Jpn. J. Infect. Dis., 53, 2000

Laboratory and Epidemiology Communications

Acute Hepatitis Outbreak in Tokyo Caused by Hepatitis A Virus ofCommon Origin Transmitted through Oral and Sexual Routes
Masashi Baba, Hiroyuki Oka, MasakoAsayama, Syuya Yoshinaga, Hiroko Yamashita,
Natsuo TachikawaI, Jun‑ichi Akiyama, Akira Yasuokal, Shin‑ichi Okal, ShigeruYamato,Ryosuke Shoda, ToruMuraoka, Naohiko Masaki, Kei Matsueda,
Emi Shimq】o and Shigeki Hayashi*Department of Gasly10enterOlogy and IAIDS Therapy and ReseayICh Center,
International Medical Center ofJapan,
Toyama 1‑21‑I, Shinjuku‑ku, Too/o I62‑8655
Communicat￠d by Hiroshi Yoshikura(Accepted June 22, 2000)

Hepatitis A virus (HAV) is transmitted by fecal‑Oral routes.

national hospitals in 1990 and 1 15 cases were reported inOutbreaks can occur in families (1)and among homosexuals

1991. The number ofHAV cases gradually declined a洗er 1991

(2). Infection acquired byingesdon of infected clams or oysters

and in 1995‑1998, only 20‑50 cases were reported armually.

is frequent (3). Japan experienced large outbreaks in 1 990andIn I 999,anunusually large number ofHAV‑infected patients
visited our climiC: three patients were seen in January‑March,four patients in May‑June, five patients in July‑September,and two patients in October‑December. Patients'clinical

1 991. One hundred and eighty‑seven cases were reported at*Corresponding author: E‑mail : shayashi@imcj. hosp.go.jp

127Jpn. J. Infect. Dis., 53, 2000
Table I. Patients'characteristics

patient Age Da(Suo,fa.?.nns)etl' severity2, ,S.TeTbd othermarken
126

2/07

240

3/07

343

3/26 (78)4374/03

542

4/25

620

727

835

930

sexual HBsAg(+), HBeAg(+)(26)

H I V(+)/asymptomatic

101

41

12shell+sh(‑)

(‑)

(40)

oyster(‑)(28)

uncl飽r(‑)

6/15 (34)

unclear(‑)

6/29

sexual HBeAb(+), HBeAg(‑)

7/07

(27)

(22)

(22)

9/18 (23)1334

10/06 (35)

1455

12/21

shellfish(‑)

unclear(‑)

unclear HBeAb(+), HBeAg(‑)

7/23 (82)
8/28

47

G

oyster

7/06 (103)

37
1(54)

shellRsh(‑)

unclear(‑)

sexual HBeAb(+), HBeAg(‑)
H IV(+)/asymptomatic(30)+oyster(‑)

Acute renal failure1)MontM)ay (Days from onset ofillness to return of alanine aminotransferase levels below100).

2)Criteria of severity was a prothrombin time below 40%and/or presence of other serious
complications. +: severe cases. ‑: not severe cases.

3)Route of infection was deduced &om circumstantial evidence, for example, homosexuality,
Ingestion of clams or oysters, travel abroad, etc.

Table 2. Laboratory findings

patient (:･Zlii) (DJdBill･) (IUS/I) (IUL/I) (LD/T) (IUL/;)てI‑uG/I)p (:I) TcTiFIT
12

2.2

1.7

1.1

1.0

3

8. 1

4

8.5

5

5.6

3.5

1.4

7.5

6

1

6. 1

4.5

3.5

8

5.8

4.0

9

9.3

8.3

10

15.0

11.8

11

1.0

0.5

1194

298

1842

498

492
1198

184
1281

5.2

5264

1440

589

324

36.6

547

449

313

40.3

5.3

2370

4540

1210

1068

522

78.0

5.3

92.0

5.8

174

708

223

625

61

1790

400

457

270

154

2666

304

728

517

1479

759

505

121

676

3 16

79.0
82.0

179
412

5.4
5.5

99.1

1058

714

1401

770

234

1 003

1 79

81.7

95.0127.9

5.2

774

2137

398

587

327

93.7

13&. 1

5.6

1476

2961

469

577

335

71.4

14&. 1

12257

9857

8192

852

6.9

4.4
3.95090

1798
195.0
73.5

1078

4042

6.0

7467

885

2665554∠U 2 00 748.7

T. Bil. : Totalbilirubin D. Bil. : Direct bilirubin AST:Aspartate aminotransferase
AIJ: Alanine aminotransferase LDH: Lactate dehydrogenase ALP: Alkaline phosphatase
γ‑GTP: γ‑glutamyl transpeptidase PT: Prothrombin time HA IgM: Anti‑HA IgM Antibody

C.0.I.: Cut̲off index

In the previous outbreaks in 1990 and 1991, the infection

profiles and laboratory findingsare shownin Tables 1 and 2.
VPll2A reglOn Of HAV was PCR‑amplified from ten
serum/plasma preparations. Among them, eight sequences

was clustered in January‑April. In 1 999, however, infection
was distributed evenly throughout the year. In 1990‑1991 ,only one transitional base change. Thus, these nine patients

infected oysters or clams were the most likely major sourcesof infection, whereas in 1 999, infections contractedvia sexualand other routes were observed. A similar situation has been

were considered to have beeninfected by a strainofHAV of thereported (4).

(patients 1, 2, 4, 8, 9, 10, ll and 13) were identical. HAVfrom patient 7 was different from that of the others, but bysame origin. TYLe Sequence had a homology tothe HAW IB group,
GBM strain, which caused a large outbreak in Germany ln
1997. HAVfrom patient 3 had a quite different sequence;theREFERENCES

1. Frosner, G. G., Overby, L R., Flelmig, B., Gerth, H. J.,

sequence was close to that of the IA group, which causedHaas, H., Decker, R. H., Ling, C. M., Zuckerman, A. J.

outbreaks in Japan in 1990‑1991.

128

Jpn. J. Infect. Dis., 53, 2000
Patient Numberl50

1, 2, 4, 8, 9, 10, 1 1, 13

5㌧ TmCCTAGAGCTCCATTGAATTCAAATGCTATGTTGTCCACTGAGTCTA

73‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑I‑‑A‑‑I‑‑‑‑‑‑‑ll‑‑‑‑‑‑‑‑‑‑‑‑I‑‑‑‑C‑51

100

TGATGAGTAGAATTG C AG C TGGAGAC TTGGAGT C ATC AGTGGATGAT C C T

1‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑I‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑G‑‑‑‑‑‑‑‑‑‑‑‑101150

AGAT CAGAGGAGGATAGAAGATTTGAGAGT C ATATAGAATGTAGGAAAC C‑‑‑‑‑‑‑‑‑‑‑‑‑‑C‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑151

200

ATACAAGGAATTGAGATTGGAGGTTGGGAAACAAAGAC TTAAATATG C T C‑‑‑‑‑‑A‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑C‑‑‑‑‑‑‑‑‑‑201

250

AGGAAGAGTTGT CAAATGAAG TG C TTC C AC C TC C TAGGAAAATGAAGGG‑‑I‑‑‑‑‑‑‑ll‑ll‑‑‑‑‑‑I‑‑‑‑‑‑‑‑‑‑‑‑‑I‑‑‑‑‑‑I‑‑G‑‑‑‑‑‑‑一一一‑‑‑一一‑C‑‑‑‑‑‑‑‑A‑‑‑‑‑‑‑‑一一一一‑‑‑‑‑‑‑I‑‑G‑‑‑251284GTTTTCTCTCAGGCTAAAATTTCTCTTTTTTATA ‑3 I
一一A一一T一一A一一一一一一一一一一一一一一一一一一一一一一一一一Figure. Sequence of the HAY VP 1 ‑2A reglOn amplified by PCR.
RNA was extracted舟om 80 LEI of serum or plasma preparations byusing Sumai‑test (Sumitomo, Tokyo). VP I ‑2A

reg10n Was RT‑PCR‑amplified with external PCR primers, 5 ㌧GGTTTCTATTCAGATTGCAAATTA‑3 'and 5 ㌔

AGmAGAACTCCAGCATCCATCTC‑3 一and intemal prlmerS, 5 '‑TTmGTTGTTATTTGTCTGTC‑3 一and 5 '‑CATTATTTCATGCTCCTCAG13 '･ PCR products we.re purified by WizardRPCR prep (Promega, Madison･ Wis･･USA)and sequenced by Bigdyeterminatorcycle sequenclng r飽dy reaction kit (ABI Ltd.). The sequences wereanalyzed

by Neighbour‑Joining method by using CLASTAR W so氏ware.

and Frosner, H. 良. (I 977): Seroepidemiological investi一J. M.and Liu, 0. C. (1966): Accumuladonand eliminadon

gation of patients and family contacts in an epidemic ofofpoliovirus by the Eastem oyster. Am. J. Epidemio1.,
84, 40‑50.

hepatitisA. ∫. Med. Viro1., 1, 163‑173.

2. Corey, L. and Holemes, K. K. (1980): Sexual transmis‑

4. Gust, I. D. and Feinstone, S. M.(1988): Epidemiology.

sion of hepatitis A in homosexual men. N. Engl. J. Med.,

p. 163‑192. In Boca Raton, F. F. (ed.), Hepatitis A. CRC
Press, Inc., Boca Raton, Fla., USA.

302, 435‑438.
3. Mitchell, ∫. 良., Presnell, M. W., Atkin, E. W, Cummins,

129