CHINESE CENTER FOR DISEASE CONTROL AND PREVENTION Human Avian Influenza Surveillance in mainland of...

CHINESE CENTER FOR DISEASE CONTROL AND PREVENTION

Human Avian Influenza

Surveillance in mainland of China

Yuelong Shu

Chinese National Influenza CenterNational Institute for Viral Disease

Control and PreventionChina CDC

2009-8-19, Beijing


Human Avian Influenza Surveillance in mainland of China

Routine surveillance: Chinese Human Avian Influenza Surveillance SystemPneumonia 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 SurveillanceAfter 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 ）


Temporal Distribution of Confirmed HPAI Cases’ Onset Time(N=38)


Geography Distribution Map of HPAI Cases during 2005 ～ 2009(N=38 ）

数据来源：卫生部、农业部数据来源：卫生部、农业部China CDCChina 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


Demographic Characteristics of HPAI Cases(N=38)

Age

Male 　 Female 　 Total

Cases Percent

age(%)

　 Cases Percent

age(%)

　 Cases Percentag

e(%)

0-6 0 0.0 　 1 2.6 　 1 2.6

6-14 2 5.3 　 3 7.9 　 5 13.2

15-29 9 23.7 　 9 23.7 　 18 47.4

30-49 5 13.2 　 7 18.4 　 12 31.6

50-62 2 5.3 　 0 0.0 　 2 5.3

合计 18 47.4 　 20 52.6 　 38 100.0

Age Male Female

Median 24 26.5

Range (6-62) (2-44)


Estimate on incubation Period of HPAI Cases

Time interval between Exposure

and Onset (day)

First Exposure Last 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


Mortality Rate of HPAI Cases

Group Incidence DeathMortality Rate(%)

Male 13 8 62

Female 15 10 67

＜ 15 5 2 40

≥15 23 16 70

Urban 11 9 82

Rural 17 9 53

Total 28 18 64Note: 2 military cases were not included


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.


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.


Basic information of 29 VirusesNo. Strains Onset Date Sampling Date Sampling Spot Survived1 A/Anhui/1/2005(H5N1) 2005-11-2 2005-11-8 Anhui province2 A/Anhui/2/2005(H5N1) 2005-11-11 2005-11-17 Anhui province3 A/Guangxi/1/2005(H5N1) 2005-11-23 2005-11-29 Guangxi autonomous region4 A/Jiangxi/1/2005(H5N1) 2005-12-4 2005-12-10 Jiangxi province5 A/Fujian/1/2005(H5N1) 2005-12-7 2005-12-12 Fujian province6 A/Sichuan/1/2006(H5N1) 2006-1-3 2006-1-11 Sichuan province7 A/Sichuan/2/2006(H5N1) 2006-1-11 2006-1-17 Sichuan province8 A/Hunan/1/2006(H5N1) 2006-1-27 2006-2-4 Hunan province9 A/Anhui/1/2006(H5N1) 2006-2-11 2006-2-19 Anhui province Yes10 A/Zhejiang/1/2006(H5N1) 2006-2-10 2006-2-21 Zhejiang province11 A/Guangdong/1/2006(H5N1) 2006-2-22 2006-3-4 Guangdong province12 A/Shanghai/1/2006(H5N1) 2006-3-15 2006-3-21 Shanghai City13 A/Hubei/1/2006(H5N1) 2006-4-1 2006-4-13 Hubei Province14 A/Sichuan/3/2006(H5N1) 2006-4-16 2006-4-24 Sichuan province Yes15 A/Guangdong/2/2006(H5N1) 2006-6-3 2006-6-11 Guangdong province Yes16 A/Xinjiang/1/2006(H5N1) 2006-6-19 2006-7-2 Xinjiang autonomous region17 A/Fujian/1/2007(H5N1) 2007-2-18 2007-2-25 Fujian province Yes18 A/Anhui/1/2007(H5N1) 2007-3-17 2007-3-23 Anhui province19 A/Jiangsu/1/2007(H5N1) 2007-11-24 2007-12-1 Jiangsu province20 A/Jiangsu/2/2007(H5N1) 2007-12-4 2007-12-5 Jiangsu province Yes21 A/Hunan/1/2008(H5N1) 2008-1-16 2008-1-24 Hunan province22 A/Guangxi/1/2008(H5N1) 2008-2-12 2008-2-19 Guangxi province23 A/Guangdong/1/2008(H5N1) 2008-2-16 2008-2-23 Guangdong province24 A/Beijing/1/2009(H5N1) 2008-12-24 2009-1-5 Beijing City25 A/Shandong/1/2009(H5N1) 2009-1-5 2009-1-17 Shandong province26 A/Hunan/1/2009(H5N1) 2009-1-8 2009-1-16 Hunan province27 A/Guizhou/1/2009(H5N1) 2009-1-15 2009-1-22 Guizhou province Yes28 A/Xinjiang/1/2009(H5N1) 2009-1-10 2009-1-21 Xinjiang autonomous region29 A/Guangxi/1/2009(H5N1) 2009-1-19 2009-1-24 Guangxi autonomous region


Phylogenetic Analysis

HA

● Strains of Chinese Human■ Candidate of Vaccine


Molecular CharacterizationNo. Strains Cleavage Site◇ PB2 627AA# NS1 92 AA△ HA 226-228 AA☆

1 A/Anhui/1/2005(H5N1) LRERRRKRG AAAPPEQ YLTDM QSG

2 A/Anhui/2/2005(H5N1) LRERRRKRG AAAPPEQ YLTDM RSG

3 A/Guangxi/1/2005(H5N1) LRERRRKRG AAAPPEQ YLTDM QSG

4 A/Jiangxi/1/2005(H5N1) LRERRRKRG AAAPPKQ YLTDM QSG

5 A/Fujian/1/2005(H5N1) LRERRRKRG AAAPPKQ YLTDM QSG

6 A/Sichuan/1/2006(H5N1) LRERRRKRG AAAPPEQ YLTDM QSG


8 A/Hunan/1/2006(H5N1) LRERRRKRG AAAPPEQ YLTDM QSG


10 A/Zhejiang/1/2006(H5N1) LRERRRKRG AAAPPEQ YLTDM QSG

11 A/Guangdong/1/2006(H5N1) LRERRRKRG AAAPPEQ YLTDM QSG

12 A/Shanghai/1/2006(H5N1) LRERRRKRG AAAPPEQ YLTDM QSG

13 A/Hubei/1/2006(H5N1) LRERRRKRG AAAPPEQ YLTDM QSG


15 A/Guangdong/2/2006(H5N1) LRERRRKRG AAAPPKQ YLTDM QSG

16 A/Xinjiang/1/2006(H5N1) QGERRRKKRG AAAPPKQ YLTDM QSG

17 A/Fujian/1/2007(H5N1) LRERRRKRG AAAPPEQ YLTDM QSG


19 A/Jiangsu/1/2007(H5N1) LRERRRKRG AAAPPEQ YLTDM QSG

20 A/Jiangsu/2/2007(H5N1) LRERRRKRG AAAPPEQ YLTDM QSG


22 A/Guangxi/1/2008(H5N1) LRERRRKRG AAAPPKQ YLTDM QSG

23 A/Guangdong/1/2008(H5N1) LRERRRKRG AAAPPEQ YLTDM QSG

24 A/Beijing/1/2009(H5N1) LRERRRKRG AAAPPEQ YLTDM QSG

25 A/Shandong/1/2009(H5N1) LRERRRKRG AAAPPEQ YLTDM QSG


27 A/Guizhou/1/2009(H5N1) LRERRRKRG AAAPPKQ YLTDM QSG

28 A/Xinjiang/1/2009(H5N1) LRERRRKRG AAAPPKQ YLTDM QSG

29 A/Guangxi/1/2009(H5N1) QRERRRRKRG AAAPPEQ YLTDM QSG

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.


Drug ResistanceNo. Strains NA 274AA ＃ M2 25-42AA△

1 A/Anhui/1/2005(H5N1) LNAPNYHYEE PLVVAASIIGILHLILWIL

2 A/Anhui/2/2005(H5N1) LNAPNYHYEE PLVVAASIIGILHLILWIL

3 A/Guangxi/1/2005(H5N1) LNAPNYHYEE PLVVAASIIGILHLILWIL

4 A/Jiangxi/1/2005(H5N1) LDAPNYHYEE PLVVAASIIGILHLILWIL

5 A/Fujian/1/2005(H5N1) LDAPNYHYEE PLVVAASIIGILHLILWIL

6 A/Sichuan/1/2006(H5N1) LNAPNYHYEE PLVVAASIIGILHLILWIL


8 A/Hunan/1/2006(H5N1) LNAPNYHYEE PLVVAASIIGILHLILWIL

9 A/Anhui/1/2006(H5N1) LDAPNYHYEE PLVVAASIIGILHLILWIL

10 A/Zhejiang/1/2006(H5N1) LNAPNYHYEE PLVVAASIIGILHLILWIL

11 A/Guangdong/1/2006(H5N1) LDAPNYHYEE PLVVAASIIGILHLILWIL

12 A/Shanghai/1/2006(H5N1) LDAPNYHYEE PLVVAASIIGILHLILWIL

13 A/Hubei/1/2006(H5N1) LNAPNYHYEE PLVVAASIIGILHLILWIL


15 A/Guangdong/2/2006(H5N1) LNAPNYHYEE PLVVAASIIGILHLILWIL

16 A/Xinjiang/1/2006(H5N1) LNAPNYHYEE PLVVAASIIGILHLILWIL

17 A/Anhui/1/2007(H5N1) LDAPNYHYEE PLVVAASIIGILHLILWIL

18 A/Fujian/1/2007(H5N1) LDAPNYHYEE PLVVAANIIGILHLILWIL

19 A/Jiangsu/1/2007(H5N1) LDAPNYHYEE PLVVAASIIGILHLILWIL

20 A/Jiangsu/2/2007(H5N1) LNAPNYHYEE PLVVAASIIGILHLILWIL


22 A/Guangxi/1/2008(H5N1) LDAPNYHYEE PLVVAASIIGILHLILWIL

23 A/Guangdong/1/2008(H5N1) LDAPNYHYEE PLVVAASIIGILHLILWIL

24 A/Beijing/1/2009(H5N1) LNAPNYHYEE PLVVAANIIGILHLILWIL

25 A/Shandong/1/2009(H5N1) LNAPNYHYEE PLVVAANIIGILHLILWIL


27 A/Guizhou/1/2009(H5N1) LNAPNYHYEE PLVVAASIIGILHLILWIL

28 A/Xinjiang/1/2009(H5N1) LNAPNYHYEE PLVVAASIIGILHLILWIL

29 A/Guangxi/1/2009(H5N1) LNAPNYHYEE PLVVAASIIGILHLILWIL

Note ：＃ H, predicted to be sensitive to oseltamivir..△ N, mutation in the matrix protein 2, which confers resistance to amantadine.


　　 1 绿色与人一致　　 2 红色与禽一致　　 3 粉色未知

Gene Position Distance Human H1N1 H2N2 H3N2 H5N1 Avian Persistence china_23　　　　 1918 1957 1968 　　　　　 M1 115 0.967 I V I I V V 99.27% 　 V 　 121 0.962 A A A A T T 99.92% 　 T 　 137 0.958 A T A A T T 99.10% 　 T 　

　　　 NP 16 0.953 D D D D G G 99.41% 　 G 　 61 0.973 L I L L I I 99.32% 　 I 　 283 0.981 P P P P L L 99.24% 　 L 　 305 0.96 K R K K R R 99.07% 　 R 　 313 0.973 Y Y Y Y F F 99.32% 　 F 　 357 0.964 K K K K Q Q 99.32% 　 Q 　

　　　 NS1 81 0.958 M I M M deleted I 99.32% deleted 215 0.955 T P T T P P 99.74% 　 L(15) P(8) 227 0.966 R K R R E E 99.40% 　 E 　

　　　 PA 28 0.988 L L L L P P 99.45% 　 P 　 55 0.984 N N N N D D 99.73% 　 D 　 57 0.958 Q R Q Q R R 99.27% 　 R 　 100 0.955 A A A A V V 99.54% 　 V 　 225 0.969 C S C C S S 99.36% 　 S 　 268 0.951 I L I I L L 99.09% 　 L 　 337 0.978 S A S S A A 99.91% 　 A(22) T(1) 404 0.967 S A S S A A 99.27% S(19) A(4) 　 409 0.959 N S N N S S 99.54% 　 S 　 552 0.999 S S S S T T 99.91% 　 T 　

　　　 PB2 44 0.966 S A S S A A 99.11% 　 A 　 64 0.954 T M T T I M 99.82% T(7) M(10) I(6) 199 0.997 S S S S A A 100.00% 　 A 　 271 0.958 A T A A T T 99.38% 　 T 　 475 0.994 M M M M L L 99.91% 　 L 　 567 0.977 N N N N D D 99.29% 　 D 　 588 0.971 I A I I A A 99.38% 　 A(22) T(1) 627 0.977 K K K K E E 99.82% 　 E(18) K(5) 674 0.969 T A T T A A 99.47% 　 A(22) S(1) 702 0.955 R R R R K K 99.38% 　 K 　



















Characteristics of HPAI Viruses Prevailing in mainland of China


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.


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.


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


Thank you

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