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Summary T he influenza pandemics of 1918, 1957, and 1968 offer a warning to the world about the potential dangers of the influenza virus. In 2006, after a series of cases and clusters of the highly pathogenic H5N1 avian virus made clear the threat of a possible pandemic, the U.S. Con- gress allocated $39 million to the Department of Defense Global Emerging Infections Surveillance and Response System (DoD-GEIS) to increase and improve its worldwide influenza surveillance network through upgrades to its domestic and overseas laboratories’ capabilities. Though the twentieth century saw the emergence of three influenza pandemics, the one that remains most widely researched is the 1918-1919 pandemic, commonly referred to as the “Spanish flu.” This pandemic killed an estimated 50 million to 100 million people, thereby qualifying as the most deadly disease outbreak in history (Tumpey et al., 2005). In addition to the 1918 pandemic, the twentieth century experienced two other influ- enza pandemics which were milder and less devastating than the outbreak of 1918. The first of these occurred in 1957 and was known as the Asian flu pandemic (H2N2) (Potter, 2001). The Hong Kong pandemic of 1968, due to an antigenic shift to H3 (H3N2), was even milder than the 1957 pan- demic, yet still reportedly killed half a million people worldwide (Dowdle, 1999; Kilbourne, 2006). Almost three decades later, a new strain of influenza virus was discov- ered in China. Since 1997, the World Health Organization (WHO) has confirmed 318 human cases of H5N1 infection in 12 different countries, 192 of which were fatal (WHO, 2007). Approximately 150 million poultry 

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 REVIEW OF THE DOD-GEIS INFLUENZA PROGRAMS have died since January 2004, either from the virus directly or as a result of culling efforts to contain the virus. H5N1 is already considered endemic in poultry in China, Vietnam, Thailand, Indonesia, and perhaps Cambodia and Laos (WHO, 2005). The Executive Office of the President issued the Presidential Decision Directive NSTC-7 (National Science and Technology Council, Executive Office of the President, Presidential Decision Directive) in 1996, which declared that national and international capabilities for infectious disease surveillance, prevention, and response were inadequate to protect the health of U.S. citizens from emerging infectious diseases and called for a more robust national policy to improve these capabilities (IOM, 2001). This directive expanded the mission of the DoD to include support of global surveillance, training, research, and response to emerging infectious disease threats. In response to the NSTC-7 directive, DoD-GEIS was established in 1997 by the Assistant Secretary of Defense for Health Affairs to serve as the focal point for “initiating and coordinating the identification, reporting and responding to emerging infectious disease problems.” GEIS is a tri-service program, and its activities are implemented within all three branches (Army, Navy, and Air Force) of the armed forces, although GEIS has no direct com- mand authority over the facilities that implement its activities. The DoD overseas laboratories provide forward sites for GEIS activities. At present the DoD has five overseas laboratories: the U.S. Naval Medical Research Center Detachment (NMRCD) based in Lima, Peru; the U.S. Naval Medical Research Unit No. 2 (NAMRU-2) in Jakarta, Indonesia; the Armed Forces Research Institute of Medical Sciences (AFRIMS) in Bangkok, Thailand; the U.S. Naval Medical Research Unit No. 3 (NAMRU-3) in Cairo, Egypt; and the U.S. Army Medical Research Unit Kenya (USAMRU-K) in Nairobi. These laboratories, varying in size and capability, have field activities that operate in nearby countries and beyond, often with limited facilities within their regions of operation. In conjunction with the two domestic laborato- ries, the Naval Health Research Center in San Diego, California (NHRC) and the Air Force Institute for Operational Health in San Antonio, Texas (AFIOH), they work together to address the four stated goals of GEIS: • Surveillance and detection • Response and readiness • Integration and innovation • Cooperation and capacity building Beginning with its creation in 1996, DoD-GEIS has focused on influ- enza, well aware of its potential to grow to pandemic proportions. The DoD-GEIS surveillance network was established to monitor host-country populations in areas where little was known about disease epidemiology,

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 SUMMARY and this network currently includes patient enrollment sites in more than 20 countries in South America, the Middle East, sub-Saharan Africa, and central and southeast Asia (Canas et al., 2000). In a number of countries, including Indonesia, this DoD-GEIS network is the only way through which information on circulating influenza strains flows to WHO (Chretien et al., 2006a). Between October 1, 2005 and February 28, 2006, the DoD-GEIS laboratories, working in conjunction with WHO, the Centers for Disease Control and Prevention (CDC), host country governments, and other key governmental and nongovernmental organizations, responded to 66 out- breaks in 22 countries worldwide. A number of these outbreak responses led to the identification of disease emergence or reemergence, notably in- fluenza A (H5N1) in Egypt, Indonesia, Iraq, Kazakhstan, and Turkey. Ad- ditionally, the laboratories provide laboratory and field support, train host country and U.S. military medical personnel, and aid in the development of host country surveillance systems (Chretien et al., 2006b). On January 2, 2005, the 109th Congress passed H.R. 1815, Sec. 748, “Pandemic Avian Flu Preparedness,” which listed DoD-GEIS by name and called upon the secretary of defense to address “. . . surveillance efforts domestically and internationally.” Subsequently, the DoD-GEIS was tasked by the assistant secretary of defense for health affairs to take the lead on the following activities laid out in Sec. 748, H.R. 1815: • Surveillance efforts domestically and internationally, including those utilizing the Global Emerging Infections Systems (GEIS), and how such efforts are integrated with other ongoing surveillance systems • Integration of pandemic and response planning with those of other federal departments, including the Department of Health and Human Ser- vices (HHS), Department of the Veterans Affairs, Department of State, and U.S. Agency for International Development • Collaboration (as appropriate) with international entities engaged in pandemic preparedness and response The congressional supplemental appropriation of $39.28 million as- sociated with Sec. 748, H.R. 1815 was received by DoD-GEIS in March of 2006 and a variety of avian and pandemic influenza activities were imple- mented by DoD-GEIS-supported entities (Malone, 2005). THE STUDY An Institute of Medicine (IOM) committee was subsequently formed to evaluate the effectiveness of these laboratory-based programs in rela-

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 REVIEW OF THE DOD-GEIS INFLUENZA PROGRAMS tion to the supplemental funding, and the report that follows details the committee’s findings. The committee that prepared this report, the Committee for the As- sessment of DoD-GEIS Influenza Surveillance and Response Programs, was convened at the request of DoD-GEIS management to evaluate the execution of the fiscal year 2006 supplemental funding for avian influenza/ pandemic influenza (AI/PI) surveillance and response. The committee was tasked with evaluating the DoD-GEIS AI/PI surveillance program for a. the worth of each funded project’s contribution to a comprehensive AI/PI surveillance program; b. the adequacy of the program in view of the evolving epidemiologic factors; c. responsiveness to the intent of Congress as expressed in Sec. 748, H.R.1815, Pandemic Avian Flu Preparedness; d. consistency with the DoD and national plans; and e. coordination of efforts with CDC, WHO, and local governments. The committee focused its review on the development of conclusions and recommendations with long-term, program-level relevance as well as conclusions and recommendations regarding the improvement of specific DoD-GEIS projects. The committee used WHO and CDC guidelines as ref- erence tools in conducting this review. Chapter 1, this report’s introduction, offers a discussion of the committee’s approach to addressing its charge along with additional background information regarding DoD-GEIS. As part of this review, members of the committee visited NMRCD in Peru; NAMRU-2 in Indonesia; AFRIMS in Thailand; NAMRU-3 in Egypt; USAMRU-K in Kenya; the NHRC in San Diego, California; AFIOH in San Antonio, Texas; and DoD-GEIS Headquarters in Silver Spring, Maryland. Chapters 2 through 9 of this report present the committee’s assessments of DoD-GEIS implementation at the overseas laboratories, at sites within the infrastructure of the military health system and at the DoD-GEIS head- quarters. These chapters include discussions of each DoD unit’s AI/PI ac- tivities as they related to management and planning, surveillance, response capacity, capacity building, and collaboration and coordination.1 Chapter 10 of this report presents overarching conclusions and recommendations regarding DoD-GEIS’s AI/PI activities as a whole. These overarching rec- ommendations are excerpted and presented below as well. The boxes at the end of this summary provide, in brief, recommendations regarding the implementation of GEIS at the overseas laboratories, within the infrastruc- 1 The chapters on the two domestic laboratories do not include sections on capacity building.

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 SUMMARY ture of the military health system and at the DoD-GEIS headquarters. By their very nature, recommendations focus on areas of program implemen- tation where there is room for improvement. For a more complete picture of DoD-GEIS AI/PI activities, readers are encouraged to refer to chapters 1 through 10 of this report. SUMMARY CONCLUSION The Committee finds that DoD-GEIS has effectively executed and man- aged the fiscal year 2006 AI/PI supplemental funding, especially given the condensed timeframes that were available for planning and implementa- tion. At DoD-GEIS headquarters as well as at the domestic and overseas laboratories, DoD-GEIS personnel absorbed the large increase in funding into programs aimed to successfully build DoD and host-country labora- tory and human resource capacity, to globally expand information about avian influenza and acute respiratory diseases, to benefit the health of U.S. military personnel, and to strengthen U.S. relations within the global community. SUMMARY OF RECOMMENDATIONS Overarching Recommendations Department of Defense Plans—Executive Agency Before 1997 the DoD influenza surveillance program consisted largely of the surveillance program of the U.S. Air Force (AFIOH, 2006). With the establishment of GEIS in the late 1990s and, more recently, with the $39 million fiscal year 2006 avian influenza supplement, the program has grown to include efforts far beyond those of the historic Air Force program. These efforts include multimillion-dollar programs at the five DoD overseas labs and at the Naval Health Research Center in San Diego. Some of these new players have built enough independent laboratory capacity that they no longer are dependent on the laboratory services of the Air Force Insti- tute for Operational Health (AFIOH). This has effectively moved AFIOH toward the margin. DoD-GEIS headquarters has the potential to provide unified technical and management oversight for DoD’s integrated influenza and respiratory disease programs through a broad base of expertise and proximity to various service commands for the overseas labs, the Food and Drug Administration (FDA), and other federal agencies involved in influ- enza. The 2006 appropriations legislation2 and DoD directives have already 2 H.R. 1815, Sec. 748.

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 REVIEW OF THE DOD-GEIS INFLUENZA PROGRAMS expanded the responsibility of DoD-GEIS headquarters for providing active project coordination and guidance across all DoD-GEIS-funded facilities. A multi-service executive agent has the potential to further improve the DoD influenza program, including maintaining consistency between DoD and national plans, limiting redundancy, and maximizing resources for AI/PI activities. RECOMMENDATION 10-1. The executive agency functions of the DoD influenza and respiratory disease surveillance program should be reexamined in light of the evolution of the program in response to the potential of pandemic influenza. DoD-GEIS headquarters should be formally charged with providing managerial and technical over- sight (quality assurance, safety, etc.) of the multi-service influenza and respiratory disease program and of the revised structure, including a codified chain of accountability. Department of Defense Plans—DoD Communication and Coordination The current level of collaboration among domestic and overseas labo- ratories and between the overseas laboratories and the DoD-GEIS head- quarters is commendable, but it could be improved. Despite efforts to foster inter-laboratory dialogue and information sharing, certain laboratories appeared to be working in isolation and would benefit from additional in- formation sharing and closer collaboration. Most laboratories are relatively new to the influenza field, and the learning curve over the past fiscal year has been steep. RECOMMENDATION 10-2. Structured communication mechanisms should be established between DoD-GEIS headquarters and field sites (domestic and international) as well as among sites to create a func- tional network to enhance coordination of influenza and respiratory disease surveillance activities (epidemiologic, clinical, and laboratory) and to share best practices among all sites. Each laboratory has learned valuable lessons in using the first year of the supplemental AI/PI funds, and, if shared, these lessons would greatly improve the continued program development of AI/PI activities at all DoD- GEIS sites. Increased inter-laboratory dialogue could decrease the likelihood of unintentional overlap of activities between different units and encourage more coordination of activities. RECOMMENDATION 10-3. In Asia, the Naval Medical Research Unit No. 2 (Indonesia) and the Armed Forces Research Institute of

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 SUMMARY Medical Sciences (Thailand) should work together with DoD-GEIS headquarters to clarify the regional roles of each laboratory and to identify critical geographic areas requiring assistance to strengthen AI/PI surveillance programs in conjunction with World Health Orga- nization and member states regional plans. The laboratories should coordinate the assignment of additional activities as well as prepare contingency plans to cover for each other in the event of a crisis (politi- cal, geologic, etc). The same recommendation applies to Africa and the roles of the Naval Medical Research Unit No. 3 (Egypt) and the U.S. Army Medical Research Unit-Kenya. DoD-GEIS headquarters should also work with the Naval Medical Research Center Detachment (Peru) to optimize its regional role in conjunction with Pan American Health Organization and member states regional plans. National Plans DoD-GEIS, through its AI/PI activities at the overseas laboratories and headquarters, has contributed greatly to the development of laboratory and communications infrastructures within partner countries. Beneficial effects can be seen from current DoD-GEIS efforts in 56 countries to assist its public health partners in building capacity through training and support of laboratory and communications infrastructures. In their continued imple- mentation of AI/PI projects, GEIS headquarters and laboratories should consider the need to establish sustainable efforts to provide capacity to the host country even if funding is cut. RECOMMENDATION 10-4. DoD-GEIS funding should be coordi- nated with funding from all sources to assure the likelihood that sur- veillance activities for influenza, other respiratory infections, and other emerging infections will be sustainable in overseas sites for the long term. The Utility of Each Funded Project’s Contribution to a Comprehensive AI/PI Surveillance Program The DoD units were established at various times between 1942 and 1983, each with a fundamental mission of carrying out research relevant to the health of military personnel (DoD-GEIS, 2007). Over the years, the overseas laboratories have expanded their roles in host countries and in the surrounding geographic regions to include training activities and collabora- tive studies of pathogens of importance to the general public, but taking on a surveillance role, such as the AI/PI surveillance program, has been a significant departure from the historical research orientation. Strategic

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 REVIEW OF THE DOD-GEIS INFLUENZA PROGRAMS long-term planning for pandemic influenza-preparedness surveillance and response programs, supported by stable funding, would enable the DoD laboratories to determine the appropriate combination of research and public health surveillance needed to best meet the challenge of pandemic influenza as well as other possible emerging pathogens in their areas of responsibility. RECOMMENDATION 10-5. DoD should issue a directive reaffirm- ing that these traditionally research-oriented laboratories, particularly overseas, have a public health mission with respect to the host country and region; the directive should also provide strategic direction on the balance of military medicine-related research and public health activities. Adequacy of the Program in View of Evolving Epidemiologic Factors— Human Influenza Surveillance Using supplemental funding, DoD laboratories have established or im- proved influenza surveillance in all of their areas of responsibility. Acute re- spiratory diseases, including viral pathogens such as influenza, are of special interest to all militaries. The influenza pandemic of 1918 had a devastating impact upon military operations. One of the benefits of implementing a febrile respiratory infections surveillance and response program through a DoD entity is the strong relationship with the host-country military that DoD-GEIS laboratories can build upon. DoD-GEIS has opportunities to partner with militaries from host countries to improve surveillance capabili- ties and public health infrastructure (Chretien et al., 2007). RECOMMENDATION 10-6. DoD-GEIS programs in the overseas laboratories should explore opportunities to develop or strengthen mili- tary influenza surveillance activities in collaboration with host-country military populations. Adequacy of the Program in View of Evolving Epidemiologic Factors— Animal Influenza Surveillance Most of the DoD-GEIS laboratories that received AI/PI supplemental funds are implementing animal surveillance programs, the majority of which are in wild bird populations. Despite the challenges, wild bird sur- veillance can, if done well, yield useful information on highly pathogenic in- fluenza viruses. DoD-GEIS could provide valuable expertise at the country level in the integration of animal and human surveillance activities. Better

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 SUMMARY coordination is needed at all levels between human surveillance activities and surveillance for influenza viruses in domestic birds (which have more opportunities to transmit influenza viruses to humans than do free flying birds) and in other animals. RECOMMENDATION 10-7. DoD-GEIS headquarters should assess all of the current wild and domestic bird and animal surveillance activi- ties and firmly establish goals, specifically targeting species and situ- ations to fulfill these goals. DoD-GEIS headquarters and laboratories should seek collaborative opportunities to partner with organizations already studying influenza transmission in wild and domestic birds and animals in their areas. Adequacy of the Program in View of Evolving Epidemiologic Factors—Laboratory The AI/PI supplemental funding has been allocated to expanding or en- hancing physical structure and laboratory capacity in all of the DoD-GEIS- supported sites. Many of the sites have used the supplemental funding to increase laboratory throughput, diagnostic capacity, and biosafety levels in order to manage highly pathogenic human and animal influenza A viruses, as well as to hire laboratory personnel. RECOMMENDATION 10-8. To achieve successful influenza virus surveillance, each of the DoD overseas labs should have the capacity to provide reliable, definitive influenza diagnostic results in a safe and timely way. Additionally, the expansion of laboratory capacity in domestic and overseas DoD laboratories has the potential to expand each laboratory’s autonomy and self-sufficiency in terms of virus isolation and identification as well as in terms of decreasing the reliance on off-site and sometimes distant laboratory facilities. RECOMMENDATION 10-9. In keeping with the goal of detecting newly recognized drifted or shifted influenza virus (or other emerging pathogens), the DoD-GEIS AI/PI surveillance system should be de- signed to capture influenza illness that could potentially present with different or unusual symptoms (e.g., conjunctivitis and diarrhea), bring- ing in outside help and support in the case of novel findings.

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0 REVIEW OF THE DOD-GEIS INFLUENZA PROGRAMS Adequacy of the Program in View of Evolving Epidemiologic Factors— Response Capacity Laboratories must be prepared for expanded laboratory-based surveil- lance activities during this critical period between the initial epidemiologic harbingers of an influenza pandemic and eventual global spread. Laborato- ries currently testing a few samples a day, a week, or a month will be called upon to test many more during this period. Without necessarily adding new instruments or expanding in space, these laboratories could gear up to work more shifts if they could deploy trained lab technicians from other parts of the lab and rely upon sufficient supplies of reagents to perform the tests. Making the decision to redeploy technicians and work in shifts would be facilitated if labs have already devised a surge capacity plan, trained the other lab staff, and secured a source of reagents and supplies. Developing a surge capacity plan prior to human-to-human transmission could mean adapting to the increase in the number of samples in a few hours instead of days or weeks. RECOMMENDATION 10-10. The DoD-GEIS influenza surveillance programs in the overseas laboratories should be complementary to the host-country laboratory system and help to increase surge capacity at the host country levels. DoD-GEIS should work with CDC, WHO, the U.S. Department of Agriculture, the Food and Agricultural Organiza- tion, and other entities at the headquarters and in-country levels to develop a plan to handle an increased number of influenza samples from humans or animals. Adequacy of the Program in View of Evolving Epidemiologic Factors— Information Sharing Current DoD-GEIS efforts to communicate influenza virus surveillance and other information within the DoD-GEIS consortium, within the DoD, to public health partners, and to the public are improving but remain in- sufficient. Of particular concern is the need for effective communication and dissemination of results as well as isolates at both the executive-agent and in-country levels. There must be a clear understanding of how and when information is to be communicated from the laboratories to WHO through the host country government and to the U.S. public health system via DoD. There is an established international system organized by WHO for flow of information and of influenza virus isolates from humans and animals. It was unclear in some places how DoD-GEIS laboratories were working with host governments to ensure that information was being fed into the WHO system. The channels of information flow from DoD-GEIS-

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 SUMMARY supported activities and isolate distribution must be clearly understood by the host country and relevant international organizations. RECOMMENDATION 10-11. DoD-GEIS influenza surveillance pro- grams in the overseas laboratories in each host country should have a written understanding among all national and international partners delineating the reporting of influenza virus detections and the appro- priate channels for exchanging isolates and communicating virological results. Such a document should include a clear statement of the labora- tory designated by WHO as the reference laboratory for isolates from the host country. Coordination and Collaboration—International Partners While significant effort has been put into strengthening the coordina- tion of avian and pandemic influenza activities, the overseas laboratories must continue their efforts to work within each country’s national plan, thereby increasing national capacity and avoiding unintentionally working against the national plan. DoD influenza protocols should be executed in such a way that they cause a net strengthening of national and international capacity. As part of these collaborations, the overseas laboratories should also take opportunities to assist the host country in the development and implementation of disease-control guidelines and pandemic preparedness where appropriate and necessary. In some countries, for example, the committee found a lack of evidence at the local hospital level of influenza pandemic preparedness. RECOMMENDATION 10-12. Overseas laboratories, with the stra- tegic guidance of DoD-GEIS headquarters, should coordinate with national and regional influenza pandemic and enzootic response plans to establish the role for each laboratory in country and regionally. Where possible, DoD-GEIS laboratories should engage in host-country influenza coordinating activities, including tabletop response exercises and distribution of testing capacity, in concert with WHO and other international agencies. An important goal will be to strengthen linkages between laboratories and entities with key resources. Coordination and Collaboration—U.S. Government Partners DoD domestic and overseas laboratories have been working to im- prove their collaborations with other relevant U.S. agencies working in the same locations, including other DoD entities, CDC, the U.S. Agency for International Development (USAID), the U.S. Department of Agriculture

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 REVIEW OF THE DOD-GEIS INFLUENZA PROGRAMS (USDA), and the National Aeronautics and Space Administration. The roles of various DoD laboratories in the event of a pandemic are less clear in the host country setting. The responsibilities of each U.S. government agency should be agreed upon by each U.S. agency and outlined by the host country government. The relationship between the CDC and the DoD warrants particular attention. The CDC now has a presence in almost all of the countries where the overseas laboratories are located. In the past the DoD and the CDC have provided each other with backup support and entered into collabora- tive relationships on an as-needed basis. As influenza activities evolve, col- laboration between the CDC and the DoD will be of utmost importance if both are to make efficient and effective use of limited resources. Similarly, strong relationships with other U.S. government partners such as USAID and USDA ensure most efficient use of U.S. funds. RECOMMENDATION 10-13. DoD-GEIS should further strengthen its coordination and collaboration on pandemic influenza and other emerging infectious diseases with all U.S. partners, both domestically and in its overseas operations. These partners include HHS, CDC, the National Institutes of Health, FDA, USDA, the Department of State, the U.S. Agency for International Development, the Department of Homeland Security, and other relevant U.S. government efforts.

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 SUMMARY DEPARTMENT OF DEFENSE UNIT- SPECIFIC RECOMMENDATIONS BOX S-1 Chapter 2 Recommendations DoD-GEIS Headquarters DoD-GEIS headquarters should strengthen its leadership role in the execution of DoD-GEIS influenza activities through strategic planning and distribution of future funding. In order to assure the most effective use of the resources and varied expertise at the different DoD sites, mechanisms should be put into place to have systematic communication among the sites with respect to the various influenza-related projects and activities, including the development of a structured communication mechanism within each laboratory that would interact with headquarters to coor- dinate influenza activities, and the creation of regular opportunities for sharing of best practices facilitated by DoD-GEIS headquarters. DoD-GEIS headquarters should continue to strengthen its in-house influenza expertise as necessary in order to give DoD laboratories and other relevant in- stitutions the assistance needed to implement quality influenza surveillance and response activities. DoD-GEIS headquarters should continue to work with U.S. and multilateral part- ners to ensure coordination among global influenza efforts. BOX S-2 Chapter 3 Recommendations Naval Medical Research Unit No. 2 Indonesia NAMRU-2 should vigorously pursue work with novel findings that have a bearing on surveillance and the spread of virus, e.g., influenza/diarrheal studies. NAMRU-2 should continue to strengthen its relationship with AFRIMS and to coordinate DoD-GEIS influenza activities in the region.

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 REVIEW OF THE DOD-GEIS INFLUENZA PROGRAMS BOX S-3 Chapter 4 Recommendations Armed Forces Research Institute of Medical Sciences Thailand AFRIMS should establish more intensified surveillance for seasonal and novel strains of influenza at sites in temperate and tropical/subtropical parts of Nepal, in locales with commercial poultry production units, and at migratory bird resting sites. AFRIMS should continue to work toward self-sufficiency in its isolation and iden- tification systems in order to release PCR results more quickly to its national partners while taking appropriate steps to ensure laboratory containment and quality assurance. AFRIMS should continue to provide relevant training, including epidemiologi- cal training, to U.S. and local personnel to enable its expansion of laboratory capabilities. AFRIMS should continue to strengthen its relationship with NAMRU-2 in Indone- sia and evaluate its roles in Asia and identify, where possible, critical geographic regions that are not covered by one or the other of these AI/PI programs.

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 SUMMARY BOX S-4 Chapter 5 Recommendations Naval Medical Research Unit 3 Egypt NAMRU-3 should prepare a short-term (2-3 years) strategic plan that identifies its priorities (surveillance/research and implementation/service delivery) in the AI/PI program and indicates NAMRU-3’s role in the pre-pandemic stage. NAMRU-3 should develop and implement a comprehensive information manage- ment system as soon as possible to prepare for the expanded needs that will be present during a potential pandemic and to improve routine information sharing in the EMRO region. NAMRU-3 should assist the host country to develop the capacity to find emerging influenza pathogens beyond H5N1 and should integrate seasonal influenza and AI/PI programs as much as possible. NAMRU-3 should explore opportunities to support the Ministry of Agriculture in increasing surveillance of domestic birds kept in homes and backyards. NAMRU-3 should explore the expansion of laboratory capacity to include multiplex diagnostic equipment for respiratory diseases. NAMRU-3 should develop a plan to expand its laboratory capacity in an early pan- demic phase based on an assessment of how instrumentation and cross-training can be employed to optimize the laboratory and move from moderate throughput to high throughput with minimal staffing changes. In order to assure the quality and sustainability of the regional influenza surveil- lance system, NAMRU-3 should work to establish standards and foundation documents for each of the steps in its laboratory-establishment process as well as to provide technical assistance for a new regional quality-assurance entity including (1) the development of a solid plan of strengthening regional countries’ laboratory capacity with regard to avian influenza and maintaining this capacity through training, quality assurance, and proficiency testing; (2) continued col- laboration with WHO to develop an external quality-assurance system for national central laboratories in the EMRO region; and (3) the use of NAMRU-3’s extensive experience in capacity building (training, supervision, and mentoring) to develop structured (yet adaptable to each context) laboratory assessment checklists, train- ing guidelines, and monitoring tools. NAMRU-3 should continue to serve in a technical advisory role to the Egyptian Ministry of Health and carry out medical diplomacy by developing informal re- lationships with strategic partners while maintaining its role as an independent research agency with primary allegiances to the U.S. Navy. NAMRU-3 should develop country- and region-specific 3-year strategies that focus on host sustainability as well as on the development, expansion, and maintenance of an influenza early warning system.

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 REVIEW OF THE DOD-GEIS INFLUENZA PROGRAMS BOX S-5 Chapter 6 Recommendations U.S. Army Medical Research Unit Kenya The total number of adults and children each day who present to the clinics with acute respiratory illness for specimen collection under the current protocol should be logged, even though only five young children and five older children or adults will be sampled. By recording the total number of such patients and having the proportion of the five-patient samples that are positive, an estimate can be made of the burden of disease leading persons to seek attention at the sentinel health care facilities. Without collecting the number of syndromic eligible cases, burden cannot be estimated. To foster collaboration and illustrate the value of the surveillance activities to stake- holders, USAMRU-K should consider supporting a weekly or biweekly summary of the number of cases of acute respiratory illness and of influenza virus isolations, by age group, to be sent to all the surveillance sites to provide feedback to the clinicians involved in the surveillance system. USAMRU-K should draw on the experience of other DoD OCONUS laboratories in animal influenza surveillance. For example, the USAMRU-K veterinarian could be sent to NAMRU-2 in Indonesia to gain experience in performing tracheal cultures on trapped wild birds. USAMRU-K should consider the expansion of laboratory capacity to include multi- tasking diagnostic equipment for respiratory diseases. Based on the close proximity of laboratory space at KEMRI and the potential overlap in influenza activities, USAMRU-K should increase its efforts to facilitate communications between principal investigators at the USAMRU-K/NIC and CDC and the staff of the two laboratories, including joint seminars, data sharing, and cross training on equipment and BSL-3 principles and practices. As part of this communication, USAMRU-K and the NIC should develop a written understanding among all partners concerning WHO expectations about the reporting of influenza virus isolations and appropriate communication channels. In order to maximize the AI/PI funds in Uganda, USAMRU-K should explore all options, including UVRI, in developing influenza virus diagnostic capacity within Uganda to ensure optimal use of national and external resources, promote col- laboration among all sectors, and maximize potential for sustainability.

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 SUMMARY BOX S-6 Chapter 7 Recommendations Naval Medical Research Center Detachment Peru NMRCD should continue to work to increase information sharing with both the DoD-GEIS headquarters staff and staff at other overseas laboratories. NMRCD should support additional tabletop simulation exercises in which NMRCD has the potential to identify areas of the Peruvian plan that need strengthening. NMRCD should consider expanding its surveillance activities to include popula- tions at high risk of contracting avian influenza, including poultry farm workers, live bird market workers, and military training camps. In conjunction with improved sharing of facilities for testing avian viruses at SENASA, NMRCD should develop mechanisms to enable testing of avian and human influenza isolates in separate laboratory facilities and plan to obtain resources to expand its BSL-3 laboratory, including showering-out facilities. NMRCD should continue to support in-house and webcast training in epidemio- logical surveillance and laboratory methods. Outbreak response should receive additional emphasis, including Peru’s Field Epidemiology Training Program. A close working relationship, the sharing of facilities, the training of technicians, the sharing of specimens, support for maintenance, support to meet cold-chain needs, and other forms of integration with the INS and SENASA laboratories should continue to be cultivated by NMRCD. A common surveillance database with both NMRCD and INS results would be desirable. BOX S-7 Chapter 8 Recommendations Naval Health Research Center San Diego NHRC should investigate factors contributing to the ability or inability of the eight military training sites to meet maximum FRI surveillance targets as well as continue to explore methods to validate the reliability of virus-effectiveness data, which are available from no other populations on a consistent basis. The services should explore interpretation of the syndromic surveillance mandate to include laboratory diagnostic testing of clinically ill subjects in order to facili- tate crucial febrile respiratory illness and other infectious disease surveillance in military populations. The NHRC team should look into other virus culture methods to speed isolation.

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 REVIEW OF THE DOD-GEIS INFLUENZA PROGRAMS BOX S-8 Chapter 9 Recommendations Air Force Institute for Operational Health San Antonio AFIOH’s influenza program should employ a strong doctoral-level molecular bi- ologist with demonstrated technical and leadership skills. These should include a strong background in laboratory quality control methods. The program staff should be well-versed in the data analytic approaches desired by the FDA influenza vaccine committee. The laboratory should regularly obtain technical guidance from appropriate sources (e.g., CDC, FDA, academia, and GEIS headquarters) to ensure that it is using state-of-the-art methods and is targeting appropriate specimen sources. In order to minimize potential for contamination in the molecular biology section and to improve the data generated by this section, AFIOH should seek expertise in molecular biology techniques and their implementation in a diagnostic labora- tory setting. AFIOH should consider the expansion of its laboratory capacity to include multi- tasking diagnostic equipment for respiratory diseases. AFIOH should create a sustainable and useful archive of the original patient sam- ple and virus isolate materials in this laboratory to ensure this national resource can be used to fulfill the missions of the DoD-GEIS AI/PI program. AFIOH should collaborate with both the National Institutes of Health and Los Alamos National Laboratory, and provide sequencing data and samples when appropriate. AFIOH should seek out cutting-edge academic collaborators in order to expand the methodologies available to identify agents responsible for mixed infections, which could possibly result in the identification of new agents responsible for respiratory infections. AFIOH should continue to conduct periodic training exercises and dry runs in order to further develop and test the surge plan. In conjunction with DoD-GEIS headquarters, AFIOH should examine the current activities at AFIOH, and strategies for strengthening the AFIOH operations should be identified and supported.

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