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1 Infectious Agents Surveillance Report (IASR) SFTS 3, SFTS 4, SFTSV 5, SFTSV : 7, 03 SFTS 40 8, SFTS 9, SFTS 0, AHpdm09, 03/4 AHpdm09, 3, Zika fever 5, 6, CA 8, 03 CA6 9, HHV6 0, CRS, Vol. 35 No Vol.35 No. No.408 ISSN Tel ,,, :,,, severe fever with thrombocytopenia syndrome: SFTS, SFTS virus SFTSV, ,,,,,,,,, AST, ALT, LDH,, SFTS 0, 03 SFTSV : SFTSV, SFTSV, SFTSV, Haemaphysalis longicornis Rhipicephalus microplus SFTSV, SFTSV, SFTS Amblyomma testudinarium SFTSV SFTSV,,, SFTS : 0,,,, SFTSV,, SFTSV, SFTS IASR 34: 404, 03, SFTS rapid/graph/pt398.gif , SFTS SFTS 8 SFTS IASR 34: 0809 & 0, 03, 0 3 SFTS SFTS, 4, 6 3

2 , 5,, 8 SFTSV,,,,, 5 03 SFTS : SFTS 4 : kekkakukansenshou/00443.html, SFTSV IASR 34: 0, 03, 4 7 SFTS 4, 03 48,, , , 00, 0 5 : IASR 34: 0, ,,, 3 4, 6, 4895, SFTS, SFTS, SFTS 9, IASR 34: 0708, 03, SFTSV, Vol. 35 No , SFTS, SFTS 8 :, SFTSV, RTPCR SFTSV, SFTSV IgG,,, RTPCR SFTSV, SFTSV SFTSV IgGELISA 0, SFTSV SFTSV IASR 34: , 03 : 03 SFTS,, SFTS, SFTS 5 3, SFTS SFTS, SFTS, SFTS,, SFTS, 3, 4SFTSV, 5 SFTSV SFTSV,

3 病原微生物検出情報 Vol. 35 No 表. SFTS患者の症状 特集関連情報 参考文献 6) 臨床症状 中国での重症熱性血小板減少症候群の発生状況 参考文献 7) 97% 00% 㣗ḧ 75% ປ 65% 94% fever with thrombocytopenia syndrome: SFTS の 䛝Ẽ 69% 76% 発生は 006 年秋の安 省の事例 患者数 4 名 が最も ③ 49% 56% 早いものと考えられる この事例はヒト顆粒球性アナ 47% 64% ᛰឤ 46% 8% ⑩ に類似していたことから, 当初同感染症との診断がな 4% 66% 䝸䞁䝟 33% されていたが, SFTS が新興感染症として認識され ③ 7% 中国における重症熱性血小板減少症候群 severe プラズマ症の症状 発熱, 白血球減少, 血小板減少等 9% 54% 69% た後に再調査の結果, SFTS であると明らかになった ものである イルスは咽頭スワブ 尿 便からも検出されるが, こ これまで中部を中心とする 省 安 省, 湖北省, れは出血した血液由来のウイルス量を反映したものと 河南省, 山東省, 遼寧省, 陝西省, 四川省, 雲南省, 広 考えられる9 回復者は抗体陽性となり, 長期にわた 西省, 江西省, 浙江省, 江蘇省 で SFTS の発生が報 り持続する6 告されている 図 Dingらの 0 0 年の 年 SFTS の原因ウイルス SFTSV の伝播経路のひと 間のまとめの報告によると, 患者数は計,047 名 男性 つは SFTSV 保有マダニの刺伵である Haemaphysalis 955 名, 女 性,09 名, 年 齢 は 90 歳 中 央 値 は 58 longicornis フ タ ト ゲ チ マ ダ ニ や Rhipicephalus 歳, 死亡は9名 男性 7名, 女性58名, 致死率 6.3, microplus オウシマダニ から SFTSV 遺伝子が検出 死亡患者の年齢中央値は 64 歳で回復者と比べ優位に もしくは SFTSV が分離されている6, 7 血液や気道分 高い, 患者の 80 以上が山岳地帯の農業もしくは林業 泌物を介したヒトからヒトへの感染例も複数報告され 従事者, 発生時期は 3 月で 5 8 月の発生が 75 ている, 03 しかしマダニの刺伵, ヒトヒト感染の 以上を占める, 非農業従事者の致死率 0. は農業 いずれも確認されない事例もある 従事者のそれ 5.8 より高い, 移入者の致死率.0 SFTS 患者が発生した地域における家畜の抗体保有 は地元民のそれ 6.3 より高い, 患者数の多い 率は高く, 特にヤギやヒツジでは が抗体陽性 省は河南省 48, 湖北省, 山東省 6 の順 である5, 46 ウシ 34 6 やニワトリ 47 にお である3 Liuらによる患者年齢の分布を図 に示す4 ける抗体陽性率も比較的高い5, 6 これらの家畜やイ 潜伏期は 6 3 日で, 発熱 血小板減少 白血球減 ヌ げっ歯類から SFTSV が分離あるいは遺伝子が検 少 血中肝酵素上昇等は 7 日間程度みられ, 血中 出されるが, 症状を示す動物は今のところ知られてい ウイルス量は copies/ml に達する5 SFTS 患 ない5, 7, 8 家畜に刺伵するマダニから SFTSV が検 回復者で 出されており6, 9, これらの動物への SFTSV の伝播 はこれらの数値は改善し, 発症後 週間程度で正常値 経路もマダニの刺伵であると考えられる 発生地域の 者に多く認められる症状を表 に示す 6, 7 に戻るが, 死亡例では経過中数値は悪化を続け, 発症 後 9 日 中央値 で多臓器不全や播種性血管内凝固症 候群により死亡する5 血中ウイルス量 肝酵素値 サイトカイン量 IL6, IL0, IFNγ ケモカイン量 IL8, MCP, MIPβ は重篤度と相関する8, 9 ウ 健常人でもわずかながら抗体陽性者が認められている 参考文献 Zhang, et al., JAMA : 6370, 008 Liu, et al., Vector Borne Zoonotic Dis : 㻝㻞㻡 㻝㻜㻜 患者数 遼寧省 㻣㻡 㻡㻜 山東省 雲南省 広西省 㻤㻡 㸺 㻤㻜 㹼 㻣㻡 㹼 㻣㻜 㹼 㻢㻡 㹼 㻢㻜 㹼 㻡㻡 㹼 㻡㻜 㹼 㻠㻡 㹼 㻠㻜 㹼 㻟㻡 㹼 㻟㻜 㹼 㻞㻡 㹼 㻞㻜 㹼 㻝㻡 㹼 㻜 㻡㹼 浙江省 江西省 㻞㻡 㻝㻜 㹼 江蘇省 省 㻜㹼 陝西省 河南省 安 湖北省 四川省 年齢 図. 0年の中国におけるSFTS患者649名の年齢分布 図. 0年の中国におけるSFTS患者の分布 Liu, et al., Rev Med Virol, 03 Dec 6. doi: 0.00/rmv.776. [Epub ahead of print]䜘䜚ᨵኚ

4 434 Vol. 35 No , 0 3Ding, et al., Clin Infect Dis 56 : 68683, 03 4Liu, et al., Rev Med Virol, 03 Dec 6, doi: 0. 00/rmv.776 [Epub ahead of print] 5Dexin, Emerg Microbes Infect : e, 03 6Yu, et al., N Engl J Med 364 6: 5353, 0 7Xu, et al., PLoS Pathogens, 7 : e00369, 0 8Zhang, et al., Clin Infect Dis 54 4: 57533, 0 9Sun, et al., J Infect Dis 06 7: , 0 0Gai, et al., Clin Infect Dis 54 : 495, 0 Bao, et al., Clin Infect Dis 53 : 084, 0 Chen, et al., Int J Infect Dis 7 3: e06e08, 03 3Tang, et al., J Infect Dis 07 5: , 03 4Zhao, et al., Emerg Infect Dis 8 6:963965, 0 5Cui, et al., Am J Trop Med Hyg 88 3: 50 5, 03 6Jiao, et al., J Clin Microbiol 50 : 37377, 0 7Bao, et al., N Engl J Med 365 9: 86865, 0 8Niu, et al., Emerg Infect Dis 9 5: , 03 9Zhang, et al., J Virol 86 5: , 0 :, severe fever with thrombocytopenia syndrome: SFTS, ,, SFTS 0 3,,,,,,,,,,, SFTS SFTSV,,,,. SFTS,,,,, SFTS,,,,, SFTS, ,, SFTS ,,, nih.go.jp/niid/images/iasr/rapid/graph/pt398. gif,,,, 0 4 SFTS 0, SFTS,,,,,, Q & A,,,,,,. SFTS, 3,, SFTS,

5 Vol. 35 No SFTSV, SFTS, SFTS,,,,,,, SFTSV,, 3 4 SFTS, SFTSV,,, SFTS,, SFTS, 3. SFTS SFTS,, SFTS, SFTS, CDC SFTSV, SFTS,, PCR, 3 SFTS, SFTS,,, SFTSV,,,, 5,, SFTS,,,,, SFTSV,,,,,,,,, SFTSV,,,,, SFTS, SFTS,, SFTS,,,,,,,,,,, SFTS SFTS severe fever with thrombocytopenia syndrome: SFTS 0 8, SFTS SFTSVSFTSV S, M, L RTPCR, SFTSV 4, 8 SFTSV, S, M, L, SFTSV, 8 SFTSV,, 3 6, SPL004A 7,

6 636 Vol. 35 No. 04. (A) Segment S A (B) Segment M A (C) Segment L A B B B Japan Japan Japan. SFTSV. SFTSV Chinese Lineage S Japanese Lineage A B 3 N NS JS4 HN6 HB9 JS3 YG 003A 004A 005A 00A 030A 03A 035A JS HN HB JS YG SPL003A SPL004A SPL005A SPL00A SPL030A SPL03A SPL035A M Chinese Lineage A B 3 Japanese Lineage GPC JS4 HN6 HB9 JS3 YG 003A 004A 005A 00A 030A 03A 035A JS HN HB JS YG SPL003A SPL004A SPL005A SPL00A SPL030A SPL03A SPL035A L Chinese Lineage Japanese Lineage A B 3 RdRp JS4 HN6 HB9 JS3 YG 003A 004A 005A 00A 030A 03A 035A JS HN HB JS YG SPL003A SPL004A SPL005A SPL00A SPL030A SPL03A SPL035A

7 Vol. 35 No SFTSV S, M, L, L RNA RNA RdRp, M GPC, S N, NS, S, M, L, SPL004A 98, M 94 7, 99, 97 SFTSV, SFTS,, :. severe fever with thrombocytopenia syndrome virus: SFTSV,,, CFR the Code of Federal Regulations:, SFTSV,,,, BSL3 SFTS,,, BSL3, SFTSV, 03 3, SFTSV 7 SFTSV 56 6, SFTSV,,,,,, SFTSV SFTS,, SFTSV BSL,, SFTS 4, SFTS,,., SFTSV, 6,, 5, 9070,,,, SFTSV 6, SFTSV, SFTSV SFTSV,,,, SFTSV,, SFTS,,,,,,, SFTSV, 7,, 0 9 /ml

8 838 Vol. 35 No. 04.,, SFTS, SFTSV,,, 8 SFTS,, Bao CJ, et al., Clin Infect Dis 53: 084, 0 Liu Y, et al., Vector Borne Zoonotic Dis : 56 60, 0 3Gai Z, et al., Clin Infect Dis 54: 495, 0 4Tang X, et al., J Infect Dis 07: , 03 5Chen H, et al., Int J Infect Dis 7: e06e08, 03 6,, IASR 34: 333, 03 7Zhang YZ, et al., Clin Infect Dis 54: 57533, 0 8,, IASR 34: 6970, severe fever with thrombocytopenia syndrome: SFTS 03, 3 4 8, 4 48, , 5, SFTSn=40 03SFTSn= , 73, , , 83, p0.0, Wilcoxon rank sam test , n=8, 8 5,,, , 3 53, 53, 7 8 SFTS,,, SFTS, SFTS SFTS, ,,,, , 5,,, SFTS 30,,,,

9 Vol. 35 No Takahashi T, et al., J Infect Dis, 03 Dec, doi: 0.093/infdis/jit603 [Epub ahead of print] Zhang YZ, et al., Clin Infect Dis 54 4: 57533, 0 3 SFTS 030, Yu XJ, et al., New Engl J Med 364 6: 53 53, 0 5Ding F, et al., Clin Infect Dis 56 : 68683, 03 severe fever with thrombocytopenia syndrome: SFTS, 0 SFTS SFTSV 03, 005 SFTS, 3.5,,, : 60 :, : : 990 :, 03, 3 :,, : , 4 39,, cefepime 3 4 6, WBC,000/l, Plt 5./l, AST 607 IU/l, ALT 09 IU/l,,,,, : 65cm, 63kg,, 0/70mmHg, 76/min, 39., SpO 94, :, :,,, :, :, :, : WBC,700/l, Plt 4.4/l, AST 64 IU/l, ALT IU/l,GTP 5 IU/l, LDH 77 IU/ l, CK 530 IU/l, BUN mg/dl, Cr 0.97 mg/dl, CRP 0. mg/dl, BUN 6.6 mg/dl, 0.9 ng/ml,,90 ng/ml, silr,8 U/ml, PT INR.07, APTT 40. sec, FDP.9g/ml, Ddimer 6.3g/ml, 4, 3, : slight hypocellular bone marrow,, X, CT, CT : : SFTSV RTPCR :, IgG, IgM : 4/6 5/5 Orientia tsutsugamushi, Rickettsia japonica IgG, IgM : 4/6, 5/5 : 5,,,, SFTSV,, minocycline, ciprof loxacin,, DIC,,,, minocycline ciprof loxacin,, DAY DAY7 DAY4 MINO 00mg/ CPFX 600mg/ WB (μl),700 3,500 3,900 3,800 4,900 Platelet (/μl) AST (IU/l) LDH (IU/l) CK (IU/l) CRP (mg/dl)

10 040 Vol. 35 No. 04.,, SFTSV SFTS 3,, SFTS,,, Yu XJ, et al., N Engl J Med 364 6: 53 53, 0 Takahashi T, et al., J Infect Dis, 03 Dec, doi: 0.093/infdis/jit603 [Epub ahead of print] 3Gai ZT, et al., J Infect Dis 06 7: 0950, 0,,, SFTSV SFTSV PCR,,, SFTS SFTSV RTPCR,, SFTSV, RTPCR,,,,,,,, SFTSV PCR PCR, 0 severe fever with thrombocytopenia syndrome: SFTS, SFTS SFTSV SFTSV SFTS 03 SFTS,,, SFTS SFTS EcoRI, EcoRI 03 3, SFTSV SFTSV,,, SFTSV primer set primer set primer set primer set NTC P.C NTC P.C Uncut Cut Uncut Cut PCR

11 Vol. 35 No IgGIgM, IgG IgM SFTSV : 3,, SFTSV IgG IgM, SFTS, SFTSV IgG ELISA Vero,, SFTSV SFTSV SFTSV, BSL3,, SFTSV, SFTSV, PCR,, SFTSV ELISA SFTS, Yu XJ, et al., N Engl J Med 364: 5353, 0 AHpdm09, 03, AHpdm09 : 39, HIV, 0, 03 37, 6, 38.0 A, 9 CT, A ARDS, ICU MRSA,, 3, : 9 Lamp, Lamp AHpdm09, 0 HI, A/California/07/ 009HNpdm09 HI : 0, : 30, A/Texas/50/0H3N, B/ Massachusetts//0, B/Brisbane/60/ 008Victoria : 0, AHpdm09,, 9 3, 300mg/, 50mg/ 8, 30, : 03 4 AH3, 5AHpdm09,, AHpdm09, 00900

12 4 Vol. 35 No. 04., 3, 4, 5,,,, A,,,,,,,, 48 sapporo.jp/eiken/infect/trend/graph/l50.html Chowell G, et al., N Eng J Med 36: , 009 3CDC, MMWR 58: 07074, 009 4IASR 33: 8594, 0 5Inf luenza update, WHO, luenza/surveillance_ monitoring/updates/03 09_surveillance_ update_00.pdf 03/4 AHNpdm09 03/4, AH3N, AHNpdm09, B 7 AH3N 3, AHNpdm09 5, B AHNpdm09, AHNpdm09 NA H75Y,, 03/4 AHNpdm09 5,, 5 H75Y,,,, H75Y 5,,,, AHNpdm09, RNA,, 5 H75Y 03/4 6, 4 0,,, 6 HA NA, 6,, 3,, 9 AH3N, AHNpdm09, 03/ AHNpdm09, 0.3% 4,, AHNpdm09 57,

13 Vol. 35 No , 4, 007/08 AHN, 008/09, 00, H75Y,,, AHN NA, H75Y, RQV34M, HA T8K, K4E R89K 3,, 5, 6, AHNpdm09, NA V4I, N369K N386S 3 H75Y 7, 3 V4I N369K, 6, V4I N369K, N386K 386 K S H75Y, NA H75Y,, 80,,,, AHNpdm09, 4,, 500,,,,, Takashita E, et al., Euro Surveill 9: pii: 0666, 04,, IASR 35: 44, 04 lum/f luiasrs/ 46pr4073.html 3Takashita E, et al., Inf luenza Other Respir Viruses 7: , 03 4US CDC, FluView 0304 Inf luenza Season Week 5 ending December, 03 5Bloom JD, et al., Science 38: 775, 00 6Ginting TE, et al., J Virol 86: 7, 0 7Hurt AC, et al., J Infect Dis 06: 4857, 0 8Kawai N, et al., J Infect 59: 07, 009 9Kawai N, et al., Clin Infect Dis 49: 88835, 009 0Saito R, et al., Pediatr Infect Dis J 9: , 00 Baum EZ, et al., Antiviral Res 59: 3, 003 Baz M, et al., Antiviral Res 74: 596, 007 AHNpdm09 03/4, AHNpdm09, AHNpdm09 5, 03, 03, AHNpdm09, ,, AHNpdm NA TaqMan RTPCR

14 444 Vol. 35 No AHNpdm0903/4 75 H Y H75Y H75Y : H75Y S43G MDCK A97T AHNpdm09 RNA NA 7 S85T A/Mie/7/03, MDCK H75Y A/Mie/7/03 TaqMan RT D97N PCR, A/Mie/7/03 NA, V4I, N369K, N386K NA : A/Mie/7/03NA S03T,,,, P83S I3V IC nM, 6.5nM, 0.8nM, 0.93nM,, HA : 7 6 AHNpdm09 HA, HA D97N, S85T 6 A/Mie/7/03, 03/ A/Mie//03, A/Mie/3/03 4 HA, 3 : 5, 69, 83 H75Y :,, 03 0 H75Y /9/4 03/9/ A/Mie// /9/4 03/9/ A/Mie/3/ /9/5 03/9/ A/Mie/4/ //5 03// H75Y A/Mie/7/ //3 04// A/Mie// //5 04//6 40 A/Mie// //9 04// A/Mie/3/04 03/4 0/3 S84G H38Q A/Turkey/605/03 JAN A/Saipan/697/03 FEB A/MIE//03 JAN A/New Mexico/07/03 MAR A/Slovenia/505/03 FEB A/FUKUOKAC/8/03 MAY K63I A/YOKOHAMA//03 JAN A/MIE//03 JAN A/NAGANOC/3/03 JAN A/SAPPORO/63/0 MAR A/Hong Kong/0/03 JAN A/NAGANO/3/03 MAY A86T A/Bangladesh/0/0 JUL A/Cambodia/3/03 JAN A/OSAKA/34/03 APR A/Wisconsin//03 JUN A/Florida/0/03 JUL A/MIE//03 MAY K83E A/KANAGAWA/4/03 MAY A/Haiti/030/03 JUN A/MIE//04 JAN A/MIE/4/03SEP T5S E83D A/SAPPORO/07/03 NOV A/MIE/7/03 DEC 4,, 5,,,,, A AHNpdm09, 7 H75Y A/Stockholm/3/0 OCT A/Florida/9/03 JUL A/England/358/03 FEB A/Hawaii/0/03 MAY A/MIE//04 JAN K63Q V34I A/MIE//03 SEP 039 A56T D69E A/MIE/3/03 SEP A/Delaware/03/0 /03/0 FEB 5 A/Georgia/07/0 MAR A/Christchurch/6/00 JUL A/Brisbane/0/00 APR 4 A/NARA/59/0 MAR A/Kenya/04/03 FEB A/SAITAMA/88/0 NOV 8 A/Cameroon/LEID/07//870/0 JUL A/Nigeria/538/0 AUG A/Mexico/08/0 MAR A/FUKUI/67/0 MAR A/GuangdongXiangzhou/63/0 JUL A/New Mexico/07/0 MER A/ISHIKAWA/70/0 MAR A/Pakistan/680/0 JUL A/Narita/0/009 MAY A/Mexico/InDRE4487/009 APR A/California/07/009 APR 3. AHNpdm09HA 6

15 Vol. 35 No ,,, 03, AHNpdm09 5, 009,, 6,,,,, AHNpdm09, :, NA,,,, lum/068f lu/ f ludr/,, IASR 35: 443, 04 lum/f luiasrs/ 43pr408.html 3, 03/4 lu/ bunri/bunrihyou34.htm 4,, IASR 34: ,, IASR 35: 44, 04 lum/f luiasrs/ 46pr4073.html 6, 38 : 060, 00 Zika fever, Zika Zika fever Zika fever : , 38 0, 3, 37.,,, 3,30/l, 4.9/l NS, IgM IgG 3 realtime RTPCR Zika virus ZIKVRNA,, : , 337, 9, 3,,,, ,,,,, 3,470/ l, 4.7/l NS, IgM IgG 3, realtime RTPCR ZIKV RNA, Zika fever ZIKV, Aedes africanus, Ae. apicoargenteus, Ae. luteocephalus, Ae. aegypti, Ae. vittatus, Ae. furcifer, Ae. hensilii ZIKV,,, ZIKV 007, Centers for Disease Control and

16 646 Vol. 35 No. 04. Prevention CDC 03 ZIKV, Zika fever,,,,,, 4 7 PCR ZIKV RNA, IgM,,,,,,,,,,, Zika fever Centers for Disease Control and Prevention, Zika Fever in French Polynesia Tahiti Hayes EB, Emerg Infect Dis 5 9: , ,, 999 4, PCV , 00 5 PCV7 007, 0 0, 7, 5, 008 Haemophilus inf luenzae b Hib, 00 5 Hib, 03 4 Hib, 0 0, 9, PCV7 Hib A, invasive pneumococcal disease: IPD invasive Haemophilus inf luenzae disease : IHD 5,, 03 : NESID ,,,,,,. : PCR,. :, PCR,, 3. :,.,,., 3., 3 : IPD 67, IHD 89 IHD IPD 3.3 IPD, IHD IPD IHD, IPD, IHD 5 60,, IHD, IPD, IHD 6 IPD, IHD 5.8, 8.0, IPD, 64,,, IPD,, 4,

17 Vol. 35 No IHD, 64, IHD, 60, 6 : IPD IHD IPD 6, 64,,, PCV7, 70, 50, IPD, PCV7 NSW IPD 3 IPD 4, NSW IPD 7 8, IPD, PCV7 6B, 4, 3F, 9F, PCV7, 9A, 6B, 4, 3F, PCV7 9A, 5A, 5B, 5C, F, 6C, PCV7 IPD 77., 44.4, PCV7 PCV7 IPD, 03 5 PCV7 3, 9A IPD Hib, IHD 9, 8, IHD, 5, IHD, IHD,, 4 IHD, Hib 97, nontypable H. inf luenzae; NTHi 3, Hib 83, NTHi 7 NTHi Hib NTHi IHD 5, 6, a Hia IHD 7 PCV Hib IPD IHD,,,,, 5, 0 IPD IHD 8,

18 848 Vol. 35 No. 04. :,, IASR 34: 5556, 03 IASR 34: 8586, 03 3McIntyre P, et al., NSW Public Health Bulletin 4: 8589, 003 4Livorsi DJ, et al., J Infect 65: , 0 5Dworkin MS, et al., Clin Infect Dis 44: 8086, 007 6Kastrin T, et al., Eur J Clin Microbiol Infect Dis 9: 66668, 00 7Ulanova M, Tsang RSW, Lancet Infect Dis 4: 708, A,, , A CA, , 7, 38.3, 39,,,,,,,, PCR, NCBI Blast, CA VP CODEHOP PCR VP, 35bp, CA JN , C VP, CA, A549, CPE, C, CA 0, CA CA4 0 4 CA, CA CA, CA, 3, 00, 85 AB863033/F360P/Tokyo/03 * AB863034/F37P/Tokyo/03 * JN69053./Humancoxsackievirus A GQ3976./Human coxsackievirus A4 AY9958./Human coxsackievirus A JX53567./Human coxsackievirus A3 AY994./Human coxsackievirus A AF08307./Human coxsackievirus A8 AY99568./Human coxsackievirus A7 KC76377./Human enterovirus A7 FJ5595./Human coxsackievirus A6 *

19 Vol. 35 No ,,,, CA,,, J Clin Microbiol 44: , 006 Emerg Infect Dis 8: 884, 0 3Virus Genes 45: 077, 0 03 A6 03, 5, , 0 6., RDA 37 3 CPE,,, VP VP4, RNA, CODEHOP PCR VP,,, , CPE, A6CVA6, 6, 0 6 CPE, 4 CVA6 7 CVA6 6, CVA, 6 CODEHOP PCR,, CVA6 4, 3, CVA CVA6 CODEHOP PCR 376bp, 330bp,, CVA6 VP, 0JapanB 4, 0 CVA6, 3 03Kumamoto, CVA6 0 CVA6, CVA6,, 5 0JapanA CVA6, 0 8, 0 03, 3 03Kumamoto, CVA6, 03 7 RDA CPE,, 0 CVA6,,

20 050 Vol. 35 No CVA6VP85bp Allan W, et al., J Clin Microbiol 44: , 006 IASR 33: 606, 0 3IASR 34: 33, 03 HHV ,, , 3 : 63, 6 HHV6: 68, : 40, RS RSV: 7, : 7, HPeV: HHV6/RSV / 5, 4, HHV6, 68 EV68, HPeV A6 CA6, ,,,, 39.3,, RSV, HHV6,, EV,, 3 0 /l HHV6, RSV,, EV, EV68, RDA, Vero E6, FL, LLCMK, Caco HEp, RDA CPE, EV, EV CPE HPeV 3, HPeV realtime RTPCR 4, HPeV 03, EV7 CA6 CA6,, CA6 HHV6, HHV7 5 HPeV,,

21 Vol. 35 No Day Day , EV HPeV 03 9, 4, 3 4,, EV68, HPeV, 8 Echo8 HPeV,, HHV6, HHV6 DNA,, EV68, HPeV CA6 NESID HHV6,,,,, HHV6,,,,,,, Saito Y, et al., Brain & Development 34: , 0,, 7: 8393, 999 3Pham NTK, et al., J Clin Microbiol 48: 59, 00 4Nix WA, et al., J Clin Microbiol 46: 5954, 008 5

22 5 Vol. 35 No. 04., , WHO RCV RCV, , RCV, RCV 3, 4 94 RCV, 8 6 RCV, 89 0, EUR30,536 WPR44,75 9,9,000,,,, RCV AMR, 009 CRS, CRS EUR, 0 30,536, 000 6,039 95, 0 EURWPR,,,,, 0 RCV 83 vs 43,, CRS CDC, MMWR 6 48: , 03, , WPV, 0 98, 0 58, , 0 WPV 0, 9 84 FATA KP, WPV , 45 4 OPV, 6 5 3, WPV 5, cvdpv, OPV VDPV 0 5 cvdpv cvdpv 0 4,, 03 FATA 30, cvdpv 5, , 6 50 OPV, 4 OPV 7 33 WPV 3, 0, 0 FATA 3, 0 4 AFP 89, FATA 73, KP 85, 5 0 AFP NPAFP 6.3, FATA 7.9, KP 9. AFP, 80, NPAFP OPV3 89, 0 NPAFP, 6 3 NPAFP 65, 8, FATA 38, KP , 5, SIAs 7, SIAs 9, 0 7, 5 7 FATA SIAs SIAs , FATA, KP, 0,,,,, WHO, WER, 88 47: 50508, 03 :,,

23 Vol. 35 No Verotoxinproducing E.coli ( ) 0 6 ( ) ( ) 9 ( ) Enterotoxigenic enic E.coli ( ) 5 Enteroinvasive E.coli Enteropathogenic E.coli ( ) Enteroaggregative E.coli ( ) Other diarrheagenic E.coli Salmonella Typhi 3 ( ) ( ) ( ) ( ) Salmonella Paratyphi A ( ) ( ) ( ) 3 ( ) ( ) Salmonella O ( ) 8 Salmonella O ( ) ( ) Salmonella O Salmonella O ( ) Salmonella O3,0 3 Salmonella O,3,99 Salmonella O Salmonella O3 Salmonella O8 Salmonella O30 Salmonella O35 Salmonella O39 Salmonella group unknown 4 Vibrio cholerae O:El Tor Ogawa,CT+ ( ) Vibrio cholerae nono&o39 Vibrio parahaemolyticus 7 Vibrio furnissii Aeromonas hydrophila Plesiomonas shigelloides Campylobacter jejuni Campylobacter coli 7 5 Campylobacter jejuni/coli Staphylococcus aureus Clostridium perfringens Bacillus cereus 7 Listeria monocytogenes Yersinia enterocolitica 4 Shigella dysenteriae 4 ( ) Shigella flexneri a Shigella flexneri b ( ) ( ) Shigella flexneri a 3 Shigella flexneri b ( ) Shigella flexneri 3a Shigella flexneri 4 Shigella flexneri 6 Shigella flexneri other serovars ( ) Shigella flexneri untypable ( ) Shigella boydii 4 Shigella boydii 8 Shigella sonnei ( ) 3 ( 8) ( ) 3 ( ) ( ) ( ) 4 ( ) ( ) Entamoeba histolytica Streptococcus tococcus group A Streptococcus group B Streptococcus group C Streptococcus tococcus group G 3 Streptococcus tococcus other groups S.dysgalactiae subsp.equisimilis Streptococcus pneumoniae Bordetella pertussis Legionella pneumophila Mycobacterium tuberculosis Mycobacterium bovis Mycoplasma pneumoniae Haemophilus influenzae b Haemophilus influenzae nonb Klebsiella pneumoniae 0 Neisseria meningitidis Enterococcus faecalis Enterococcus faecium Enterococcus gallinarum Enterococcus casseliflavus Pseudomonas aeruginosa Leptospira interogans Leptospira sp. Cryptococcus neoformans 595 ( ) 807 ( ) 6 ( ) 50 ( 4) 344 ( 4) 339 ( 5) 8 ( 5) 7 ( 6) 06 ( ) 96 ( 4)

24 454 Vol. 35 No ( ) ( ) 09 ( ) ( 0) Verotoxinproducing E.coli ( ) 8 ( ) ( 4) Enterotoxigenic enic E.coli Enteroinvasive E.coli ( ) Enteropathogenic E.coli ( ) Enteroaggregative E.coli 4 98 Other diarrheagenic E.coli ( ) 4 ( ) 4 ( ) ( ) ( ) 5 ( 4) Salmonella Typhi ( ) ( ) ( ) ( ) ( ) 4 ( 3) Salmonella Paratyphi A ( ) 5 5 ( ) Salmonella O ( 3) Salmonella O Salmonella O ( ) Salmonella O9 9 Salmonella O3,0 4 Salmonella O,3,99 Salmonella O 5 Salmonella O3 Salmonella O8 Salmonella O30 Salmonella O35 Salmonella O39 Salmonella group unknown ( ) ( ) ( ) 4 ( 4) Vibrio cholerae O:El Tor Ogawa awa,ct+ 4 Vibrio cholerae nono&o Vibrio parahaemolyticus Vibrio furnissii 3 Aeromonas hydrophila Plesiomonas shigelloides Campylobacter jejuni Campylobacter coli 3 Campylobacter jejuni/coli Staphylococcus aureus Clostridium perfringens 3 Bacillus cereus Listeria monocytogenes Yersinia enterocolitica ( ) Shigella dysenteriae 4 Shigella flexneri a ( ) Shigella flexneri b 4 Shigella flexneri a 4 ( ) Shigella flexneri b ( ) ( ) Shigella flexneri 3a Shigella flexneri 4 ( ) ( ) Shigella flexneri 6 4 ( ) Shigella flexneri other serovars ( ) Shigella flexneri untypable Shigella boydii 4 Shigella boydii 8 ( ) 5 ( 4) 6 ( ) 6 ( 3) ( ) 54 ( 9) Shigella sonnei Entamoeba histolytica Streptococcus tococcus group A 4 Streptococcus group B Streptococcus group C 3 Streptococcus tococcus group G 5 Streptococcus tococcus other groups 6 S.dysgalactiae subsp.equisimilis Streptococcus pneumoniae Bordetella pertussis Legionella pneumophila Mycobacterium tuberculosis Mycobacterium bovis Mycoplasma pneumoniae Haemophilus influenzae b Haemophilus influenzae nonb Klebsiella pneumoniae 5 Neisseria meningitidis 5 Enterococcus faecalis 0 5 Enterococcus faecium Enterococcus gallinarum Enterococcus casseliflavus 0 Pseudomonas aeruginosa 3 Leptospira interogans Leptospira sp. Cryptococcus neoformans 86 ( 3) 38 ( 7) 65 ( 3) 64 ( 9) 49 ( 3) 335 ( 5) 43 ( 5) 83 ( ) 787 ( 9)

25 Vol. 35 No Verotoxinproducing E.coli 7 47 Enteropathogenic E.coli Enteroaggregative E.coli Other diarrheagenic E.coli Salmonella Paratyphi A Salmonella O4 Salmonella O7 9 Salmonella O8 Salmonella O9 Salmonella O3,0 Campylobacter jejuni Campylobacter coli Campylobacter jejuni/coli Staphylococcus aureus 3 Clostridium perfringens Shigella sonnei Streptococcus tococcus group A Streptococcus tococcus group B Streptococcus tococcus group G Streptococcus pneumoniae 7 Legionella pneumophila Mycobacterium tuberculosis Mycoplasma pneumoniae 7 Enterococcus faecium Salmonella O4 Saintpaul O4 Schwarzengrund O4 Brandenburg O4 I 4:i: O7 Infantis 3 O7 Thompson O7 Oranienburg O7 Braenderup 5 O7 Rissen O7 Not typed O8 Corvallis O8 Not typed O9 Enteritidis O9 Not typed O3,0 Weltevreden T T4 T6 T 3 T5 T8 TB364 Untypable

26 656 Vol. 35 No Verotoxinproducing E.coli 3 Enteropathogenic E.coli 4 Enteroaggregative E.coli Other diarrheagenic E.coli ( ) ( ) Salmonella Paratyphi A 5 Salmonella O4 3 Salmonella O7 3 Salmonella O8 Salmonella O9 Salmonella O3,0 64 Campylobacter jejuni Campylobacter coli Campylobacter jejuni/coli 3 Staphylococcus aureus 43 Clostridium perfringens Shigella sonnei Streptococcus tococcus group A Streptococcus tococcus group B Streptococcus tococcus group G 0 Streptococcus pneumoniae Legionella pneumophila Mycobacterium tuberculosis 8 Mycoplasma pneumoniae Enterococcus faecium 3 ( ) 4 83 ( ) Salmonella O4 Saintpaul O4 Schwarzengrund O4 Brandenburg O4 I 4:i: 3 O7 Infantis O7 Thompson O7 Oranienburg 6 O7 Braenderup O7 Rissen O7 Not typed O8 Corvallis O8 Not typed O9 Enteritidis O9 Not typed O3,0 Weltevreden T 3 T4 T6 5 T T5 T8 5 TB364 3 Untypable

27 Vol. 35 No Verotoxinproducing E.coli Enteropathogenic E.coli Enteroaggregative E.coli 4 4 Salmonella O4 Salmonella O3,0 Campylobacter jejuni Staphylococcus aureus 3 Streptococcus pyogenes 0 Streptococcus agalactiae Streptococcus group C S.dysgalactiae subsp.equisimilis Streptococcus pneumoniae 3 Legionella pneumophila SG Mycoplasma pneumoniae Influenza virus A Hpdm Influenza virus A H3 5 6 Influenza virus B/Victoria Influenza virus B/Yamagat ata Measles virus genotype B3 4 5 Measles virus genotype D8 Measles virus genotype D9 Dengue virus NT Dengue virus Dengue virus Dengue virus 4 Hepatitis A virus IA Hepatitis A virus IIIA Plasmodium falciparum Dengue virus Dengue virus 4 / NT :

28 858 Vol. 35 No Picornavirus NT Enterovirus NT Coxsackievirus A NT Coxsackievirus A Coxsackievirus A Coxsackievirus A Coxsackievirus A Coxsackievirus A7 Coxsackievirus A Coxsackievirus A Coxsackievirus A Coxsackievirus A Coxsackievirus A4 8 Coxsackievirus A Coxsackievirus A Coxsackievirus B Coxsackievirus B Coxsackievirus B Coxsackievirus B Coxsackievirus B Coxsackievirus B6 NT Poliovirus Poliovirus Poliovirus 3 3 Enterovirus Enterovirus Parechovirus NT Parechovirus Parechovirus 3 3 Rhinovirus Aichivirus Influenza virus A not subtyped Influenza virus A Hpdm Influenza virus A H Influenza virus B NT Influenza virus B/Victoria Influenza virus B/Yamagata Parainfluenza virus Respiratory syncytial virus Human metapneumovirus Other coronavirus Mumps virus Measles virus genotype NT 6 Measles virus genotype A Measles virus genotype B Measles virus genotype D Measles virus genotype D9 9 Measles virus genotype H 6 Rubella virus genotype NT Rubella virus genotype a 3 Rubella virus genotype E Rubella virus genotype B Japanese encephalitis virus Dengue virus Chikungunya virus 5 SFTS virus 4 5 Reovirus Rotavirus group unknown Rotavirus group A Rotavirus group C Astrovirus Norovirus genogroup unknown Norovirus genogroup I Norovirus genogroup II Sapovirus genogroup unknown Sapovirus genogroup I Sapovirus genogroup II Sapovirus genogroup III Sapovirus genogroup IV NT / / Herpes simplex virus NT Herpes simplex virus Herpes simplex virus Varicellazoster virus Cytomegalovirus Human herpes virus Human herpes virus EpsteinBarr virus Hepatitis A virus NT 7 Hepatitis A virus IA Hepatitis A virus IB Hepatitis A virus IIIA Hepatitis E virus 5 Human papilloma virus B9 virus Human bocavirus Virus NT Chlamydia trachomatis Chlamydophila pneumoniae Orientia tsutsugamushi Rickettsia japonica NT :

29 Vol. 35 No Enterovirus NT Coxsackievirus A Coxsackievirus A4 4 5 Coxsackievirus A Coxsackievirus A Coxsackievirus A Coxsackievirus A9 7 3 Coxsackievirus A0 4 7 Coxsackievirus A 4 6 Coxsackievirus A Coxsackievirus A Coxsackievirus B Coxsackievirus B Coxsackievirus B Coxsackievirus B Coxsackievirus B NT Enterovirus Enterovirus Parechovirus NT 8 4 Parechovirus Parechovirus Rhinovirus Influenza virus A Hpdm0 dm Influenza virus A H Influenza virus B NT Influenza virus B/Victoria Influenza virus B/Yamagat ata Parainfluenza virus Respiratory syncytial virus Human metapneumoviru neumovirus 0 Other coronavirus Mumps virus 7 3 Measles virus genotype NT Measles virus genotype A Measles virus genotype B Measles virus genotype D8 3 6 Measles virus genotype D9 3 Rubella virus genotype NT Rubella virus genotype E Rubella virus genotype B Japanese anese encephalitis virus Dengue virus Chikungunya virus Reovirus Rotavirus group A Astrovirus Norovirus genogroup unknown 7 9 Norovirus genogroup I Norovirus genogroup II Sapovirus genogroup unknown 85 0 Sapovirus genogroup I Sapovirus genogroup II 8 8 NT / / Herpes es simplex virus NT 5 Herpes es simplex virus Herpes es simplex virus 3 7 Varicellazoster virus 6 30 Cytomegalovirus Human herpes es virus Human herpes es virus EpsteinBarr virus Hepatitis A virus NT Hepatitis A virus IA 5 Hepatitis A virus IIIA Hepatitis E virus Human papilloma virus 4 5 B9 virus Human bocavirus 9 9 Orientia tsutsugamush amushi Rickettsia japonica NT :

30 Entero N Entero NT Coxsackie A Coxsackie A Coxsackie A4 Coxsackie A4 Coxsackie A Coxsackie A Coxsackie A Coxsackie A Coxsackie A Coxsackie A8 3 4 Coxsackie A Coxsackie A9 4 3 Coxsackie A0 Coxsackie A0 3 3 Coxsackie A Coxsackie A Coxsackie A6 Coxsackie A6 3 3 Coxsackie A Coxsackie A Coxsackie B Coxsackie B Coxsackie B Coxsackie B Coxsackie B Coxsackie B Coxsackie B4 Coxsackie B4 5 5 Coxsackie B5 Coxsackie B Echo NT Echo NT Echo 3 Echo 3 Echo 6 Echo 6 3 Echo 7 Echo 7 Echo 9 Echo Echo Echo Echo 8 Echo Echo 9 Echo 9 Echo 5 Echo Echo 30 Echo ntero E ntero E Parecho NT Parecho NT arecho P Parecho 3 Parecho Rhino Influenza A Hpdm0 Influenza A Hpdm Influenza A H Influenza A H Influenza B NT Influenza B NT 9 Influenza B/Victori Influenza B/Victoria Influenza B/Yamagat Influenza B/Yamagata Parainfluenza Parainfluenza Respiratory syncytial Respiratory syncytial Human metapneum Human metapneumo 5 Other corona Other corona 9 Mumps Mumps Measles genotype NT Measles genotype NT Measles genotype Measles genotype A Measles genotype B3 Measles genotype B Measles genotype D8 Measles genotype D8 Measles genotype D9 Measles genotype D9 Rubella genotype NT Rubella genotype NT 0 Rubella genotype E Rubella genotype E Rubella genotype B Rubella genotype B Japanese encephalitis Japanese encephalitis Dengue Dengue 3 Chikungunya Chikungunya Reo Reo Rota group A Rota group A Astro Astro Noro genogroup unknown Noro genogroup unknown Noro genogroup Noro genogroup I 3 Noro genogroup I Noro genogroup II Sapo genogroup unknown Sapo genogroup unknown 4 8 Sapo genogroup I Sapo genogroup I Sapo genogroup II Sapo genogroup II Adeno NT Adeno NT Adeno Adeno deno A Adeno 3 Adeno deno A Adeno 5 Adeno 5 Adeno 6 Adeno 6 Adeno 7 Adeno 7 Adeno 8 Adeno 8 4 Adeno 9 Adeno 9 Adeno 3 Adeno 3 Adeno 37 Adeno 37 3 Adeno 40/4 Adeno 40/4 Adeno 4 Adeno 4 4 Adeno 53/ Adeno 53/ Adeno 54 Adeno 54 4 Adeno 56 Adeno 56 Herpes simplex NT Herpes simplex NT 5 Herpes simplex Herpes simplex 5 3 Herpes simplex Herpes simplex 3 3 Varicellazoster Varicellazoster 9 Cytomegalo Cytomegalo Human herpes Human herpes Human herpes Human herpes EpsteinBarr EpsteinBarr 8 4 Hepatitis A NT Hepatitis A NT Hepatitis A IA Hepatitis A IA Hepatitis A IIIA Hepatitis A IIIA Hepatitis E Hepatitis E Human papilloma Human papilloma 5 B9 B9 Human boca Human boca Orientia tsutsugamushi Orientia tsutsugamushi 7 Rickettsia japonica Rickettsia japonica NT : Vol. 35 No

31 Entero NT Entero NT Coxsackie A Coxsackie A 5 Coxsackie A4 Coxsackie A4 3 3 Coxsackie A5 Coxsackie A Coxsackie A6 Coxsackie A Coxsackie A8 Coxsackie A Coxsackie A9 Coxsackie A Coxsackie A0 Coxsackie A0 6 Coxsackie A Coxsackie A Coxsackie A6 Coxsackie A6 Coxsackie A Coxsackie A Coxsackie B Coxsackie B Coxsackie B Coxsackie B Coxsackie B3 Coxsackie B3 3 3 Coxsackie B4 Coxsackie B Coxsackie B5 Coxsackie B5 Echo NT Echo NT Echo 3 Echo Echo 6 Echo 6 Echo 7 Echo 7 3 Echo 9 Echo Echo Echo Echo 8 Echo Echo 9 Echo Echo 5 Echo Echo 30 Echo Entero 68 Entero Entero 7 Entero Parecho NT Parecho NT Parecho Parecho 3 Parecho 3 Parecho Rhino Rhino Influenza A Hpdm09 Influenza A Hpdm Influenza A H3 Influenza A H Influenza B NT Influenza B NT Influenza B/Victoria Influenza B/Victoria Influenza B/Yamagata Influenza B/Yamagata Parainfluenza Parainfluenza Respiratory syncytial Respiratory syncytial 3 Human metapneumo Human metapneumo Other corona Other corona Mumps Mumps Measles genotype NT Measles genotype NT Measles genotype A Measles genotype A 3 3 Measles genotype B3 Measles genotype B3 6 Measles genotype D8 Measles genotype D8 3 Measles genotype D9 Measles genotype D Rubella genotype NT Rubella genotype NT Rubella genotype E Rubella genotype E Rubella genotype B Rubella genotype B Japanese encephalitis Japanese encephalitis Dengue Dengue Chikungunya Chikungunya Reo Reo Rota group A Rota group A 3 3 Astro Astro Noro genogroup unknown Noro genogroup unknown 8 Noro genogroup I Noro genogroup I Noro genogroup II Noro genogroup II Sapo genogroup unknown Sapo genogroup unknown Sapo genogroup I Sapo genogroup I 3 8 Sapo genogroup II Sapo genogroup II Adeno NT Adeno NT Adeno Adeno Adeno Adeno Adeno 3 Adeno Adeno 4 Adeno Adeno 5 Adeno Adeno 6 Adeno 6 Adeno 7 Adeno 7 6 Adeno 8 Adeno 8 Adeno 9 Adeno 9 3 Adeno 3 Adeno 3 5 Adeno 37 Adeno Adeno 40/4 Adeno 40/ Adeno 4 Adeno 4 Adeno 53/ Adeno 53/ 5 Adeno 54 Adeno 54 6 Adeno 56 Adeno 56 5 Herpes simplex NT Herpes simplex NT 3 38 Herpes simplex Herpes simplex 7 7 Herpes simplex Herpes simplex Varicellazoster Varicellazoster Cytomegalo Cytomegalo Human herpes 6 Human herpes Human herpes 7 Human herpes EpsteinBarr EpsteinBarr Hepatitis A NT Hepatitis A NT 5 Hepatitis A IA Hepatitis A IA Hepatitis A IIIA Hepatitis A IIIA Hepatitis E Hepatitis E 5 5 Human papilloma Human papilloma 6 6 B9 B9 9 9 Human boca Human boca Orientia tsutsugamushi Orientia tsutsugamushi Rickettsia japonica Rickettsia japonica NT : Vol. 35 No

32 Enterovirus N Enterovirus NT Coxsackievirus A Coxsackievirus A Coxsackievirus A Coxsackievirus A4 3 5 Coxsackievirus A Coxsackievirus A Coxsackievirus A Coxsackievirus A Coxsackievirus A Coxsackievirus A Coxsackievirus A Coxsackievirus A Coxsackievirus A Coxsackievirus A Coxsackievirus A Coxsackievirus A 4 6 Coxsackievirus A Coxsackievirus A Coxsackievirus A Coxsackievirus A Coxsackievirus B Coxsackievirus B Coxsackievirus B Coxsackievirus B Coxsackievirus B Coxsackievirus B Coxsackievirus B Coxsackievirus B Coxsackievirus B Coxsackievirus B NT chovirus E 3 chovirus E 6 chovirus E chovirus E 9 chovirus E 6 chovirus E chovirus E chovirus E 4 5 chovirus E chovirus E nterovirus E nterovirus E Parechovirus N Parechovirus NT arechovirus P arechovirus P 3 hinovirus R Influenza virus A Hpdm0 Influenza virus A Hpdm Influenza virus A H Influenza virus A H Influenza virus B N Influenza virus B NT Influenza virus B/Victori Influenza virus B/Victoria Influenza virus B/Yamagat Influenza virus B/Yamagata Parainfluenza viru Parainfluenza virus Respiratory syncytial viru Respiratory syncytial virus Human metapneumoviru Human metapneumovirus 9 Other coronaviru Other coronavirus virus umps M 8 3 Measles virus genotype NT Measles virus genotype NT Measles virus genotype A Measles virus genotype A Measles virus genotype B3 Measles virus genotype B Measles virus genotype D8 Measles virus genotype D8 6 6 Measles virus genotype D9 Measles virus genotype D9 3 Rubella virus genotype NT Rubella virus genotype NT Rubella virus genotype E Rubella virus genotype E Rubella virus genotype B Rubella virus genotype B Japanese encephalitis virus Japanese encephalitis virus Dengue virus Dengue virus Chikungunya viru Chikungunya virus Reovirus Reovirus Rotavirus group Rotavirus group A 9 3 strovirus A Norovirus genogroup unknown Norovirus genogroup unknown Norovirus genogroup I Norovirus genogroup I Norovirus genogroup II Norovirus genogroup II Sapovirus genogroup unknown Sapovirus genogroup unknown Sapovirus genogroup I Sapovirus genogroup I Sapovirus genogroup I Sapovirus genogroup II 7 8 NT NT denovirus A denovirus A denovirus A denovirus A denovirus A denovirus A 4 7 denovirus A 8 denovirus A denovirus A 3 denovirus A denovirus A /4 40/ denovirus A 9 53/ 53/ 54 denovirus A 56 denovirus A 6 6 Herpes simplex virus N Herpes simplex virus NT 5 5 Herpes simplex virus Herpes simplex virus Herpes simplex virus Herpes simplex virus Varicellazoster viru Varicellazoster virus Cytomegaloviru Cytomegalovirus Human herpes virus Human herpes virus Human herpes virus Human herpes virus EpsteinBarr viru EpsteinBarr virus Hepatitis A virus N Hepatitis A virus NT Hepatitis A virus I Hepatitis A virus IA 5 5 Hepatitis A virus III Hepatitis A virus IIIA Hepatitis E viru Hepatitis E virus Human papilloma viru Human papilloma virus virus B Human bocaviru Human bocavirus Orientia tsutsugamushi Orientia tsutsugamushi Rickettsia japonica Rickettsia japonica NT NT : Vol. 35 No

33 Vol. 35 No IASR Vol. 35 No. February 04 Infectious Agents Surveillance Report ISSN National Institute of Infectious Diseases and Tuberculosis and Infectious Diseases Control Division, Ministry of Health, Labour and Welfare Epidemiology of severe fever with thrombocytopenia syndrome (SFTS) in China33 SFTS: its regulation as a newly identified infectious disease Genomic phylogenetic analysis of SFTSV isolated from SFTS patients in Japan Biosafety and other guidelines for prevention of familial and hospital infections of SFTSV Summary report of 40 clinical cases of SFTS in 03National Epidemiological Surveillance of Infectious Diseases A mild SFTS case whose clinical differential diagnosis from rickettsiosis was difficult, April Laboratory tests of SFTS Severe influenza pneumonia encountered in the early 03/4 season in a healthy adult person infected by A(H)pdm09 Sapporo City... 4 Antiinfluenza drugresistant A(HN)pdm09 viruses detected in the early 03/4 season in Sapporo City... 4 Antiinfluenza drugresistant A(HN)pdm09 isolated from a child, who was suspected familial infection but had not been administered with oseltamivir, December Two clinical cases diagnosed as Zika fever after return from Bora Bora Island, French Polynesia, December Epidemiological trends of invasive pneumococcal infections and invasive Haemophilus influenzae infectionsnotification as category V infectious disease since April Isolation of coxsackievirus A from two sporadic cases, AugustSeptember 03Tokyo Coxsackievirus A6 detected from hand, foot and mouth disease cases in 03Sendai City An acute encephalopathy case of one year nine month boy, from whom HHV6 and a number of picornavirus were detected, September <THE TOPIC OF THIS MONTH> Severe fever with thrombocytopenia syndrome (SFTS) in Japan, 03 Severe fever with thrombocytopenia syndrome (SFTS) is a tickborne systemic infectious disease. It is caused by SFTS virus (SFTSV), a novel virus belonging to Genus Phlebovirus, Family Bunyaviridae (Fig. ), which was first reported from China in 0 (see p. 33 of this issue). Latency is 63 days and the main symptoms are fever and gastrointestinal symptoms, such as nausea, vomiting, abdominal pain, diarrhea, and melena. Hematuria and proteinuria are frequently observed. Leukopenia and thrombocytopenia are usually seen in peripheral blood, and hemophagocytosis with cellular hypoplasia are also demonstrated in the bone marrow. Blood biochemistry shows elevation of AST, ALT and LDH. Neurological symptoms, such as disturbed consciousness, are often associated with poor prognosis. SFTS has been reported from China since 0 and from Japan and the Republic of Korea since 03. Natural history of SFTSV and transmission to humans: In nature, SFTSV is maintained through vertical transmission from adult ticks to their offspring through transovarial transmission (ticktick cycle) and also by transmission from infected mammals to ticks and vice versa (tickmammal cycle). Two tick species, Haemaphysalis longicornis and Rhipicephalus microplus, frequently found in areas inhabited by humans in China, are considered to be the natural reservoir of SFTSV; 5.0% and 0.6% of these two species, respectively, were found to harbor SFTSV or its genome. In Japan, the ticks responsible for SFTSV transmission to humans are probably H. longicornis and Amblyomma testudinarium (Fig. ), because these ticks were found on the patients body surface. The infection route to humans is mainly tick bite; transmission to family members or to medical providers, mediated by blood and other body fluids, have also been reported from China. No airborne or dropletborne infection has been reported so far. Identification of SFTS patient in Japan and retrospective clinical and epidemiological studies: An adult with no history of travel abroad developed fever, vomiting and bloody diarrhea in autumn of 0, and died of systemic organ failure. SFTSV was isolated from the patient s blood and pathological examinations revealed SFTSV antigens in various affected organs. This was the first patient diagnosed as having SFTS in Japan (IASR 34: 404, 03). The Ministry of Health, Labour and Welfare (MHLW) issued a case definition for the surveillance of SFTS on January 30, 03 ( so as to effectively collect information on SFTS patients in Japan. Retrospective studies using the MHLW s case definition identified 8 patients with severe SFTS in or before 0 (including the first clinical case) (IASR 34: 0, 03). Subsequently, 3 additional severe or fatal cases before 03 were also identified, bringing the total number to. Among the patients, 6 died and all the patients were reported from western Japan. Among 5 patients in whom bone marrow was examined, all exhibited the findings characteristic to the hemophagocytic syndrome, and many of the patients suffered from blood coagulation abnormality and/or systemic organ failure. SFTSV was isolated from 8 patients. Phylogenetic analysis revealed that Japanese strains formed an independent cluster from those of the Chinese strains, indicating that Japanese strains are indigenous to Japan and evolved independently from Chinese strains (see p. 35 of this issue). Fig.. Electron micrograph of SFTSV isolated from an SFTS patient Fig.. Haemaphysalis longicornis (left) and Amblyomma testudinarium (right) 3 Continued on page 3

34 64 THE TOPIC OF THIS MONTHContinued Figure 3. Monthly cases of severe fever with thrombocytopenia syndrome (SFTS), 03, Japan Onset in 03 (n=40) 0 Onset before 03 (n=8) Jan. Feb. Mar. Apr. May Jun. Jul. Aug. Sep. Oct. Nov. Dec. Onset (National Epidemiological Surveillance of Infectious Diseases: As of December 3, 03) Cases Vol. 35 No. 04. Figure 4. Incidence of severe fever with thrombocytopenia syndrome (SFTS) by prefecture, 03 IASR Vol. 35 No. Feb Figure 5. Age distribution of SFTS cases, by gender, 03, Japan (n=48) 0 8 Males Deaths 6 (n=) Age group 0 8 Females (n=6) 6 Cases Cases Age group including 8 cases of onset in or before 0 (National Epidemiological Surveillance of Infectious Diseases: As of December 3, 03) Onset in 03 (n=40) Onset before 03 (n=8) (National Epidemiological Surveillance of Infectious Diseases: As of December 3, 03) Japanese SFTS patients reported in 03: On March 4, 03, SFTS was designated as a category IV infectious disease, requiring notification to the designated public health center (see for notification criteria), and SFTSV as a biosafety level group 3 pathogen (IASR 34: 0, 03) (see p. 34 & 37 of this issue). Physicians, who have treated a patient diagnosed virologically as SFTS, must notify the information to the designated public health center within 4 hours. The number of SFTS patients reported in compliance with the Infectious Diseases Control Law under the National Epidemiological Surveillance of Infectious Diseases was 48 until the end of 03; 40 were developed in 03 (see p. 38 of this issue), and 8 in or before 0 ( cases in 005; case in 00; 5 cases in 0; IASR 34: 0, 03). The seasonal peak was in May (Fig. 3). Patients were reported from 3 prefectures in Kyushu, Shikoku and Chugoku regions (Fig. 4). Twentytwo cases were males and 6 females. Patients ages ranged from 48 to 95 years (median 7 years) (Fig. 5). Seventeen of 48 had died. With increased recognition of SFTS, mild SFTS cases were discovered (see p. 39 of this issue; IASR 34: 0708, 03). Tickbites were not always found on the body surface of the patients. It is, therefore, advised to conduct laboratory diagnosis if a patient is suspected of having SFTS, even if the clinical pictures, including presence of bites, do not fit perfectly to the previous case definitions (see p. 38 of this issue). Laboratory diagnosis available in Japan: Virological diagnosis includes detection/isolation of SFTSV from acute phase patients blood and other body fluids (throat swab, urine), and/or the demonstration of a significant rise in IgG antibody titers in paired sera between acute and convalescent phases. Diagnosis using RTPCR detection of SFTSV genome is available within the network of prefectural and municipal public health institutes (PHIs). Furthermore, indirect fluorescent antibody test using the SFTSVinfected cells and IgGELISA using the SFTSV antigen are also available in the National Institute of Infectious Disease (NIID), Department of Virology I (see p. 40 of this issue). Methods for the detection of SFTSV genome in ticks inhabiting Japan and antibody detection methods in mammals have been developed and the surveillance of SFTSV genome prevalence in some species of ticks and antibody levels in wild animals are being conducted (IASR 34: , 03). Measures to be taken: An SFTS patient was first reported in January 03 in Japan. Subsequent retrospective and prospective surveillance has revealed the existence of SFTS in western Japan. PHIs and NIID established a laboratory diagnosis system, which should be maintained and developed further. In 03, an MHLWfunded 3year project Comprehensive research on control of SFTS (chief investigator T. Kurata) started. The project includes ) detailed epidemiological and clinical studies on SFTS to elucidate the clinical and pathological characteristics; ) development of rapid SFTSV detection kit; 3) basic research for vaccine development; 4) assessment of risk of SFTSV infection and risk communication on SFTS; and 5) elucidation of SFTSV prevalence among ticks inhabiting Japan, geographical distribution of SFTSVpositive ticks, seroepidemiology of wild animals, and geographical spread of SFTSV in Japan. The statistics in this report are based on ) the data concerning patients and laboratory findings obtained by the National Epidemiological Surveillance of Infectious Diseases undertaken in compliance with the Law Concerning the Prevention of Infectious Diseases and Medical Care for Patients of Infections, and ) other data covering various aspects of infectious diseases. The prefectural and municipal health centers and public health institutes (PHIs), the Department of Food Safety, the Ministry of Health, Labour and Welfare, and quarantine stations, have provided the above data. Infectious Disease Surveillance Center, National Institute of Infectious Diseases Toyama 3, Shinjukuku, Tokyo 68640, JAPAN Tel (+83)585