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"Surveillance and capacity building in South-East Asia:

SISEA project"

International Pasteur Institutes Network

Plan 1.  What is SISEA? 2.  Main SISEA’s outcomes

a.  Improving surveillance through a better knowledge of some EIDs: ARI&AES b.  Capacity strenghtening

  Equipment, consumables   HR   Public Health capacities: detection&response of potentially at risk outbreaks

3.  Conclusions & perspectives

International Pasteur Institutes Network

1.  What is SISEA? 2.  Main SISEA’s outcomes

a.  Improving surveillance through a better knowledge of some EIDs: ARI&AES b.  Capacity strenghtening

  Equipment, consumables   HR   Public Health capacities: detection&response of potentially at risk outbreaks

3.  Conclusions & perspectives

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Surveillance et Investigation des Situations Epidemiques en Asie du Sud-Est

Context: "   Outbreak as global social crisis in South-East Asia: SARS (2003-2004, 8096 cases/774 fatalities); avian influenza (2005 and sqq.; 467 cases/282 fatalities on Dec. 31st 2009)

"  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

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"  A convention was signed in June 2006 for 5 years, between AFD and Pasteur Institute of Paris (DG)

"  Following, conventions were signed between DAI/IPP and each partner implementing a piece of the project set up through a participative approach

"  5.6 M€ over 4 effective years with 6 partners (5 IPIN’s members) in SEA:

"   Chine: IP Shanghai "   Vietnam: NIHE, IP Nha Trang, IP HCM "   Cambodge: IP Phnom Penh "   Lao PDR: NCLE (not IPIN)

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Type of disbursement Amount (€) %

Equipment 720,936 12

Personnel & Training 2,215,543 38

Goods and services 2,028,234 34

Monitoring and evaluation 181,787 3

Other 369,500 6

Management fees 384,000 7

Budget breakdown – in line with the objectives

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Network .... and sub-network

International Pasteur Institutes Network – 32 members on 5 continents

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Objectives and content of the SISEA project:

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

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3 COMPONENTS

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

C2: Improving the epidemic alert on emerging viruses in each country -  Strenghtening national epidemiological surveillance system

-  Increasing the involvement of sentinel centers in the network

-  Investigating epidemic episodes C3: Strenghtening the epidemic response network at national and regional levels: - In each country, strengthening the connections and coordination between various sector involved in surveillance (IO / WHO, OIE; NGOs)

-  Developing relationships between the various countries (joint training, …)

-  Strengthening regional coordination

-  Including RIIP’Institutes in a vast network coordinated by WHO

-  Technical and scientific oversight of the SISEA project activities and dissemination of the results 10

Network of laboratories & hospital-based sentinel sites

IPS - pediatric hospital of Nanxiang

- Guangxi CDC NIHE - Provincial Hospital of Hai Duong

- District hospital of Cam Giang - 19 communes

NCLE -Setthathirath Hospital, Vientiane

IPNT - Provincial Hospital of Binh Dinh

- District Hospital of Phu Cat

IP HCMC - Ben Tre provincial hospital

- Cu Lao Minh district hospital IP Cambodia - Provincial hospital of Takkeo

- Provincial hospital of Kampong Cham Here are the nodes, and finally, the project aims at building the edges, so as it becomes a real network

International Pasteur Institutes Network 1.  What is SISEA?

2.  Main SISEA’s outcomes a.  Improving surveillance through a better

knowledge of some EIDs: ARI&AES b.  Capacity strenghtening

  Equipment, consumables   HR   Network integration and partnerships

3.  Conclusions& perspectives

International Pasteur Institutes Network Improving surveillance in China:

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) and international (Paris) Pasteur Institutes.

1.  ARI: cohort of 817 children / testing NP samples with mPCR compared with Luminex (Wang et al.)

2.  human rhinoviruses (HRV) identification performed on the same cohort of 817 samples: recombination events involving HRV-A sequences in the newly identified species of HRV-C (3). Further studies with IPC; warning on emergence of epidemics of HRV recombinants.

3.  HBoV: persistance of viruses 31 days after onset; frequent viral coinfection 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 2010 World Expo

2.  SARI surveillance in Shanghai Nanxiang Hospital (started in march 2009) 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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International Pasteur Institutes Network Improving surveillance in Cambodia – 1 (Vong S and al.):

1.  Implementation of the ALRI surveillance activities in April,2007: on Nov 2009, 3177 patients enrolled. In depth clinical classification and data validation (Pr. Mayaud and al.).

Perc

enta

ge %

Extra-respiratory pathologies Pneumonia Pleural

infections

Other respiratory infections

Viro and bacterio : # positive results / # samples tested (%)

BK : # positive / # cases (%)

International Pasteur Institutes Network Improving surveillance in Cambodia - 2 (Vong and al.):

2.  Knowledge of inflenza viruses strains circulating during 2009. From Jan to Nov 2009: 108 cases among ALRI cases in sentinel sites: 53% A(H3N2), 27% B, 10% A(H1N1)soiv, 6% A(H1N1), 4% other

3.  SISEA results included in the National Bulletin of respiratory infections since 2008 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

line treatment for ARI (high resistance of S. pneumoniae to ampicillin and cotrimoxazole) 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

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

•  Thru monitoring of a sample of patients after discharge

International Pasteur Institutes Network Improving surveillance in Vietnam (SARI and AES)- NIHE:

1.  Investigation of an outbreak of coronavirus NL-63 detected at the communal level thanks to the multiplex protocols implemented at NIHE through SISEA.

2.  NIHE: SARI Jan to Nov 2009 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 Pasteur Institutes Network Improving surveillance in Vietnam (SARI and AES) IP-Nha Trang:

1.  Influenza: 86% flu A/H3, 9% A/H1, 5% A unsubtyped 2.  SARI: 01/10/2008 to 30/09/09: 731 cases/48%+ve mPCR (41% 1-virus; 6% 2-

viruses; 1% 3-viruses)

International Pasteur Institutes Network Improving surveillance in Vietnam (SARI and AES) IP-Ho Chi Minh-

City: 1.  Activities implemented in 2009 (cumulative number of SARI cases>2000):

Objectives Activities

Strengthening the lab. capacity

-  Install office and scientific equipments (data management and diagnostic)

- Training and Technique transfer: Bacterial diagnosis (Sentinel hosp.), JEV/DENV-MAC ELISA (PMC)

Surveillance - Training: SARI/AES surveillance procedures

- Enroll 1,271 SARI cases and 122 AES cases (Jan-Oct 2009)

- 50% confirmed SARI by 15 viruses (RhinoV, RSV, Flu V, BocaV); 43% confirmed AES by JEV, DENV & EVs (with 7% arbo-enterovirus co-infection).

-  9% confirmed SARI by bacterial (Aug-Nov.2009) with 64% viral co-infection.

Investigation and intervention

- Training: AES case management, Entomological survey of JEV case

- Field investigation of Flu A/JEV confirmed cases (16 A/H1, 7A/H3, 6 JEV)

- JEV vaccination in districts having confirmed cases

Quality control - Weekly checking the CRFs

- Weekly supervise the case detection and enrollment

-  Specimen quality and timely testing

-  Set up the SOPs of sample management and testing for SARI and AES

4.92% 4.92

% 32.79

% 57.38%

Viral pathogens of AES

from Jan 2009 to Nov 2009

JE Dengue EV Negetive

1.97%

3.46% 0.55% 0.16% 2.12% 3.54% 1.26% 0.16% 0.16% 1.42%

50.59%

2.12,%

2.2% 0.31% 17.31

%

12.67%

Viral pathogens of SARI

from Jan 2009 to Nov 2009

Adenovirus

Bocavirus

Enterovirus

International Pasteur Institutes Network Improving surveillance in Vietnam: case definition of SARI

adopted:

≤ 05 y.o. > 05 y.o. Cough or breathing difficulty

AND One of the following: • Tachypnea • Chest indrawing • General signs of danger

Onset of symptoms up to and including 7 days

Fever ≥ 38o C (or history of fever) AND

Cough OR sore throat OR breathing difficulty

AND One of the following: • ≥ 30 respirations/min • New infiltrate on chest X-ray • Inability to speak full sentences • Use of accessory respiratory muscles • Arterial O2 saturation ≤ 92% on air (no oxygen therapy)

Onset of symptoms ≤ 7 days

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International Pasteur Institutes 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 Pasteur Institutes Network

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International Short Course in Biostatistics - REDI centre - Singapore, November 9-13, 2009.

Capacity strengthening

and epidemiology

24 trainees/12 from SISEA

Daily and final evaluation; very good input from SISEA trainees

Very good perception by the trainees

New ties with profesionals coming from Indonesia, and Singapore

High quality of the collaboration with REDI and NUS, who are demanding for other collaboration in training 22

Reaching common administrative standards. June 10, 2008: = Management and Administrative Routines Workshop held in Nha Trang, Vietnam on 29-30 May.

On-site training/Transfert of technology: - February 2008, Institut Pasteur Cambodia. PCR multiplex. 2 weeks/2 virologist from IP NT

- September/October 2009, Institut Pasteur Cambodia: PCR multiplex 2 weeks/2 virologist from NCLE (Vientiane, PDR Lao)

- November 2009: 1 bacteriologist from NCLE for 1 month in IPC

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HKU-Pasteur Virology Course 2009

• 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

International Pasteur Institutes Network

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First Forum GMS forum on Japanese Encephalitis/viral 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

International Pasteur Institutes Network

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Public health and research = mutual feeding Research → Public health: cf. Previous slides

Public health → research : Publications supported by the activities of SISEA.

Limitations: data have been collected according to a surveillance objective, and no research design has been really set up regarding to scientific research questions, and financial support is provided for public health concerns

However, the observation of the data rises fundamental or applied research questions: co-infections, diagnosis tools, negative samples (more or less 50%...)

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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.

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

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.

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 response, and co-infection with other respiratory viruses in children with acute respiratory infection. J. Clin. Virol. (in press)

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 expressing influenza hemagglutinin and neuraminidase. Vaccine. 2009 Sep 2. [Epub ahead of print]

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/content/15/10/1641.htm

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.

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)

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Next steps …

• Epidemiological and clinical description of various bacterial or viral infections

• Bacterial resistance: characterization and determinants

• Risk factors for severe infections by pathogen

• Phenotypic and genotypic determinants of viral virulence

• Viral resistance to antivirals

• Diagnosis of SARI by use of scoring system for severity

• Bacteria of interest: M. tuberculosis, B. pseudomalleii, K pneumoniae

• Viruses of interest: influenzas, HRV, RSV, hMPV, BocaV

• Clinical outcomes: guidelines/recommendations/GCP for improving patient management, both in ARI and AES

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After 2010 ...?

"  Needs and wishes from the partners

"  Funding ? Who ("WHO"?, AFD, ADB, US-CDC, DHHS, ...)

"  Network of laboratories and of hospital-based sentinel sites set up at the end of the project = sustainability of the system

"  Knowledge, know-how, applicable for many lab techniques

"  Geographical expansion within a country or to other countries?

"  Other pathologies (rabies, …), or other EID concerns as viral/bacterial resistance as an emerging infectious disease event

"  Improving connection between human and animal surveillance (in line with “One World One Health" initiative

"  Integration with environmental issues and climate change under the scope of risk assessment

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≠

OR

≠

Better understanding should teach us to avoid such mistakes !

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“Knowledge is the heritage of humanity.”

« Science doesn't belongs to one country, or rather science encompass the whole humanity"

Louis Pasteur (1822-1895)

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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 the sentinel surveillance THANK YOU FOR

YOUR ATTENTION