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Technical assistance for early detection and
laboratory diagnosis of biological events in Japan
Technical assistance for early detection and
laboratory diagnosis of biological events in Japan
Ministry of Foreign AffairsMinistry of Health, Labour and WelfareNational Institute of Infectious Diseases
Japan
Surveillance System in JapanSurveillance System in JapanSentinel-Reporting diseases
Sentinel clinics / hosp. Clinical isolates and specimens
Health centers
Case Report Summary Report (wk/mo)
Quarantine stations
National IDSC(NIID)
Laboratories (NIID)MHLW
ReportsSpecimens
Computer networkPatient (data entry by HCs)Infectious agent (data entry by PHIs)
Information dissemination
Notifiable diseases
All clinics / hosp.
Pref. Health Depts. Pref. IDSCs Pref. PHIs
limitationlimitation
No diagnosis, No reportNo suspect, No order of laboratory diagnosisNo knowledge, No suspect
Early detection strategyEarly detection strategy
Case-based suspected case surveillance
Cluster surveillance
Syndromic surveillanceEvent-based surveillance
Ambulance call surveillance<Tokyo metropolitan ambulance>
Ambulance call surveillance<Tokyo metropolitan ambulance>
records
analysis
Routine work
detection
Graphical presentation
Analysis serverData server
Database
Pharmacy A Pharmacy B
Automatic Data collection
feedback）collation
Public Health Authorities
Detection Algorithm
result
Dispensing Pharmacy(Prescribed Drug) surveillance4131 dispensing pharmacy(9.2% coverage as of 24 April 2010)
Daily subscription dataAcyclovir, antivirals, , antipyretics, antitussive, etc
Full Automation
0
1,000
2,000
3,000
4,000
5,000
6,000
7,000
8,000
9,000
10,000
4/20 4/27 5/4 5/11 5/18 5/25 6/1 6/8 6/15 6/22 6/29 7/6 7/13 7/20 7/27 8/3 8/10
薬局サーベイランス推定患者数
全数報告
（発症日別報告数
）
0
0.5
1
1.5
2
2.5
3
3.5
4
発生動向調査
（定点あたり
）
薬局サーベイランス推定患者数
全数報告(発症日別報告数）
発生動向調査(定点あたり）
Antiviral surveillance in the spring 2009
Antiviral surveillance in the spring 2009
First case at airport
First outbreak in school
8
Real-time School absenteesm surveillance
Real-time School absenteesm surveillance
SchoolServer
Internet
Dep. Edu of city
Consultation
Public
Security gateway
PHC
Dep. Edu
Dep. Health
Pref
Doctors
Trigger of investigationTrigger of investigation
Early detection of suspected eventsInitial investigationLaboratory investigation
Diagnosis of the first smallpox caseDiagnosis of the first smallpox case
Suspected case
Medical institution Local Public Health Laboratory
NIID
Prefectural governor,Mayor of a city where health center belongs
MHLWSmallpox Technical Committee
Specimens
・Rapid response team from NIID
・12 – 24 hours for specimen delivery
・12 hours (3 – 4 hours) for laboratory diagnosis
・Smallpox Technical Committee will be held within 24 hours
Lesson learned from white powder events
Lesson learned from white powder events
88% of local Public Health Institutes had experiences to test white powder(as of 2008)– Police transports samples by police cars using conventinal
containers(95％)– Laboratory test (average 3.17days), Final report
(average 3.72days)– Total 1052 events(2001:average 16events/55PHIs,
2002: 4.6/28, 2003: 2/12, 2004: 1.1/7, 2005: 1.3/3, 2006: 1/3, 2007: １/1, 2008: 1/4)
Enough capacity in 27％ of 77PHIs– Manual availble in 86％。– Request for test kit and lab network88％。
Several suspected positive result by Rapid field test kit at fire emergency stationsNeed to assess the performance of field test kit
Evaluation of rapid test kitEvaluation of rapid test kitEvaluating detection and diagnostic decision support systems for bioterrorism response. EID 2004,10:100-108
55 detection system & 23 diagnostic decision support system
The U.S. Department of HHS at this time recommends against use by first responders of hand-held assays to evaluate and respond to an incident involving unknown powders suspected to be anthrax or other biological agents.-CDC-
Sensitivity is not goodRapid diagnosis is not always necessary
Laboratories of the National Institute of Infectious Diseases
Prefectural and Municipal Public Health Institutes (76)
• Technical advice• Reference materials • Clinical isolates
if necessary
Network of laboratoriesNetwork of laboratories
Laboratory diagnostic process plan of samples for suspected bioterrorism
Samples (Clinicians)
Medium and low risk samples High risk samples
Local PHIs
Laboratory test
Positive Negative
NIID (Risk assessment)
•High sensitivity assay
•EM, Pathological exam,
Negative Positive Positive for class 1 pathogens
If necessary
•Notification to the government
•Report to clinician
Dr. Morikawa, NIID
Need for simple, safe and Rapid screening test
1. 96 wells plate with FAM- and HEX labeled probe in 1 well (two viruses for 1 well)
2. Detection for 163 viruses using 10ug DNA, RNA (3 hours)
3. Multiplex one step-real time RT PCR for both DNA and RNA viruses
4. Already verified with positive controls and no cross reactions
Kit for Multi-virus real time PCR assay
Rapid and simple method could be used in
Local public health laboratories
Quantitect2x master mixRNA
DNA
+RT
Quantitect2x master mix
+
+
Sample
2x Probe & primer mix
DNA virus
RNA virusReal time PCRMachine
Add
• Easy method for multiplex multivirus real time PCR
• With detailed manual• With transportation and storage methods
Under field testing
Dr. Morikawa, NIID
Well Tube FAM Hex (VIC, JOE)A1 1 NTC NTCA2 2 Standard 10 Standard 107
A3 3 Standard 102 Standard 106
A4 4 Standard 103 Standard 105
A5 5 Standard 104 Standard 104
A6 6 Standard 105 Standard 103
A7 7 Standard 106 Standard 102
A8 8 Standard 107 Standard 10A9 9 Beta-actin (control) hGAPDH-DNA (control)
A10 10 単純ヘルペスウイルス１型
水痘帯状疱疹ウイルス
A11 11 サル痘ウイルス 天然痘ウイルス(1)A12 12 Bウイルス 天然痘ウイルス(2)B1 13 hGAPDH-
RNA(control)Beta-2-microgloburin (control)
B2 14 マールブルグ エボラウイルスB3 15 腎症候性出血熱ウイ
ルス ハンターンクリミアコンゴ出血熱ウイルス
B4 16 腎症候性出血熱ウイルス プーマラ
腎症候性出血熱ウイルス ドブラバ
B5 17 リフトバレーウイルス 腎症候性出血熱ウイルス ソウル
B6 18 ラッサウイルス ハンタウイルス肺症候群ウイルス(Sin Nombre)
B7 19 南米出血熱ウイルス
ガナリト
南米出血熱ウイルス フニン
B8 20 南米出血熱ウイルス
サビア
南米出血熱ウイルス マチュポ
B9 21 東部馬脳炎ウイルス ベネズエラ馬脳炎ウイルスB10 22 狂犬病ウイルス 西部馬脳炎ウイルスB11 23 インフルエンザA SARSコロナウイルス
B12 24 新型インフルエンザウイルスH1N1
高病原性鳥インフルエンザウイルスH5N1
Multi-virus real time PCR
assay for Bioterrorism
Simple and east kit
FAM- and HEX- labeled probes
27 viruses in 3 hours
Multiplex one step-real time RT
PCR
Easy and rapid detection of
nucleic acids of Viruses could
be used for bioterrorism
Purpose
Probe sets
Dr. Katano, NIID
Multi-virus real time PCR
assay for orthopoxviridae
SYBR Green Assay
Specific for orthopoxviridae including
smallpox
Sensitivity : several to 10
copies/sample
Easy and rapid detection kit of nucleic
acids of Orthopox viridae
Purpose
Probe set
virus strain
smallpox India 1964
Bangladesh 1975
Sumatra 1970
Nepal 1973
Monkeypox Zr-599
Vaccinia Lister
WR
IHDW
Cowpox Brighton Red
Camelpox J1
Ectromelia Hamstead
Dr. Morikawa, NIID
Suspected pathogen never been known before： in silico Subtraction method
All DNA extracted from samples and analyze
－ ＝
Dr. Kuroda and Dr, Ohnishi, NIID
Rapid and accurate diagnosis Rapid and accurate diagnosis
High speed DNA polymerase (Hot start version) 100bp/sec
Newly developedSuper speed PCR machine
Real time monitoringand melt curve analysis of PCR products (Total 20min)
“Hyper‐PCR”
Dr. Fujimoto, NIID
(C)
Heat stableSeals
Reaction mixture in a sample
well
(A) (B)
(D)
Amplification time:10 – 15 minutes
（PCR,RT-PCR)
Melting curve analysis:5 minutes⇒ total <20 min
Technical assistance to the local governments
Technical assistance to the local governments
Tools to assist early alert and responseTools to assist rapid and accurate diagnosisEasily applied in the local governments and laboratoriesContribute to the early and effective response
National notification system for biological events
National notification system for biological events
-
Cabinet Intelligence and ResearchOffice Situation Center
Notification
Cabinet Members (Prime Minister, Deputy Chief Cabinet Secretary,Deputy Chief Cabinet Secretary for Crisis Management)
Rapid Report
MHLW
Monitor incidence by gathering information from all relevant agencies such as National Police Agency and Fire & Disaster Management Agency
Cabinet Secretariat
Relevant Agencies
Information
Hospital/Laboratory/Local governments
Notification
Coordination at national levelCoordination at national level
Cabinet SecretariatEstablishment of Emergency Response System
- Establishment of Cabinet Intelligence and Research Office Situation Center (24 hour-monitoring system)
- Establishment of Crisis Management Department governed by Deputy Chief Cabinet Secretary for Crisis Management, enabling relevant agencies to liaise and collaborate effectively
Coordination at national levelCoordination at national level
Cabinet Secretariat (cntd)- Enactment of the Law Concerning measures to
Protect the People in a Situation of Armed Attack (June ’04)
In situations of (impending) mass killing resulting from a bioterrorism, on decision of the government to take actions in order to protect the lives and properties of citizens, measures will be taken concerning the evacuation of people, assistance to evacuated people and responses to disasters, etc.
Coordination at national levelCoordination at national level
National Police Agency, Fire & Disaster Management Agency, National Defence Agency
- Establishment of highly equipped Counter-NBC terrorism squad
- Implementation of counter-NBC terrorism exercises- Establishment of local cooperation system
Ministry of Agriculture, Forestry and Fishery- Surveillance of Notifiable Animal Infectious Diseases
(based upon the Domestic Animal Infectious Diseases Control Law), sharing information with MHLW concerning zoonosis
Coordination at international level
Coordination at international level
WHO IHR focal pointWHO/GOARNGHSAG Emergency Contact NetworkGHSAG Lab-NetASEAN+3 Laboratory Network
Thank you for your attention.Thank you for your attention.
