Activity Report 2009 – SISEA project January 1st to December 31st 2009 1 Summary The aim of the Surveillance and Investigation of Endemic Situations in Southeast Asia (SISEA) program is to contribute to the improvement of the detection and handling of epidemic situations in the region. The specific goal of SISEA is to set up in four of the region’s countries (China, Laos, Vietnam, and Cambodia) a surveillance and investigation program of epidemic situations. The specific SISEA goal or objective will be achieved once the following three results have been obtained: Result N°1: The network of IP laboratories in China (Shanghai), Vietnam, and Cambodia has been strengthened, in terms of its reference function and NCLE (Laos) has been strengthened and enabled to participate in SISEA network. Result N°2: The epidemic surveillance and warning programs on emerging viruses are strengthened in each of the countries associated with the project. Result N°3: The epidemic response networks are strengthened at a regional level. During 2009 all partners have implemented surveillance of respiratory infections in the designated sentinel hospitals and monthly reports have allowed monitoring of pathogen prevalence. In addition, surveillance of acute encephalitis has begun in Vietnam and has immediately produced a significant impact in Public Health awareness and policies to control disease spread. For example, thanks to SISEA activities, new cases of Japanese Encephalitis have been detected in Ben Tre province. This has led to entomology and field investigations, as well as to the implementation of a comprehensive plan of immunization with JE vaccine. The recruitment of Dr Jean‐Jacques Bernatas as Medical Regional Coordinator, has resulted in the further development of the regional dimension of the project by strengthening several contacts with other organizations operating in this area, mainly WHO (both at national and regional offices), REDI Center (a partnership between US‐
DHHS and the Ministry of Health in Singapore), Asian Development Bank (GMS‐CDC Project), US‐CDC. Special attention has been given to the continuing support to NCLE and field activities in Lao PDR (thanks to the recruitment of Dr Somvay and Dr Mathida), with regular visits to sentinel hospitals, monitoring of sample handling and transportation, and routine reports feeding the national surveillance system on Influenza Like Illness (ILI). 2 The Coordination Unit (CU) has organized a scientific week in Ho Chi Minh City during which the results of SISEA have been shared with several regional partners (viz., ADB, MBDS, US‐CDC, Wellcome Trust, Chinese‐CDC, CIRAD, REDI Center) and presented for evaluation to the Scientific Advisory Board (SAB). The results of the evaluation (see SAB report in Annex) have comforted the strategic decisions taken in response to the first evaluation (Shanghai 2007) and pointed to a number of aspects that need to be improved to meet the final targets of the project. The SAB has particularly praised the results obtained with respect to wealth of information that is being generated, harmonization of procedures and building of a strong team that represents a solid foundation for the long‐term impact of SISEA. A selection of representative achievements of 2009 is presented below. These milestones clearly attest to the advancement of the project and have formed the basis for the activities planned in 2010‐2011 (see Annex 2). Result N°1: 1. NIHE (Hanoi, Vietnam), IP Ho Chi Minh City (Ho Chi Minh City, Vietnam), IPC (Cambodia) and IPS (Shanghai, China)have been working closely together for the development of JE diagnosis based on NS1 protein identification; 2. In response to the new pandemic of SOI‐H1N1 in 2009, the multiplex PCR assay developed and in use for the SISEA project was improved by adding new specific primers and probes to differentiate seasonal flu (H1 and H3 subtype) from the new SOI‐H1N1 in only one tube. The technique was set up in collaboration with Hong Kong University and HKU­Pasteur Research Center (Drs Malik Peiris and Leo Poon) and IPC (Drs Mardy Sek and Philippe Buchy); 3. The Virology laboratories at NCLE (Lao PDR), NIHE (Vietnam), IP Nha Trang (Vietnam), and IP Ho Chi Minh City (Vietnam) have been upgraded with the purchase of last generation equipment for the implementation of multiplex PCR. Result N°2: 1. Integration of ALRI (Acute Lower Respiratory Infections) reports initiated through SISEA in the monthly bulletin of the Ministry of Health in Cambodia and inclusion of data from ALRI monitoring in the weekly report on Influenza surveillance in Lao PDR; 2. Outbreak investigations implemented: in Vietnam after detection of new cases of Japanese Encephalitis in the Ben Tre province (in collaboration with the Provincial Department of Preventive Medicine of Ben Tre and the District Department of Preventive Medicine in Cu Lao Minh); 3 3. Data of ALRI/SARI surveillance supported by SISEA in all 4 countries have contributed to close monitoring of the evolution of pandemic (H1N1) influenza virus in Southeast Asia. Result N°3: 1. Networking: A scientific forum on Acute Encephalitis Syndrome (Ho Chi Minh City, June 2009) and a Workshop on Japanese Encephalitis (Hué, November 2009) have reinforced the scientific communication at the regional level, with the participation of a strong panel of international experts; 2. Strengthening the regional collaboration through a program of regional courses tailored to meet the needs of trainees from China, Lao PDR, Vietnam, Cambodia, Singapore, and Indonesia. This included in 2009 the HKU‐Pasteur Virology Course on Neurotropic Viruses (Hong Kong, 7‐24 July 2009) and a course on Biostatistics and Data Management, in collaboration with REDI Centre and NUS ‐ National University of Singapore (Singapore, 9‐13 November 2009); 3. Bridging human and animal health in the context of climate changes and with an evolutionary perspective is crucial to produce effective interventions that will control the spread of zoonotic infections that are targeted by the SISEA surveillance program. The CeroPATH meeting held in Siem Reap (18‐20 November 2009) gave the floor to scientists from various origins, including SISEA partners, and opened new avenues for future regional collaborations in Southeast Asia, from Lao PDR, China, Vietnam, Cambodia, Thailand, Malaysia, Singapore and Indonesia. 4 Introduction During 2009, all partners have implemented the activities at a sustained pace. At the same time, a concerted effort in communicating SISEA’s achievements has driven to a real integration of the SISEA project as a regional platform of expertise that cannot be overlooked. Partners of SISEA had to face specific constrains owing to specific sanitary situation and logistical features, but all worked together to tackle the novel pandemic (H1N1) virus that quickly affected the Southeast Asia region. SISEA has been on the front line, as each partner also participates in the national surveillance system. SISEA funds have quickly and efficiently supported this international effort to control the first pandemic of the 21st century. A number of activities and achievements made possible thanks to SISEA has been described in scientific papers published in peer‐reviewed journals, a clear indication of the high scientific level of SISEA. Nevertheless, the main accomplishment of the project is certainly the capacity building deployed in a network of laboratories, according to the needs and demands expressed by each partner, to address the central objective of strengthening the response of Public Health systems at the national and regional level. Coordination Unit The Coordination Unit (CU) of the SISEA project is currently formed by the following team members: Silvia Ostberg (SO), Project manager (PgM), Dr Jean‐Jacques Bernatas (JJB), Medical Regional Coordinator (MRC) and Dr Roberto Bruzzone (RB), Scientific Coordinator (ScC). This unit has been working closely with Dr Isabelle Catala (IC), consultant at the “Division Internationale” – Institut Pasteur, Paris The CU office is based in Vientiane Lao PDR, where both SO and JJB are based, whereas RB permanent address is at HKU‐Pasteur Research Centre. The role of the Coordination Unit has been to support the implementation of SISEA program, both at partners’ level, with particular emphasis to the planning and execution of their own activities, and at the regional level, through planning and implementation of actions to strengthen the regional network. This support includes activities’ follow‐up, guidance on administrative and financial matters, facilitation of communication and information sharing among partners, coordination of joint activities, etc. Furthermore, the PgM (SO) is responsible for all the managerial aspects (budget, financial follow‐up, logistic) at the Coordination Unit’s office. The CU has since May 2009 being strengthened with the recruitment of Dr. Jean‐Jacques Bernatas, Epidemiologist and expert in Public Health, as Medical Regional Coordinator. He is working full‐time in Vientiane and has replaced Dr. Cavailler, who served as part‐
5 time Medical Coordinator from his basis in Phnom Penh at IPC.Dr. Roberto Bruzzone, who has been involved in the CU from the beginning of SISEA, continues his functions as Scientific Coordinator (based in his office in Hong Kong). The Technical Advisor to NCLE, Dr. Juliet Bryant resigned and left her functions at the end of May. The recruitment of a new technical assistant, with a professional profile agreed with NCLE has been finalized. The new TA, Mrs. Anne‐Charlotte Sentilhes, will take up her duties on January 2010 for a 1‐year position. She will support NCLE both on virology and bacteriology. The Administrative Assistant Ms. Daovy Luanduanchanh resigned and left the office on May 8th. The recruitment of a new assistant – M. Soradeth Voravong ‐ has been achieved in September 2009. The Coordination Unit and the SISEA partners were audited by Grant Thornton (GT) during February‐March. The results of the audit of the office of the CU, with specific observations and recommendations, have been presented in the Management Letter. The CU has ‐ as far as it has been possible considering the actual staff and other constraints ‐ implemented the recommendations of GT. It has been planned to set up the next audit by GT on January/February 2010. 4th 2009 Steering Committee, Ho Chi Minh City, June 2009. SISEA’s fourth Steering Committee Meeting was held in Ho Chi Minh City, on June 12th 2009, to conclude SISEA’s International Network Meeting (8‐11 June). This meeting gave the opportunity to discuss the level of implementation and consolidation of SISEA activities. Special attention was paid to the development of a comprehensive plan of regional activities aimed at fulfilling the objectives of SISEA. In addition, the SC examined the status of the actual expenditures in comparison with the planned budget of the project and discussed the possibility of the reallocation of funds if this proves to be a need. Finally, the SC was briefed on the results and conclusions of the Scientific Forum and of the Technical Workshop on Encephalitis surveillance. In particular, the SC received the preliminary report of the evaluation given by the Scientific Advisory Board following the on‐site visite in HCMC (June 8‐10). The report of the SAB touched on four points: i) general implementation of the SISEA project in relation to recommendations issued after the special meeting held in Shanghai in November 2007; ii) future of the program, in terms of content, organization, financing; iii) articulation of SISEA with respect to other initiatives in the region; iv) quality of management and governance of the overall organization. The SAB stressed that SISEA has resulted in a clear success in organizing a true local capacity and has established an excellent molecular diagnostic platform, which will be very useful not only for present, but also future activities (for instance response to the threat posed by the outbreak of the new H1N1). The SAB recognized the enormous progress achieved in terms of 6 commitment to the project at the individual and institutional level and is very pleased to note that the actual commitment of the team is impressive. In addition, the SAB has expressed strong support for the maintenance of the current partnership structure, which should be extended to interfacing with other regional initiatives (with clearly defined objectives), in order to build a solid and sustainable network thanks to SISEA program. 5th Steering Committee, Phnom Penh, December 2009 SISEA’s fifth Steering Committee Meeting was held in Institut Pasteur of Cambodia, Phnom Penh, on December 14th to 15th 2009. Dr Christophe Paquet, in charge of the SISEA project’s follow‐up at AFD, attended the meeting, after having had a short visit of SISEA’s activities in IP Ho Chi Minh‐City and the provincial Hospital of Ben Tre. In the “Minutes”, the main issues raised concerned: → The remaining budget for the activities that should be implemented in 2010 → Transversal activities and priorities for 2010, last year of the project, with the identification of working groups to complete SISEA’s priorities for 2010 o Clinical management and classification leaders (leaders: Sirenda Vong and Chan Quang Luong) o Surveillance indicators (leader: Laurence Borand) o Bacteriology (leaders: Bertrand Guillard and Cong Khanh) o SOP manuals and algorithms (leaders: Huong Vu Thi Que and Wei Wang) o QA and QC (leaders: Huong Vu Thi Que and Wei Wang) o Publications (leaders: Philippe Buchy and the CU) o Regional analysis of viral diversity (leaders: Philippe Buchy and Huong Vu Thi Que and Wei Wang) o Plans initiatives with other networks CU → Approvals from the Steering committee o Due to the absence of 2 directors and the lack of financial data, no approbation has been vote during the SC. o The vote is schedule for the next directors’ conf call (end Jan or beginning of Feb). o National, regional plans and 2010 budgets are request for the conf call and should be send to the Coordination → Finally, it has been clearly stated by Dr C. Paquet ‐ representing AFD – that no additional funding will be provided by AFD for a following project, even if AFD has expressed its congratulations for SISEA’s achievements in year 2009. The issue is not SISEA’s outcomes, but the funds available for this kind of project regarding to the AFD’s strategy for the next years. Coordination Meeting for SISEA partners in Vietnam (Nha Trang, April 22­24, 2009). A coordination meeting was held in Nha Trang in the presence of the directors, one virologist and one epidemiologist for each of three SISEA partners in Vietnam, the three members of the CU and of Institut Pasteur, Paris, represented by Dr. Isabelle Catala. 7 The meeting analyzed the implementation of the surveillance project with specific emphasis on the collaboration with the sentinel hospitals. Following the earlier consensus to consolidate SISEA’s core activities on respiratory infections and viral encephalitis based on a common epidemiological, clinical and molecular approach, this meeting was useful to ensure the standardisation of tools/protocols through working groups that looked at different parts of the protocols applied in SISEA. Follow up missions and meeting with international partners: The ScC gave a seminar to present the goals and strategic plan of SISEA at the headquarters of the Regional Emerging Disease Intervention (REDI) Center in Singapore (March, 25, 2009). This initial contact has led to the development of a strong partnership between REDI and the International Pasteur Network of the Asia‐Pacific region, which is now being implemented through a series of training programs for the SISEA project. The main objectives of SISEA were also discussed and presented to the Singapore Immunology Network (SIgN), during a meeting held in Singapore, June 14‐14, 2009. The MRC undertook an introduction and follow up visit to Hanoi from June 15th to 19th.This was the opportunity to meet potential partners that have been already contacted and expressed an interest in developing joint activities: → WHO office team in Hanoi (Dr Nicole Smith as team leader) presented their collaboration with Vietnamese health authorities, and presented a comprehensive overview of their national needs’ estimation in infectious diseases control : in strengthening laboratory capacities and epidemiology skills through various training program for the three Vietnamese institutions’ staff, SISEA project was considered to be efficient and relevant. Needs of better communication concerning the activities implemented through SISEA was emphasized → GMS‐CDC coordination unit presented their on‐going activities, more focused on communication, networking and support to the organization of forum and workshop within the Mekong Region’s countries. We proposed to co‐organize the next “Japanese Encephalitis” that should be held in Vietnam in October 2009, in partnership with NIHE → US‐CDC in Vietnam: we met Dr David Dennis and exposed the SISEA’s activities and output, and tried together to define the scope of a possible collaboration. This meeting was in line with the MoU signed between Pasteur Institute and US‐CDC, in Atlanta, during the first quarter of 2009. US‐CDC is more focused on ILI community surveillance in distinct provinces from those covered by SISEA: this kind of complementarities should be the basis of a possible partnership → NIHE: we set up a field trip to Hai Duong province, including a visit at the Provincial Hospital, the Provincial Department of Preventive Medicine, the district Hospital of Cam Giang and the District Department of Preventive Medicine. As an outcome of the previous meeting with US‐CDC, we invited Dr Dennis to this field trip, and what we observed illustrated exactly the possibilities of joint activities that we arose the day before. 8 The MRC participated in a meeting of the Pasteur network that was held in Paris (September 3‐4, 2009) in response to the emergence of the novel H1N1 (S‐OIV) influenza virus that has caused the first pandemic of the 21st centuty. Based on the experience acquired with SISEA, which gathers information from 11 hospitals across Cambodia, Vietnam, Laos and China, a new project with global coverage was drafted by the MRC with the objective to identify the epidemiological, clinical, bacteriological, virological and immunological determinants of H1N1 (S‐OIV) infection severity in developing countries, with special emphasis on the role of co‐infections and secondary infections. More specifically, the project aims to: a) describe the clinical presentation, atypical forms, duration of symptoms, complications and deaths due to H1N1 (S‐OIV) infection; b) estimate the prevalence of bacterial and viral co‐infection at intake, and the incidence of secondary bacterial infection, in patients with H1N1 (S‐OIV) infection; and c) set‐up a biobank of samples (nasopharyngeal aspirates and plasma) from H1N1 (S‐OIV) infected patients for further studies. In particular, immunological (e.g., cytokines profile) and virological (e.g., molecular markers of virulence or drug resistance) determinants of severity will be studied in separate research protocols linked to this study. The development of this ambitious plan is the direct consequence of the pioneering work carried out with SISEA and will contribute to the long‐term impact of SISEA beyond the boundaries of the Asia‐Pacific region. The project has already received initial support and negotiations are underway to secure the funds necessary to complete the budget. Organization of a SISEA International Network Week. The International Network Week took place in Ho Chi Minh City in Vietnam (8‐11 June) and was divided in two sections. → An International Scientific Forum (8‐9 June) This Forum served as platform to share the results of SISEA activities with several relevant regional actors and to learn about those actors’ activities in the region. Besides representatives of all SISEA partners, the forum counted with the presence of representatives of CDC/USA, Mekong Basin Disease Surveillance, REDI Center, the Coordination Office of ADB’s Greater Mekong Subregion‐Regional Communicable Diseases Project, Chinese CDC, CIRAD and Wellcome Trust. The forum was also attended by SISEA’s Scientific Advisory Board (SAB), which evaluated the progress of the project and prepared an independent report that included and evaluation of the implementation of SISEA activities and a series of recommendations regarding the preparation of future activities. This forum and the SAB’s report (see above) have been of the utmost importance to tighten links with regional actors and will lead to more common initiatives in the region, particularly in the area of training in epidemiology and quality control of laboratory diagnostic. → A Technical Workshop on Encephalitis (10‐11 June) A 2‐day regional workshop on acute encephalitis syndrome (AES) was organized to review the situation in South East Asia and outline the best strategy to confront the challenge posed by this group of diseases in the long term. Besides the presentations of SISEA partners, there 9 were several invited speakers from Asia and Europe who gave their expert opinion on the clinic biology, pathogenesis and epidemiology of AES. In addition, two sessions gave an overview of the latest information on encephalitic virus circulation in Asia and on the current laboratory tests available. The workshop included parallel working sessions to draft guidelines, algorithms, training programs and define priorities and milestones for future coordinated actions. The chairpersons and organizers prepared an initial report that defined the two main objectives of the surveillance and investigation of encephalitis in Southeast Asia initiated through SISEA: •
Provide an algorithm to improve the diagnosis of meningo‐encephalitis necessary for clinical management of the patients and initiate a surveillance system to improve early detection and response of any outbreak of CNS infection; •
Study the aetiology of meningo‐encephalitis in SEA and set up a network of expertise in the Asian region for clinical recognition and diagnosis of CNS. The SISEA’s International Network Week, hosted by Institut Pasteur of Ho Chi Minh City was, as stated earlier, fruitful for the future consolidation of SISEA activities. The organisational support from IPHCMC and its staff were elementary to achieve these positive results. The International Network Week was concluded with a Steering Committee Meeting. Scientific Forum: 1st GMS­CDC forum on Japanese Encephalitis prevention and Control, Hué (Vietnam) 29­30 Oct. 2009. Following the workshop in June, this meeting was hosted by NIHE with the co‐sponsorship and collaboration of SISEA and ADB/GMS‐CDC project. The forum was opened in the presence of representatives of the Ministries of Health of Cambodia, Laos, Vietnam and China. The forum gathered together the best international experts coming from Cambodia, China, France, Japan, Laos, Malaysia, Singapore, USA and Vietnam. The main objectives of the Forum were to review: → the disease burden and control & prevention activities in the region; → lessons learnt from the use of vaccines for Japanese encephalitis in the region;‐ existing diagnostic tools for viral encephalitis; → the epidemiology of other pathogens of acute encephalitis; → current funding for the control of viral encephalitis. Recent advances in diagnosis techniques, vaccine development as well as possibilities of financial support to improve the situation were also on the agenda. The Forum has issued a series of recommendations and agreements to foster regional cooperation among the different actors, and to set priorities for concrete initiatives aimed at easing the burden caused by Japanese Encephalitis and Viral Encephalitis in the Great Mekong Sub Region. As a result from this encounter, a network of experts concerned by JE in SEA has been set up and new collaborations are in place. 10 CU was member of the organization committee and the PgM has strongly supported the logistic and closely monitored the course of this workshop. 15 members from SISEA network were present among 43 participants. See at http://www.gms‐cdc.org/the‐gms‐cdc‐project/regional‐activities/regional‐technical‐
forums/676‐press‐release.html
Regional workshop on “Molecular epidemiology and evolutionary patterns of infectious diseases in South East Asia”, Siem Reap, 18­20 Nov. 2009. CERoPath project (Community ecology of rodents and their pathogens in South‐East Asia: effects of biodiversity changes and implications in health ecology; CNRS ‐ Montpellier2 University (France) ‐ CIRAD ‐ Kassetsar University ‐ Mahidol University ‐ Ministry of Agriculture and Forestry of Lao PDR ‐ Finnish Forest Research Institute ‐ INRA ‐ CEMAGREF ‐ University of Liege ‐ Institut Pasteur Cambodia ‐ IRD ‐ Museum d’Histoire Naturelle ‐ Institut Pasteur de Lille ‐Université Lille 2. During this workshop a whole session was been dedicated to SISEA achievements presentation to all the representants coming from the above institutions. Most of the SISEA partners have presented their own results by themselves. Other activities with regional outreach: → Presentation of SISEA results at the XIth International Symposium on Respiratory Viral Infections – February 19‐22, 2009 – Bangkok, Thailand. Dr Sirenda Vong and Simon Chu (Institut Pasteur‐Cambodia) presented their work for the SISEA project in Cambodia at the XIth International Symposium on Respiratory Viral Infections held in Bangkok on February 19‐22, 2009. Dr Sirenda Vong had a platform presentation on ARI Impact and Surveillance in Cambodia, while Simon Chu introduced a poster entitled “H5 pseudotyped lentiviral particles: a new tool for H5N1 infection sero‐
diagnosis”, the result of a collaboration with HKU‐Pasteur Research Centre. → Presentation of SISEA results at the 8th Asia Pacific Congress on Medical Virology, Viral Diseases: New Challenges – New Solutions, February 26‐28, 2009, Hong Kong. Pr Vincent Deubel, Director of Institut Pasteur Shanghai – Chinese Academy of Sciences and Dr Philippe Buchy, Head of Molecular Virology lab at Institut Pasteur Cambodia were among the invited speakers. They illustrated the results of surveillance of acute respiratory infections and the development of new diagnostic tests. → Several publications describing work directly related to SISEA have appeared in 2009 or have been accepted for publication, listed below. Huang T, Wang W, Bessaud M, Ren P, Sheng J, Yan H, Zhang J, Lin X, Wang Y, Delpeyroux F, Deubel V. (2009) Evidence of recombination and genetic diversity in human rhinoviruses in children with acute respiratory infection. PLoS One. 27;4(7):e6355. 11 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. (2009) Measurement of neutralizing antibody responses against H5N1 clades in immunized mice and ferrets using pseudotypes expressing influenza hemagglutinin and neuraminidase. Vaccine 12:6777‐6790 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(1‐2):40‐5. Bruzzone R, Dubois‐Dalcq M, Grau GE, Griffin DE, Kristensson K. (2009) Infectious diseases of the nervous system and their impact in developing countries. PLoS Pathog. Feb;5(2):e1000199. Wang W, Ren P, Sek M, Hou L, Cai C, Chan KH, Chen P, Shen J, Buchy P, Sun B, Toyoda T, Lim W, Peiris JS, Zhou P, Deubel V. (2009) Design of multiplexed detection assays for the diagnosis of human pathogenic avian influenza A subtypes by SmartCycler real‐time reverse transcription‐PCR. J Clin Microbiol. Jan;47(1):86‐92. Wang K, Wang W, Yan H, Ren P, Zhang J, Shen J, Deubel V. (2010) Correlation between bocavirus infection and humoral response, and co‐infection with other respiratory viruses in children with acute respiratory infection.Optimization and evaluation of an influenza A (H5) pseudotyped lentiviral particle ‐ based serological assay. J Clin Virol, 47:148‐155. Cavailler P, Chu S, Ly S, Garcia JM, Ha DQ, Bergeri I, Som L, Ly S, Sok T, Vong S, Buchy P. (2010) Seroprevalence of anti‐H5 antibodies in rural Cambodia, 2007. Emerg Infect Dis (in press). Regional Training During the year, several training occasions have been organized with financial support from SISEA. The contents, methodology and the participants to the different training occasions have been decided according to specific regional and/or individual partners’ needs, as follows: → 4 SISEA fellows (2 from Vietnam, 1 from Lao and 1 from Cambodia) went to Paris in April to participate in a 3 weeks training on data management using STATA. → 4 SISEA fellows (from Vietnam and China) and one Senior in biosafety from Cambodia attended a Regional Metrology and biosafety Course for one week course in HCMC . → 12 SISEA fellows participated in the Regional Training on Biostatistics and Data Management – Singapore, Nov. 9th to 13th. This training is the outcome of the collaboration between SISEA and REDI Centre in Singapore (partnership between US‐
DHHS and MoH of Singapore). Technical partners were: National University of Singapore (NUS), EPICONCEPT and a technical support has been provided the MRC for the conception as well as facilitator for the training. The ScC, member of the organization committee, represented the International Pasteur Institute Network during the training. → 4 SISEA fellows (from Institut Pasteur‐Shanghai) participated in the 6th HKU‐Pasteur Virology course, focused on Neurotropic viruses. Several experts from SISEA and regional partners were invited as instructors to present their work and discuss the 12 impact of encephalitis syndomes for public health in their countries. These exchanges allowed to strengthen the collaborations with some of the experts who gathered in HoChi Minh City for the technical workshop on encephalitis. → Two other training courses will be organized in partnership with REDI Centre during 2010: o Respiratory Infection Prevention and Control, with WHO o Outbreak investigation, with European CDC, WHO and NUS. → The program of the SISEA regional course on Ethics issues in developing contries has been discussed with the Ethical Committee of the Institut Pasteur in Paris and the Ethical Committee of the Assistance publique Hôpitaux de Paris. Participation of Marie Charlotte Bouesseau (WHO), Jerry MENIKOFF (OHRP, USA), Peteris ZILGALVIS (European Comission) would be possible for a one week course, initially proposed for October‐November 2009, but that should included in the 2010 regional training programme. Technical and administrative support to NCLE Besides the regional responsibilities, the CU has a clear defined mandate to provide technical suport to NCLE in the areas of epidemiology and laboratory. Furthermore, given the fact that the CU is located in Vientiane and the limited resources of NCLE has led to develop a close relationship between both offices that includes a a continuous follow‐up of the implementation of SISEA with especial emphasis on support to the organisational and financial aspects of the project. Furthermore, the CU has a very close collaboration with other international partners to NCLE in order to coordinate the efforts to strengtheng the NCLE, to ensure avoiding overlapping actions and,hopefully, to guarantee long lasting results. Epidemiology and general technical support In Laos the MRC is part of the Surveillance Working Group, integrated by several national and international actors and hosted by WHO’s office, and part of the reference group of NAHICO, the National Human Influenza Coordination Office. He has participated in several meetings held by these two groups. The participation in these working groups has led to close coordination with other donors supporting NCLE, making it possible to target specific objectives avoiding duplication of efforts and redundant initiatives. Refurbishing the laboratories and the construction of the new influenza center, with the coordinated support of WHO, NAMRU/CDC and SISEA, reflect the improved efficiency in SISEA’s support to NCLE. Supporting the 2 junior epidemiologists (Dr Somvay and Dr Matthida), an updated database for SISEA patients has been set up using EPIDATA, taking the opportunity of the SISEA/REDI training course held in Singapore that Dr Matthida attended. 13 The issue of infection control and nosocomial infection has been also addressed, as Setthathirath hospital ‐ the sentinel site of SISEA ALRI surveillance in Lao PDR ‐ has been designated to be the focal point and pilot site for the implementation of a nationwide programme. Supporting this national initiative ‐ through at least a technical support ‐ makes sens as SISEA is an hospital‐based surveillance project addressing the issue of communicable diseases and potential outbreaks in which the hospital setting could play a major role. This is considered as as an extension of SISEA’s public health’s outcomes in health care facilities. Administrative and logistical support The CU and more specifically the PgM is in charge of accompanying NCLE in the administrative and financial follow up of the SISEA implementation. This has included planning of actions, budget preparation and financial follow up along the implementation, As well, due to logistic problems the accounting of NCLE as well as financial reporting is taken care of at the CU by the PgM. Concrete support to the logistic officer in charge of purchase to ensure that NCLE fulfils the conditions established by the Management Guide and Purchase Procedures approved by AFD has also been given. In terms of direct administrative responsibility, besides the support to NCLE, the PgM has been in charge of the purchase of equipment for partners in Vietnam: Following the bid process for selection of equipment to be purchased for partners in Vietnam, the CU/PgM started the purchase of “urgently needed” equipment for a value totaling about 100,000 EUROS at the beginning of the year. The purchase of the second lot of equipment for SISEA partners in Vietnam has also been taken care of by the CU, which has been an important extra load of work. On Dec. 31st, 95% of this equipment has been delivered properly to the 3 vietnamese institutions, the reamining ones should be delivered during the beginning of 2010. The formal and official hand over of the total lot of equipment donated to SISEA partners in Vietnam with in SISEA with the support of AFD should take place in 2010 in the presence of health authorities and representatives of AFD and French Embassy in Vietnam. Conclusion Valuable outputs are now regularly produced by the national partners thanks to SISEA support. This contributes widely to strengthen surveillance capacities, both in laboratories and in epidemiology units, in line with the objectives of the project, and therefore to improve the quality of the surveillance at the regional level. The relevance of such a support has been illustrated by the contribution of all the SISEA network member to the response to the A(H1N1)s‐oiv pandemic in their own contry. 14 SISEA: Conclusion and perspectives During 2009 there has been progress in several areas of the SISEA project, namely in the quality and timeliness of the collection of samples and data acquisition from all sentinel sites involved in surveillance of acute respiratory infections. In addition, the focus on acute encephalitis has gained momentum with the organization of several workshops that have put the project at the center of a regional effort to intensify measures to monitor the impact of this group of diseases and contribute to the implementation of appropriate public health guidelines. Finally, the program has been reviewed by the Scientific Advisory Board, which has underlined the important achievements of the past 2 years. The SAB has also pointed out the areas that require special attention in order to meet the objectives set out at the beginning of the project. In particular, the development of stronger partnership with regional and national WHO offices to ensure that both the strategy of the SISEA project and the wealth of information obtained can contribute to the application of a Public Agenda for Health Research that is being proposed by WHO. 15 Annex 1: Scientific Advisory Board report June 8­9, 2009 16 SAB Report HCMC, SISEA Meeting, June8‐9 2009 Prepared by Yves Champey, Hans‐Dieter Klenk, Charles Mayaud (Jeremy Farrar and Francois Freymuth excused) General evaluation of the SISEA project The report of the SAB in divided into four parts. It will: 1. Comment on the general implementation of the SISEA project in relation to recommendations issued after the special meeting held in Shanghai in November 2007; 2. Comment and discuss the future of the program, in terms of content, organization, financing; 3. Comment on the articulation of SISEA with respect to other initiatives in the region that were presented during the Scientific Forum; the SAB will also comment on the two new proposals that were made for inclusion in the SISEA project; 4. Last, the SAB will comment on the quality of management and governance of the overall organization. SISEA in relation to decisions made earlier The SAB appreciates that a considerable effort had been put into the follow up the previous recommendations, and that important progress has been achieved in developing tools and in the organization of the different components of the SISEA project, whether at the national or regional level. The SAB wishes to emphasize the following aspects: Clear success in organizing a true local capacity; Establishment of an excellent molecular diagnostic platform, which will be very useful not only for present, but also future activities (for instance response to the threat posed by the outbreak of the new H1N1); A very good coherence of results obtained between study sites; Achievement of common SOPs for the surveillance of respiratory infections for all partners; Very important observations on H5N1 outbreak (molecular and field investigations) have been made and this experience will be extremely useful when need will arise to confront the new H1N1. The SAB recognizes the enormous progress achieved in terms of commitment to the project at the individual and institutional level and is very pleased to note that the actual commitment of the team is impressive. 17 Future of the program: context, organization, financing The current partnership structure should be kept as it is and it should be extended to interfacing with other regional initiatives (with clearly defined objectives), in order to build a solid and sustainable network thanks to SISEA program; Important to continue to implement initiatives that reinforce the “learning together” dimension; Studies should be extended to emerging viruses with clinical and public health relevance; a close cooperation between biologists, veterinarians and physicians is strongly supported by the SAB; Prospective attention should be paid to the relevance and impact of microbiological (molecular) results, clinical management and resistance to treatments; A constant attention to Quality Control and Quality Assessment of data ad databases should be exercised; A calendar for future activities and the budget distribution for the rest of the project period should be discussed and determined now. Interactions with other networks and regional initiatives The SAB had previously expressed interest in learning more about other regional initiatives in order to foster exchange and identify opportunities for cooperation. It is clear that, after the initial period of implementation of the planned activities, SISEA has now reached a stage in which it is feasible to cooperate more closely with other networks active in the same or related subjects and in the same region. The SAB has been very pleased by the response given to the previous concerns. More specifically, the SAB has noted that there is ample opportunity for cooperation between US‐CDC and SISEA in the areas of influenza surveillance and pandemic preparedness. The SAB has also noted that the mission and activities of REDI (based in Singapore) are very interesting (technical assistance for hospital case management in Vietnam, Cambodia and Laos; strengthening the capacity for H5N1 surveillance and elimination of the virus in poultry and humans) and interactions with this initiative should be pursued. Finally, the SAB was pleased to note that contacts with the MBDS had been initiated and that SISEA had been invited to an MBDS meeting. Advice on demands presented Two specific proposals were presented with a demand of financial support from SISEA. Both proposals are focused in important and interesting subjects. However the SAB does not consider having enough information, at the moment, to give any specific advice on either project. 18 Overall organization The SAB is very impressed and pleased to note the accomplishments and very active progress made in the implementation of the SISEA activities. We are very pleased with the quality of the organization of this meeting and praise Silvia Ostberg for her constant presence and attention to make it a very successful one. The SAB would like to thank the Institut Pasteur of Ho Chi Minh City for the invitation and commitment to host the meeting. Finally, we would like to congratulate Roberto Bruzzone for the quality of the meeting and his activity for the International Netwwork of Pasteur Institutes. Virus Research There has been an impressive progress in the field of virus research. This holds true for basic virology, where new insight has been obtained on the interaction of influenza virus with its receptors, and with the identification of cellular factors involved in virus assembly and maturation, as well as with the discovery that a protein of EV71 may have channel function and, therefore, represent a major target for anti‐viral therapy. Overall, the SAB has noted a convincing progress in study design, sampling, presentation of results and model for intervention. There has been also an impressive progress in virus diagnostic. New platforms based on the use of multiplex PCR, serological techniques and virus isolation have been developed for the detection of enteroviruses, influenza and other respiratory viruses, as well as viruses causing encephalitis. There has also been an interesting study reporting the adverse effects of the immune response to SARS‐CoV infection that are important for the pathogenesis of this disease. These platforms are being successfully used for the surveillance of seasonal human influenza and for monitoring avian influenza outbreaks. Furthermore, the network has developed new diagnostic tests for the emerging H1N1 Mexican virus and is sharing SOPs and reagents among partners. H1N1 poses an important challenge in terms of preparedness and SISEA network can provide an important contribution to regional/national response. In this context the network is, therefore, well prepared for the challenge of the imminent H1N1 outbreak. Future development. Basic and applied research should be continued with the aim of surveying and controlling virus infections with clinical relevance for humans and animals. The close collaboration between physicians, veterinarians and biologists should be continued to detect emerging infections and other zoonoses. This is particularly important in an area of the world that is densely populated, where man and animals live in close proximity, and that has proven in the past to be the cradle of hitherto unknown infectious diseases. 19 Clinical aspects The SAB emphasized that it is important that SISEA continues to produce information that is relevant for the patients and has positive consequences for the clinicians' determination of treatment and for clinical management in general. This has already proved of value in the case of the detection of several cases of melioidosis in Cambodia. The SAB remarked that a comprehensive database of enrolled cases would be an important source of clinical and radiological data that may help Asian clinicians to answer very practical, yet fundamental questions. Some specific examples are given below: What are the clinical diagnostic relevance and, consequently, the therapeutic impact of the presence of certain viruses or bacteria in respiratory (or CSF) specimens in patients with ARI or AES in South East Asia? This question is particularly important for Rhinovirus, Metapneumovirus, Hemophilus and Pseudomonas species…. What could be the impact of an established relationship between defined clinico‐
radiological and microbiological data obtained through the SISEA project on the clinical management of South East Asia patients with ARI or AES? If clear relationships are established, SISEA results may provide a rationale to initiate clinical prospective studies, including the follow‐up of patients, comparing a classical diagnostic and therapeutic management (WHO recommended strategy) versus a new algorithm that takes into account the pathogen suspected on the basis of the clinico‐
radiological analysis. These questions are particularly relevant for patients with a history of bronchiectasia, with excavated pneumonia and diffuse interstitial opacities. What could be the consequence of an established relationship between clinical, radiological and microbiological data obtained through SISEA on teaching and training of SEA physicians? SISEA data may help establish a novel teaching approach, which includes radiological analysis in the fields of ARI and/or AES. The SAB recommend to concentrate these advanced efforts on two main sites, on for ARI and the other for AES, and to analyze in depth an exhaustive collection of clinical‐
radiological and microbiological data. Of course the transnational, regional aspect of the project should be taken into account when making the final decisions. 20 Annex 2: Comprehensive Plan of Regional Activities for 2010 21 Background Following the steering committee held in Phnom Penh on Dec. 14th and 15th at Institut Pasteur of Cambodia , several propositions have been made concerning the regional activities, considering that these are not only the sum of single national activities but should take advantage in developing a synergistic stream through the SISEA network. As a conclusion several proposals have been made at the end of the meeting (cf. minutes of the SC): •
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Clinical management and classification leaders (leaders: Sirenda Vong and Chan Quang Luong) Surveillance indicators (leader: Laurence Borand) Bacteriology (leaders: Bertrand Guillard and Cong Khanh) SOP manuals and algorithms (leaders: Huong Vu Thi Que and Wei Wang) QA and QC (leaders: Huong Vu Thi Que and Wei Wang) Publications (leaders: Philippe Buchy and the CU) Regional analysis of viral diversity (leaders: Philippe Buchy and Huong Vu Thi Que and Wei Wang) Plans initiatives with other networks CU Content Two kinds of regional and transversal activities will be proposed for approbation by the Steering Committee, after having made sure of the financial possibility regarding to the remaining budget for 2010, last year of the project. •
Activities in virology and field epidemiology: o A community‐based intervention to mitigate the spread of zoonotic diseases in poultry to humans – CIZOOSEA; o Regional circulation of respiratory virus variants: implementation of standards and molecular epidemiology of virus evolution for disease control; o Regional validation and standardization of molecular diagnosis and serological diagnosis for pathogens causing acute encephalitis symptoms; o Training programme on good clinical practices; o Predictive factors for severity of Acute Lower Respiratory Infection in settings of limited medical resources: o Cost‐effective Practices for Surveillance of Pneumonia in Settings of limited resources. 22 •
Training: o Respiratory Infection Prevention and Control in Health Care Facilities: with the technical financial support of WHO and REDI centre (annex 7). To be held in Vientiane at Setthathirath hospital. o Outbreak investigation: cosponsored with REDI Centre. Will be held in Singapore at NUS, with the technical support of E‐CDC, WHO, US‐CDC and NUS. o Quality control: organized by “Direction déléguée – HSQE‐DD” at Institut Pasteur. Will be held in Vietnam. ƒ 1st session: • Risques biologiques et laboratoires de confinement » • Assurance qualité en laboratoire d’expertise» ƒ 2nd session: optional o Ethics: could be also cosponsored with REDI Centre, with the technical support of NUS. Planned to be organized at IPC. Timeline •
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Activities in virology and field epidemiology: all year long until the end of the project Training: o RIPC training: May, 24th to 27th o OI training: May, 31st to June 4th, 2010 o Quality control: ƒ 1st session: 5 days in September 2010 ƒ 2nd session, possibly 5 days in October 2010 o Ethics: TBD 23