日本でもBorrelia miyamotoiに感染しうる！

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. 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. だと思っていませんか？

4. いきなりですが
症例呈示

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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 1例報告でNEJM...

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. 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. 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. 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. miyamotoiって？

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. 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. 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. 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. 日本でも回帰熱に
罹患する？

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. なんとその数・・・

32. 46例

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. 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. 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. 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. 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. 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. 後ろ向きの血清疫学調査

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. 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. 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. 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. miyamotoiは
ライム病流行地で
蔓延している？

45. ということは
日本でも・・・？

46. そもそもmiyamotoiは
北海道で発見された
わけで・・・

47. そのうち日本でも・・・
と思っていたら

48. PCRをかけまくった感染研の川端寛樹先生

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. 日本でも回帰熱に
罹患する！！

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. 日本でも回帰熱に
罹患する！！

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. 日本でも回帰熱に
罹患する！！