Recent experience to pandemic ( )A(H1N1)2009 in Japan and collaboration with Asiacollaboration with Asia

Haruo Watanabe National Institute of Infectious DiseaseNational Institute of Infectious Disease, 

Japan

Surveillance system for influenza in Japan

Pre‐existing system• Sentinel surveillance system for ILI: ‐ January 1987‐y‐ year‐round, weekly report‐ clinically diagnosed / lab‐confirmed y g /‐ sentinel sites: 5,000 ( including 3,000 pediatric clinic/hospital)

• Sentinel influenza virus surveillance‐ 1973‐‐ year‐round, daily report‐monitor the virological feature for vaccine

Surveillance system for influenza in Japan, Pre‐existing system‐cont’d

• School absentee reporting system for ILI• School absentee reporting system for ILI

‐ 1973‐

‐ Late Oct – Mid July ( about 40 – 30 epi wk ) 

‐ day‐care center, Kindergarten, elementary and middle high school

‐ school should report the number of absentees pand closed classes

‐ local health care center should take samples from‐ local health care center should take samples from the cluster(s) of absentee in a flu‐season for laboratory testlaboratory test 

Surveillance system for A(H1N1)2009 in Japan

Case‐based surveillance‐ 28 April ‐ 23 July‐ Lab‐confirmed cases‐ Daily report by faxDaily report by fax ‐ Case fefinition:

‐ suspected case of influenza A(H1N1)v virus infection is defined as a person with high fever (>38°C) OR at least two acute respiratory symptoms (nasal g p y y pobstruction/rhinorrhea, sore throat, cough, fever/feverishness) AND who meets at least one of the following criteria:

a) within the last seven days returned from a country or region with an ) y y gepidemic of influenza A(H1N1)v;b) was in close contact (within two meters) with a confirmed case within the 

past seven days;c) handled samples suspected of containing influenza A(H1N1)v virus in ac) handled samples suspected of containing influenza A(H1N1)v virus in a 

laboratory or other setting within the past seven days;

‐ confirmed case of influenza A(H1N1)v virus infection is defined as a person with high fever (>38°C) OR at least two acute respiratory symptoms (nasalwith high fever (>38 C) OR at least two acute respiratory symptoms (nasal obstruction/rhinorrhea, sore throat, cough, fever/feverishness) AND influenza A(H1N1)v virus infection that has been laboratory confirmed by real‐time PCR and/or viral isolation.

Timeline of situation of A(H1N1)2009 i Jin Japan

Notification about Swine flu 

2009 WHO declared the emergence of the novel flu25 Apr

2009

28

WHO declared the emergence of the novel flu•Japanese gov’t: launched case‐based surveillance for novel flu and 

strengthened quarantine to travelers from affected areas29  Primer for RT‐PCR  became 

il bl(5 May)

9 May1st cases :travelers  •Ceased  strengthened quarantine 

available

Outbreaks among several schools

1st domestic case

returned from Canada 16 May • Shifted to cluster surveillance and hospitalized‐case surveillance13 

June

g q

• Expanded School absentee reporting  

27July

Extensive school closure: over 4,200 schools w/  650,000 

system16July

All 47 prefectures t dchildren/students

15Aug

1st fatal case

reported cases

Reported cases w/ A(H1N1)2009, 28 Apr‐23 July （ 4 496*）（n=4,496*）

（By case‐based surveillance;*Cases the data of onset available ）

Cumulative number, RtReported cases, Lt

Effectiveness of school closures inEffectiveness of school closures in Osaka and Kobe

Extensive school closure

ILI cases from sentinel sites:Sentinel surveillance from 5 000 sitesfrom 5,000 sites

Number of ILI cases/sentinel/week Number of ILI cases/sentinel/week  in in Japan(from 2000 to 2010)Japan(from 2000 to 2010)Number / sentinel60.00Number / sentinel

50.00

0

Lower peak, and highest numberof ILR patients in 2009

40.000

1

2

3

4

of ILR patients, in 2009

30.00 5

6

7

8

20.00 9

10

10.00

0.00

1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 33 35 37 39 41 43 45 47 49 51 53

2000～2010, week 13（upto April 4, 2010）

W k 36

Geographical spread of A(H1N1)2009 during Aug. to Nov.Week 36 

Week 37 

Week 40 

Week 39 Week 44   Week 47  

Reported and estimated No. of patientsReported and estimated No. of patients

Reported ILI Total estimated ILIp2003‐04                        0.77 million 9.23 m2004‐05                        1.5   m 17.70 m

2009.29w～2010.13w ( by H1N1pdm)   Estimated ILI cases  20.7m                           

(infection rate per population: 15.1%)at 30 March    Confirmed Admitted patients No.     17,646  

with underling diseases                      6,599in ICU                                                       1,022pregnant women 74pregnant women                                      74Influenza encephalopathy                    543  Fatal case No.                                            171

* Japanese population 130 m                    

Age distribution of ILI （2009.28w～2010.10w）

600

インフルエンザ推計受診患者数年齢群別推移（2009年第28～2010年第10週）単位：万人

E ti t d t t l ILI 20 7インフルエンザ推計受診患者数男女別割合（2009年第28週～2010

年第10週）

500

Estimated total ILI＝20.7m 年第10週）

malefemale

400 男, 1066, 51.6%

女, 1000, 48.4%

男

女

520476

300

229280

219100

200

155

10047 17 15

0

100

0～4歳 5～9歳 10～14歳 15～19歳 20～29歳 30～39歳 40～49歳 50～59歳 60～69歳 70歳～0～4歳 5～9歳 10～14歳 15～19歳 20～29歳 30～39歳 40～49歳 50～59歳 60～69歳 70歳～

Age distribution of admitted patients

新型インフルエンザ入院例年齢群別グラフ（2009年11月3日まで）

Age distribution of admitted patients

2500

1500

2000

1000

1500

500

0

0 4歳 5 9歳 10 14歳 15 19歳 20 39歳 40 59歳 60 79歳 80歳以上0～4歳 5～9歳 10～14歳 15～19歳 20～39歳 40～59歳 60～79歳 80歳以上

2009年11月3日現在

Age distribution for fatal cases of PI

32

34

新型インフルエンザ死亡例年齢群別基礎疾患別グラフ（2010年3月16日まで）新型インフルエンザ死亡例基礎疾患の有無割合グラフ（2010年3月16日まで）

24

26

28

30

32

138, 69.7%

60, 30.3%

基礎疾患有り

基礎疾患無し

16

18

20

22

24

With underlingdiseases

8

10

12

14

16

0

2

4

6

8

0

1歳未満 1～4歳 5～9歳 10～14歳 15～19歳 20～29歳 30～39歳 40～49歳 50～59歳 60～69歳 70～79歳 80歳以上

基礎疾患有り 基礎疾患無し

2010年3月16日現在

Mortality rate of PI among 100,000 population Mortality rate of PI among 100,000 population in several countiesin several counties

US Canada Mexico Australia UK France ＮＺ Japan

Date collected

in several countiesin several counties

Date collected date 2/13 3/13 3/12 3/12 3/14 3/16 3/21 3/23

Death case No. Estimate12,000 429 1,111 191 457 309 20 198

Mortality rate (3.96) 1.32 1.05 0.93 0.76 0.50 0.48 0.15Infection rate ; 15~17% in all countries※尚、各国の死亡数に関してはそれぞれ定義が異なり、一義的に比較対象とならないことに留意が必要。

亡率

11.21.4

死亡率Canada

MexicoAustralia

0 20.40.60.81 Australia

UKFrance NZ

Japan0

0.2 Japan

出典：各国政府・WHOホームページから厚生労働省で作成 15

Influenza‐associated encephalopathy in Japan, ue a assoc a ed e cep a opa y apa ,week 1‐45, 2009

Nu

pathy

: AH1 pdm: Type A (week 28‐): Type A (‐week 28): Type B

umber of re

enceph

alop

: Type B: Undetermined: Number of reported cases of influenza per sentinel sites

eported cainflu

enza e

ses of influd cases of i

uenza* per of re

ported

Wk

sentinelNum

ber o

Wk

*including both lab‐confirmed and clinically diagnosed cases

A di ib i f i fl i d h l h i JAge distribution of influenza‐associated encephalopathy in Japan,week 28‐45, 2009

s orted case

mbe

r of rep

Num

y/o20s  30s  40s‐

Concluding Observations

Thi d i ' ll i t i ild f t t l• This pandemic's overall impact is mild, fortunately. • Patient number is estimated as 15% of population, however mortality rate 

is very low (0.15/100,000 population), in Japan.

• The global and domestic context is becoming increasingly complex & unforgiving and handling future pandemics & global public health events will become more challengingwill become more challenging

– Where are the main gaps?How do we become better prepared & more flexible?– How do we become better prepared & more flexible?

– How do we respond more effectively? 

• Influenza (not only pandemic) surveillance and control measure should be• Influenza (not only pandemic) surveillance and control measure should be strengthen more

Influenza virus surveillanceInfluenza virus surveillance

Role and International Cooperation between NIID and Neighboring Asian Countries

Influenza Virus Research Center at NIID & WHO CC on

Influenza (Tokyo Center)

National Influenza Centers (NICs)

(Korea, China, Taiwan,Myanmar Laos MongolMyanmar, Laos, Mongol,

Singapore, Vietnam)Surveillance kit (Ref viruses, antisera)

Tech Supports (Manuals, Reagents) Outbreak information

Sending staff for  training of lab staff

Host for Tech WS

Virus isolates and specimens

Sending staff to attend T‐WS

WHO CCsWHO HQ

Analyzed DataQ

NIID‐WG for Vaccine strain selection Vaccine strain selection for Northern & Southern Hems

L l G

Preparation of GuidelinesMOH, Japan

Local GovernmentsVaccine Manufacturers

Public

Vaccine ManufacturersPublic (Global)

Development of H1pdm detection systemDate Events24. Apr The sequence of H1N1 pdm virus was disclosed by CDC USA25 A Primers and probes for conv and real time RT PCR were designed by NIID25.Apr Primers and probes for conv. and real-time RT-PCR were designed by NIID

27. Apr Primers and probes were obtained28. Apr Primers and probes were obtained8 p e s a d p obes e e ob a ed29. Apr Usefulness of our detection system using swine Flu (H1N2) virus was verified

30. Apr Regents, positive control RNA(swine H1N2), primers and probes were provided to 76 Local Institutes of Health and 15 Quarantines in Japanprovided to 76 Local Institutes of Health and 15 Quarantines in Japan

2. May A/California/4/2009 (H1N1) pdm virus was sent from CDC 3. May Our detection system using H1N1 pdm virus was validated3. May Our detection system using H1N1 pdm virus was validated~ 5. May H1N1 pdm diagnosis system was established in all Local Institutes of Health

and Quarantines

6 May The information of our detection system was reported to the WHO6. May The information of our detection system was reported to the WHO (Published on 21. May)

8. May The first case traveled in Canada was detected in Narita Airport Quarantine

13. May The information of our detection system was reported to the ASEAN16. May The first case with no travel history was detected in Kobe city

Local Institutes of Health and Quarantine Laboratory in Japan

Local Institutes of Health76 places

Quarantine Laboratory15 places

NIID

fl i d d i l b l h b (Influenza virus detected in Local Pub Health Lab (2008 36w~2010 15w), in Japan

1600

1800

インフルエンザウイルス分離報告数週別グラフ（2008年第36～2010年15週）

1200

1400

600

800

1000

200

400

0

3637383940414243444546474849505152 1 2 3 4 5 6 7 8 9 1011121314151617181920212223242526272829303132333435363738394041424344454647484950515253 1 2 3 4 5 6 7 8 9 101112131415

2008 2009 2010AH1 AH3 B AH1pdm

2010年4月24日現在

Influenza virus isolation, wk28, 2008～wk47, 2009

OTV resistant H1N1pdm virusesOTV resistant- H1N1pdm viruses (as of April 2010)

67 Resistants / 5422 tested (1.2%)

All were sensitive to zanamivir

Ｔｒａｉｎｉｎｇ on laboratory diagnosis y g

P i i B i C b di I d i L PDR M l iParticipants; Burnei, Cambodia, Indonesia, Lao PDR, Malaysia, Philippines, Singapore, Thailand, Vietnam

Training and lecture; PT-PCR, Real time PCR, Sequencing(lecture)

Reagents provided;g p ;・RNase Inhibitor (Appliedbiosystems)・QuantiTect Probe RT-PCR Kit (QIAGEN) ・TaqMan MGB Probe and primers for real-time RT-PCRTaqMan MGB Probe and primers for real time RT PCR

Type A detection, H1 pdm detection・Primers for conventional RT-PCR

Type A detection H1 pdm detection H1(seasonal) detectionType A detection, H1 pdm detection, H1(seasonal) detectionH3(seasonal) detection

・Control RNA (A/Narita/1/2009(H1N1pdm)

Sakai/1

Hyogo/2

Sakai/2Osaka/180

Hyogo/1Kobe/1

Beijing/502

Shiga/1

Shiga/2Himeji/1

Okinawa/257

Osaka/1

Utsunomiya/1

Mexico/InDRE13551 MexicoCity/WR1301NOkinawa/254

Canada-PQ/RV1758

Osaka-C/2

Niigata/700

LaPaz/WR0096T

Amagasaki/1

Hunan/SWL3

Beijing/3

Korea/01

Canada-QC/RV1954

Osaka/2

Osaka-C/1

Utsunomiya/2

Okinawa/256

Amagasaki/2

Mar.13

Mar.24 1.2MC1

MC11

MC12Canada-SK/RV2486

Canada-MB/RV2023

Thailand/CU-B5

Singapore/ON1087

Shiga/1

Singapore/GP2686

New_York/3408

Mexico/InDRE13555

Utah/05Niigata/749

Shiga/3

Moscow/IIV04

Shizuoka/793

Italy/127

New_York/3551

Niigata/690Nonthaburi/102

New_York/3352

NewYork/4820

Shandong/1

Mexico/4604

New_York/4197

New_York/3260

I /1

Tokushima/1

New_York/3468

Akita/1

Shizuoka/759

Silver_Spring/SP509New_York/3389

Taiwan/T1773

New_York/3351

Kanagawa/137

1.3MC12

MC4New_York/3014

Zhejiang/1

New_York/18

Chiba-C/51

New_York/3651

California/14

New_York/3715

Denmark/524Denmark/523

Moscow/03

Chiba-C/48Yamaguchi/21

New_York/3413

New_York/3532New_York/3168

Denmark/528

Shanghai/71T

Yamaguchi/23

New_York/06

Iwate/1Yokohama/1

Moscow/IIV02

New_York/3166

Moscow/IIV03

Shizuoka/759

New York/11N Y k/3502

New_York/3170Guangdong/02

Taiwan/T0724

New_York/3898

New_York/3193New_York/3172

MC6

MC4

Hiroshima/201

Taiwan/T1338

Canada-ON/RV1589Canada-ON/RV1527

Shiga/43

New_York/3049

MexicoCity/WR1308TMie/41

Fukushima/1

New_York/3169

Taiwan/T0826

Okinawa/283

New_York/3214

Himeji/L1

New_York/20

Italy/49

Moscow/0253T

New_York/3463

New_York/23

Okinawa/259

Fuzhou/01

New_York/3234

New_York/4290

New_York/3176

New_York/11

NewYork/4870

New_York/3502

New_York/3012

MexicoCity/WR1312N

Fujian/1

New_York/3354

Sapporo/1

Kagoshima/56

Apr. 03 

Cluster 2

MC7MC2

NewYork/4777

Hiroshima/230

Zhejiang-Yiwu/11

NewYork/4576

SanSalvador/0169T

Thailand/CU H9

Brandenburg/20

Okinawa/258

Mie/41

New_York/3007

New_York/10

Niigata/717

Mie/52

Bogota/0466N

Iwate/3

Hiroshima/220

Iwate/2

Zhejiang/DTID-ZJU02

Shanghai/1

Hiroshima/207

Taiwan/T1339

Zhejiang/DTID-ZJU03

New_York/3261

Wakayama/57

New_York/3264

Taiwan/T1821

y/

Kyrgyzstan/01

Tokushima/2

Aichi/202

Shanghai/37T

Aichi/198

Malaysia/820Mar. 13 MC3

MC5Hiroshima/216

Osaka/2031

Bethesda/SP508Thailand/CU-H9

Japan/PR1070

Italy/05

New_York/3313Kobe/91993

Taiwan/526

Shiga/44

Hiroshima/200New_York/3008

Italy/85

Osaka/2032

Michigan/02

New_York/3237

Kobe/91992

Texas/08

New_York/3992

Texas/09

Tochigi/154

NewYork/4790

Gifu-C/67

Mexico/InDRE13547

Singapore/ON1050

Saitama-C/88

Saitama/85

Bethesda/SP506

Texas/04

Nanjing/3

Singapore-Q/M168

Moscow/IIV05Jan.30 

MC9

MC8

Canada-NS/RV1565

Beijing/02

Canada-NS/RV1535

New_York/1682

New_York/3455

Toronto/R8564

New_York/1669

Santo_Domingo/573N

Shizuoka-C/97

Kanagawa/140

E l d/195

Toronto/T5308

SantoDomingo/WR1068NSanto_Domingo/572N

Texas/09

Guangdong/1

Brawley/40082

Beijing/01Beijing/4

Narita/1

Washington/14

California/06

Brandenburg/19

New_York/3099

Canada-AB/RV1644

Mexico/4486

SantoDomingo/WR1059N

Indiana/09

Mexico/4108

Toronto/0462Mexico/InDRE13495

Canada-SK/RV1798

Santo_Domingo/568T

Cluster 1Feb.02 

30.0

Paris/2590

Fukuoka-C/1

New_York/3307

Vladivostok/IIV17

Managua/0536NNanjing/2

Kagoshima/1

Mexico/InDRE4487

Fukuoka-C/2

England/195

Mexico/InDRE13494

SantoDomingo/WR1068NParis/2580

California/04

Paris/2592

California/07

Sichuan/1

Fukuoka-C/3

Vladivostok/IIV18

New_York/3178

Apr .1 May .1 Jun .1 Jul .1 Aug .1 Sep .1 Nov .1MC10

1. May 1. Jun. 1. Jul. 1. Aug. 1. Sep.

Time of virus introduced in Japan, which was analyzed from the genome evolution

SapporoIwateAkita

Niigata

TochigiUtsunomiya

5.15

6.511

3

2Fukushima

gSaitama

Chiba

KanagawaShizuoka

Ai hi

Narita

Yokohama

Nagano

45.17

5.163

6 99

*

**

AichiMieGifuShiga

OsakaSakaiAmagasaki

Wakayama

1

65.25

6.9

AmagasakiKobeHyogoHimejiTokushimaHiroshima

FukuokaYamaguchi

4.225.19

5

75.25

85.29

10FukuokaKagoshimaOkinawa 5.21

10

7.2412

Extensive school closure

ConclusionConclusion

1) Rapid development of new virus detection methodsis required especially in the WHO CC on influenza

2) Technical transfer and sharing of information amongcountries are very important to control thespreading of diseases

3) Characterization of virus genomes will tell us the3) a ac e a o o us ge o es e us eevolutional steps of virus and may explain theeffectiveness of countermeasures to the influenzaisolation

Laboratory-based net work among Asia and Pacific Rim

●Construction of PulseNet Asia-●Construction of PulseNet AsiaPanpacific

●Laboratory-based net work among Asia and Pacific rimNational National Institute of InfectiousInstitute of Infectious

Japan Asia

US CDCRapid detection of pathogens emerging in Asia and prevention

ASEAN Plus Three (APL)DiseaseDisease (NIID, Japan(NIID, Japan))

US.CDC

Philippine

Taiwan. CDCemerging in Asia and prevention of their spreading

Target pathogens；Bacteria (Enteric bacteria)

1)Collection of domestic i f ti

Australia

MalaysiaBacteria (Enteric bacteria)Virus ( Dengue fever virus, JE)Parasites (Malaria etc.)

1)Standardization of protocol

WHO,WPROinformation

2)Genetic and phenotypic characterization of the pathogens

3)Development of new 1)Standardization of protocolfor the detection of pathogensand genotyping

2)Quality control, validationof the protocol

Bangladesh,ICDDR B India NICED

New Zealandmethods

China, CDCKorea,ＮＩＨ/CDC

of the protocol3)Construction of data-base4)Exchange of information and

researchers

ICDDR・B India,NICED

Local Health InstituteThailand, NＩＨ/CDC

Vietnam,ＮＩＨＥ

Local Health Institute, Quarantine station