B. miyamotoi はあなたのそばにいる

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日本でもBorrelia miyamotoiに感染しうる!

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B. miyamotoi はあなたのそばにいる

  1. 1. B. miyamotoiは あなたのそばにいる かもしれない 忽那賢志 2013/11/23-24 DEKABEN_ID annual meeting @京都
  2. 2. 回帰性といえば 輸入感染症 Am. J. Trop. Med. Hyg., 89(3), 2013, pp. 460–461 doi:10.4269/ajtmh.13-0187 Copyright © 2013 by The American Society of Tropical Medicine and Hygiene Case Report: The First Case of Imported Relapsing Fever in Japan Satoshi Kutsuna,* Hiroki Kawabata, Kei Kasahara, Ai Takano, and Keiichi Mikasa National Center for Global Health and Medicine, Disease Control and Prevention Center, Shinjuku-ku, Tokyo, Japan; National Institute of Infectious Diseases, Bacteriology, Shinjuku-ku, Tokyo, Japan; Nara Medical University, Center for Infectious Diseases, Nara City, Nara, Japan; Yamaguchi University, Joint Faculty of Veterinary Medicine, Yamaguchi-City, Yamaguchi, Japan Abstract. Tick-borne relapsing fever (TBRF) is endemic in discrete areas throughout the world; however, a domestic or imported case of relapsing fever has not been reported in Japan. Here, we report the first imported case. A previously healthy 20-year-old woman presented to our hospital on October 8, 2010, because of recurrent fever and lower leg pain. Before consultation, she had experienced four febrile episodes at 10–12-day intervals after returning from her stay in Uzbekistan from 1 to 8 September. Giemsa stain of peripheral blood showed Borrelia spirochetes. The spirochete was identified as Borrelia persica by sequencing of the amplicons of flaB using polymerase chain reaction and phylogenetic analysis. The patient was diagnosed with TBRF, and she completed a 10-day course of minocycline 100 mg twice daily. After treatment, her periodic fever subsided. Physicians should be aware of TBRF in patients with recurrent fever who have returned from TBRF-endemic countries, including areas of the former USSR. Relapsing fever caused by spirochetes of the genus Borrelia Am J Trop Med Hyg. 2013 Sep;89(3):460-1. lymphopenia (1,110 mg/mL), elevated levels of C-reactive pro-
  3. 3. だと思っていませんか?
  4. 4. いきなりですが 症例呈示
  5. 5. 症例: 80歳女性 • 主訴:4ヶ月前からボーっとしてきた • 現病歴:4ヶ月前から家族と交流をしなくなり、よろよろ歩きで、だ んだんベッドから出なくなってきた。難聴も出現し、食欲低下により 13.6kg減少した。 • 既往歴:悪性リンパ腫(濾胞型、StageIIA)     2005年2月に診断     2005年6月∼9月 R-CHOP     その後2011年8月までRを6ヶ月毎に投与     高血圧、鬱病
  6. 6. 症例: 80歳女性 • 旅行歴、ダニ曝露なし • 遊走性紅斑なし • USAのニュージャージー州に住んでいる。家禽、猫、イヌ、ネズミ、 • これまでに2回ライム病に罹患歴(2006年11月、2007年6月)があり、 鹿の曝露はある 遊走性紅斑を呈しDOXY2週間の投与で治療された。
  7. 7. preparation of CSF sediment revealed spirochetes, which were also visualized by means of Gram’s staining. The patient was admitted to the hospital on February 23, 2012, for further evaluation. On examination, she was afebrile and vital signs were stable. Physical examination was unremarkable except for a soft systolic murmur. Neurologic examination revealed that she was slow to answer questions and follow commands, was hard of hearing, and had an unsteady gait. The patient could not give any details of her history or symptoms; she did not say that she had a headache or stiff neck. A follow-up spinal tap, on February 23, again showed spirochetes on Giemsa staining (Table 1). After blood and CSF samples had been obtained for cultures, ceftriaxone, at a dose of 2 g intravenously, was administered, at 8:45 p.m. Approximately 9 hours later, at 6 a.m. on February 24, the patient had a temperature of 38.7°C (101.6°F), her systolic blood pressure was in the low 90s, and she appeared ill. She had a salutary therapeutic response to the administration of fluids and acetaminophen. The clinical presentation after the patient received ceftriaxone was suggestive of a Jarisch–Herxheimer reaction. Treatment was then switched to penicillin G at a daily dose of 24 million U given intravenously, because the specific pathogen remained unidentified. During the first 5 days of therapy, the patient’s physical condition improved dramatically; the hyponatremia resolved by February 26. Her mental condition improved progressively over the first 3 to 5 days, returning to normal at the end of the 30-day regimen of intravenous penicillin G therapy. Additional laboratory findings on February 23 included negative results on Venereal Disease Reference Laboratory testing of CSF and on serum rapid plasma reagin testing (no prozone phenomenon). No organisms or spirochetes were observed on a peripheral-blood smear. Serum electrophoresis showed a total protein level of 5.6 g per deciliter, a gamma globulin level of 0.5 g per deciliter, and no monoclonal protein; the IgA level was 70 mg per deciliter (normal range, 61 to 356), the IgM level 18 mg per deciliter (normal range, 37 to 286), and the IgG level 445 mg per deciliter (normal range, 767 to 1590). The sodium level was 127 mmol per liter, the cortisol level was 14.7 µg per deciliter (406 nmol per liter), and results of 検査結果 * To convert the values for glucose to millimoles per liter, multiply by 0.05551. Results on Giemsa Staining or Gram’s Staining Glucose* per mm3 mg/dl mg/dl per mm3 Protein cm of water Differential Count Red-Cell Count Appearance White-Cell Count Opening Pressure Date 頭部造影MRIも撮影されたが急性の変化なし(2012/2/6)。 刺を施行 • かかりつけ医にて代謝性疾患のワークアップが行われ異常なし • がんセンターに紹介となり、胸腹部骨盤CTが撮られたが異常なし。 • 髄膜炎を疑い腰椎 Table 1. Results of Repeated Examinations of Cerebrospinal Fluid. February 21 — Xanthochromic 65 23% polymorphonuclear leukocytes, 70% lymphocytes, 6% monocytes, and 1% uncharacterized cells 6 >300 33 Spirochete February 23 21 Xanthochromic 40 37% polymorphonuclear leukocytes, 49% lymphocytes, 1% bands, 9% monocytes, 1% eosinophils, and 3% uncharacterized cells 2 >300 27 (96 in serum) Spirochete March 29 16 Clear 21 91% lymphocytes and 9% monocytes 2 168 41 (87 in serum) No organism
  8. 8. preparation of CSF sediment revealed spirochetes, which were also visualized by means of Gram’s staining. The patient was admitted to the hospital on February 23, 2012, for further evaluation. On examination, she was afebrile and vital signs were stable. Physical examination was unremarkable except for a soft systolic murmur. Neurologic examination revealed that she was slow to answer questions and follow commands, was hard of hearing, and had an unsteady gait. The patient could not give any details of her history or symptoms; she did not say that she had a headache or stiff neck. A follow-up spinal tap, on February 23, again showed spirochetes on Giemsa staining (Table 1). After blood and CSF samples had been obtained for cultures, ceftriaxone, at a dose of 2 g intravenously, was administered, at 8:45 p.m. Approximately 9 hours later, at 6 a.m. on February 24, the patient had a temperature of 38.7°C (101.6°F), her systolic blood pressure was in the low 90s, and she appeared ill. She had a salutary therapeutic response to the administration of fluids and acetaminophen. The clinical presentation after the patient received ceftriaxone was suggestive of a Jarisch–Herxheimer reaction. Treatment was then switched to penicillin G at a daily dose of 24 million U given intravenously, because the specific pathogen remained unidentified. During the first 5 days of therapy, the patient’s physical condition improved dramatically; the hyponatremia resolved by February 26. Her mental condition improved progressively over the first 3 to 5 days, returning to normal at the end of the 30-day regimen of intravenous penicillin G therapy. Additional laboratory findings on February 23 included negative results on Venereal Disease Reference Laboratory testing of CSF and on serum rapid plasma reagin testing (no prozone phenomenon). No organisms or spirochetes were observed on a peripheral-blood smear. Serum electrophoresis showed a total protein level of 5.6 g per deciliter, a gamma globulin level of 0.5 g per deciliter, and no monoclonal protein; the IgA level was 70 mg per deciliter (normal range, 61 to 356), the IgM level 18 mg per deciliter (normal range, 37 to 286), and the IgG level 445 mg per deciliter (normal range, 767 to 1590). The sodium level was 127 mmol per liter, the cortisol level was 14.7 µg per deciliter (406 nmol per liter), and results of Glucose* per mm3 mg/dl mg/dl per mm3 Protein cm of water Differential Count Appearance Date February 21 — Xanthochromic 65 23% polymorphonuclear leukocytes, 70% lymphocytes, 6% monocytes, and 1% uncharacterized cells 6 >300 33 Spirochete February 23 21 Xanthochromic 40 37% polymorphonuclear leukocytes, 49% lymphocytes, 1% bands, 9% monocytes, 1% eosinophils, and 3% uncharacterized cells 2 >300 27 (96 in serum) Spirochete March 29 16 Clear 21 91% lymphocytes and 9% monocytes 2 168 41 (87 in serum) No organism e , * To convert the values for glucose to millimoles per liter, multiply by 0.05551. Results on Giemsa Staining or Gram’s Staining Red-Cell Count White-Cell Count Opening Pressure D 検査結果 C 頭部造影MRIも撮影されたが急性の変化なし(2012/2/6)。 刺を施行 • かかりつけ医にて代謝性疾患のワークアップが行われ異常なし • がんセンターに紹介となり、胸腹部骨盤CTが撮られたが異常なし。 • 髄膜炎を疑い腰椎 r s r Table 1. Results of Repeated Examinations of Cerebrospinal Fluid.
  9. 9. preparation of CSF sediment revealed spirochetes, which were also visualized by means of Gram’s staining. The patient was admitted to the hospital on February 23, 2012, for further evaluation. On examination, she was afebrile and vital signs were stable. Physical examination was unremarkable except for a soft systolic murmur. Neurologic examination revealed that she was slow to answer questions and follow commands, was hard of hearing, and had an unsteady gait. The patient could not give any details of her history or symptoms; she did not say that she had a headache or stiff neck. A follow-up spinal tap, on February 23, again showed spirochetes on Giemsa staining (Table 1). After blood and CSF samples had been obtained for cultures, ceftriaxone, at a dose of 2 g intravenously, was administered, at 8:45 p.m. Approximately 9 hours later, at 6 a.m. on February 24, the patient had a temperature of 38.7°C (101.6°F), her systolic blood pressure was in the low 90s, and she appeared ill. She had a salutary therapeutic response to the administration of fluids and acetaminophen. The clinical presentation after the patient received ceftriaxone was suggestive of a Jarisch–Herxheimer reaction. Treatment was then switched to penicillin G at a daily dose of 24 million U given intravenously, because the specific pathogen remained unidentified. During the first 5 days of therapy, the patient’s physical condition improved dramatically; the hyponatremia resolved by February 26. Her mental condition improved progressively over the first 3 to 5 days, returning to normal at the end of the 30-day regimen of intravenous penicillin G therapy. Additional laboratory findings on February 23 included negative results on Venereal Disease Reference Laboratory testing of CSF and on serum rapid plasma reagin testing (no prozone phenomenon). No organisms or spirochetes were observed on a peripheral-blood smear. Serum electrophoresis showed a total protein level of 5.6 g per deciliter, a gamma globulin level of 0.5 g per deciliter, and no monoclonal protein; the IgA level was 70 mg per deciliter (normal range, 61 to 356), the IgM level 18 mg per deciliter (normal range, 37 to 286), and the IgG level 445 mg per deciliter (normal range, 767 to 1590). The sodium level was 127 mmol per liter, the cortisol level was 14.7 µg per deciliter (406 nmol per liter), and results of 検査結果 頭部造影MRIも撮影されたが急性の変化なし(2012/2/6)。 刺を施行 • かかりつけ医にて代謝性疾患のワークアップが行われ異常なし • がんセンターに紹介となり、胸腹部骨盤CTが撮られたが異常なし。 • 髄膜炎を疑い腰椎 Table 1. Results of Repeated Examinations of Cerebrospinal Fluid. Protein Glucose* per mm3 mg/dl mg/dl 65 23% polymorphonuclear leukocytes, 70% lymphocytes, 6% monocytes, and 1% uncharacterized cells 6 >300 33 Spirochete 40 37% polymorphonuclear leukocytes, 49% lymphocytes, 1% bands, 9% monocytes, 1% eosinophils, and 3% uncharacterized cells 2 >300 27 (96 in serum) Spirochete 21 91% lymphocytes and 9% monocytes 2 168 41 (87 in serum) No organism なんかおる per mm3 February 21 — Xanthochromic February 23 21 Xanthochromic March 29 16 Clear ? cm of water Differential Count Appearance Date e , * To convert the values for glucose to millimoles per liter, multiply by 0.05551. Results on Giemsa Staining or Gram’s Staining Red-Cell Count White-Cell Count Opening Pressure D C r s r
  10. 10. 精査のため入院 • Vital Sign:発熱なし、その他バイタル異常なし • 身体所見:軽い収縮期雑音あり。 • 神経学的所見:質問に対する回答や指示に対する反応が緩慢        難聴、歩行時のふらつき        頭痛の訴えや項部硬直なし • フォローアップの髄液検査でもグラム染色でスピロヘータを認めた
  11. 11. 入院後経過 • 血液培養、髄液を採取した後にCTRX 2g div 開始 • その9時間後・・・38.9℃の発熱、血圧低下・・・ショック状態! • 輸液とアセトアミノフェンで対応 • JHRと考えられた • 治療はPCG 2400万単位/日に変更した • 治療開始後3∼5日で全身状態、意識障害は改善 • 30日間の投与でPCGは終了
  12. 12. 微生物検査 • 末梢血でスピロヘータを認めず • 髄液培養陰性 • クリプトコッカス抗原陰性 • 抗酸菌塗抹陰性 • 髄液ではスピロヘータ塗抹陽性 • 血液培養ではCNSが陽性であったがコンタミと考えられた
  13. 13. 顕微鏡検査と免疫染色 • 400倍の鏡検で、7-10μmのスピロヘータが観察された。形態学的にB. burgdorferi sensu latoとは異なっており(特に軸方向運動と細胞のコイ リングが違うらしい・・・)、まずB. burgdorferi sensu latoではないと 考えられた。 • 免疫染色で Borrelia sp.のフラジェリンモノクローナル抗体である H9724と反応が見られたため Borrelia sp.であると判明したが、B. burgdorferiの表面蛋白であるH5332モノクローナル抗体には反応せず、 やはりライム病ボレリアではないと考えられた。
  14. 14. rochete was probably . A B C D propagate in Barbour– Motility was not obubation. h B. burgdorferi antigen , <1) for IgM, IgA, and d CSF specimens obse of disease and after ay of serum specimens ctivity to B. microti or rved. the use of genuswide that the patient’s inied a borrelia species, wever, negative results ic PCR assay targeting yme neuroborreliosis. e CSF spirochete was ation of two separate f primers specific for p and was confirmed enetic analysis of the Figure 1. Morphologic Features of Spirochetes Detected in Cerebrospinal Fluid. Panels A and B show the spirochetes as viewed with the use of dark-field microscopy. Panels C and D show the spirochetes as viewed with the use of bright-field microscopy, with Giemsa staining and a pH of 7.0. The bar indicates 2 µm.
  15. 15. 遺伝子解析 • 全ボレリア属のプライマーを使ったリアルタイムPCRでは、CSFがボ レリア遺伝子を含むことが分かり、OpsA遺伝子を標的にしたPCRが 陰性であったことからライム病は除外された。 • B. miyamotoiに特異的なプライマーを用いた2つの分割された標的遺伝 子の増幅で陽性となり、16s rRNAとフラジェリン遺伝子を用いたシー クエンスと系統発生解析によってB. miyamotoiのアメリカ分岐群の菌種 であると同定された。 • 治療後のCSFはPCR陰性であった
  16. 16. B. burgdorferi AF467957 B. duttonii GU350712 B.B. bissettii AJ224141 afzelii FR733687 B. valaisiana NR036807 B. andersonii L46701 B Flagellin Gene Target B. garinii HM007279 B. burgdorferiscapularis AY374135 (New York) Ixodes persulcatus JF951384 (Russia) 0.005 I. AF467957 B. bissettii AJ224141 Apodemus argenteus AY604976 (Japan) I. scapularis AY374134 (New York) 0.005 mostly in patients presenting with nonspe A 16S Ribosomal RNA Gene Target prolonged fever. These patients had serorea ity to B. burgdorferi sensu lato antigen on enz immunoassay, and AY024344 (Connecticut) suggeste the cause was I. persulcatus 025861 (Japan) I. scapularis North Human GU797331 (Russia) amplificationCSF (New(Massachusetts) DNA from the of B. Jersey) miyamotoi America Borrelia B Flagellin Gene Target I. dammini I. ricinus JF951382 (Russia) miyamotoi I. recent report showed that se I. ricinus JF951383 (Russia) tients’ blood. A pacificus DQ025525 (California) I. scapularis AY374135 (New York) I. pacificus DQ025526 (California) clade I. ricinus AF529085 (France) I. scapularis AY374134 (New York) I. ricinus AF529084 (France)residents of New samples from 1 to 3% of I. dammini (United States) I. scapularis AY024344 (Connecticut) North I. ricinus FJ874925 (Poland) I. scapularis AY024345(United States) CSF (New Lyme disease is Jersey) gland sitesI.I.where(Massachusetts) Europe endemic w ricinus JF951389 (Russia) America CSF (New Jersey) dammini I. ricinus JF951388 (Russia) B. lonestari AY166715 pacificus DQ025525 reactive in anI.experimental (California) assay ta Human GU797341 (Russia) serologic B. theileri DQ872186 I. pacificus DQ025526 persulcatus D43777 (Japan) (California) ing the B.I.I.miyamotoi GlpQ antigen, a finding B. hermsii GQ175067 ricinus AF529084 (France) Asia I. persulcatus JF951392 (Russia) B. turicatae AY934605 I. ricinus FJ874925 (Poland) suggests Human GU797342 (Russia) relatively common that exposure is Europe B. parkeri AF307100 I. ricinusB. lonestari (Russia) JF951389 AY850064 B. coriaceae AF210136 I. ricinusB. lonestari AY166716 In northernJF951388 (Russia) (and in many o New Jersey B. persica HQ610930 Human GU797341 (Russia) B. hispanica GU350707 northeastern U.S. sites), there are diverse e I. persulcatus D43777 (Japan) 0.01 Asia B. recurrentis AF107358 I. persulcatus JF951392 (Russia) otic borreliae other(Russia) B. burgdorferi sensu st B. duttonii GU350712 Human GU797342 than B. afzelii FR733687 Figure 2. Phylogenetic Analysis of DNA agents of zoonotic infection. B. Sequences Obtained by Polymerasethat could be lonestari AY850064 B. valaisiana NR036807 B. lonestari AY166716 Chain-Reaction Amplification of the Patient’s Cerebrospinal Fluid. B. andersonii L46701 rabbit tick, I. dentatus, harbors B. andersonii, w The 0.01 maximum-likelihood algorithm was implemented in the MEGA 5.05 B. garinii HM007279 has not been associated includes accessions B. burgdorferi AF467957 program.13 The branch labels are from GenBank, which with infection in 0.005 B. bissettii AJ224141 deposited with datamans.that the sequences came from Ixodes dammini plag stating Much of eastern New Jersey is Figure 2. Phylogeneticthat they came from I. scapularis. Panel Aby PolymeraseAnalysis of DNA Sequences Obtained shows the 16S and others stating by the the Patient’s a 1127-base-pair portion and Chain-Reaction Amplification ofLone Star tick, A. americanum, infecte ribosomal RNA gene target, with the use of Cerebrospinal Fluid. B Flagellin Gene Target B. lonestari,27 a candidate etiologic The the Hasegawa–Kishino–Yano withwas implemented in the MEGA 5.05 agent maximum-likelihood algorithm invariant sites (HKY+G+I) plus gamma I. scapularis AY374135 (New York) program.13 The B shows the are from GenBank, which includes 456-baseMasters’ disease, also known as southern t I. scapularis AY374134 (New York)model. Panelbranch labelsflagellin gene target, with the use of a accessions pair deposited with and stating that parameter (T92) model. The arrowdammini from Ixodes marks I. scapularis AY024344 (Connecticut) portion data the Tamura 2the rash illness (STARI). Finally, wher North associated sequences camescale bars denote the CSF (New Jersey) and the spirochete in thethey came from I. scapularis. Panel A shows the 16S others stating that sample from our patient. The America I. dammini (Massachusetts) geneticRNA gene target, with substitutions 1127-base-pair present, B. miy nucleotide the use I. a per site. ribosomal distance in I. dammini and of scapularis are portion and I. pacificus DQ025525 (California) toi may also be found.24 Thus, gamma the Hasegawa–Kishino–Yano with invariant sites (HKY+G+I) plusthe spiroch I. pacificus DQ025526 (California) I. ricinus AF529084 (France) model. Panel B shows found in the CSF ofwith the use of acould have b the flagellin gene target, our patient 456-baseI. ricinus FJ874925 (Poland) pair portion and the Tamura 2 parameter (T92) model. The arrow marks vectorof these organisms, particularlyprevaas B. burgdorferi sensu lato,24 but its when Europe any I. ricinus JF951389 (Russia) the spirochete in the samplein ticks is only 10%scale barsfor B. burgdorlence from our patient. The of that denote the I. ricinus JF951388 (Russia) liminary antigenic and morphologic ana genetic distance in nucleotide substitutions per site. Human GU797341 (Russia) feri, ranging from 0.7% in I. pacificus in CaliforI. persulcatus D43777 (Japan) appeared to rule out B. burgdorferi sensu stricto 22 21
  17. 17. The n e w e ng l a n d j o u r na l of m e dic i n e brief report Meningoencephalitis from Borrelia miyamotoi in an Immunocompromised Patient Joseph L. Gugliotta, M.D., Heidi K. Goethert, Sc.D., Victor P. Berardi, B.S., and Sam R. Telford III, Sc.D. SUM M A R Y Ixodes ticks serve as vectors for Borrelia burgdorferi, the agent of Lyme disease. Globally, these ticks often concurrently harbor B. miyamotoi, a spirochete that is classified
  18. 18. NEJM症例報告の考察 • Ixodes(マダニ)はライム病の原因であるBorrelia burgdoferiのベクターで あるが、同時に回帰熱グループのスピロヘータに分類されるB. miyamotoiもしばしば保有している。おそらく人間はB. miyamotoiに頻繁 に曝露しているが、それによって起こる疾患のデータは限られている • B. miyamotoiはライム病の流行地域では特に見逃されている可能性があ る。
  19. 19. 1例報告でNEJM...
  20. 20. Case Report Science Photo Library 1例報告でlancet... A case of meningoencephalitis by the relapsing fever spirochaete Borrelia miyamotoi in Europe Science Photo Library Joppe W R Hovius, Bob de Wever, Maaike Sohne, Matthijs C Brouwer, Jeroen Coumou, Alex Wagemakers, Anneke Oei, Henrike Knol, Sukanya Narasimhan, Caspar J Hodiamont, Setareh Jahfari, Steven T Pals, Hugo M Horlings, Erol Fikrig, Hein Sprong, Marinus H J van Oers On April 1 2012, a 70-year-old patient came to our clinic reporting slow cognitive processing, memory deficits, and a disturbed gait, all of which had gradually developed over several months and progressed during the last few weeks before the patient’s initial visit. He did not report fever, and he had not been outside the country for several years. He had recently been treated with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone), polychemotherapy, and rituximab (last dose on Aug 2, 2011) for a stage 4 diffuse large B cell lymphoma. Netherlands, proved to be positive for B miyamotoi by qPCR (appendix). Amplification and sequencing of the glpQ and p66 genes confirmed B miyamotoi as the causative agent and showed 100% identical sequences in ticks and the patient’s clinical samples (appendix). We were unable to culture the spirochaetes in modified Barbour-Stoenner-Kelly medium from stored blood and cerebrospinal fluid samples. Finally, ELISA and Western blot did not show anti-GlpQ antibodies in blood and CSF. Relapsing fever is caused by various Borrelia species, Ixodes ricinus Lancet 2013; 382: 658 a o w f y p l A H p
  21. 21. Lancet症例報告の概要 70歳の患者が数ヶ月の経過で動作の緩慢、記憶障害、歩行困難を主訴 に受診 • • DLBCLでR-CHOPの治療を受けていた • 後になってmiyamotoiの可能性が考えられたため、CTRX投与前の髄液 を暗視野顕微鏡で観察したところスピロヘータを認め、またmiyamotoi flagellin遺伝子が髄液と血液のqPCRで陽性であった。 • 患者の自宅近くのオランダのZandvoortに生息するIxodes ricinusの2.2% がqPCRでmiyamotoi陽性であった。 Science Photo Library • 血清検査では陰性だったがNeuroborreliosisが疑われCTRX 2g/day 2wks で治療された。その後、症状は完全に元に戻った Ixodes ricinus Lancet 2013; 382: 658 a o w f y p l A H p
  22. 22. human granulocytic Lyme disease. Conclusion: 2例報告でannals... The presence of B erienced by 2 case blood and the patients’ eventu but did not rapidly cline are consistent with the hy no laboratory evithis newly recognized spiroche Original Research n. Annals of Internal Medicine tients acutely presenting with Borrelia miyamotoi Infection Presenting as Human layed response to doxycycline t Granulocytic Anaplasmosis A Case Report results for HGA should be an achusetts and New miyamotoi infection. Hanumara Ram Chowdri, MD; Joseph L. Gugliotta, MD; Victor P. Berardi; Heidi K. Goethert, ScD; Philip J. Molloy, MD; Sherri L. Sterling, MBA, MLS; and Sam R. Telford III, ScD Background: The diverse tickborne infections of the northeastern United States can present as undifferentiated flu-like illnesses. In areas endemic for Lyme and other tickborne diseases, patients presenting with acute febrile illness with myalgia, headache, neutropenia, thrombocytopenia, and elevated hepatic aminotransferase levels are presumptively diagnosed as having human granulocytic anaplasmosis (HGA). Results: Molecular diagnostic assays detected Borrelia miyamotoi in the peripheral blood of both patients. There was no evidence of infection with other tickborne pathogens commonly diagnosed in the referral areas. Objective: To assign a cause for illness experienced by 2 case patients who were initially diagnosed with HGA but did not rapidly defervesce with doxycycline treatment and had no laboratory evidence of Anaplasma phagocytophilum infection. Conclusion: The presence of B. miyamotoi DNA in the peripheral blood and the patients’ eventual therapeutic response to doxycycline are consistent with the hypothesis that their illness was due to this newly recognized spirochete. Samples from tick-exposed patients acutely presenting with signs of HGA but who have a delayed response to doxycycline therapy or negative confirmatory test results for HGA should be analyzed carefully for evidence of B. h fever. gent by polymerase Design: Case report. Primary Funding Source: Na Evelyn Lilly Lutz Foundation. Limitation: One of the case patients may have had concurrent Lyme disease. Ann Intern Med. 2013;159:21-27.
  23. 23. human granulocytic Lyme disease. Annals症例報告の概要 Conclusion: The presence of B erienced by 2 case blood and the patients’ eventu but did not rapidly cline are consistent with the hy no laboratory evithis newly recognized spiroche • 背景:ライム病やその他のダニ媒介感染症の流行するアメリカ北西部 n. ではflu-like illnessを呈し好中球減少・血小板減少・肝酵素上昇を認め tients acutely presenting with る症例はヒト顆粒球アナプラズマ症(HGA)と臨床診断されやすい layed response to doxycycline t • 目的:2例のHGAと臨床診断されたが血清学的な証拠がなくDOXY投 与のみで解熱が得られた2症例について results for HGA should be an • and New achusetts 結果:急性の発熱を呈した2例の末梢血のPCRでmiyamotoiのDNAが検 miyamotoi infection. 出された。その他のダニ媒介感染症の病原微生物は検出されなかった (1例はライム病の共感染だった) • h fever. Primary Funding Source: Na Evelyn Lilly Lutz Foundation. 結論:HGAと臨床診断されてもDOXYのみで治癒する症例では miyamotoi感染症を疑い検査を行うべきである gent by polymerase Ann Intern Med. 2013;159:21-27.
  24. 24. miyamotoiって?
  25. 25. JOURNAL SYSTEMATIC BACTERIOLOGY, 1995, p. 804-810 OF OCt. 0020-7713/95/$04.00.t 0 Copyright 0 1995, International Union of Microbiological Societies INTERNATIONAL Vol. 45, No. 4 Genetic and Phenotypic Analysis of Borrelia miyamotoi sp. nov., Isolated from the Ixodid Tick Ixodes persulcatus, the Vector for Lyme Disease in Japan MASAHITO FUKUNAGA,' * YUKIE TAKAHASH1,l YASUTO TSURUTA,l OSAMU MATSUSHITA,* DAVID RALPH,3 MICHAEL McCLELLAND,~AND MINORU NAKA04 Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Fukuyama, Hiroshima 729-02,' Department of Microbiology, Kagawa Medical School, Ikenobe, Kita-gun, Kagawa 761-07, and Department of Parasitology, Asahikawa Medical College, Nishikagura, Hokkaido 078, Japan, and California Institute of Biological Research, La Jolla, California 920373 The ixodid tick Ixodes persulcatus is the most important vector of Lyme disease in Japan. Most spirochete isolates obtained from I. persulcatus ticks have been classified as Borrelia burgdorferi sensu lato because of their genetic, biological, and immunological characteristics. However, we found that a small number of isolates obtained from I. persulcatus contained a smaller 38-kDa endoflagellar protein and single 23s-5s rRNA gene unit. Representative isolate HT31T (T = type strain) had the same 23s rRNA gene physical map as Borrelia turicatae. The DNA base composition of strain HT31T was 28.6 mol% G+C. DNA-DNA hybridization experiments revealed that strain HT31T exhibited moderate levels of DNA relatedness (24 to 51%) with Borrelia hemsii, B. turicatae, Borrelia parkeri, and Borrelia coriaceae. However, the levels of DNA reassociation with the previously described Lyme disease borreliae (B. burgdorferi,Borrelia garinii, and Borrelia afielii) were only 8 to 13%. None of the previously described species examined exhibited a high level of DNA relatedness with strain 日本で最初にみつかった!!
  26. 26. B. miyamotoiとは? • 1995年に北海道の根室に生息するIxodes persulcatus (シュルツェマダ • (たぶん)元旭川医科大学医動物学助教授の宮本健司先生に由来 • Ixodes persulcatus が生息する地域(日本、韓国、中国、モンゴル、モ ニ)から初めて分離された回帰熱スピロヘータ スクワ以東の旧ソビエト連邦)でも潜在的に蔓延している可能性が高 いと考えられている • 今回のNEJM, Lancet, Annalsの報告で、I. ricinus、I. scapularis、I. pacificusが 生息する欧州・米国でも蔓延していることがわかった
  27. 27. B. miyamotoiとは? • ボレリア属は病像から大きく2つに分けられる、すなわちライム病と • ライム病を起こすスピロヘータはB. burgdorferi sensu latoと呼ばれる。 回帰熱である。 そのプロトタイプであるB. burgdorferi sensu strictoはアメリカでライム 病を起こす唯一の菌種である。 • B. burgdorferi sensu latoに分類されるボレリアはマダニの中のカタダニ hard ticksが保有している。アメリカ東部ではライム病のベクターはI. damminiとI. scapularisである。このうちI. scapularisの方がB. miyamotoiのベ クターでもあることが分かっている
  28. 28. B. miyamotoiとは? • 回帰熱グループの菌種は遺伝子的に分かれており、その大部分が特徴 的な周期性発熱を起こす。回帰熱グループのボレリアはヒメダニsoft ticksが保有するが、B. recurrentisは例外でありシラミに媒介される。 • M. miyamotoiは回帰熱グループに属するがカタダニhard ticksに保有され ているという特徴があり、日本ではロシアなどと同様にIxodes persulcatus (シュルツェマダニ)が保有している
  29. 29. 日本でも回帰熱に 罹患する?
  30. 30. 実はこれ以前に1例、2例報告よりも 多いcase seriesがあります
  31. 31. なんとその数・・・
  32. 32. 46例
  33. 33. RESEARCH Humans Infected with Relapsing Fever Spirochete Borrelia miyamotoi, Russia Alexander E. Platonov, Ludmila S. Karan, Nadezhda M. Kolyasnikova, Natalya A. Makhneva, Marina G. Toporkova, Victor V. Maleev, Durland Fish, and Peter J. Krause Borrelia miyamotoi is distantly related to B. burgdorferi transovarially and transstadially by ticks and coexists with
  34. 34. miyamotoiを保有する ダニの比率 地域によっては1割以 上のダニが保有 Figure 1. Percentage of Ixodes persulcatus (I. p.) and I. ricinus (I. r.) ticks infected with Borrelia miyamotoi in Russia. The number of ticks that were tested is given in parenthesis. Star indicates study location of human B. miyamotoi infection.
  35. 35. infection and patients from the United States with B. from analysis the 4 B. miyamotoi patients with EM who burgdorferi infection were similar in age and sex. Time might have been co-infected with B. burgdorferi s.l. from tick bite to onset of symptoms was longer and time Humans Infected with Borrelia miyamotoi from symptom onset to hospital admission was shorter for Therapy and Clinical Outcome B. miyamotoi patients than for B. garinii patients (Table 2). Antimicrobial drug therapy for the B. miyamotoi More systemic manifestations, including fever and patients was started 1 week after admission when IgMTable 1. Classification of suspected tick-borne infections, Yekaterinburg City, Russia, May–August 2009* headache, were reported for B. miyamotoi patients than for based serologic tests results PCR rmed theAntibody diagnosis Amplifiable DNA/RNA, by confi No. patients B. garinii and B. burgdorferi patients (Table 3). Maximum (median 7 days, B. burgdorferi days). Therapy consisted IQR 6–10 Total no. with erythema Borrelia Borrelia TBEV Classification patients migrans s.l. TBEV IgM miyamotoi temperatures measured at home and in the hospital were of ceftriaxone, 2 g intravenously every 24 IgM hours for 2 B. miyamotoi infection, confirmed 46 4 46 0 0 higher for B. miyamotoi patients (39.0°C, interquartile weeks (42 patients) or 0 doxycycline 100 mg 46 orally every B. miyamotoi 2 0 2 0 0 0 range [IQR]infection, unconfirmed for B. garinii patients 12 hours for 2 weeks (2 patients). 0Two patients received 38.8–39.5°C) than B. miyamotoi infection, TBEV co-infection 3 0 3 0 0 2 3 (37.6°C, IQR 38.8–39.5°C; p<0.001). Duration of fever no antimicrobial drug while hospitalized; 1 later received B. garinii infection, confirmed 21 19 0 21 0 21 0 was relatively short and did not differ significantly for B. doxycycline at home, and the other was readmitted 0to B. burgdorferi s.l. infection 83 83 0 0 0 59 miyamotoi and B. garinii patients (3.4 ± 1.442 3.3 ± 2.8 the hospital for relapse 0 received ceftriaxone. Patients and and Borrelia spp. infection, unconfirmed 0 0 0 42 0 days, respectively). Body temperature began to return to with B. garinii infection received 5 doxycycline (71%)21 or TBEV infection, confirmed 21 0 0 0 0 reference burgdorferi s.l. co-infection TBEV, B. range before antimicrobial drug 9therapy was ceftriaxone (29%) immediately after admission because 9 0 0 2 ND 9 TBEV, Borrelia spp. co-infection 0 0 11 11 initiated, as has been described for relapsing 11 fever patients, diagnosis 0 borreliosis, based on 3presence of EM, was of Other inflammatory disease 64 0 0 0 0 in all but 1 B. miyamotoi patient. Hospital stay was longer made at the time of admission. B. burgdorferi0patients 0 all *TBEV, for B. tick-borne encephalitis virus; Ig, immunoglobulin; ND, not determined. received doxycycline, 100 mg orally every 12 hours, or miyamotoi patients (median 20 days, IQR 15–22 確定例: 末梢血中にmiyamotoi DNA/RNAを検出した症例 in acute-Patient characteristics and infection timeline for Borrelia spp. days) than for B. garinii patients (median 10 days, IQR and/or convalescent-phase serum, and 24 had EM infections, by species* Table 2. alone); 42 had unconfirmed Borrelia spp. infections with 10–13 days; p<0.001). timeline, median no. days (IQR) Infection anti-borreliae IgM but lacked EM and werePatient characteristics Although mean peripheral leukocyte and platelet counts Borrelia spp. No. patients Tick bite to symptom Symptom onset to negativespecies had fever of unknown were no. (%) for patients with B. miyamotoi than B. garinii Borrelia on PCR; 41 had TBE; 37Median age, y (range) infected Male sex, lower onset hospital admission 46 54 (21–77) 24 (52) 1 (1–2) B. miyamotoi origin after tick bite; and 27 had other diagnoses, including infection, they were 15 (12–16) reference range. Proteinuria within the 21 11 transient elevation(7–13)† 10 of serum alanine aminotransferase 5 (2–9)† B. garinii enteroviral infection, mononucleosis, 58 (18–87) or pyelonephritis. and(52) 50 (14–79) 49 aspartate aminotransferase concentrations were found NA NA B. burgdorferi None of the 302 patients 92 any PCR-based evidence of and(53) had *IQR, interquartile range; NA, not available. B. afzelii, A. phagocytophillum, or E. muris infection. for 3 more B. miyamotoi patients than B. garinii patients †p<0.001 in comparison with patients with B. miyamotoi infection. (51% and 68% vs. 15% and 20%, respectively, p<0.01), but no nephritis or hepatitis was clinically apparent. We found Clinical Manifestations Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 17, No. 10, October 2011 1819 Patients from Russia with B. miyamotoi and B. garinii similar clinical and laboratory results when we omitted infection and patients from the United States with B. from analysis the 4 B. miyamotoi patients with EM who burgdorferi infection were similar in age and sex. Time might have been co-infected with B. burgdorferi s.l. 患者年齢の中央値は54歳、潜伏期は2週間程度
  36. 36. EMを呈した患者が9人・・・ライムとの共感染? RESEARCH Table 3. Clinical manifestations in patients with Borrelia spp. infection, Yekaterinburg City, Russia, 2009, and northeastern United States, 1991–2008* % Patients p value B. miyamotoi, B. garinii, B. burgdorferi, B. garinii vs. B. miyamotoi B. miyamotoi vs. n = 46 n = 21 n = 92 vs. B. garinii Manifestation B. burgdorferi B. burgdorferi Individual EM 9 91 89 <0.001 <0.001 >0.999 0 14 7 0.03 0.18 0.36 Multiple EM 98 67 32 0.001 <0.001 0.005 Fever† Fatigue 98 86 74 0.09 <0.001 0.4 89 57 63 0.007 0.001 0.63 Headache 35 10 43 0.04 0.36 0.005 Chills Myalgia 59 52 63 0.8 0.71 0.46 28 29 62 >0.999 <0.001 0.007 Arthralgia Nausea 30 10 24 0.07 0.420 0.24 7 5 7 >0.999 >0.999 >0.999 Vomiting 2 0 38 >0.999 <0.001 <0.001 Neck stiffness Overall No. symptoms, mean ± SD 4.5 ± 1.4 4.2 ± 2.0 5.0 ± 2.3 0.43 0.13 0.13 No. symptoms (excluding EM 4.5 ± 1.4 3.1 ± 1.9 4.1 ± 2.3 0.007 0.46 0.09 and multiple EM), mean ± SD *EM, erythema migrans. †Maximum axillary temperature >37.2°C for patients in Russia and maximum oral temperature >37.7°C for patients in the United States. amoxicillin, 500 mg orally every 8 hours, for 2–4 weeks. A Jarisch-Herxheimer reaction was noted for 7 (15%) of the 46 B. miyamotoi patients. More such reactions might have been expected if treatment had not been delayed until 1 week after admission. A single course of ceftriaxone or (GenBank accession nos. GU797336, GU797337, GU797338, GU797346, JF951378–JF951392). ライムと比較して発熱+全身症状が多い Genetic Characteristics of B. miyamotoi The nucleotide sequences of 16S rRNA and flagellin
  37. 37. B. miyamotoi infection seems to constitute at least 1/4 of all clinical tick-borne borreliosis cases in Yekaterinburg. If other Borrelia spp.–endemic areas have a similar rate of B. miyamotoi infection as Yekaterinburg (and our tick data suggest that this assumption is reasonable), >1,000 B. miyamotoi cases might occur in Russia each year. More studies are necessary to determine if this projection is accurate. Acute B. miyamotoi infection was more severe than early stage B. burgdorferi infection. The time from symptom onset to hospital admission was shorter, and the number of clinical manifestations was greater for patients with B. miyamotoi infection than with B. garinii infection. Relapsing febrile episodes were only reported for B. miyamotoi patients. Such multiple disease episodes not only have an adverse effect on a patient’s health but also may result in costly medical bills, many days or weeks of lost wages, and medical misdiagnosis (19–22). Co-infection of B. miyamotoi with other ixodid tick– transmitted agents may increase disease severity (15,23). Additional problems that might occur with B. miyamotoi infection are ocular, neurologic, respiratory, cardiac, and pregnancy complications associated with relapsing fever (19–22). Our study had several limitations. Attempts to detect B. miyamotoi on blood smear or in culture were not successful, although we confirmed B. miyamotoi infection with a combination of qPCR, genetic sequencing, clinical, and seroconversion evidence. The comparison of clinical manifestations of Borrelia spp. infection of patients from 2例で周期性発熱が観察された B. miyamotoiのヒト感染例が 回帰熱を起こすことを示した 初の報告 Figure 2. Examples of relapsing fever episodes in 2 patients with Borrelia miyamotoi infection. Arrows indicate the timing of tick bite, hospital admission, PCR testing, anti-borreliae immunoglobulin (Ig) M testing, and initiation of antimicrobial drug therapy.
  38. 38. Figure 3. Phylogenetic tree of Borrelia spp. detected in persons and ticks, based on flagellin gene fragment (A) and16S rRNA gene fragment (B). Sequences were aligned and analyzed by using MEGA4.1 software (www.megasoftware.net). Genetic trees were constructed from the partial nucleotide sequences of the flagellin gene and the 16S rRNA gene by using the Kimura 2-parameter model and the unweighted pair group method with arithmetic mean. Arrow indicates the 16 Borrelia spp. from Yekaterinburg in 2009 that had the same nucleotide sequence. Circles indicate sequences that we listed in GenBank (accession nos. GU797331–GU797346 and JF951378–JF951392). Sequences for B. burgdorferi sensu lato and relapsing fever borreliae are shown for comparison. Scale bars indicate genetic distance.
  39. 39. 後ろ向きの血清疫学調査
  40. 40. ライム病流行地域であるロードアイランド州Block 島と Prudence島およびマサチューセッツ州Brimfield 在住者の 健常者584名 The n e w e ng l a n d j o u r na l of m e dic i n e 春から秋のマダニ活動期に採血されているが、採血時は健康であった集団 Table 1. Serologic and Clinical Characteristics of Borrelia miyamotoi Infection in Study Patients.* Group, Patient No., and Serum Phase† Assay Method ELISA Coinfection‡ No. of Symptoms Western Blot IgM IgG Group 1 Patient 1 Positive at 1:320 dilution Positive Positive None None Patient 2 Positive at 1:320 dilution Positive Negative None None Patient 3 Positive at 1:320 dilution Positive Positive None None Patient 4 Positive at ≥1:320 dilution§ Not done Positive None None Patient 5 Positive at ≥1:320 dilution§ Not done Positive None None Patient 6 Positive at 1:320 dilution Positive Positive None None Positive at ≥1:320 dilution§ Not done Positive None 5 Positive at 1:320 dilution Negative Positive None 9 Positive at 1:320 dilution Negative Positive None 8 Group 2 Patient 7 Patient 8 Patient 9 6人/584人がB. miyamotoi IgMまたはIgGが陽性
  41. 41. ELISA Western Blot ニューイングランド州南部の在住者でライム病が疑われた Group 1 IgM The IgG 患者277名 n e w e ng l a n d j o u r na l Patient 1 Positive at 1:320 dilution Positive Patient 2 Positive at 1:320 dilution of Positive m e dic i n e Positive None None Negative None None Table 1. Serologic and Clinical Positive at 1:320of Borrelia miyamotoi Infection in Study Patients.* Characteristics dilution Patient 3 Positive Positive None None Patient 4 Group, Patient No., and Serum Patient 5Phase† Patient 6 Positive at ≥1:320 dilution§ Not done Positive None Assay Positive at ≥1:320 dilution§Method done Not Positive Coinfection‡ None ELISA Positive at 1:320 dilution Western Blot Positive Positive Noneof No. Symptoms None None None IgM IgG Positive at ≥1:320 dilution§ Not done Positive None 5 Patient 1 Patient 8 Positive at 1:320 dilution Positive at 1:320 dilution Positive Negative Positive Positive None None None 9 Patient 2 Patient 9 Positive at 1:320 dilution Positive at 1:320 dilution Positive Negative Negative Positive None None None 8 Patient 3 Patient 10 Positive ≥1:320 dilution Positive atat 1:320 dilution§ Positive Not done Positive Positive None None None 6 Patient 4 Patient 11 Positive at ≥1:320 dilution§ Positive at ≥1:320 dilution§ Not done Not done Positive Positive None None None 3 Patient 5 Patient 12 Positive at ≥1:320 dilution§ 1:1280 dilution Not done Negative Positive Positive None Lyme disease None 4 Patient 6 Patient 13 Positive at 1:320 dilution Positive at 1:320 dilution Positive Negative Positive Positive None Lyme disease None Uncertain Group 2 14 Patient Positive at 1:320 dilution Positive Positive Lyme disease Uncertain Patient 15 Patient 7 Positive at ≥1:320 dilution§ Not done Positive None 5 Acute Patient 8 Negative at 1:320 dilution Positive 1:160 Negative Negative Negative Positive Babesiosis None 12 9 Convalescent Patient 9 Positive at 1:1280 dilution Positive at 1:320 dilution Positive Negative Positive Positive None 8 None 6 None None 3 5 Group 2 Group 1 7 Patient Group 3 10 Patient Patient 11 Patient 16 Positive at ≥1:320 dilution§ Not done Positive 9人/277人がB. miyamotoi IgMまたはIgGが陽性 Positive at ≥1:320 dilution§ 1:1280 dilution Not done Positive Positive Positive
  42. 42. Patient 8 Positive at 1:320 dilution Negative Positive None 9 Patient 9 Positive at 1:320 dilution Negative Positive None 8 None 3 マダニ活動期である晩春∼夏に、ニューヨーク州南部のライム病クリニック を訪れた患者のうち、上気道もしくは腸管性のウイルス感染が否定的で、か6 Patient 10 Positive at ≥1:320 dilution§ Not done Positive None Patient 11 Patient 12 つ何らかのウイルス感染症様症状を伴った Positive at ≥1:320 dilution§ Not done Positive n e w e ng l a n d j o u r na l o f m e dic i n e The 患者14名 Positive at 1:1280 dilution Negative Positive Lyme disease 4 Positive at 1:320 dilution Negative Positive Lyme disease Uncertain Table 1. Serologic and Clinical Characteristics ofdilution miyamotoi Infection in Study Patients.* Patient 14 Positive at 1:320 Borrelia Positive Positive Lyme disease Uncertain Patient 15 Group, Patient No., and Serum Phase† Acute Coinfection‡ Babesiosis No. of Symptoms 12 Patient 13 Convalescent Assay Negative at 1:160 dilutionMethod Negative ELISA Positive at 1:1280 dilution Negative Western Blot Positive Positive IgM IgG Positive at 1:1280 dilution Positive Positive None 5 Patient 1 Patient 17 Positive at 1:320 dilution Positive Positive None None Patient 2 Acute Positive atat 1:80 dilution Negative 1:320 Positive Positive Negative Negative None None None 10 Patient 3 Convalescent Positive at 1:320 dilution Positive at 1:320 dilution Positive Positive Positive Positive None None Patient 4 Patient 18 Positive at ≥1:320 dilution§ Not done Positive None None Patient 5 Acute Positive at ≥1:320 dilution§ Negative at 1:80 dilution Not done Positive Positive Positive None Lyme disease None 12 Positive at 1:320 dilution Positive at 1:320 dilution Positive Negative Positive Positive None None Group 3 Group 1 16 Patient Patient 6 Convalescent Group 2 * ELISA denotes enzyme-linked immunosorbent assay. Not done Positive None 5 † SeePatient 7 for the definition Positive at ≥1:320 dilution§ the text of the various groups. ‡ ThePatient 8 of Lyme diseasePositive at 1:320 dilutionerythema migrans skin lesion in Patients 12, 13, 14, and 9 diagnosis was based on a typical 18. Negative Positive None Patients 8 and 16 had an atypical erythema migrans skin lesion (<5 cm in diameter). Patient 9 Positive at 1:320 serum Negative None 8 § Tests to determine the presence of antibody miyamotoi IgMまたはIgGが陽性 not performed. 1:320 were 3人/14人がB. in dilutiondilutions greater thanPositive Patient 10 Positive at ≥1:320 dilution§ Not done Positive None 6
  43. 43. 概要 • ライム病流行地域では、健常者の1%で miyamotoi抗体陽性者がいる(知らず知らずの うちに感染している?) • ライム病が疑われた患者の3.2%でmiyamotoi抗体 陽性だった(ライム病との共感染または miyamotoi単独感染) • ライム病流行地域でful-like illnessを呈した患者 の21%でmiyamotoi抗体陽性だった(miyamotoi単 独感染症?)
  44. 44. miyamotoiは ライム病流行地で 蔓延している?
  45. 45. ということは 日本でも・・・?
  46. 46. そもそもmiyamotoiは 北海道で発見された わけで・・・
  47. 47. そのうち日本でも・・・ と思っていたら
  48. 48. PCRをかけまくった感染研の川端寛樹先生
  49. 49. 概要 • 過去にライム病が疑われた患者血清約800検体を用いた後ろ向き疫学 調査を実施し、このうち発症後の有熱期に採血された2検体からB. miyamotoi DNAを検出した。またこのうちの1検体ではB. miyamotoi HT31株由来の組換えGlpQ抗原を用いたB.miyamotoi特異的な抗体検査 により、回復期ペア血清で抗体上昇が確認された。 • これら2検体は北海道在住の患者より採取されたものであり、いずれ • これら2症例は国内でのマダニ刺 もライム病血清診断でも抗体陽性と判定されている。 により感染したものと考えられて いる。いずれの症例もミノサイクリンもしくはセフトリアキソン投与 により回復している。
  50. 50. 日本でも回帰熱に 罹患する!!
  51. 51. I. persulcatusの分布 北海道に多いとされているが 全国に分布している J Clin Microbiol. 2002 Jun;40(6):2176-81.
  52. 52. 日本でも回帰熱に 罹患する!!
  53. 53. miyamotoi診断のための 現実的なアプローチ • ライム病疑いの患者では血清を採取してmiyamotoi抗 体も同時に依頼 (感染研 川端寛樹先生) • I. persucatusの生息する地域でのダニ曝露後にfull-like illnessを呈した患者で、原因が分からないものに関 してはmiyamotoi検査を考慮(特に回帰性発熱を呈す る患者では積極的に疑う)
  54. 54. 日本でも回帰熱に 罹患する!!

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