/μL or more). However, they cannot be found during the subpyergenic period. BSK medium is used to isolate and culture the bacteria, making it possible to isolate the pathogen from blood during the fever phase (isolation medium is always available at the National Institute of Infectious Diseases). Syphilis serology is positive in 5-10% of cases. PCR is also a useful method.
Differential diagnoses include systemic febrile diseases such as malaria, ehrlichiosis, babesiosis, influenza, typhoid fever, tularemia, brucellosis, rickettsiosis, dengue fever, leptospirosis, rat-bite fever, meningococcemia, and viral hepatitis.
Treatment and prevention Penicillin or tetracycline are the drugs of choice. Cephalosporins and macrolides are also considered effective. For lice transmission, a single dose of 500 mg tetracycline or 500 mg erythromycin is sufficient (recurrence rate is less than 5%). For tick transmission, a single dose has a recurrence rate of over 20%, and 100 mg doxycycline twice a day or 500 mg erythromycin four times a day is used for 5 to 10 days. A Jarisch-Herxheimer reaction may occur following treatment. There is no vaccine yet, so the key to prevention is to avoid contact with vector mites and lice. [Tachikawa Natsuo]
■ References <br /> Kutsunna, K., Kasahara, T., et al.: A case of imported relapsing fever. IASR, 31, 358-359, 2010.

Table 4-8-1
Relapsing fever Borrelia species, vectors, and distribution areas

Table 4-8-1

Table 4-8-2
Comparison of clinical symptoms and characteristics ">

Table 4-8-2

Source : Internal Medicine, 10th Edition About Internal Medicine, 10th Edition Information

Japanese:

発熱と解熱を繰り返す回帰熱はわが国では非常にまれな感染症であり，感染症法では四類感染症である．
原因・病因
　病原体はボレリア（Borrelia）でスピロヘータに属し，少なくとも十数種類が確認されている（表4-8-1）．菌は齧歯類小動物，鳥類などを保菌動物とし，シラミ（louse-borne relapsing fever）やダニ（tick-borne relapsing fever）によって媒介される．媒介ダニの分布地域とダニ媒介回帰熱発生地域はほぼ一致する．
　発熱期には菌体は血流内で増加し10万個/μLに達する．その後免疫の応答により菌体は血流より排除され解熱期に至る．菌は抗原性を変異させることで免疫（特異抗体）から逃避し，再び血流内で菌体量が増え，発熱期となる．
疫学
　わが国では数十年報告されていなかったが，2010年にはウズベキスタンで1週間ボランティア活動後に帰国した20歳女性の罹患例（B. persica）が報告されている（忽那ら， 2010）．B. recurrentisはシラミを介して人から人に伝播するため，戦争や飢饉など不衛生な状態で人が密集する場合には大発生する．第2次世界大戦時には北アフリカ，欧州で5万人が死亡したと推定されている．現在でもアメリカ大陸，アフリカ，中東，欧州で報告されている．ダニ媒介回帰熱は人畜共通感染症と考えられる．
臨床症状
　臨床症状はシラミ媒介・ダニ媒介で類似している（表4-8-2）．症状は突然の発熱で始まり，激しい頭痛，関節痛，筋肉痛を伴い，ときに項部硬直，咳，肺雑音，リンパ節腫脹などの症状を伴う．最初の発熱は3～6日で突然解熱する．最初の発熱が解熱する頃に皮疹を伴うことがある．7～10日の解熱期を経て再び発熱が出現する．シラミ媒介では通常再発回数は1回であり，ダニ媒介では数回である．まれに心筋炎，脳出血，肝不全，急性呼吸促迫症候群（ARDS）を合併するが，これらが死因になりうる．
　心筋炎も合併するが，重症例に多い．ダニ媒介では菌体の中枢神経系への直接侵入が多く，髄膜炎や髄膜脳炎を起こし，麻痺などの後遺症を残す場合がある．検査では特徴的な検査値変化はない．
診断
　確定診断は発熱期の血液を染色（Giemsa染色またはWright染色）して菌体を同定することであり，70％で可能（菌体10万/μL以上であれば可能）である．しかし解熱期には見つけることはできない．菌の分離培養にはBSK 培地が用いられ，発熱期の血液から病原体分離が可能である（分離用培地は国立感染症研究所で常備されている）．5～10％で梅毒血清反応が陽性となる．またPCR法は有用な方法である．
　鑑別診断としては，マラリア，エーリキア症，バベシア症，インフルエンザ，腸チフス，ツラレミア（野兎病），ブルセラ症，リケッチア症，デング熱，レプトスピラ症，鼠咬症，髄膜炎菌血症，ウイルス性肝炎など全身性発熱性疾患となる．
治療・予防
　ペニシリンやテトラサイクリンが選択される．セファロスポリンやマクロライドも有効と考えられる．シラミ媒介ではテトラサイクリン500 mgまたはエリスロマイシン500 mgの単回投与でよい（再発率は5％未満）．ダニ媒介では1回投与では20％以上の再発率があり，ドキシサイクリン100 mgを1日2回またはエリスロマイシン500 mgを1日4回を5～10日間使用する．治療に伴いJarisch-Herxheimer 反応がみられることがある．　まだワクチンはなく，予防には，媒介ダニ，シラミとの接触をさけることが重要である．［立川夏夫］
■文献
忽那賢志，笠原　敬，他：輸入回帰熱の一例.　IASR, 31, 358-359, 2010.

表4-8-1
回帰熱ボレリアの菌種と媒介動物および分布地域">

表4-8-1

表4-8-2
臨床症状・特徴の比較">

表4-8-2

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