CENTERS OF EXCELLENCE FOR INFLUENZA RESEARCH AND SURVEILLANCE

NIAID CENTERS OF EXCELLENCE FOR INFLUENZA RESEARCH AND SURVEILLANCE Centers of Excellence for Influenza Research and Surveillance: Report of the Expert Panel Review Division of Microbiology and Infectious Diseases National Institute of Allergy and Infectious Diseases National Institutes of Health Panel meeting date: October 14, 2011

Summary The National Institute of Allergy and Infectious Diseases Centers of Excellence for Influenza Research and Surveillance program has built a vital infrastructure for global surveillance of influenza in animals, research on influenza pathogenesis, and international training of influenza researchers and scientists. The multidisciplinary nature of the Centers, and their ability to respond to global pandemic events, make them a critical component of national and international efforts to control influenza. The ability to respond rapidly as events and conditions warrant provides a significant advantage for public health efforts when compared with other traditional NIH funding mechanisms. The Centers of Excellence for Influenza Research and Surveillance (CEIRS) program fulfills an important niche for the influenza community, and the future of the CEIRS network should include emphasizing targeted expansion of activities with increased collaborations to maximize scientific gains and avoid duplication of efforts. The network has also made significant scientific contributions to influenza research, and the panel had tremendous enthusiasm for its continuation. Introduction On October 14, 2011, the Division of Microbiology and Infectious Diseases (DMID), National Institute of Allergy and Infectious Diseases (NIAID), convened an expert panel to evaluate the scope, objectives, current structure and progress of the Centers of Excellence for Influenza Research and Surveillance (CEIRS) network; make recommendations about opportunities to improve its effectiveness; and provide guidance on the future of the program. See Appendix 1 and 2 for the CEIRS network sites, Principal Investigators and surveillance partners. The expert panel included representatives from academia, the U.S. Department of Health and Human Services (HHS), the Centers for Disease Control and Prevention, the U.S. Department of Agriculture (USDA), the World Health Organization (WHO), the World Organisation for Animal Health, and the Association of American Veterinary Medical Colleges. Dr. Samuel Stanley, President of Stony Brook University, served as chair. See Appendix 3 for expert panel members. Background The CEIRS network grew out of the recommendations of the 2006 NIAID Blue Ribbon Panel on Influenza Research [www.niaid.nih.gov/topics/flu/documents/influenzablueribbonpanel2006.pdf]. The goal of this panel was to identify specific aspects of influenza research in which there were substantial gaps in knowledge. One of the overarching guiding principles that emerged repeatedly during the Blue Ribbon Panel s deliberations was the importance of promoting innovative multidisciplinary research. The Panel identified the following eight specific areas of influenza research where progress was needed: Influenza at the Animal-Human Interface; Influenza in Individuals; Influenza in Human Populations; Animal Models; Vaccines; Therapies; Assay Technologies; and Resources. The establishment of the CEIRS network in 2007 was designed to address a number of the Panel s recommendations within the eight areas and to integrate influenza surveillance efforts with pathogenesis and host response research. 1

CEIRS Expert Panel Review Meeting Prior to the meeting, panel members were provided extensive background information about the CEIRS network as well as the NIAID influenza research program in general. The panel meeting was organized into several sessions that provided panelists the opportunity to hear about the program from (and get questions answered by) the NIAID Director, the current CEIRS Program Officer, and the CEIRS Principal Investigators. In addition, the panel was given time for discussion with the Principal Investigators, both with and without NIAID staff present. See Appendix 4 for the Expert Panel meeting agenda. Welcome and Objectives Dr. Anthony S. Fauci, Director of NIAID, welcomed the panel members and provided background information on seasonal influenza, H5N1 influenza, and the pandemics of the 20 th century, noting that influenza emerges and re-emerges and that the dichotomy between seasonal and pandemic influenza is artificial. He explained to the group that the CEIRS program fulfills NIAID s dual mandate by conducting basic and applied influenza research, and maintaining readiness to rapidly respond to emerging public health threats. Dr. Fauci charged the panel to provide concrete recommendations to increase the effectiveness of the centers, as well as to give suggestions on how to best move the program forward. Sustaining an Influenza Research Legacy Dr. Robert Webster, St. Jude Children s Research Hospital, reviewed the history of his NIAID influenza research grants and contracts from 1972 until the present. The early grants helped to establish the natural history and ecology principles for influenza surveillance as well as provide reference reagents for all hemagglutinin and neuraminidase subtypes. Dr. Webster explained that during a period of global apathy towards influenza (1970s and 1980s) there was a gap in surveillance which may have played a role in delaying identification of lethal H5N1 in Hong Kong in the late 1990s. Dr. Malik Peiris, University of Hong Kong (a subcontract to St. Jude s Children s Research Hospital), provided background on influenza in Hong Kong in 1997, when there were multiple human cases originating from poultry markets. This brought to light the importance of avian influenza as a human pandemic threat. Human and avian influenza cases fell to zero after live birds were culled and the markets were closed, but this had a significant impact on Hong Kong s economy. In 1999, NIAID awarded a contract to St. Jude Children s Research Hospital entitled Pandemic Preparedness in Asia. In addition to its very successful research program, this contract provided training for significant numbers of young investigators and played a role in identifying the SARS virus in China in 2003. This contract served as the precursor to the CEIRS program. CEIRS Network Overview and Structure Dr. Diane Post, NIAID CEIRS Program Officer, provided an overview of the CEIRS network and structure. The CEIRS program was conceived as a novel, unified network that would combine 2

basic influenza research, surveillance, and diverse scientific expertise in a way that would advance basic science while serving as a resource for the broader influenza research community. NIAID initiated the CEIRS network as a result of recommendations from the NIAID Blue Ribbon Panel on Influenza Research, and as one facet of the HHS pandemic response and preparedness plan. The goals and expectations for the CEIRS program articulated at the time of contract solicitation included: Through basic and surveillance-related research efforts, the CEIRS Centers would lay the groundwork for new and improved control measures against influenza. Multidisciplinary studies investigating the natural history of influenza would be expanded. Research in key areas would be conducted to fill knowledge gaps and move the influenza research field forward. By providing resources including training and reagents, the investigators would serve as resources for the scientific community. In the event of a pandemic, the Centers would be able to assist with response efforts by conducting essential research. In addition, it was envisioned that the Centers would form a collaborative network. On March 30th, 2007, NIAID established the CEIRS network by awarding contracts totaling $23 million per year for a 7-year period. The network is composed of five centers, many with domestic and international partners. It brings together multidisciplinary teams of researchers that perform surveillance-related research integrated with research on host immune responses, viral pathogenesis, and the factors that control the emergence and transmission of influenza viruses among animal reservoirs. The CEIRS network provides an important complement to several other U.S. Government agencies performing related work on influenza. Research supported and conducted by other agencies, including samples collected for other projects, are used in the CEIRS network to address important research questions. In addition to basic research projects, several of the Centers support training programs. Each Center has an external scientific review committee that meets on an annual basis to review the data obtained during the previous year, and to provide recommendations on the direction of research projects. These external committees have been instrumental in providing advice and expertise to the CEIRS network. Over the past five years, the CEIRS network has made many significant contributions to influenza research. Among the most important was the response to the 2009 H1N1 pandemic: the CEIRS network played an instrumental role in early virus characterization studies and preclinical evaluation of vaccine material. Other highlights include development of the Influenza Research Database (a NIAID-supported, freely available resource of datasets and bioinformatics tools), as well as contributions to influenza resource and data sharing. Equally important to the influenza research community are the training and capacity-building activities the Centers are conducting. These activities build infrastructure not only for influenza research and surveillance, but can also be applied to other infectious diseases as well. More than 420 3

publications have resulted from CEIRS funding, many of which appear in prominent journals. The CEIRS research accomplishments continue to contribute to a strong scientific foundation that is being translated into new interventions and control strategies aimed at improving global health. CEIRS Surveillance-Related Research Dr. Richard Webby, St. Jude Children s Research Hospital, provided an overview of surveillance activities conducted by the CEIRS network. The network is responsible for providing the Federal government with information, public health tools, and strategies needed to control and lessen the impact of epidemic influenza and the increasing threat of pandemic influenza; determining the prevalence of avian influenza viruses in close contact with humans; and understanding how these viruses evolve, adapt, and transmit. The ultimate goal is to make surveillance predictive in order to detect and recognize events of public health concern. Because of the integration of surveillance and basic research, the CEIRS network is uniquely positioned to answer key questions related to detection and recognition of avian influenza viruses. The network performs surveillance on both sides of the human-animal interface, covering hosts from natural reservoirs and hosts with close contact to humans. The surveillance data is used to understand evolutionary paths and to guide fundamental research, including research on transmission and pathogenesis. For global surveillance, the network aims to expand the number of samples collected and provide a better characterization of avian influenza viruses. Two critical components of the network are flexibility to conduct influenza virus surveillance wherever it is needed, and collaborations that the network has established with key national and international organizations. Dr. Webby emphasized that after the contract ends, it will be important to sustain the extensive infrastructure that has been established by the network, including the broad interdisciplinary mix of scientific expertise that is represented. CEIRS Research on Pathogenesis Dr. Adolfo Garcia-Sastre, Mt. Sinai School of Medicine, discussed the breadth of information that is available on influenza viruses, including evolution and transmission, as well as the determinants and symptoms of disease caused by them. However, there are still a number of research gaps in influenza pathogenesis including questions about viral structure, biochemical pathways and host-virus interactions. In addition, questions remain about predicting antigentic drift and creating therapeutic antibodies and universal vaccines. Dr. Garcia-Sastre described the ways in which the CEIRS network is advancing research in these areas and laying the groundwork for new and improved control measures. As the network has evolved, the collaborations between Centers have continued to increase. The challenge of decreasing resources may be somewhat countered by continuing to train the next generation of influenza virus researchers, and by continuing to work as a multidisciplinary, multi-center, synergistic network focused on achieving a more comprehensive picture of influenza replication, transmission, host tropism and disease. 4

CEIRS Research Response to the 2009 H1N1 Pandemic Dr. Michael Osterholm, University of Minnesota, noted that the pinnacle of influenza events is a pandemic, and given its unpredictable nature it is important to continually be ready to respond quickly. Although the CEIRS network is not a front line responder for outbreaks like the Centers for Disease Control and Prevention is, CEIRS had a direct impact on the public health response to the 2009 H1N1 pandemic. Dr. Osterholm described how the network redirected its full focus to the pandemic influenza strain, and performed targeted studies to identify and characterize the virus, and examine the host immune response. These studies provided important information to public health officials, answered questions about the pandemic virus, and helped in implementing the most effective countermeasures. In addition, the network also provided critical scientific resources for the response including scientific expertise and reagents. In the time since the 2009 pandemic, the network has spent considerable effort evaluating its response in order to improve preparedness in the future. Expert Panel Findings and Recommendations At the end of the meeting the panel met in closed session to finalize their findings and recommendations, which are divided into three distinct areas: significant contributions made by the CEIRS network, influenza research gaps and challenges, and recommendations for the future. Significant Contributions By providing a multidisciplinary, multi-faceted approach, the CEIRS network is in a unique position to fulfill the dual mandate of NIAID by conducting basic research and rapidly responding to emerging infectious disease threats. The network has created an environment where the sharing of reagents and data is expected, critical to making advances globally. The response to the 2009 H1N1 pandemic demonstrated that the network can have a direct impact on the public health response to an emerging health threat by providing applied research and critical scientific resources (e.g., genomic studies, viral characterization, surveillance). During the pandemic, the ability of the program to quickly redirect resources in a coordinated manner to the most important activities was critical to its success. Under the Broad Agency Announcement contract mechanism, each Center is able to take advantage of its own strengths and unique capabilities, allowing for complementarity, synergy, and minimal duplication of effort. The CEIRS program creates important influenza reagents that are made available to the larger research community. The CEIRS program continually builds capacity by engaging in a pilot project program. This program provides funding for highly innovative projects. The CEIRS program is also creating ongoing training for the influenza research community, and encouraging the professional advancement of young/junior investigators. In particular, the training programs are vital components for training future influenza scientists. 5

Partnerships with other government agencies, international partners, and foreign ministries of health have allowed the network to significantly leverage its funding for sample collection and research. The WHO depends on CEIRS as a key contributor of data used in making vaccine strategy decisions as well as providing input into the WHO public health research agenda. Research Gaps and Challenges Expansion of human surveillance research, with particular emphasis on hot-spots of disease, could provide insight into how to better protect the most at-risk populations. Better and more sensitive assays are needed to improve identification of individuals with active influenza infection and those who have been exposed. This could help answer important questions such as: How does the virus spread and are there models to predict potential pandemics? How do people respond to infection and why do some experience severe disease while others are asymptomatic? How does the virus change over time and are host factors involved? Research efforts should include focus on influenza risk factors, host factors, and susceptibility. Animal influenza surveillance should be expanded, especially in agricultural settings, through increased collaborations with national agencies such as the USDA and CDC, and other international partners. Balance is necessary between new areas of research and existing projects. Targeted expansion will help avoid duplication of effort and maximize scientific gains. DMID should ensure that CEIRS research efforts are complementary to other research in areas such as human immunology or systems biology. Additional Recommendations DMID should continue the CEIRS program with its current structure, scope and focus. DMID, in collaboration with the CEIRS program, should focus on enhanced efforts to publicize the significant accomplishments of the network. DMID should explore allowing the network to focus on early product development activities (e.g., investigating potential lead candidates). The scope of international and domestic influenza surveillance efforts should be evaluated with the goal of decreasing duplicative efforts and low-yield sites while optimizing sampling. Collaborations with other agencies/entities (e.g., WHO, CDC, FDA, USDA) should be expanded to increase surveillance activities. These collaborations should take advantage of each organization s strengths without duplicating efforts. Future of the CEIRS network Due to the accomplishments of and unique niche filled by the CEIRS network, the panel recommended that NIAID maintain and continue to support this critical program. 6

Appendix 1. CEIRS Centers and Primary Investigators Contract HHSN266200700005C: St. Jude Children s Research Hospital St. Jude Center of Excellence for Influenza Research and Surveillance (SJCEIRS) Principal Investigator: Dr. Richard Webby Subcontractors: Hong Kong University Kansas State University University of Tennessee National Research Centre (Giza, Egypt) National University of Singapore University of California, Los Angeles University of California, Berkeley National Animal Disease Center, USDA The Institute of Environmental Science and Research, New Zealand Summary of SJCEIRS Scope of Work SJCEIRS is continuing to utilize surveillance related research to better understand how pandemic influenza viruses emerge in humans and how these viruses behave in their animal reservoirs and continued to build on the strength of collaboration with Hong Kong University. SJCEIRS has several projects that include the evaluation of the role of mutations on drugresistant strains, elucidation of the molecular mechanisms by which influenza viruses acquire increased pathogenicity and transmission, investigations on the role of immune mechanisms in the prevention of mortality by H5N1, genetic factors involved in the spread and adaptation of influenza viruses in different hosts and the contribution of ph stability of the HA protein to avian influenza virus adaptation, pathogenesis, transmissibility and drug sensitivity. 7

Contract HHSN266200700006C: Emory University Influenza Pathogenesis & Immunology Research Center (IPIRC) Principal Investigator: Dr. Walter Orenstein Subcontractors: University of Georgia University of Chicago National Taiwan University (Taipei, Taiwan) Summary of IPIRC Scope of Work The IPIRC center brings together investigators who have broad expertise in infectious diseases and vaccines. IPIRC has several projects that include the functional characterization of hemagglutinin glycoproteins of avian viruses with pandemic potential, determination of transmissibility of influenza reassortant viruses, B cell memory and original antigenic sin and studies on the human immune responses to influenza viruses. In addition, IPIRC and the National Taiwan University began surveillance studies in 2009 in Taipei, Taiwan on avian influenza in wild birds and domestic poultry as part of a surveillance capacity building program. 8

Contract HHSN266200700007C: University of Minnesota Minnesota Center of Excellence for Influenza Research and Surveillance (MCEIRS) Principal Investigator: Dr. Michael Osterholm Subcontractors: Chulalongkorn University (Bangkok, Thailand) Kenya Medical Research Institute/CDC Sokoine University of Agriculture (Morogoro, Tanzania) Southeast Poultry Research Laboratory/USDA Wildlife Conservation Society Ohio State University University of California, Davis University of Georgia National Wildlife Health Center, USGS Summary of MCEIRS Scope of Work The Minnesota Center of Excellence for Influenza Research and Surveillance (MCEIRS) sponsors surveillance-related research on (1) the epidemiology, ecology, transmission, and pathogenesis of influenza viruses and infections in wild birds, poultry, swine and selected high risk human populations; (2) methods for detecting and measuring influenza viruses and host immune responses; and (3) intervention and mitigation strategies for reducing the risk of influenza transmission across the animal-human interface. MCEIRS currently conducts 20 studies in the United States, Canada/North Atlantic region, East Africa, Southeast Asia, and Mongolia. MCEIRS focuses on translating research findings into effective public health interventions and evidencebased policies for pandemic preparedness, prevention and control, providing scientific and technical expertise to NIH and the Federal government before or during and influenza pandemic. In addition, MCEIRS seeks to strengthen global capacity in animal and human virologic, epidemiologic, and disease surveillance through the development of an influenza training program, which features 14 learning modules publicly accessible through an online portal, national and international train the trainer sessions, and one-on-one training. 9

Contract HHSN266200700008C: University of Rochester New York Influenza Center of Excellence (NYICE) Principal Investigator: Dr. John Treanor Subcontractors: Cornell University Northwestern University Summary of NYICE Scope of Work The New York Influenza Center of Excellence (NYICE) provides a collaborative, interdisciplinary approach involving investigators in the fields of immunology, virology, biochemistry, medicine, pediatrics, statistics and bioinformatics that is focused on shedding light on important issues of cross-protective immunity and virus adaptation to the mammalian host. NYICE emphasizes translational research, using a highly active clinical core to perform both forward and reverse translation of influenza research findings. A central objective is to understand the breadth and specificity of T and B cell responses to infection and immunization, and to reveal potential mechanisms of cross protection. NYICE investigators are also performing in vivo studies of the viral factors that control host range and pathogenesis in humans, focusing initially on three critical components of the virus: the hemagglutinin and fusion, the polymerase complex and replication, and assembly and release. Immunologic consequences of changes in these factors are also being evaluated. 10

Contract HHSN266200700010C: Mt. Sinai School of Medicine Center for Research on Influenza Pathogenesis (CRIP) Principal Investigator: Dr. Adolfo Garcia-Sastre Subcontractors: Erasmus Medical College University of Maryland, College Park University of Wisconsin-Madison Massachusetts Institute of Technology University of California, Davis Summary of CRIP Scope of Work The Center for Research on Influenza Pathogenesis (CRIP) is dedicated to understanding influenza by conducting novel collaborative research into virus pathogenesis, host restriction, transmission, evolution and host adaptation, interactions between influenza virus proteins and gene segments, evasion of immunity, and induction of host responses. Through this research program, scientists at CRIP are promoting a better understanding of the host range of influenza viruses and the molecular and immunological factors leading to pandemic flu. CRIP also has an animal surveillance related research program that involves collaborative partners around the world. Their goal is to understand the ecological and virological factors that drive the transmission and emergence of influenza viruses within and across species, especially wild birds. 11

Appendix 2: CEIRS Surveillance partners CRIP International Surveillance Partners Deakin University, Melbourne, Geelong, Australia. The climate of Australia is characterized by periods of intense rainfall followed by periods of intense drought. The aim of sampling Australian waterfowl and other potential Australian reservoir species (notably socializing shorebirds, parrots and songbirds) longitudinally is to test the hypothesis that avian influenza virus (AIV) prevalence increases dramatically during periods of intense drought when AIV naïve birds aggregate in high densities on the few remaining water bodies. PI: Prof. Marcel Klaassen International Centre for Diarrhoeal Disease Research Bangladesh (ICDDRB), Dhaka, Bangladesh; Department of Zoology, University of Dhaka, Bangladesh; Wetlands International, Ede, the Netherlands; FAO, Rome, Italy. The aim of sampling Anseriformes and Charadriiformes in Bangladesh is to detect HPAI H5 viruses. Bangladesh is of particularly interest as HPAI H5 viruses have been reported in humans in 2008 and 2011, and less is known about the role of wild birds in the circulation and dispersal of AIV in Bangladesh. Sampling activities are temporarily on hold. PI: Taej Mundkur (Wetlands International), Dr. Salah Uddin Khan (ICDDRB), Prof. Anwarul Islam (University of Dhaka), Dr. Mat Yamage (FAO) Alterra Wageningen University, Wageningen, the Netherlands. The aim of ringing and sampling White-fronted Goose and Red-breasted Goose during their overwintering stage in Bulgaria in spring is to connect AIVs detected in these species with the migration behaviour of their hosts and with similar goose species ringed and sampled for AIV in overwintering areas elsewhere in Europe, e.g. the Netherlands, Hungary. PI: David Kleijn, Gerard Muskens Naval Medical Research Unit (NAMRU), Cairo, Egypt; Ministry of state for Environmental Affairs, Maadi-Cairo, Egypt; BLI/UNDP/GEF Migratory Soaring Birds (MSB) Project - Egypt Nature Conservation Sector, Egyptian Environmental Affairs Agency; Wetlands International, Ede, the Netherlands; FAO, Rome, Italy. The aim of sampling Anseriformes and Charadriiformes in Egypt is to detect HPAI H5 viruses. Egypt is of special interest as HPAI H5 viruses were reported in humans on a regularly basis since 2006 and are still being reported to infect humans. We aim at the detection of HPAI H5 viruses in wild birds to clarify the role of wild birds in the circulation and spread of HPAI H5 viruses within Egypt. Sampling activities are temporarily on hold. PI: Taej Mundkur (Wetlands International), Dr. Lu'ay Elsayed Ahmed (Ministry of state for Environmental Affairs), Wed Abdel Latif Ibrahim (BLI/UNDP/GEF Migratory Soaring Birds (MSB) Project). 12

Georgian Centre for the Conservation of Wildlife, Tblisi, Georgia/Cambridge University, Cambridge, UK. The aim of longitudinal sampling of wild birds in Georgia is to detect AIV in Anseriformes (mainly Mallards) and Charadriifomres (mainly Armenian gulls and Black-headed gulls). We test the hypothesis if Georgia acts as mixing area for European and Asian influenza viruses. PI: Zura Javakhisvili/Nicola Lewis University of West-Hungary, Department of Wildlife Management, Sopron, Hungary. The purpose of avian influenza surveillance in wild birds at this site is to link AIVs isolated from wild birds belonging to the order Anseriformes and Charadriiformes with their migration behavior and with populations of the same species sampled elsewhere in Europe, e.g. Netherlands, Lithuania. We hypothesize that AIVs detected in Eastern European wild birds are genetically highly similar to AIVs detected in Western Europe. In addition to this, we would like to improve the knowledge on the temporal and spatial pattern of AIV in wild birds belonging to the order Anseriformes and Charadriiformes within Europe. PI: Daniel Winkler/Marta Ferenczi Institute of Ecology of Vilnius University, Vilnius, Lithuania. The aims of sampling activities in Lithuania are similar to these mentioned for Hungary. PI: Dr. Saulius Svazas Erasmus Medical College, Rotterdam, the Netherlands. In the Netherlands Anseriformes (predominantly Mallards and White-fronted Geese) and Charadriiformes (predominantly Blackheaded Gulls) were sampled for virus and antibody detection longitudinally. We hypothesize, amongst others, that AIVs circulate in resident Mallards that subsequently infect migrating Mallards, that White-fronted Geese infect less abundant geese species in the Netherlands, that wild birds introduce AIVs into poultry, that farms located near water bodies and high wild bird densities are more often infected with AIVs, that AIV detected in gulls evolve in a different manner than AIV detected in Mallards, and more. In addition to this we would like to use data collected on H13 and H16 AIV on Black-headed gull colonies in the Netherlands to develop a model to understand the multiple AIV subtype infections that occur in ducks. Results of these studies are available to NIH. AIV surveillance activities in the Netherlands were sponsored by grants from the Dutch Ministry of Agriculture, the EU DG Sanco monitoring program and EU Framework six program NewFluBird (044490). PI: Prof Ron A.M. Fouchier Working Group International Waterbird and Wetland Research (WIWO), Oman. The aim of sampling and ringing Charadriiformes (waders and shorebirds) in Oman is to clarify migration routes and to investigate whether high shorebird density area like Delaware Bay (and hence high AIV prevalence) exists elsewhere. In addition to this migration routes of Turnstones and several gull species cover both Egypt and Oman. Sampling these species in Oman therefore is of interest as HPAI H5 viruses are known to infect humans in Egypt since 2006 and less is known of the role of wild birds in the dispersal of these viruses. Sampling activities are currently on hold due to funding limitations with respect to upcoming expedition to Oman. PI: Jim de Fouw 13

Alterra Wageningen University, Wageningen, the Netherlands. The aim of sampling Whitefronted Geese on their breeding grounds in Kolguev and in Kologriv in Russia in spring is to test the hypothesis that White-fronted Geese are infected with AIVs on their breeding grounds in Northern Russia (Kolguev). PI: David Kleijn, Gerard Muskens. From 2006-2009 1451 cloacal swabs and blood samples have been collected, despite multiple efforts made to get the results and/or samples out of Russia no results and/or samples have been received so far. Wetlands International, Ede, the Netherlands. The aim of sampling and ringing Charadriiformes (waders and shorebirds) in Sudan is to clarify migration routes and to test the hypothesis that HPAI H5 AIV are present in wild birds in Sudan. Sudan is of interest as it is located next to Egypt, where HPAI H5 AIV were detected since 2006, and birds in Sudan are likely to use the same migratory flyway as wild birds in Egypt. PI: Jan Veen, Taej Mundkur (Wetlands International). Sampling activities in Sudan were limited to a single expedition as the ornithologists currently do not have further plans for continuation of the ringing and sampling of wild birds in Sudan, combined with the difficulties of sample export. Ornithological Research Center, Ondokuz Mayis University, Kurupelit Samsun, Turkey. Wetlands International, Ede, the Netherlands. The aims of sampling activities in Turkey are similar to these mentioned for Hungary. Sampling activities are temporarily on hold, partly due to funding limitations and limitations in laboratory capacity. PI: Kiraz Erciyas (Ornithological Research Center, Turkey), Taej Mundkur (Wetlands International) National Institute of Hygiene and Epidemiology, Hanoi, Vietnam. The goal of this surveillance project is to assess the prevalence of H5N1 viruses in chickens and ducks in Northern Vietnam. All isolated H5N1 viruses are sequenced and characterized for their virulence. PI: Dr. Mai Quynh Le Laboratorio de Aves y Porcinos, Instituto de Virología, Instituto Nacional de Tecnología Agropecuaria (INTA): The goal of this project is to generate data to better describe the ecology of animal influenza viruses in Argentina, specifically from isolates obtained from wild waterfowl and swine. This includes molecular and pathogenic studies of these viruses. PI: Ariel Pereda 14

CRIP Domestic Surveillance Partners UAF/Massachusetts Institute of Technology. The group conducts surveillance of low pathogenic and high pathogenic avian influenza virus (L/HPAI) and isolates, cultivates and analyzes virus from up to 25,000 samples per season. We are focusing, in collaboration with other teams, on understanding the ecology, epizootiology, and evolution of the influenza virus in natural carrier species and of potential pandemic strains. This focus is aided by long term study sites established in Alaska and with collaborators. These studies have thus far focused on Alaska and the Northern Pacific Rim countries, examining the complex relationships between Avian Influenza virus and the abundance of birds along major migratory flyways. PI: Jonathan Runstadler Alaska Bird Observatory (ABO), Fairbanks, Alaska. Our long-term collaboration allows us to monitor AI prevalence in up to 72 species of migratory and resident bird species banded here in Alaska's Interior. The goal of this research project is to determine if influenza viruses can be isolated from non-waterfowl species in close proximity to major migratory stopover sites, to determine which subtypes are present and perpetuated in these species and to examine whether there is a difference between viruses isolated from land-based birds and aquatic birds at the intersections of major flyways at their northern extremes. PI: Sue Guers Prince William Sound Science Center (PWSSC), Cordova, Alaska. The PWSSC samples gulls and shorebirds in south-central Alaska s Prince William Sound/ Copper River Delta area. This basic surveillance research is focused on understanding the unique ecology of influenza in gulls, on understanding the site-specific differences in viral prevalence and abundance in shorebirds, and to understand the role of anthropogenic influences in structuring the influenza virus transmission and persistence in these populations. The goal is to describe the relationship of isolated viruses to the movement of viruses in these bird groups worldwide. PI: Mary Anne Bishop DEC & Alaska SeaLife Center, Seward, Alaska. This collaboration with the Alaska State Veterinarian at the Department of Environmental Conservation samples of stranded or sick marine mammals and shorebirds or other species reported to the State offices. The goal of this research is to isolate viruses that are potentially causing illness in natural populations and to compare differences in these viruses to previously isolated strains. PI: Robert Gerlach IPIRC International Surveillance Partner National Taiwan University, Taipei. The goals of this partnership are to carry out surveillance integrated with virological and immunological studies in collaboration with investigators in Taiwan and at Emory University in Atlanta. Dr. King is a Professor at the Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University. Her group conducts virological and serological surveillance of AIV in poultry markets (domestic chickens and ducks), farms, and wild birds. At Emory, Dr. Chinglai Yang s group investigates immunogenicity of the HA and NA from AIV isolates obtained through surveillance activities to 15

determine the antigenic relationship between these isolates with those from other geographic regions, and compares molecular and antigenic variations of AIV isolates of the same subtype over different time periods, geographical areas and host species. The two teams have also formed a training partnership to improve surveillance capacity and foster more efficient research progress at both institutes. PI at Emory: Dr. Chinglai Yang; PI at National Taiwan University: Dr. Chwan Chuen King MCEIRS International Surveillance Partners Chulalongkorn University (CU), Bangkok, Thailand: CU researchers have successfully investigated two reported outbreaks of highly pathogenic avian influenza virus among poultry in Thailand, with targeted specimen collection and testing among wild birds, poultry, and swine. They also monitored subtypes of influenza A viruses circulating in Thai live bird markets and local food markets, conducted systematic surveillance for swine influenza viruses among swine farms in several regions of Thailand, and identified unique characteristics and molecular epidemiology of influenza A viruses in Thai swine. In human studies, CU researchers analyzed the whole-genome characteristics of 2009 H1N1 influenza A viruses in Thailand and compared them phylogenetically with pandemic H1N1 viruses in other countries. PIs: Dr. Yong Poovorawan and Dr. Alongkorn Amonsin Kenya Medical Research Institute (KEMRI)/CDC, Kibera, Kenya: KEMRI s research team is assessing the prevalence of 2009 H1N1 infection among domestic animals and in the communal environment in the Kibera urban settlement near Nairobi, Kenya, and characterizing exposure to influenza A viruses among swine at a local pig slaughterhouse. This study is being conducted in collaboration with KEMRI s existing program in population-based infectious disease surveillance in humans in Kibera, enabling linkage of influenza A surveillance data from the human and animal populations within this site. PI: Dr. Kariuki Njenga Sokoine University of Agriculture, Sokoine, Tanzania: Researchers at Sokoine University, the University of Minnesota and the University of California, Davis are currently leading an animalhuman interface study in Tanzania, examining the prevalence and risk of transmission of influenza among domestic poultry species and their owners in villages and live bird markets in Morogoro and Dar es Salaam. The goals of the study include identifying high-risk handling and preparation behaviors along with market layout or resource (e.g., water) access that impact the transmission of avian influenza viruses. PI: Dr. Carol Cardona National Wildlife Health Center/USGS, North Atlantic region of Canada: In collaboration with partners in Canada, Greenland and Iceland, Dr. Hall is currently conducting surveillance among wild birds from Canada and the North Atlantic region to evaluate genetic relatedness of influenza A viruses for evidence of intercontinental virus movement (Eurasian viruses to North America or North American viruses to Europe). PI: Dr. Jeffrey Hall 16

Wildlife Conservation Society (WCS), Mongolia, Lao PDR, Cambodia and Vietnam: In collaboration with Hong Kong University, WCS studies have focused on (1) ecological and demographic factors in avian influenza transmission cycles in East Asia, assessment of seasonal variation in avian influenza prevalence in migratory ducks in the East Asian Flyway and environmental correlates of highly pathogenic H5N1 influenza outbreaks among wild birds at Mongolian lakes; and (2) surveillance in wild birds in East and Southeast Asia using serological methods on archived and newly collected serum samples from Vietnam, Lao PDR, Cambodia, and/or Mongolia. In Year 5, Dr. Gilbert is focusing on the ecology of avian influenza virus in migratory ducks in the East Asian flyway, particularly the ecological and environmental factors that affect timing and distribution of H5N1 outbreaks at Mongolian lakes. PI: Dr. Martin Gilbert MCEIRS Domestic Surveillance Partners Ohio State University: Efforts at Ohio State University initially focused on the natural history and genomic dynamics of influenza A viruses in waterfowl along the Mississippi and Central Flyways. In a second study, Dr. Slemons team is evaluating selected host, agent and environmental factors associated with host-specific frequencies of influenza A infections in Wood ducks and Mallards at established study sites in northern Ohio. In 2009-2011, Dr. Slemons team conducted surveillance among swine at Ohio county fairs to isolate and characterize swine influenza viruses using antigenic and genetic analyses. Additional efforts focused on initiating surveillance among commercial swine producers in Ohio. PI: Dr. Richard Slemons University of Georgia: The overall goal of MCEIRS studies at UGA is to better understand the natural history of avian influenza viruses in wild bird reservoirs. The studies also focus on enhancing the efficiency of surveillance in wild birds and enhancing our understanding of the risk of influenza transmission from wild birds to domestic animals and to human populations. In Year 5, UGA researchers are focusing surveillance efforts on Minnesota, Louisiana, Texas, New York and Delaware Bay in collaboration with St. Jude CEIRS. PI: Dr. David Stallknecht University of Iowa: The goal of Dr. Gray s study is to identify specific risk factors for avian influenza (AI) virus transmission to bird banders. During the course of this study, which concluded in 2011, Dr. Gray s team assessed evidence for previous AI infection (H4-H11) among bird banders; demographic, behavioral, geographic, and occupational risk factors for these previous influenza virus infections; incident influenza virus infection (H4-H11); and risk factors for incident influenza virus (H4-H11). PI: Dr. Gregory Gray National Wildlife Health Center: Conduct surveillance of peridomestic mammalian species in Texas with the potential to harbor and transmit influenza virus to humans or agricultural hosts. This study, which concluded in Year 4, Monitor and define the roles of wild mammalian species in the disease ecology of influenza. Evaluate genetic relatedness of influenza viruses isolated from wild mammalian species from Mexico, Southwest USA, and/or Costa Rica. 17

University of Minnesota: Current surveillance studies at the University of Minnesota include: Research on the presence and extent of quasispecies of influenza A viruses in primary clinical samples obtained from waterfowl surveillance (Dr. Srinand Sreevatsan, PI, in collaboration with Dr. Stallknecht, UGA) ; Surveillance among production swine in the Midwest region (Dr. Montserrat Torremorell) and and epidemiologic evaluation of the risk of influenza infection among conservation/natural resources professionals (Larissa Minicucci, PI). Past studies at the University of Minnesota include: Analysis of the potential for environmental transmission of influenza A viruses from pigs to people (Dr. Marie Gramer, PI); Genetic characterization of influenza viruses of perceived increased virulence from ill swine (Dr. Gramer, PI) and AIV Surveillance in Waterfowl in the Upper Midwest (Dr. Patrick Redig, PI). SJCEIRS International Surveillance Partners Jahangirnagar University, Savar, Dhaka: The goals of this basic research project are to determine if influenza viruses can be isolated from poultry markets in Bangladesh, which subtypes are present and perpetuated in the poultry markets and whether there is a difference between viruses isolated from land-based birds and aquatic birds. PI: Dr. Mohammaed Mostafa Feeroz The Laboratoire De Diagnostic Veterinaire Et De Serosurveillance (LADISERO), Parakou: This site is conducting basic research to determine if influenza viruses can still be isolated from poultry in Benin since the reported HP clade 2.2 H5N1 outbreaks in 2007 and to determine if influenza viruses can be isolated from pigs. The goal is to compare similarities and differences between the avian and swine viruses and between different regions of Africa. PI: Dr. Gilbert Luc Aplogan National Centre for Animal Health in Serbithang, Thimphu, Bhutan: This goal of this research project is to determine if influenza viruses are present in domestic birds (poultry and ducks) as well as swine in Bhutan. Bhutan falls in a unique geographic region between India/Bangladesh and China on the Central Asia Flyways for migratory birds. As such, surveillance here will answer important questions on how viruses transmit in this region. PI: Dr. N. Dahal Departmento de Microbiologia, Universidade de Sao Paulo, Brazil. To obtain samples from wintering ruddy turnstones (and other shorebirds) in Brazil. The purpose of this research is to understand the factors that make Delaware Bay a hot spot for influenza viruses (we are sampling the same birds at different stages of migration). PI: Edison L. Durigon National Diagnostic and Research Veterinary Medical Institute, NVS, Varna Bulgaria: H5N1 influenza viruses re-emerged in Western Europe in 2005-2006 although it was not maintained. This site is conducting surveillance in wild birds and farmed mule ducks to determine the presence of influenza viruses circulating in Bulgaria and to understand the transmission of viruses from wild to domestic birds in this region. PI: Dr. Atanaska Marinova 18

Canadian Wildlife. This is a continuation of a long term longitudinal study to understand the nature and dynamics of influenza viruses in their natural host. PI: Dr. Frank Baldwin Facultad de Medicina Veterinaria y Zootecnia, Universidad de los Llanos and Universidad de Antioquia Medical and Veterinary Schools in Medellin, Colombia in collaboration with the Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin: The goals of this basic research project is to determine if influenza viruses can be isolated from diverse animal and bird species from urban and rural parts of Colombia, which subtypes are present, and whether live bird markets or migratory birds pose a public health risk. Recent work suggests a separate South American gene pool hence this work will provide further details on these findings. PI: Dr. Jorge Osorio Congo/Democratic Republic of Congo (DRC)/Cameroon: University of California, Los Angeles, California: A project has been initiated to systematically monitor avian influenza in domestic poultry, swine and associated wild birds in the Congo Basin to investigate potential sources of recent outbreaks of H5N1, as well as monitor other virus strains in animals including H1N1. PI: Dr. Thomas Smith LANADA / Central Laboratory for Animal Diseases, Bingerville, Côte d Ivoire: Côte d Ivoire reported HP clade 2.2 H5N1 outbreaks in 2006. Backyard poultry represents an important percentage of the birds bred and consumed in the country and all the HP H5N1 outbreaks reported occurred in small backyard flocks. Moreover, pigs have only been screened for influenza virus in Côte d Ivoire since last year within the framework of our collaboration. The purpose of the present studies is to determine: if influenza viruses can still be isolated from backyard poultry and which subtypes are present irrespective of their pathogenicity; whether the subtypes are perpetuated in poultry markets; whether influenza viruses can be isolated from pigs and, if yes, are there similarities between avian and swine viruses? PI: Dr. Emmanuel Couacy-Hymann National Research Centre, Giza, Egypt: We conduct prospective surveillance among poultry in backyard flocks, commercial farms, live bird markets, and slaughterhouses with the aim of identifying and characterizing avian influenza viruses and to identify the parameters which make H5N1 endemic I this country. We also perform a prospective seroepidemiological study to determine the prevalence and incidences of AI infection among individuals occupationally exposed to poultry, and determine risk/protective factors of infection. We are also involved in conducting comparative H5 vaccine efficacy in poultry as well as molecular studies to identify molecular determinants of H5N1 pathogenicity. PI: Dr. Mohamed Ahmed Ahmed Ali Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Accra, Ghana: To describe the epidemiology of avian influenza in areas with previous outbreaks in poultry in Ghana and establish a swine surveillance program in 49 Communities in 7 Districts of the three target regions in Ghana. Samples are sent to St Jude CEIRS (avian) and 19

National Research Center in Egypt (swine) for isolation and further characterization. PI: Dr. William Ampofo The University of Hong Kong, Hong Kong: This is a continuation of a long term longitudinal studies to understand the nature and dynamics of influenza viruses in a number of hosts in the SE Asia region. The purpose is to detail the transmission of viruses in these hosts and to understand the evolutionary changes that accompany these events. PI: Dr. Malik Peiris and Dr. Yi Guan National Institute of Virology, India in collaboration with HKU: Influenza surveillance was conducted at live-poultry markets in Pune in response to the 2009 pandemic outbreak as well as the collection of serum samples from poultry in the West Bengal where HPAI H5N1 virus outbreaks occurred in 2008 and 2009. However, the project was eliminated due to poor performance of this collaboration. PI: Dr. Akhilesh C. Mishra (NIV) and Dr. Yi Guan (HKU) National Animal Health Center, Vientiane Capital, Lao PDR: Department of Livestock and Fisheries, Vientiane Capital: The goals of this surveillance project are (1) to determine the subtypes of influenza A viruses circulating in and being introduced into domestic poultry (ducks and chickens); (2) to assess the distribution of influenza A, particularly H5N1, in 9 provinces that have previously experienced outbreaks of HPAI H5N1 or contain major trade routes; (3) to further assess risk factors with respect to different poultry production types (backyard, farms, life bird markets); (4) to assess seasonality of influenza A in Lao PDR by sampling four times during 2010, and twice in 2011. For 2012 two sampling rounds are planned and funding for sampling is provided by the FAO. SJCEIRS provides reagents for screening of swabs and sera in Lao PDR, and laboratory space and reagents for virus isolation, sequencing, and HI-typing of serum antibodies. PI: Dr. Bounlom Douangngeun American University of Beirut, Beirut, Lebanon: The aims of the seroepidemiological study in Lebanon were to determine the seroprevalence of AI in poultry-exposed and non-exposed human populations and to identify risk factors associated with AI infections in occupationallyexposed poultry workers. We also conducted cross-sectional surveillance for AI viruses among domestic birds in low biosecurity farms and backyard flocks. PI: Dr. Elie Barbour Monterrey Institute of Technology, Mexico. The goals of this basic research project is to determine if influenza viruses can be isolated from diverse animal and bird species in Nuevo Leon, Mexico, which subtypes are present and perpetuated and pose a public health risk. PI: Dr. Manuel Zertuche Institute of Veterinary Medicine, Ulaanbaatar, Mongolia in collaboration with University of Florida, Gainesville, Florida: There has been a shift in focus in our surveillance program in Mongolia with respect to the animals sampled and screened as it has become apparent that wild birds in Mongolia are being overrepresented in global surveillance (at least 5 active groups). As Mongolia has more than 2.1M horses and 300,000 Bactrian camels, they often 20

suffer from epizootics of equine influenza. Other than the outbreak reporting, there is essentially no surveillance for influenza among horses and camels in Mongolia. A project began in early fall 2010 to sample horses and camels by collecting nasal swabs from 50 horses and 20 camels with ILI every month from three project sites. Swabs with evidence of influenza A will be further studied with culture and molecular amplification and sequencing of H, N, and M genes at University of Florida. PI: Dr. Batsukh Zayat and Dr. Greg Gray WHO National Influenza Centre, Institute of Environmental Science & Research Limited, Porirua, New Zealand: To determine the incidence of influenza viruses in swine in an island nation with limited import of external animals. The frequency of zoonotic transmission will also be examined. PI: Dr. Sue Huang National Reference Lab for Poultry Diseases, Animal Sciences Institute, National Agricultural Research Centre, Islamabad, Pakistan: There is still interest from both Dr. Naeem and St. Jude CEIRS to initiate a FFS agreement to collect swabs or environmental samples and sera from birds. The plan is to initiate these studies in this contract period. PI: Dr. Khalid Naeem Papua New Guinea Institute of Medical Research, Goroka, Eastern Highlands Province, Papua New Guinea: Surveillance and typing of avian influenzas in Papua New Guinea has never been conducted. The relentless spread of H5N1 avian influenza throughout Southeast Asia is a very real threat to the countries avian and human populations. Papua New Guinea represents a strategic expansion of our efforts in SE Asia, particularly with its close proximity to Indonesia, and H5N1 endemic region. Therefore, surveillance in domestic and wild birds and virus characterization is being conducted to determine the prevalence and subtypes of avian influenzas in PNG poultry populations. PI: Dr. Paul Horwood Center for Health Policies and Public Health (CHPPH), Babeş-Bolyai University Cluj-Napoca, Romania in collaboration with the University of Florida, Gainesville, Florida. The Danube Delta is the Europe's largest wetlands and a major migratory route for wild birds and in 2005, the virus entered Romania carried by wild migratory birds that visit the Danube Delta each year. Since then, Romania has suffered a series of avian H5N1 influenza outbreaks. A sentinel bird study has been established at 7 sites in the Danube Delta allowing exposure to wild birds migrating in this area. The goal is to determine the epidemiology of avian influenza and to characterize influenza isolates through molecular studies. PI: Dr. Alexandru Coman (CPPH) and Dr. Greg Gray (UF) State Research Center of Virology and Biotechnology VECTOR, Russia. An agreement is in place to determine antigenic and genetic variability of influenza viruses circulating in wild and domestic birds in Russia and the susceptibility of avian influenza viruses circulating in Russia to available antiviral agents, and to develop reverse genetics technique for the preparation of candidate avian influenza vaccine strains based on highly pathogenic viruses isolated in Russia. PI: Dr. Alexander Shestapolav 21

Faculty of Medicine, University of Kelaniya, Sri Lanka: The purpose of these studies is to elucidate the activity at the human/animal interface. Swine, birds, and humans will be examined. PI: Dr. Malik Peiris (HKU) Laboratoire vétérinaire de Lomé, Lomé, Togo: Togo reported HP clade 2.2 H5N1 outbreaks in 2007 and 2008. Samples will be collected from domestic poultry form live bird markets and domestic swine. These studies will involve will establish the subtypes of influenza viruses that are present and provide information on the gene pool of influenza viruses currently circulating in Togo. PI: Mr. Kodzo Agbelesessi Awoume Makerere University Walter Reed Project, Kampala, Uganda: The goal of this project is to support active abattoir surveillance for influenza viruses in swine in order to provide background for more detailed focused surveillance. We also collaborate with this team to analyze influenza viruses isolated from humans. PI: Dr. Denis K Byarugaba Ukraine Anti Plague Institute, Odessa, Ukraine: Surveillance in wild birds was initiated to determine if avian influenza was circulating in the wild bird population in Ukraine. Of the 148 samples (cloacal or fecal) we received, all were negative. No further activity is planned at this time. PI: Dr. Sergiy V. Pozdnyakov SJCEIRS Domestic Surveillance Partners Delaware Bay, New Jersey: This is a continuation of a long term longitudinal study to understand the nature and dynamics of influenza viruses in their natural host. PI: Dr. Robert Webster and Scott Krauss University of California, Berkeley, Berkeley, California: University of California, Berkeley, Managua, Nicaragua: The goal of this immunological project is to determine the role of cellular immunity in the rates of transmission and severity of disease in a household cohort study. Paired samples from sequential years will be analyzed for numbers and functionality of CD4 and CD8 T cells. PI: Dr. Aubree Gordon Veterinary Diagnostic Laboratory, University of Minnesota. The goal of this project is to sequence swine samples virus isolate samples from passive surveillance to follow the evolution of viruses in this important reservoir. PI: Dr. Kurt Rossow. 22

Appendix 3: CEIRS Program Review Panel Members CEIRS Program Review Panel Chair: Dr. Samuel Stanley, Stony Brook University CEIRS Program Review Panel Members: Dr. Beth Bell, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention Dr. Tom Braciale, University of Virginia Dr. Sylvie Briand and/or Dr. Nikki Shindo, World Health Organization Dr. John Clifford, Animal and Plant Health Inspection Service, US Department of Agriculture Dr. Robert Couch, Baylor College of Medicine Dr. Bruce Gellin, National Vaccine Program Office, Department of Health and Human Services Dr. Keith Hamilton, World Organization for Animal Health Dr. Alan Hay, National Institute for Medical Research Dr. Marguerite Pappaioanou, Association of American Veterinary Medical Colleges Dr. John Pasick, National Centre for Foreign Animal Disease 23

Appendix 4: CEIRS Program Review Meeting Agenda NIAID/DMID Centers of Excellence for Influenza Research and Surveillance (CEIRS) Program Review October 14, 2011 Fernwood Conference Room 2C-13 Bethesda, MD 8:00 8:15 AM: Welcome and Objectives for the Meeting Dr. Anthony Fauci, National Institute of Allergy and Infectious Diseases, NIH 8:15 8:30 AM: Comments from the Review Panel Chair Dr. Samuel Stanley, Stony Brook University 8:30 9:00 AM: Sustaining an Influenza Research Legacy Dr. Robert Webster, St. Jude Children s Research Hospital 9:00 9:30 AM: CEIRS Overview and Structure Dr. Diane Post, CEIRS Project Officer 9:30 10:15 AM: CEIRS Surveillance Related Research: Highlights, Gaps and Future Directions Dr. Richard Webby, St. Jude Children s Research Hospital 10:15 10:35 AM: BREAK 10:35 11:20 AM: CEIRS Research on Pathogenesis and Host Responses: Highlights, Gaps and Future Directions Dr. Adolfo Garcia-Sastre, Mt. Sinai School of Medicine 11:20 12:00 PM: CEIRS 2009 H1N1 Pandemic Research Response and Efforts for Pandemic Prepardness Dr. Mike Osterholm, University of Minnesota 12:00 1:00 PM: WORKING LUNCH Discussion and questions for the CEIRS investigators and DMID staff 1:00 3:00 PM: Closed Consultative Discussion Panel Members Discussion of DMID staff questions and other relevant issues 3:00-3:15 PM: Coffee Break 24

3:15 3:45 PM: Discussion Continuation Option 1: Continuation of closed discussions Option 2: Open session discussions with DMID staff 3:45 4:45 PM: Presentation of summary from Closed Panel Discussion 4:45 5:00 PM: Final Comments and Wrap Up 5:00 PM: Adjourn 25