SISEA project implemented by the International Pasteur Institutes Network

1. 11/02/10
International
Pasteur Institutes
Network
"Surveillance and capacity Plan
building in South-East Asia: 1. What is SISEA?
2. Main SISEA’s outcomes
SISEA project" a.
b.
Improving surveillance through a better knowledge of some EIDs: ARI&AES
Capacity strenghtening
 Equipment, consumables
 HR
 Public Health capacities: detection&response of potentially at risk outbreaks
3. Conclusions & perspectives
International
Pasteur Institutes
Network Surveillance et Investigation des Situations Epidemiques
en Asie du Sud-Est
1. What is SISEA? Context:
2. Main SISEA’s outcomes " Outbreak as global social crisis in South-East Asia: SARS
a. Improving surveillance through a better knowledge of some EIDs: ARI&AES
b. Capacity strenghtening
(2003-2004, 8096 cases/774 fatalities); avian influenza (2005
 Equipment, consumables and sqq.; 467 cases/282 fatalities on Dec. 31st 2009)
 HR
 Public Health capacities: detection&response of potentially at risk outbreaks
3. Conclusions & perspectives " International concern and mobilization as soon as northern
countries felt themselves in danger (what will be called by WHO
from 2005: “PHEIC” included in the IHR-2005)
" And the beginning of an international involvement and
commitments from multilateral and bilateral institutions
4
Budget breakdown – in line with the objectives
" A convention was signed in June 2006 for 5 years, between
AFD and Pasteur Institute of Paris (DG)
Type of disbursement Amount (€) %
" Following, conventions were signed between DAI/IPP and
each partner implementing a piece of the project set up Equipment 720,936 12
through a participative approach Personnel & Training 2,215,543 38
" 5.6 M€ over 4 effective years with 6 partners (5 IPIN’s
Goods and services 2,028,234 34
members) in SEA:
Monitoring and evaluation 181,787 3
" Chine: IP Shanghai
" Vietnam: NIHE, IP Nha Trang, IP HCM Other 369,500 6
" Cambodge: IP Phnom Penh
" Lao PDR: NCLE (not IPIN)
Management fees 384,000 7
5 6
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2. 11/02/10
Objectives and content of the SISEA project:
Network .... and sub-network
The aim of SISEA project is to contribute to improving the
detection and the treatment of epidemic episodes in South-East
Asia
The specific objectives of the SISEA project aim to:
" Establish a program for epidemiological surveillance and
investigation of epidemics caused by emerging viruses
" Establish a network of laboratories and develop
regional
coordination in these fields in association of WHO
International Pasteur Institutes Network – 32 members on 5 continents
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3 COMPONENTS
Network of laboratories & hospital-based sentinel sites
C1: Strenghtening the reference laboratories and establishing a network among
them. Increasing the capacities of the lab. to identify pathogens, particularly viral pathogens, and
qualify them IPS
- pediatric hospital of Nanxiang
NIHE - Guangxi CDC
C2: Improving the epidemic alert on emerging viruses in each country - Provincial Hospital of Hai Duong
- District hospital of Cam Giang
- Strenghtening national epidemiological surveillance system - 19 communes
IPNT
- Increasing the involvement of sentinel centers in the network - Provincial Hospital of Binh Dinh
NCLE - District Hospital of Phu Cat
- Investigating epidemic episodes -Setthathirath Hospital, Vientiane
C3: Strenghtening the epidemic response network at national and regional levels:
- In each country, strengthening the connections and coordination between various sector involved IP HCMC
in surveillance (IO / WHO, OIE; NGOs) - Ben Tre provincial hospital
- Cu Lao Minh district hospital
IP Cambodia
- Developing relationships between the various countries (joint training, …) - Provincial hospital of Takkeo
- Provincial hospital of Kampong Cham
- Strengthening regional coordination
Here are the nodes, and finally, the project
- Including RIIP’Institutes in a vast network coordinated by WHO aims at building the edges, so as it
9 10
- Technical and scientific oversight of the SISEA project activities and dissemination of the results becomes a real network
International International
Pasteur Institutes Pasteur Institutes
Network Network
Improving surveillance in China:
1. What is SISEA? 1. IPS: implementation of a respiratory virus diagnosis platform based on multiplex and
real-time RT-PCR, and serology (1,2,3,4) working with regional (Hong Kong, Cambodia)
2. Main SISEA’s outcomes and international (Paris) Pasteur Institutes.
1. ARI: cohort of 817 children / testing NP samples with mPCR compared with
Luminex (Wang et al.)
a. Improving surveillance through a better 2. human rhinoviruses (HRV) identification performed on the same cohort of 817
samples: recombination events involving HRV-A sequences in the newly identified
knowledge of some EIDs: ARI&AES species of HRV-C (3). Further studies with IPC; warning on emergence of epidemics
of HRV recombinants.
b. Capacity strenghtening 3. HBoV: persistance of viruses 31 days after onset; frequent viral coinfection
 Equipment, consumables 4. Technology transfer of multiplex RT-PCR to the laboratory of Shanghai Public
Health Center to reinforce the preparedness of the alert system during the Shanghai
 HR 2010 World Expo
 Network integration and partnerships 2. SARI surveillance in Shanghai Nanxiang Hospital (started in march 2009)
3. Conclusions& perspectives 3. Isolation and characterization of JEV and development of new diagnostic tool (NS1
protein, Deubel et Al.) with a collaboration with Guotong China CDC and NIHE in
Vietnam)
4. Study of encephalitis of unknown origin in 2009 in Guangxi province is ongoing. 131
patients included and sampled from January to June 2009 by Guangxi CDC.
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3. 11/02/10
International International
Pasteur Institutes Pasteur Institutes
Network Network
Improving surveillance in Cambodia – 1 (Vong S and al.): Improving surveillance in Cambodia - 2 (Vong and al.):
2. Knowledge of inflenza viruses strains circulating during 2009. From Jan to Nov 2009: 108 cases
1. Implementation of the ALRI surveillance activities in April,2007: on Nov 2009, among ALRI cases in sentinel sites: 53% A(H3N2), 27% B, 10% A(H1N1)soiv, 6% A(H1N1), 4% other
3177 patients enrolled. In depth clinical classification and data validation (Pr. 3. SISEA results included in the National Bulletin of respiratory infections since 2008
Mayaud and al.). 4. Numerous requests from NGOs and other public hospitals for bacterial etiologies of ARI and their
susceptibility to ATB
5. Publication of first data on melioidosis in a National Medical Journal (Health Messenger)
6. Use of SISEA results by national experts to advocate for changing MoH recommendations on first
Percentage %
line treatment for ARI (high resistance of S. pneumoniae to ampicillin and cotrimoxazole)
Viro and bacterio : # positive results /
# samples tested (%)
7. Presentation of SISEA data by some site clinicians in national and international conferences
8. Expertise sharing on pathologies between clinicians in Laos and Cambodia
BK : # positive / # cases (%)
And also, as a main outcome: improving patient care management
• Follow-up of clinical process indicators:
– Monitoring of the number of discrepancies and incoherence in SISEA CRF
• Thru ascertainment of diagnosis
Extra-respiratory Other
Pneumonia Pleural
pathologies respiratory
infections • Thru monitoring of a sample of patients after discharge
infections
International International
Pasteur Institutes Pasteur Institutes
Network Network
Improving surveillance in Vietnam (SARI and AES)- NIHE: Improving surveillance in Vietnam (SARI and AES) IP-Nha Trang:
1. Investigation of an outbreak of coronavirus NL-63 detected at the communal 1. Influenza: 86% flu A/H3, 9% A/H1, 5% A unsubtyped
level thanks to the multiplex protocols implemented at NIHE through SISEA. 2. SARI: 01/10/2008 to 30/09/09: 731 cases/48%+ve mPCR (41% 1-virus; 6% 2-
2. NIHE: SARI Jan to Nov 2009 viruses; 1% 3-viruses)
Eligible
cases
297
Number
cases
enrolled
290
(97.6%)
Nega;ve
:
33.4
%
(n=97)
Posi;ve
:
66.6
%
(n=193)
Agent 1st 2nd 3rd n %
1 H1N1/09* 71 9 80 41.5
2 RHINO 31 7 38 19.7
3 FluB 19 6 1 26 13.5
4 hMPV 12 6 4 22 11.4
5 PARA 1 10 3 1 14 7.3
6 Flu A 10 2 2 14 7.3
7 Others 40 9 1 49 25.4
Total 193 42 9 100
International International
Pasteur Institutes Pasteur Institutes
Network Network
Improving surveillance in Vietnam (SARI and AES) IP-Ho Chi Minh- Improving surveillance in Vietnam: case definition of SARI
City: adopted:
1. Activities implemented in 2009 (cumulative number of SARI cases>2000):
Objectives Activities ≤ 05 y.o. > 05 y.o.
Viral pathogens of Strengthening
the lab. capacity
- Install office and scientific equipments (data management and diagnostic)
Cough or breathing difficulty Fever ≥ 38o C (or history of fever)
- Training and Technique transfer: Bacterial diagnosis (Sentinel hosp.), JEV/DENV-MAC AND
AES ELISA (PMC)
AND
Cough OR sore throat OR breathing
from Jan 2009 to One of the following: difficulty
Surveillance - Training: SARI/AES surveillance procedures • Tachypnea AND
Nov4.92 4.92
2009 Viral pathogens of SARI cases and 122 AES cases (Jan-Oct 2009)
- Enroll 1,271 • Chest indrawing One of the following:
% - 50% confirmed SARI by 15 viruses (RhinoV, RSV, Flu V, BocaV); 43% confirmed AES by • General signs of danger • ≥ 30 respirations/min
% SARI JEV, DENV & EVs (with 7% arbo-enterovirus co-infection). • New infiltrate on chest X-ray
32.79 • Inability to speak full sentences
57.38 from1.97% 2009 to
Jan - 9% confirmed SARI by bacterial (Aug-Nov.2009) with 64% viral co-infection. Onset of symptoms up to and
%
12.67 including 7 days • Use of accessory respiratory muscles
% Nov 2009
Investigation - Training: AES case management, Entomological survey of JEV case • Arterial O2 saturation ≤ 92% on air
17.31 intervention
and % 0.16%
0.55%
3.46% - Field investigation of Flu A/JEV confirmed cases (16 A/H1, 7A/H3, 6 JEV)
2.12% (no oxygen therapy)
% 2.2% 3.54% 0.16%
0.31% 1.26%
2.12, - 0.16%
JEV vaccination in districts having confirmed cases
JE Dengue EV Negetive % 1.42%
Adenovirus- Weekly checking the CRFs
Onset of symptoms ≤ 7 days
Quality control 50.59
%
Bocavirus - Weekly supervise the case detection and enrollment
Enterovirus- Specimen quality and timely testing
- Set up the SOPs of sample management and testing for SARI and AES
3

4. 11/02/10
International International
Pasteur Institutes Pasteur Institutes
Network Network
Improving surveillance in Lao PDR:
1. Technical assistance in microbiology and epidemiology
2. ALRI surveillance, complementary approach to the other surveillance system
implemented (EWORS, EWARN, ILI):
1. ILI: 2007 to 2008 : 507 ILI specimens collected → 142 (28 %) +ve for IAV and IBV, 2009 : 533
specimens collected → 139 (26 %) +ve for Influenza IAV and IVB.
2. ALRI: Jul 08 to Oct 09: 222 specimens collected → 26(11.7%) +ve for IAV and IVB; 24 sputum
specimens collected for bacteriology testing: 11(45.8%) +ve: S. pneumonia, H. influenza, S.
aureus, P. aeruginosa, K. pneumonia (+ C. albicans)
3. Contribution to ILI surveillance
4. Strenghtening virology, bacteriology, epi
5. Implementing a new sentinel site in Luanprabang
International Short Course in Biostatistics - REDI Reaching common administrative standards. June 10,
centre - Singapore, November 9-13, 2009. 2008:
= Management and Administrative Routines Workshop held in Nha
Trang, Vietnam on 29-30 May.
Capacity
strengthening
and
epidemiology
On-site training/Transfert of technology:
- February 2008, Institut Pasteur Cambodia. PCR multiplex. 2 weeks/2 virologist from
IP NT
24 trainees/12 from SISEA
Daily and final evaluation;
very good input from SISEA - September/October 2009, Institut Pasteur Cambodia: PCR multiplex 2 weeks/2
trainees
virologist from NCLE (Vientiane, PDR Lao)
Very good perception by the
trainees
- November 2009: 1 bacteriologist from NCLE for 1 month in IPC
New ties with profesionals
coming from Indonesia, and
Singapore
High quality of the
collaboration with REDI and
NUS, who are demanding for 21 22
other collaboration in training
International
Pasteur Institutes
HKU-Pasteur Virology Course 2009 Network
• Focus on neurotropic viruses
• Neurobiology, clinical, molecular virology
• Practical sessions (molecular, cellular, bioinformatics)
• 24 students, 4 from IPS
• 4 speakers from IP, 3 Asian experts
• SISEA session
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5. 11/02/10
International
Pasteur Institutes
First Forum GMS forum on Japanese Encephalitis/viral Network
Encephalitis prevention and control: Achievements and
orientation,
29-30 October 2009, Hué City, Vietnam: over 40 experts from Cambodia, China,
France, Japan, Laos, Malaysia, Singapore, USA and Vietnam. Cosponsored with ADB/
GMS-CDC project
CEROPATH Workshop, Siem Reap 17-20 November 2009
Community ecology of rodents and their pathogens in South-East Asia
Biodiversity changes and implications in health ecology.
ANR; many universities and institutions from France, Thailand, Belgium, Finland and
Laos.
Partnership with CIRAD
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Overtoom R, Khieu V, Overtoom R, Khieu V, Hem S, Cavailler P, Te V, Chan S, Lau P, Guillard B, Vong S. A first report of pulmonary
melioidosis in Cambodia. Trans R Soc Trop Med Hyg. 2008 Dec;102 Suppl 1:S21-5
Vallée J, Dubot-Pérès A, Ounaphom P, Sayavong C, Bryant JE, Gonzalez JP.Spatial distribution and risk factors of dengue and
Japanese encephalitis virus infection in urban settings: the case of Vientiane, Lao PDR.Trop Med Int Health. 2009 Sep;14(9):
1134-42. Epub 2009 Jun 28.
Public health and research = mutual feeding Wang W, Ren P, Hou L, Tsai C, Chan KH, Chen P, Shen J, Buchy P, Sun B, Toyoda T, Lim W, Peiris JSM, Zhou P, Deubel V. (2009). Design
of multiplexed detection assays for identification of avian influenza a virus subtypes pathogenic to humans by SmartCycler real-
time reverse transcription-PCR. J Clin Microbiol. 47:86-92
Research → Public health: cf. Previous slides
Wang W, Ren P, Sheng J, Mardy S, Yan H, Zhang J, Hou L, Vabret A, Buchy P, Freymuth F, Deubel V. (2009). Simultaneous detection of
respiratory viruses in children with acute respiratory infection using two different multiplex reverse transcription-PCR assays. J
Virol Methods 162:40-45.
Public health → research : Publications supported by the activities of
SISEA. Huang T, Wang W, Bessaud M, Ren P, Sheng J, Yan H, Zhang J, Lin X, Wang Y, Delpeyroux F, Deubel V. Evidence of recombination and
genetic diversity in human rhinoviruses in children with acute respiratory infection. PLoS One. Jul 27;4:e6355
Wang K, Wang W, Yan H., Ren PJ, Zhong J, Shen J, Deubel V. Correlation between human bocavirus infection and humoral
Limitations: data have been collected according to a surveillance objective, response, and co-infection with other respiratory viruses in children with acute respiratory infection. J. Clin. Virol. (in press)
and no research design has been really set up regarding to scientific Tsai C, Caillet C, Hu H, Zhou F, Ding H, Zhang G, Zhou B, Wang S, Lu S, Buchy P, Deubel V, Vogel FR, Zhou P.
Measurement of neutralizing antibody responses against H5N1 clades in immunized mice and ferrets using pseudotypes
research questions, and financial support is provided for public health expressing influenza hemagglutinin and neuraminidase.
Vaccine. 2009 Sep 2. [Epub ahead of print]
concerns
Buchy P., Fourment M., Mardy S., Sarn S., Davun H., Vong S, Peiris J.S.M., van der Werf S. Molecular Epidemiology of Clade 1
Influenza A Viruses (H5N1), Southern Indochina Peninsula, 2004-2007. Emerg Infect Dis. 2009 Sep available at www.cdc.gov/eid/
However, the observation of the data rises fundamental or applied research content/15/10/1641.htm
questions: co-infections, diagnosis tools, negative samples (more or less Fourment M, Mardy S, Channa M, Buchy P. Evidence for viral persistence, antiviral resistance and reassortment events in seasonal
influenza viruses circulating in Cambodia. J Clin Microbiol. 2009 Nov 4.
50%...)
Buecher C. , Mardy S. , Wang W. , Duong V. , Vong S., Vabret A. , Freymuth F., Deubel V., Buchy P. Use of a multiplex PCR/RT-PCR
approach to assess the viral causes of influenza-like illnesses in Cambodia during three consecutive dry seasons. J. Med. Virol. (in
press)
27 28
Next steps … After 2010 ...?
• Epidemiological and clinical description of various bacterial or viral infections " Needs and wishes from the partners
• Bacterial resistance: characterization and determinants
" Funding ? Who ("WHO"?, AFD, ADB, US-CDC, DHHS, ...)
• Risk factors for severe infections by pathogen
• Phenotypic and genotypic determinants of viral virulence
" Network of laboratories and of hospital-based sentinel sites set up at the end
of the project = sustainability of the system
• Viral resistance to antivirals
" Knowledge, know-how, applicable for many lab techniques
• Diagnosis of SARI by use of scoring system for severity
• Bacteria of interest: M. tuberculosis, B. pseudomalleii, K pneumoniae
" Geographical expansion within a country or to other countries?
• Viruses of interest: influenzas, HRV, RSV, hMPV, BocaV " Other pathologies (rabies, …), or other EID concerns as viral/bacterial
resistance as an emerging infectious disease event
• Clinical outcomes: guidelines/recommendations/GCP for improving patient
management, both in ARI and AES " I mproving connection between human and animal surveillance (in line with
“One World One Health" initiative
29
" I ntegration with environmental issues and climate change under the scope of 30
risk assessment
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6. 11/02/10
Better “Knowledge is the
understanding heritage of humanity.”
≠ should teach us
to avoid such
mistakes ! « Science doesn't belongs to one
OR country, or rather science
encompass the whole humanity"
≠
Louis Pasteur (1822-1895)
31 32
Many
thanks
to:
Ins;tut
Pasteur
du
Cambodge
:
Dr
Sirenda
Vong,
Dr
Sowath,
Dr
Laurence
Borand,
Sophie
Goyet,
Dr
Philippe
Buchy,
Dr
Bertrand
Guillard.
Pr
Jean-­‐Louis
Sarthou,
NIHE
:
Pr
Nguyen
Tran
Hien,
Dr
Nguyen
Thi
Thuong,
Dr.
Nguyen
Van
Duong
Ins;tut
Pasteur
Nha
Trang
:
Pr
Bui
Trong
Chien,
Dr.
Vien
Quang
Mai,
Dr.Trinh
Thi
Xuan
Mai
Ins;tut
Pasteur
Ho
Chi
Minh
Ville
:
Pr
Tran
Ngoc
Huu,
Dr.Kien
Quoc,
Dr.
Huong
Vu
Thi
Hu
Que
Ins;tut
Pasteur
de
Shanghai
:
Dr
Wei
Wang,
Dr
Peijun
Ren,
Dr
Jin
Zhang,
Dr
Changgui
Dong,
Dr
Yize
Li,
Dr
Peng
Lu,
Dr
Vincent
Deubel,
M.
I.
Robin
NCLE
:
Dr
Phengta
Vongprachanh,
Dr
Hansila
Phoupaseuth,
Dr.
Somvay
Ongkhammy,
Dr
MaShida,
Dr
Darouny
Phonekeo,
Dr.
Noikaseumsy
Sithivong,
Dr
Thongchanh
Sissouk,
M.
Phayvan,
Unité
de
Coordina;on
:
Mme
Silvia
Ostberg,
Dr
Roberto
Bruzzone
(HKU-­‐Pasteur
InsVtute
–
scienVfic
advisor)
DAI
:
Dr
Isabelle
Catala,
Dr
Marc
Jouan
And to all the hospital's staff involved in
THANK YOU FOR the sentinel surveillance 33
YOUR ATTENTION
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