人感染H7N9禽流感病毒病原学特点及实验室检测

人感染H7N9禽流感病毒病原学特点及实验室检测

中国疾病预防控制中心卫生应急中心

CHINESE CENTER FOR DISEASE CONTROL AND PREVENTION

既往禽H7Nx病毒简介

CHINESE CENTER FOR DISEASE CONTROL AND PREVENTION

HPAI H7N3 LPAI H7N9

HPAI H7N7 、 H7N3、 H7N1 LPAI H7Nx、H7N2、H7N3、 H7N1、H7N9

LPAI H7N9

LPAI H7N8、H7N9 (Korea)

HPAI H7N3 LPAI H7N9

HPAI H7N3 (Pakistan)

HPAI H7N7、 H7N3 、 H7N4

禽中暴发的H72006年前暴发的均为HPAI H7 欧洲：意大利、英国、德国、比利时、荷兰、丹麦、挪威、 捷克、西班牙、瑞典 CHINESE CENTER FOR DISEASE CONTROL AND PREVENTION

近年来人感染禽流感病毒病例病毒亚型 A/H7N7 A/H7N7 A/H5N1 A/H9N2 A/H9N2 A/H7N2 A/H9N2 A/H5N1 A/H7N7 病原来源 鸥 鸭 禽 鸡 禽 禽 禽 禽 禽 时间/国家 1980/美国 1996/英国 1997/香港 1998/中国广东 1999/香港 2002/北美(Virginia) 2003/香港 2003/香港 2003/荷兰 病例数/临床表现 3/结膜炎 1/结膜炎 18/ILI,肺炎 5/ ILI,肺炎 2/ILI 1/ILI,血清学诊断 1/ILI 2/ ILI,肺炎 89/结膜炎、ILI、肺炎; 1名死亡病例

A/H5N1A/H7N2(NY/107) A/H7N3 A/H5N2 A/H7N2 A/H9N2 A/H10N7 A/H10N7

禽来源不清 禽 禽 禽 来源不清 鸭 来源于疫区的鸟

2003至今, 15个国家2003/北美(New York), 2004/加拿大 2005/日本(Ibaraki) 2007/英国(Wales) 2007/香港 2004/埃及( Ismaillia)

602/ ILI, 肺炎1/肺炎 2/结膜炎、ILI; 1名LPAI;1名HPAI 13/无临床症状，血清学诊断 1/结膜炎、ILI 1/ ILI 2/ ILI

血清学证据：人感染H4, H5, H6, H7,H9,H10, H11 AIVs. CHINESE CENTER FOR DISEASE CONTROL AND PREVENTION

2010/悉尼(New South Wales) 7/上呼吸道感染症状、结膜炎

HPAI1/USA H7N71959 4/USA H7N7 1/USA H7N7 1996 2002

89/ Netherlands H7N7 1/ Canada 1 died H7N32003 2004

2/ Mexico H7N3

2006 2007

LPAI

1977 19791/England 7/ Italy 1/ USA 1/ Canada 4/ Wales 1980 H7N7 H7N3 H7N2 H7N2 H7N3 1/ USA 1/ Norfolk H7N2 H7N3H7感染人(>100人)美国、英国、意大利、荷兰、加拿大

CHINESE CENTER FOR DISEASE CONTROL AND PREVENTION

H7N9病毒 共25株 均为LPAI

亚洲, 7 欧洲, 5

美 洲, 13

亚洲：7株均来自野禽 5株—韩国 2株—蒙古

无感染人病例

CHINESE CENTER FOR DISEASE CONTROL AND PREVENTION

H7N9的致病力和传播力HPAI H7N3

HPAI H7N3

LPAI H7N9

LPAI H7N9

LPAI H7N9

Nose (white bars) , lung (black bars) HPAI H7N3和LAPI H7N9均不需经过适应便可在小鼠体 高致病性的HPAI H7N3致小鼠死亡，在雪貂

内有效复制，且均能在雪貂上下呼吸道有效复制。

模型中可通过接触传播，但LAPI H7N9在雪貂模型中不传播。

CHINESE CENTER FOR DISEASE CONTROL AND PREVENTION

中国地区H7 AIVA/Baer's pochard/HuNan/414/2010(H7N1) A/chicken/Hebei/1/2002(H7N2) A/duck/Guangdong/1/1996(H7N3) A/duck/Hubei/126/1985(H7N8) A/duck/Jiangxi/1742/03(H7N7) A/duck/Jiangxi/1760/03(H7N7) A/duck/Jiangxi/1786/03(H7N7) A/duck/Jiangx

i/1814/03(H7N7) A/duck/Nanchang/1904/1992(H7N1) A/duck/Nanchang/1944/92(H7N1) A/duck/Zhejiang/10/2011(H7N3) A/duck/Zhejiang/12/2011(H7N3) A/duck/Zhejiang/2/2011(H7N3) A/magpie-robin/China/28710/93(H7)

亚型： H7N1, H7N2, H7N3, H7N7, H

7N8 野禽居多

LPAI

CHINESE CENTER FOR DISEASE CONTROL AND PREVENTION

人感染H7N9禽流感病毒实验室检测

CHINESE CENTER FOR DISEASE CONTROL AND PREVENTION

核酸检测

CHINESE CENTER FOR DISEASE CONTROL AND PREVENTION

病毒分离

从3个病例中分离到3株病毒 A/Shanghai/1/2013(H7N9) A/Shanghai/2/2013(H7N9) A/Anhui/1/2013(H7N9)

CHINESE CENTER FOR DISEASE CONTROL AND PREVENTION

序列测定

PB2 PB1 PA HA NP NA MP NS

6个内部片段来源于H9N2

三株H7N9病毒为同一基因类型CHINESE CENTER FOR DISEASE CONTROL AND PREVENTION

序列特点 耐药性分析 对烷胺类药物是耐药的，即M2蛋白25-42位氨基酸发生S31N突变。 均对神经氨酸酶抑制剂类药物，如奥斯他韦(达菲)和扎那米韦(依乐韦)敏感。 HA连接肽分析

HA蛋白339位连接肽由单个(PKGRGLFG)碱性氨基酸组成，根据既往研究，具有这种序列特点的病毒对禽类呈低致病性。 受体结合位点及其它重要位点分析 Shanghai/1/2013的HA蛋白 226-228位氨基酸属于禽源受体结合位点(为QSG)。 Shanghai/2/2013和Anhui/1/2013的HA蛋白 226-228位氨基酸受体结合位点(为LSG)

PB2蛋白627位氨基酸为K,提示致病性增强。 NS1蛋白92位氨基酸为D,与禽流感病毒一致，而与人流感病毒不同。 CHINESE CENTER FOR DISEASE CONTROL AND PREVENTION

HA核酸同源性比较

CHINESE CENTER FOR DISEASE CONTROL AND PREVENTION

H7进化树 红色标记为本次病例 ●H7 人感染病例

100

100

A/northern_pintail/Akita/1370/2008_H7N7_Japan A/mallard/Korea/GG3/2007_H7N7_South_Korea A/environment/Mongolia/1-51/2007_H7N7_Mongolia A/duck/Korea/BC10/2007_H7N3_South_Korea A/duck/Mongolia/119/2008_H7N9_Mongolia A/duck/Korea/A349/2009_H7N2_South_Korea 99 A/duck/Thailand/CU-LM7291T/2010_H7N6_Thailand 89 A/quail/Thailand/CU-J2882/2009_H7N1_Thailand 98 92 A/wild_bird/Korea/5-77/2005_H7N8_South_Korea A/duck/Zhejiang/12/2011_H7N3_China A/Shanghai/1/2013 99 100 A/Shanghai/2/2013 100 A/Anhui/1/2013 99 A/duck/Jiangxi/1742/03_H7N7_China A/wild_bird_feces/Korea/HDR16/2003_H7N2_South_Korea 86 A/duck/Mongolia/867/2002_H7N1_Mongolia 98 AY338455_A/Netherlands/127/03_H7N7_Netherlands 71 100 AY338457_A/Netherlands/33/03_H7N7_Netherlands AY338459_A/Netherlands/219/2003_H7N7_Netherlands A/chicken/Italy/444/99_H7N1_Italy A/chicken/Italy/322/2001_H7N1_Italy A/quail/Italy/4610/2003_H7N2_Italy 76 97 A/turkey/Italy/5425/2007_H7N3_Italy A/mallard/Sweden/100993/2008_H7N7_Sweden 98 88 98 A/mute_swan/Hungary/5973/2007_H7N7_Hungary A/mallard/Italy/497-35/2006_H7_Italy A/goose/Czech_Republic/1848-K9/2009_H7N9_Czech_Republic 98 A/mallard/Korea/822/2010_H7N7_South_Korea 91 A/duck/Thailand/

CU-10507T/2011_H7N4_Thailand 78 A/wild_goose/Dongting/PC0360/2012_H7N7_China 100 A/spot-billed_duck/Korea/447/2011_H7N9_South_Korea 84 A/parrot/England/1174/94_H7N1_United_Kingdom A/ostrich/South_Africa/5352/92_H7N1_South_Africa 96 AF028020_A/England/268/1996_H7N7_United_Kingdom 78 GU053110_A/England/AV877/1996_H7N7_United_Kingdom 100 A/England/AV877/1996_H7N7_United_Kingdom A/chicken/Pakistan/16/99/95_H7N3_Pakistan 100 A/chicken/Karachi/NARC-23/2003_H7N3_Pakistan A/quail/Aichi/1/2009_H7N6_Japan 87 A/duck/Hong_Kong/301/1978_H7N2_Hong_Kong 99 A/black_kite/Egypt/054/2004_H7N7_Egypt A/chicken/Jena/1816/87_H7N7_Germany 87 89 A/chicken/Hebei/1/2002_H7N2_China 78 100 A/African_starling/England-Q/983/1979_H7N1_United_Kingdom A/duck/Vietnam/OIE-0178/2012_H7N1_Viet_Nam A/mallard/New_Zealand/1365-355/2005_H7N7_New_Zealand 94 A/equine/Prague/1/1956_H7N7_Czech_Republic 100 100 A/equine/Cambridge/1/63_H7N7_United_Kingdom A/equine/Argentina/1/1977_H7N7_Argentina A/chicken/Chile/184240-1/2002_H7N3_Chile 100 A/cinnamon_teal/Bolivia/4537/2001_H7N3_Bolivia 92 A/turkey/Oregon/1971_H7N3_USA A/shorebird/Delaware_Bay/274/1994_H7N5_USA 100 A/mallard/Delaware/418/2005_H7N3_USA 100 82 A/blue-winged_teal/Ohio/566/2006_H7N9_USA 100 73 A/green-winged_teal/MD/648/2004_H7N3_USA CY015006_A/Canada/rv504/2004_H7N3_Canada A/goose/Nebraska/17097-4/2011_H7N9_USA CY125728_A/Mexico/InDRE7218/2012_H7N3_Mexico 100 100 A/chicken/Jalisco/CPA1/2012_H7N3_Mexico 100 A/pheasant/Minnesota/917/1980_H7N3_USA 99 88 A/green-winged_teal/ALB/228/1985_H7N3_Canada A/laughing_gull/Delaware/22/2002_H7N3_USA A/duck/Guangdong/1/1996_H7N3_China 81 A/turkey/New_York/Sg-00255/1994_H7N2_USA A/quail/PA/20304/1998_H7N2_USA A/Guinea_fowl/New_York/10196-7/2005_H7N2_USA A/chicken/New_York/63806-12/2005_H7N2_USA 78 100 A/turkey/VA/66/02_H7N2_USA 99 EU587368_A/New_York/107/2003_H7N2_USA A/Guinea_fowl/New_York/31621-8/2005_H7N2_USA A/chicken/Victoria/1976_H7N7_Australia A/duck/Tasmania/277/2007_H7N2_Australia 100 100 A/duck/Victoria/512/2007_H7N6_Australia A/chicken/Queensland/1994_H7N3_Australia 100 A/chicken/New_South_Wales/2/1997_H7N4_Australia 91 A/fowl/Egypt/45_H7N1_Egypt A/chicken/Japan/1925_H7N7_Japan 100 A/duck/Taiwan/33/1993_H7N7_Taiwan A/chicken/Rostock/45/1934_H7N1_Germany A/FPV/Dutch/1927_H7N7_United_Kingdom A/chicken/Brescia/1902_H7N7_Italy100 93 70 100

Eurasian

E q ui ne

American

CHINESE CENTER FOR DISEASE CONTROL AND PREVENTION0. 05

N9 进化树 红色标记为本次病例99 96 73

83 100

99 97 77

CHINESE CENTER FOR DISEASE CONTROL AND PREVENTION0. 02

A/mallard/Minnesota/Sg-00177/2007__USA_H12N9 A/mallard/Ohio/2033/2009__USA_H4N9 A/American_black_duck/New_Brunswick/03451/2009__Canada_H3N9 A/mallard/Alberta/64/2000__Canada_H11N9 A/mallard/MN/158/2000__USA_H3N9 75 A/northern_shoveler/California/8675/2008__USA_H11N9 A/ruddy_turnstone/Delaware_Bay/220/1995__USA_H7N9 A/mallard/Alberta/193/2000__Canada_H11N9 A/black_duck/Ohio/161/1999__USA_H11N9 89 A/ruddy_turnstone/DE/1538/2000__USA_H7N9 A/Ame

rican_black_duck/New_Brunswick/02485/2007__Canada_H11N9 A/American_white_pelican/Minnesota/Sg-0611/2008__USA_H13N9 100 A/shorebird/Delaware_Bay/424/2007__USA_H13N9 100 A/shorebird/Delaware_Bay/48/2002__USA_H11N9 80 A/ruddy_turnstone/New_Jersey/980/2002__USA_H2N9 100 A/ruddy_turnstone/Delaware_Bay/96/2002__USA_H1N9 A/thick-billed_murre/Alaska/44085-090/2006__USA_H11N9 100 A/glaucous_gull/Alaska/44199-104/2006__USA_H13N9 A/guinea_fowl/Nebraska/17096-1/2011__USA_H7N9 100 89 A/northern_shoverl/Mississippi/11OS145/2011__USA_H7N9 A/king_eider/Alaska/44397-858/2008__USA_H10N9 92 A/blue-winged_teal/Guatemala/CIP049-01/2008__Guatemala_H7N9 81 A/turkey/Minnesota/1/1988__USA_H7N9 A/gull/Maryland/18/1977__USA_H2N9 A/pintail/Alberta/293/1977__Canada_H2N9 A/Black_Duck/Ohio/239/1986__USA_H11N9 A/ruddy_turnstone/Delaware/2368/1988__USA_H4N9 A/redhead_duck/Alberta/357/1983__Canada_H11N9 A/turkey/Wisconsin/1/1968__USA_H5N9 A/tern/Australia/G70C/1975__Australia_H11N9 A/duck/Vietnam/OIE-2386/2009__Viet_Nam_H11N9 100 A/duck/Vietnam/OIE-3301/2011__Viet_Nam_H6N9 A/goose/Zambia/09/2009__Zambia_H11N9 A/mallard/New_Zealand/1440-365/2005__New_Zealand_H11N9 A/mallard/Czech_Republic/15902-18K/2009__Czech_Republic_H6N9 93 100 A/goose/Czech_Republic/1848-K9/2009__Czech_Republic_H7N9 A/mallard/Switzerland/WV1071028/2007__Switzerland_H11N9 A/Duck/Nanchang/2-0492/2000__China_H2N9(2) A/mallard/Sweden/48/2002__Sweden_H11N9 A/gadwall/Mongolia/OIE-191/2012__Mongolia_H2N9 75 A/duck/Hunan/1590/2007__China_H6N9 A/duck/Mongolia/119/2008__Mongolia_H7N9 A/mallard/Czech_Republic/13438-29K/2010__Czech_Republic_H11N9 A/Anas_crecca/Spain/1460/2008__Spain_H7N9 90 A/duck/Vietnam/LBM81/2012__Viet_Nam_H11N9 99 A/wild_duck/Korea/SH20-27/2008__South_Korea_H7N9 A/shorebird/Korea/S8/2006__South_Korea_H11N9 A/duck/Chiba/7/2006__Japan_H11N9 A/duck/Hokkaido/W245/2004__Japan_H11N9 A/shorebird/Korea/S331/2006__South_Korea_H10N9 A/wild_bird/Korea/A3/2011__South_Korea_H7N9 99 A/wild_bird/Korea/A14/2011__South_Korea_H7N9 A/Shanghai/1/2013 86 A/Shanghai/2/2013 100 98 A/Anhui/1/2013 A/kelp_gull/Argentina/LDC4/2006__Argentina_H13N9 A/emu/NY/12716/1994__USA_H5N9 A/shoveler/Netherlands/19/1999__Netherlands_H11N9 100 A/chicken/Italy/22A/1998__Italy_H5N9 100 100 A/wedge-tailed_shearwater/Western_Australia/2327/1983__Australia_H15N9 A/shearWater/Australia/2576/1979__Australia_H15N9 A/duck/Hong_Kong/278/1978__Hong_Kong_H2N9 A/duck/Hong_Kong/562/1979__Hong_Kong_H10N9 10098 99 92

American

Eurasian

PB2进化树 红色标记为本次病例 ●H7 人感染病例

100

70

99 90

86

CHINESE CENTER FOR DISEASE CONTROL AND PREVENTION0. 02

A/Shanghai/1/2013 A/Shanghai/2/2013 A/Anhui/1/2013 A/brambling/Beijing/16/2012_H9N2 98 A/chicken/Shanghai/C1/2012_H9N2 A/chicken/Zhejiang/329/2011_H9N2 100 A/chicken/Shandong/02/2010_H9N2 A/chicken/Shandong/H/2009_H9N2 A/equine/Guangxi/3/2011_H9N2 99 A/chicken/Zhejiang/607/2011_H9N2 A/chicken/Anhui/HF/2010_H9N2 A/chicken/Jiangsu/Q3/2010_H9N2 82 A/chicken/Shuanggou/1/2011_H9N2 100 A/d

uck/Shandong/009/2008_China_H5N1 100 A/avian/Japan/8KI0162/2008_Japan_H3N8 93 99 A/avian/Japan/8KI0068/2008_Japan_H3N6 A/environment/Korea/CSM05/2004_South_Korea_H3N1 A/mallard/Jiangxi/8341/2004_China_H6N5 100 90 A/environment/Korea/ESD18/2004_South_Korea_H3N6 A/duck/Guangxi/3333/2006_China_H6N1 A/duck/Guangxi/1248/2006_China_H6N2 99 100 A/wild_bird/Korea/YJ117/2007_South_Korea_H4N6 A/turkey/Italy/977/1999_Italy_H7N1 100 A/turkey/Italy/1067/99__Italy_H7N1 A/turkey/Italy/1265/1999_Italy_H7N1 A/mallard/Czech_Republic/13438-29K/2010_H11N9 88 A/avian/Egypt/920431/2006_H9N2 A/spot-billed_duck/Korea/447/2011_H7N9 81 A/wild_bird/Korea/A14/2011_H7N9 100 A/wild_bird/Korea/A3/2011_H7N9 74 100 A/goose/Czech_Republic/1848-K9/2009_H7N9 A/goose/Czech_Republic/1848-T14/2009_H7N9 PC0360_H7N7-PB2.seq 98 A/duck/Jiangxi/1814/03_China_H7N7 A/wild_duck/Mongolia/1-241/2008_H7N9 A/Anas_crecca/Spain/1460/2008_H7N9 A/mallard/Sweden/105/2002_Sweden_H7N7 81 A/gadwall/Netherlands/1/2006_H9N2 90 A/Netherlands/219/2003_Netherlands_H7N7 88 A/chicken/Netherlands/2586/2003_Netherlands_H7N7 100 A/England/AV877/1996_United_Kingdom_H7N7 A/chicken/Israel/184/2009_H9N2 A/chicken/Korea/MS96-CE6/1996_H9N2 A/chicken/China/Guangxi14/2000_H9N2 A/chicken/Guangdong/6/97_H9N2 A/chicken/Pakistan/4/99_H9N2 100 A/chicken/Pakistan/UDL-03/2008_H9N2 A/duck/Zhejiang/12/2011_H7N3 A/swine/Hong_Kong/9/98_H9N2 88 100 A/swine/Guangxi/7/2007_H9N2 99 A/chicken/Yokohama/aq120/2001_H9N2 A/wild_bird/Korea/A9/2011_H7N9 100 A/chicken/Korea/A146/2009_H9N2 A/chicken/Guangxi/55/2005_H9N2 A/duck/Nanchang/4-361/2001_H9N2 A/chicken/Shandong/KD/2009_H9N2 100 A/chicken/Hebei/A/2007_H9N2 78 A/duck/Fujian/FQ2/2007_H9N2 83 A/swine/Guangxi/S11/2005_H9N2 A/chicken/Yokohama/aq134/2002_H9N2 A/turkey/Minnesota/1/1988_H7N9 A/Canada/rv504/2004_Canada_H7N3 A/New_York/107/2003_USA_H7N2 A/ruddy_turnstone/Delaware_Bay/220/1995_H7N9 A/northern_shoverl/Mississippi/11OS145/2011_H7N9 A/blue-winged_teal/Ohio/566/2006_H7N9 A/ruddy_turnstone/DE/1538/2000_H7N9 A/Mexico/InDRE7218/2012_Mexico_H7N3 A/blue-winged_teal/Guatemala/CIP049-01/2008_H7N9 A/blue-winged_teal/Guatemala/CIP049-02/2008_H7N9 10071 91 89

检测策略 不明原因肺炎病例标本检测： 建议各流感监测网络实验室收到不明原因肺炎标本后，要在12小时内 进行标本处理和核酸检测，同时进行甲型通用引物，甲型H1N1流感 病毒，季节性H3N2流感，A(H5)、A (H7N9)亚型流感病毒的检测

。如果H5或H7亚型检测阳性，在生物安全三级实验室进行流感病毒的分离鉴定，无病毒分离条件的实验室，将标本在24小时内送国家流 感中心进行复核鉴定和病毒分离。

CHINESE CENTER FOR DISEASE CONTROL AND PREVENTION

全国不明原因肺炎病例监测、排查和管理 (2007版)

中国疾病预防控制中心卫生应急中心

CHINESE CENTER FOR DISEASE CONTROL AND PREVENTION

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