1. CHINESE CENTER FOR DISEASE CONTROL AND PREVENTION Human Avian Influenza Surveillance in mainland of China Yuelong Shu Chinese National Influenza Center National Institute for Viral Disease Control and Prevention China CDC 2009-8-19, Beijing

2. CHINESE CENTER FOR DISEASE CONTROL AND PREVENTION Human Avian Influenza Surveillance in mainland of China Routine surveillance: Chinese Human Avian Influenza Surveillance System Pneumonia with unknown cause reporting system Implementation Plan for National Surveillance on Pneumonia with Unknown Cause (2004) Implementation Plan for National Surveillance, Diagnosis and Treatment Guidance for Pneumonia with unknown cause (2007) Emergency Surveillance After animal or human AI epidemic situations, the corresponding regions should carry out surveillance ILI cases and close contacts. (Emergency Surveillance Plan for Human Avian Influenza Infection ）

3. CHINESE CENTER FOR DISEASE CONTROL AND PREVENTION Temporal Distribution of Confirmed HPAI Cases’ Onset Time(N=38)

4. CHINESE CENTER FOR DISEASE CONTROL AND PREVENTION Geography Distribution Map of HPAI Cases during 2005 ～ 2009(N=38 ） 数据来源：卫生部、农业部 China CDC urban cases （ 15 ） rural cases(23 ） 确诊 H5N1 动物疫情（ 59 ） 发现有病死禽地区 （ 16 ） 注：不包括 2003 年追溯诊断病例

5. CHINESE CENTER FOR DISEASE CONTROL AND PREVENTION Demographic Characteristics of HPAI Cases (N=38) Age Male Female Total Cases Percentag e (%) Cases Percentag e (%) Cases Percentage (%) 0-600.0 12.6 1 6-1425.3 37.9 513.2 15-29923.7 9 1847.4 30-49513.2 718.4 1231.6 50-6225.3 00.0 25.3 合计 1847.4 2052.6 38100.0 AgeMaleFemale Median2426.5 Range(6-62)(2-44)

6. CHINESE CENTER FOR DISEASE CONTROL AND PREVENTION Estimate on incubation Period of HPAI Cases Time interval between Exposure and Onset (day) First ExposureLast Exposure case (%)16(57)8 (29) unknown (%)12(43)20(71) Median (Range)7.5(3-22)3.5(1-5) Note: 2 military cases were not included

7. CHINESE CENTER FOR DISEASE CONTROL AND PREVENTION Mortality Rate of HPAI Cases GroupIncidenceDeathMortality Rate(%) Male13862 Female151067 ＜ 15 5240 ≥ 15 231670 Urban11982 Rural17953 Total281864 Note: 2 military cases were not included

8. CHINESE CENTER FOR DISEASE CONTROL AND PREVENTION Family Cluster of H5N1 1 case was confirmed, the other one died because of severe respiratory disease. 2 cases are of sister-brother relationship. (Hunan) 2 cases had the same exposure history to sick and dead poultry, onset time have 2 days time-lag. 2 cases were all confirmed as HPAI cases. They are father-son relationship, and the father developed symptoms while having medical observation as close contact of his son (Jiangsu) The father took long care of the son in the ward before onset. Therefore, the most possibility for infection is that he directly contacted with the respiratory secretion and intestinal excrement of his son. But the possibility of individual exposure to the same live-poultry markets could not be excluded.

9. CHINESE CENTER FOR DISEASE CONTROL AND PREVENTION Potential Infection Source of HPAI Cases 17 cases had direct or indirect contact with sick or dead avian.(For 4 cases, the animal AI outbreaks were confirmed meanwhile) 9 cases had been to the live-avian market before onset 1 case’s infection source was unknown 1 case had taken long care of another confirmed HPAI patient. Therefore, the most possibility for infection is that he directly contacted with the respiratory secretion and intestinal excrement. But the possibility of individual exposure to the same live-poultry markets could not be excluded.

10. CHINESE CENTER FOR DISEASE CONTROL AND PREVENTION Basic information of 29 Viruses No.StrainsOnset DateSampling DateSampling SpotSurvived 1 A/Anhui/1/2005(H5N1)2005-11-22005-11-8Anhui province 2 A/Anhui/2/2005(H5N1)2005-11-112005-11-17Anhui province 3 A/Guangxi/1/2005(H5N1)2005-11-232005-11-29Guangxi autonomous region 4 A/Jiangxi/1/2005(H5N1)2005-12-42005-12-10Jiangxi province 5 A/Fujian/1/2005(H5N1)2005-12-72005-12-12Fujian province 6 A/Sichuan/1/2006(H5N1)2006-1-32006-1-11Sichuan province 7 A/Sichuan/2/2006(H5N1)2006-1-112006-1-17Sichuan province 8 A/Hunan/1/2006(H5N1)2006-1-272006-2-4Hunan province 9 A/Anhui/1/2006(H5N1)2006-2-112006-2-19Anhui provinceYes 10 A/Zhejiang/1/2006(H5N1)2006-2-102006-2-21Zhejiang province 11 A/Guangdong/1/2006(H5N1)2006-2-222006-3-4Guangdong province 12 A/Shanghai/1/2006(H5N1)2006-3-152006-3-21Shanghai City 13 A/Hubei/1/2006(H5N1)2006-4-12006-4-13Hubei Province 14 A/Sichuan/3/2006(H5N1)2006-4-162006-4-24Sichuan provinceYes 15 A/Guangdong/2/2006(H5N1)2006-6-32006-6-11Guangdong provinceYes 16 A/Xinjiang/1/2006(H5N1)2006-6-192006-7-2Xinjiang autonomous region 17 A/Fujian/1/2007(H5N1)2007-2-182007-2-25Fujian provinceYes 18 A/Anhui/1/2007(H5N1)2007-3-172007-3-23Anhui province 19 A/Jiangsu/1/2007(H5N1)2007-11-242007-12-1Jiangsu province 20 A/Jiangsu/2/2007(H5N1)2007-12-42007-12-5Jiangsu provinceYes 21 A/Hunan/1/2008(H5N1)2008-1-162008-1-24Hunan province 22 A/Guangxi/1/2008(H5N1)2008-2-122008-2-19Guangxi province 23 A/Guangdong/1/2008(H5N1)2008-2-162008-2-23Guangdong province 24 A/Beijing/1/2009(H5N1)2008-12-242009-1-5Beijing City 25 A/Shandong/1/2009(H5N1)2009-1-52009-1-17Shandong province 26 A/Hunan/1/2009(H5N1)2009-1-82009-1-16Hunan province 27 A/Guizhou/1/2009(H5N1)2009-1-152009-1-22Guizhou provinceYes 28 A/Xinjiang/1/2009(H5N1)2009-1-102009-1-21Xinjiang autonomous region 29 A/Guangxi/1/2009(H5N1)2009-1-192009-1-24Guangxi autonomous region

11. CHINESE CENTER FOR DISEASE CONTROL AND PREVENTION Phylogenetic Analysis HA ● Strains of Chinese Human ■ Candidate of Vaccine

12. CHINESE CENTER FOR DISEASE CONTROL AND PREVENTION Molecular Characterization No. StrainsCleavage Site ◇ PB2 627AA # NS1 92 AA △ HA 226-228 AA ☆ 1 A/Anhui/1/2005(H5N1) LRERRRKRGAAAPPEQYLTDMQSGQSG 2 A/Anhui/2/2005(H5N1) LRERRRKRGAAAPPEQYLTDMRSG 3 A/Guangxi/1/2005(H5N1) LRERRRKRGAAAPPEQYLTDMQSGQSG 4 A/Jiangxi/1/2005(H5N1) LRERRRKRGAAAPPKQYLTDMQSGQSG 5 A/Fujian/1/2005(H5N1) LRERRRKRGAAAPPKQYLTDMQSGQSG 6 A/Sichuan/1/2006(H5N1) LRERRRKRGAAAPPEQYLTDMQSGQSG 7 A/Sichuan/2/2006(H5N1) LRERRRKRGAAAPPEQYLTDMQSGQSG 8 A/Hunan/1/2006(H5N1) LRERRRKRGAAAPPEQYLTDMQSGQSG 9 A/Anhui/1/2006(H5N1) LRERRRKRGAAAPPEQYLTDMQSGQSG 10 A/Zhejiang/1/2006(H5N1) LRERRRKRGAAAPPEQYLTDMQSGQSG 11 A/Guangdong/1/2006(H5N1) LRERRRKRGAAAPPEQYLTDMQSGQSG 12 A/Shanghai/1/2006(H5N1) LRERRRKRGAAAPPEQYLTDMQSGQSG 13 A/Hubei/1/2006(H5N1) LRERRRKRGAAAPPEQYLTDMQSGQSG 14 A/Sichuan/3/2006(H5N1) LRERRRKRGAAAPPEQYLTDMQSGQSG 15 A/Guangdong/2/2006(H5N1) LRERRRKRGAAAPPKQYLTDMQSGQSG 16 A/Xinjiang/1/2006(H5N1) QGERRRKKRGAAAPPKQYLTDMQSGQSG 17 A/Fujian/1/2007(H5N1) LRERRRKRGAAAPPEQYLTDMQSGQSG 18 A/Anhui/1/2007(H5N1) LRERRRKRGAAAPPEQYLTDMQSGQSG 19 A/Jiangsu/1/2007(H5N1) LRERRRKRGAAAPPEQYLTDMQSGQSG 20 A/Jiangsu/2/2007(H5N1) LRERRRKRGAAAPPEQYLTDMQSGQSG 21 A/Hunan/1/2008(H5N1) LRERRRKRGAAAPPEQYLTDMQSGQSG 22 A/Guangxi/1/2008(H5N1) LRERRRKRGAAAPPKQYLTDMQSGQSG 23 A/Guangdong/1/2008(H5N1) LRERRRKRGAAAPPEQYLTDMQSGQSG 24 A/Beijing/1/2009(H5N1) LRERRRKRGAAAPPEQYLTDMQSGQSG 25 A/Shandong/1/2009(H5N1) LRERRRKRGAAAPPEQYLTDMQSGQSG 26 A/Hunan/1/2009(H5N1) LRERRRKRGAAAPPEQYLTDMQSGQSG 27 A/Guizhou/1/2009(H5N1) LRERRRKRGAAAPPKQYLTDMQSGQSG 28 A/Xinjiang/1/2009(H5N1) LRERRRKRGAAAPPKQYLTDMQSGQSG 29 A/Guangxi/1/2009(H5N1) QRERRRRKRGAAAPPEQYLTDMQSGQSG Note ： ◇ multiple basic amino acids characteristic of highly pathogenic avian influenza. ＃ K, associated with increased virulence. △ E, associated with increased virulence. ☆ QSG, preferentially bind to α2,3-NeuAcGal linkages of avian cell-surface receptors.

13. CHINESE CENTER FOR DISEASE CONTROL AND PREVENTION Drug Resistance No. StrainsNA 274AA ＃ M2 25-42AA △ 1 A/Anhui/1/2005(H5N1) LNAPNY H YEEP LV VA AS II G ILHLILWIL 2 A/Anhui/2/2005(H5N1) LNAPNY H YEEP LV VA AS II G ILHLILWIL 3 A/Guangxi/1/2005(H5N1) LNAPNY H YEEP LV VA AS II G ILHLILWIL 4 A/Jiangxi/1/2005(H5N1) LDAPNY H YEEP LV VA AS II G ILHLILWIL 5 A/Fujian/1/2005(H5N1) LDAPNY H YEEP LV VA AS II G ILHLILWIL 6 A/Sichuan/1/2006(H5N1) LNAPNY H YEEP LV VA AS II G ILHLILWIL 7 A/Sichuan/2/2006(H5N1) LNAPNY H YEEP LV VA AS II G ILHLILWIL 8 A/Hunan/1/2006(H5N1) LNAPNY H YEEP LV VA AS II G ILHLILWIL 9 A/Anhui/1/2006(H5N1) LDAPNY H YEEP LV VA AS II G ILHLILWIL 10 A/Zhejiang/1/2006(H5N1) LNAPNY H YEEP LV VA AS II G ILHLILWIL 11 A/Guangdong/1/2006(H5N1) LDAPNY H YEEP LV VA AS II G ILHLILWIL 12 A/Shanghai/1/2006(H5N1) LDAPNY H YEEP LV VA AS II G ILHLILWIL 13 A/Hubei/1/2006(H5N1) LNAPNY H YEEP LV VA AS II G ILHLILWIL 14 A/Sichuan/3/2006(H5N1) LNAPNY H YEEP LV VA AS II G ILHLILWIL 15 A/Guangdong/2/2006(H5N1) LNAPNY H YEEP LV VA AS II G ILHLILWIL 16 A/Xinjiang/1/2006(H5N1) LNAPNY H YEEP LV VA AS II G ILHLILWIL 17 A/Anhui/1/2007(H5N1) LDAPNY H YEEP LV VA AS II G ILHLILWIL 18 A/Fujian/1/2007(H5N1) LDAPNY H YEEP LV VA AN II G ILHLILWIL 19 A/Jiangsu/1/2007(H5N1) LDAPNY H YEEP LV VA AS II G ILHLILWIL 20 A/Jiangsu/2/2007(H5N1) LNAPNY H YEEP LV VA AS II G ILHLILWIL 21 A/Hunan/1/2008(H5N1) LNAPNY H YEEP LV VA AS II G ILHLILWIL 22 A/Guangxi/1/2008(H5N1) LDAPNY H YEEP LV VA AS II G ILHLILWIL 23 A/Guangdong/1/2008(H5N1) LDAPNY H YEEP LV VA AS II G ILHLILWIL 24 A/Beijing/1/2009(H5N1) LNAPNY H YEEP LV VA AN II G ILHLILWIL 25 A/Shandong/1/2009(H5N1) LNAPNY H YEEP LV VA AN II G ILHLILWIL 26 A/Hunan/1/2009(H5N1) LNAPNY H YEEP LV VA AS II G ILHLILWIL 27 A/Guizhou/1/2009(H5N1) LNAPNY H YEEP LV VA AS II G ILHLILWIL 28 A/Xinjiang/1/2009(H5N1) LNAPNY H YEEP LV VA AS II G ILHLILWIL 29 A/Guangxi/1/2009(H5N1) LNAPNY H YEEP LV VA AS II G ILHLILWIL Note ： ＃ H, predicted to be sensitive to oseltamivir.. △ N, mutation in the matrix protein 2, which confers resistance to amantadine.

14. CHINESE CENTER FOR DISEASE CONTROL AND PREVENTION 1 绿色与人一致 2 红色与禽一致 3 粉色未知 GenePositionDistanceHumanH1N1H2N2H3N2H5N1AvianPersistencechina_23 1918 1957 1968 M1 115 0.967 I V I I V V99.27% V 121 0.962 A A A A T T99.92% T 137 0.958 A T A A T T99.10% T NP 16 0.953 D D D D G G99.41% G 61 0.973 L I L L I I99.32% I 283 0.981 P P P P L L99.24% L 305 0.96 K R K K R R99.07% R 313 0.973 Y Y Y Y F F99.32% F 357 0.964 K K K K Q Q99.32% Q NS1 81 0.958 M I M M deleted I99.32% deleted 215 0.955 T P T T P P99.74% L(15)P(8) 227 0.966 R K R R E E99.40% E PA 28 0.988 L L L L P P99.45% P 55 0.984 N N N N D D99.73% D 57 0.958 Q R Q Q R R99.27% R 100 0.955 A A A A V V99.54% V 225 0.969 C S C C S S99.36% S 268 0.951 I L I I L L99.09% L 337 0.978 S A S S A A99.91% A(22)T(1) 404 0.967 S A S S A A99.27%S(19)A(4) 409 0.959 N S N N S S99.54% S 552 0.999 S S S S T T99.91% T PB2 44 0.966 S A S S A A99.11% A 64 0.954 T M T T I M99.82%T(7)M(10)I(6) 199 0.997 S S S S A A100.00% A 271 0.958 A T A A T T99.38% T 475 0.994 M M M M L L99.91% L 567 0.977 N N N N D D99.29% D 588 0.971 I A I I A A99.38% A(22)T(1) 627 0.977 K K K K E E99.82% E(18)K(5) 674 0.969 T A T T A A99.47% A(22)S(1) 702 0.955 R R R R K K99.38% K 1 绿色与人一致 2 红色与禽一致 3 粉色未知 GenePositionDistanceHumanH1N1H2N2H3N2H5N1AvianPersistencechina_23 1918 1957 1968 M1 115 0.967 I V I I V V99.27% V 121 0.962 A A A A T T99.92% T 137 0.958 A T A A T T99.10% T NP 16 0.953 D D D D G G99.41% G 61 0.973 L I L L I I99.32% I 283 0.981 P P P P L L99.24% L 305 0.96 K R K K R R99.07% R 313 0.973 Y Y Y Y F F99.32% F 357 0.964 K K K K Q Q99.32% Q NS1 81 0.958 M I M M deleted I99.32% deleted 215 0.955 T P T T P P99.74% L(15)P(8) 227 0.966 R K R R E E99.40% E PA 28 0.988 L L L L P P99.45% P 55 0.984 N N N N D D99.73% D 57 0.958 Q R Q Q R R99.27% R 100 0.955 A A A A V V99.54% V 225 0.969 C S C C S S99.36% S 268 0.951 I L I I L L99.09% L 337 0.978 S A S S A A99.91% A(22)T(1) 404 0.967 S A S S A A99.27%S(19)A(4) 409 0.959 N S N N S S99.54% S 552 0.999 S S S S T T99.91% T PB2 44 0.966 S A S S A A99.11% A 64 0.954 T M T T I M99.82%T(7)M(10)I(6) 199 0.997 S S S S A A100.00% A 271 0.958 A T A A T T99.38% T 475 0.994 M M M M L L99.91% L 567 0.977 N N N N D D99.29% D 588 0.971 I A I I A A99.38% A(22)T(1) 627 0.977 K K K K E E99.82% E(18)K(5) 674 0.969 T A T T A A99.47% A(22)S(1) 702 0.955 R R R R K K99.38% K 1 绿色与人一致 2 红色与禽一致 3 粉色未知 GenePositionDistanceHumanH1N1H2N2H3N2H5N1AvianPersistencechina_23 1918 1957 1968 M1 115 0.967 I V I I V V99.27% V 121 0.962 A A A A T T99.92% T 137 0.958 A T A A T T99.10% T NP 16 0.953 D D D D G G99.41% G 61 0.973 L I L L I I99.32% I 283 0.981 P P P P L L99.24% L 305 0.96 K R K K R R99.07% R 313 0.973 Y Y Y Y F F99.32% F 357 0.964 K K K K Q Q99.32% Q NS1 81 0.958 M I M M deleted I99.32% deleted 215 0.955 T P T T P P99.74% L(15)P(8) 227 0.966 R K R R E E99.40% E PA 28 0.988 L L L L P P99.45% P 55 0.984 N N N N D D99.73% D 57 0.958 Q R Q Q R R99.27% R 100 0.955 A A A A V V99.54% V 225 0.969 C S C C S S99.36% S 268 0.951 I L I I L L99.09% L 337 0.978 S A S S A A99.91% A(22)T(1) 404 0.967 S A S S A A99.27%S(19)A(4) 409 0.959 N S N N S S99.54% S 552 0.999 S S S S T T99.91% T PB2 44 0.966 S A S S A A99.11% A 64 0.954 T M T T I M99.82%T(7)M(10)I(6) 199 0.997 S S S S A A100.00% A 271 0.958 A T A A T T99.38% T 475 0.994 M M M M L L99.91% L 567 0.977 N N N N D D99.29% D 588 0.971 I A I I A A99.38% A(22)T(1) 627 0.977 K K K K E E99.82% E(18)K(5) 674 0.969 T A T T A A99.47% A(22)S(1) 702 0.955 R R R R K K99.38% K 1 绿色与人一致 2 红色与禽一致 3 粉色未知 GenePositionDistanceHumanH1N1H2N2H3N2H5N1AvianPersistencechina_23 1918 1957 1968 M1 115 0.967 I V I I V V99.27% V 121 0.962 A A A A T T99.92% T 137 0.958 A T A A T T99.10% T NP 16 0.953 D D D D G G99.41% G 61 0.973 L I L L I I99.32% I 283 0.981 P P P P L L99.24% L 305 0.96 K R K K R R99.07% R 313 0.973 Y Y Y Y F F99.32% F 357 0.964 K K K K Q Q99.32% Q NS1 81 0.958 M I M Mdeleted I99.32%deleted 215 0.955 T P T T P P99.74% L(15)P(8) 227 0.966 R K R R E E99.40% E PA 28 0.988 L L L L P P99.45% P 55 0.984 N N N N D D99.73% D 57 0.958 Q R Q Q R R99.27% R 100 0.955 A A A A V V99.54% V 225 0.969 C S C C S S99.36% S 268 0.951 I L I I L L99.09% L 337 0.978 S A S S A A99.91% A(22)T(1) 404 0.967 S A S S A A99.27%S(19)A(4) 409 0.959 N S N N S S99.54% S 552 0.999 S S S S T T99.91% T PB2 44 0.966 S A S S A A99.11% A 64 0.954 T M T T I M99.82%T(7)M(10)I(6) 199 0.997 S S S S A A100.00% A 271 0.958 A T A A T T99.38% T 475 0.994 M M M M L L99.91% L 567 0.977 N N N N D D99.29% D 588 0.971 I A I I A A99.38% A(22)T(1) 627 0.977 K K K K E E99.82% E(18)K(5) 674 0.969 T A T T A A99.47% A(22)S(1) 702 0.955 R R R R K K99.38% K Characteristics of HPAI Viruses Prevailing in mainland of China

15. CHINESE CENTER FOR DISEASE CONTROL AND PREVENTION Summary 29 viruses isolated from 37 human cases in mainland China since 2005. All Viruses contained the motif of multiple basic amino acids at the HA cleavage site characteristic of HPAI. 29 viruses formed in 3 distinct sublineages, Xinjiang/1/2006 belonged to clade 2.2; Guangxi/1/2009 belonged to clade 2.3.2; the rest belonged to clade 2.3.4. All viruses had H274 at NA protein, which predicted to be sensitive to oseltamivir; Fujian/1/2007, Beijing/1/2009, Shandong/1/2009 had the S31N mutation in M2, that confers resistance to amantadine, all other viruses have residues indicating sensitivity to amantadine. Reassortment with prevailing human influenza A virus was not found.

16. CHINESE CENTER FOR DISEASE CONTROL AND PREVENTION Analysis on Human AI outbreaks in mainland of China Sporadic HPAI cases would appear continually; Unknown infection source cases still exist; Common exposure might caused family cluster; As new cases increase, the virus could improve its transmissibility among humans by reassortment or adaptive mutation.

17. CHINESE CENTER FOR DISEASE CONTROL AND PREVENTION Acknowledgements Chinese Ministry of Health Chinese Ministry of Science and Technology WHO China-US Collaborative Program on Emerging and Re- emerging Infectious Disease Local Centers for disease Control and Prevention

18. CHINESE CENTER FOR DISEASE CONTROL AND PREVENTION Thank you