Review of the DoD-GEIS Influenza Programs: Strengthening Global Surveillance and Response (2008)

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8 Naval Health Research Center San Diego Avian and Pandemic Influenza Activities T he Naval Respiratory Disease Laboratory (NRDL), established in 1996 to perform epidemiological studies and surveillance of re- spiratory diseases affecting U.S. military personnel, is one of six departments of the Naval Health Research Center (NHRC) in San Diego, California (NHRC, 2006b). NHRC was instrumental in demonstrating increased adenoviral morbidity among basic trainees after loss of vaccine in the late 1990s, and it remains involved in the restoration of the adeno- virus vaccine program by supporting current clinical trials at basic training centers (NHRC, 2006b). NHRC has continually expanded its scope of studies and diagnostics during the past decade, with an increased emphasis on influenza surveillance and diagnostics; molecular capabilities in par- ticular have been greatly enhanced. NHRC has become a leading reference laboratory for respiratory disease within the Department of Defense (DoD) (NHRC, 2006b). During fiscal year 2006, NHRC doubled laboratory test- ing capacity for influenza, began construction of a biosafety level 3 en- hanced (BSL-3E) laboratory, and conducted a variety of projects sponsored by the Department of Defense Global Emerging Infections Surveillance and Response System (DoD-GEIS) that contributed to force health protection. DoD-GEIS AI supplemental funding increased surge capacity in 2006- 2007. Five new staff members were added, sample target numbers for each surveillance site were doubled, the frequency of shipments to the NRDL at NHRC was increased, and laboratory equipment was updated or added. The result was more robust surveillance and faster turnaround. More than 167 

168 REVIEW OF THE DOD-GEIS INFLUENZA PROGRAMS 2,000 samples were collected and tested during the influenza season of October 2006 through February 2007. A site visit team of the Institute of Medicine (IOM) Committee for the Assessment of DoD-GEIS Influenza Surveillance and Response Programs visited NHRC on March 26-27, 2007. A list of the people met and inter- viewed and the itinerary followed can be found at the end of this chapter. MANAGEMENT AND PLANNING Administrative support for NRDL is provided by the DoD Center for Deployment Health Research at the time of the IOM review. However, in August of 2007, the Respiratory Disease Laboratory became an indepen- dent department at HHRC, Department of Respiratory Diseases Research. DoD-GEIS funding makes up more than 90 percent of the NRDL budget and is used for special projects and capital improvements. Staffing NRDL staff is composed of both Navy personnel and civilians. The GEIS-related projects at NRDL are managed by the laboratory director, co- director, and several study coordinators, who receive input from the project staff, including two Ph.D. consultants, a consulting pathologist, epidemiol- ogists, a statistician, 16 full-time technicians, 7 off-site study coordinators, and 5 staff members dedicated to quality assurance and control. The IOM committee commends the NRDL leadership for devoting both time and personnel to important aspects of diagnostic testing, that is, exploring new and advanced diagnostic platforms and incoming technolo- gies, maintaining a high level of quality control, and being open to new and improved methodologies that promote faster and more accurate test results. Technology and Information Management The laboratory information-management system used by the NHRC is an Access-based program designed specifically for the laboratory. The system operates well for the laboratory. Efforts are underway to find a bar-coding system that is compatible with and can be incorporated into the existing systems.   Prior to the committee’s visit to NHRC, the laboratory staff provided the committee with detailed background information on NHRC and the pandemic/avian influenza activities it was supporting. These materials were used in the writing of this chapter and are available from the IOM in the Public Access File. 

NAVAL HEALTH RESEARCH CENTER SAN DIEGO 169 The sequence analysis conducted in this laboratory is of the highest quality. The team at NHRC seems able to utilize the data generated for evaluations of vaccine efficacy, recognizing emerging novel viruses, and evaluations in different areas. Conclusions The committee found the NHRC staff proficient at the generation and analysis of high-quality virus and sequence data. They are timely in pro- ducing their findings as well as in reporting them back to their clients and collaborating laboratories. The NHRC data would be a tremendous asset to modeling efforts. SURVEILLANCE The missions of the NHRC are to conduct epidemiological studies to investigate the health experience of military personnel and their fami- lies and to develop and evaluate appropriate health strategies. The stated objectives of NRDL are to help enhance febrile respiratory and influenza surveillance, advance influenza diagnostics, and improve influenza field diagnostics as well as to assist with the coordination of overseas response capabilities, with the early detection of and response to respiratory disease, with enhanced communication within DoD, and with maintaining the health of U.S. military forces worldwide (NHRC, 2006a). The NRDL initiated febrile respiratory illness (FRI) surveillance for adenovirus in five basic-training sites in 1996 and was accredited by the College of American Pathologists (CAP) in 1997. In 1998 FRI surveillance increased to the present eight sites and expanded to include other viral pathogens: influenza A and B, respiratory syncytial virus, and parainfluenza types 1, 2, and 3 (Faix, 2006). Additional ongoing FRI surveillance includes personnel on board 16 Navy ships deployed worldwide and also civilian populations near the border between the United States and Mexico (Faix, 2006). Each of the three populations presents distinct FRI risks (see Figure 8-1 for a map of NRDL FRI surveillance sites). Other projects among military trainees include the etiology and epi- demiology of pneumonia, characterization of clinical Streptococcus pyo- genes, and surveillance for Bordetella pertussis. Surveillance for antibiotic resistance in invasive Streptococcus pneumonia is conducted among DoD beneficiaries. NRDL is currently involved in a collaborative phase 3 study to evaluate the safety, efficacy, and immunogenicity of the vaccines for adenovirus 4 and adenovirus 7. NRDL should consider expanding the cur- rent FRI case definition in certain situations to capture influenza illness that 

170 REVIEW OF THE DOD-GEIS INFLUENZA PROGRAMS 7th Fleet (Japan) NSTC Great Lakes CGTC Cape May Fort Leonard Wood 2nd Fleet MC RD San Diego Fort Jackson (Norf olk) Calexico, CA CDC San Ysidro, CA 3rd Fleet Fort Benning MCRD Parris Island (San Diego) Lackland AFB AFIOH Influenza Diagnostic Collaborators: Febrile Respiratory Illness (FRI) Surveillance Centers for Disease Control and Prevention (CDC) FRI Surveillance in a U.S.-Mexico Border Population Air Fo rce Institute for Operational Shipboard Surveillance for FRI Health (AFIOH) FIGURE 8-1 NHRC influenza surveillance sites and activities, 2006-2007. SOURCE: Faix, 2006. could present with different or unusual symptoms, such as conjunctivitis or diarrhea. Figure 8-1 FRI Surveillance Among Military Trainees Surveillance is conducted at eight of the ten DoD U.S. training sites, representing all service branches: the Army (Ft. Jackson, Ft. Leonard Wood, and Ft. Benning), the Navy (Naval Training Center Great Lakes), the Marines (Marine Corps Recruit Depot San Diego and Marine Corps Re- cruit Depot Parris Island), the Air Force (Lackland Air Force Base), and the Coast Guard (Training Center Cape May). The two training sites not included are Ft. Knox and Ft. Sill, the two smallest. Historically, military training centers have been associated with seasonal respiratory outbreaks during the first few weeks of training and have been ideal populations for FRI and influenza surveillance (Faix, 2006). The population is well-defined, historic data are available, FRI cases are known and accessible, and influ- enza vaccination is universal. Surveillance is population-based. FRI incidence is pathogen-specific. NRDL hires, trains, and supervises the research assistant responsible for surveillance at each site. Throat swab samples are collected from trainees 

NAVAL HEALTH RESEARCH CENTER SAN DIEGO 171 with an oral temperature greater than 38°C and a cough or sore throat, or from any case of provider-diagnosed pneumonia. Case data are recorded. The research assistant at each site ships frozen samples to NRDL at pre- arranged frequencies or weekly during influenza season. As in all NRDL surveillance activities, samples are first tested in the molecular biology laboratory before being passed to cell culture. Additional specimens have increased confidence in the estimates of how effective influenza vaccine has been in preventing laboratory-confirmed in- fluenza (Russell et al., 2005). This very imaginative use of the FRI provides a valuable rapid assessment of vaccine effectiveness—and thus the degree of correlation of the vaccine in use and the prevalent influenza strain early in the influenza season. The NRDL found that the overall vaccine effectiveness in 2006-2007 for the study population was 90 percent. FRI surveillance data from the eight military training sites are a re- source representing each section of the country and each branch of the military. Standard surveillance methodologies, on-site NRDL staff, and sample testing in a single laboratory (NRDL) make it possible to compare disease burdens at each site. Evaluation of factors contributing to site- specific FRI rates may lead to DoD-wide improvements in the trainee health environment. Conclusions The site-specific measurements of the effectiveness of influenza vac- cine generated each season by NRDL are a unique national resource with important implications for annual national and international vaccine se- lection. Annual virus-effectiveness comparisons of live and inactivated vaccines could provide valuable information on the level of protection provided by each in the event of a major antigenic drift. In addition, fac- tors contributing to trends or changes in site-specific FRI rates may be of particular importance in developing strategies for reducing or diminishing the frequency of cases of FRI among trainees. Annual site-specific influenza virus-effectiveness data (differentiated by live and inactivated) made avail- able by NRDL could also make a larger DoD contribution at the annual February meeting of the Food and Drug Administration influenza vaccine strain selection subcommittee. RECOMMENDATION 8-1. NRDL should investigate factors con- tributing 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 vaccine-effectiveness data, which are available from no other populations on a consistent basis. 

172 REVIEW OF THE DOD-GEIS INFLUENZA PROGRAMS Shipboard FRI Surveillance Shipboard surveillance was initiated in 2002. Navy personnel make port calls throughout the world in places where influenza or other respira- tory pathogens may emerge. Exposures to respiratory diseases at ports of call greatly enhance worldwide surveillance and could provide early docu- mentation of emerging pathogens. The shipboard populations, whether in port or deployed, represent well-immunized populations (greater than 90 percent immunized for influenza). Influenza outbreaks among these sen- tinel populations would be indicative of an influenza strain or strains for which the current vaccine provides reduced or no protection. Representa- tive strains may be made available to U.S. and World Health Organization laboratories more quickly through these populations than through indi- vidual countries. FRI shipboard surveillance represents a population of approximately 50,000 personnel aboard ships of the Third Fleet (seven ships) in San Diego, the Second Fleet (six ships) based in Virginia, and the Seventh Fleet (three ships) based in Japan (Faix, 2006). The basic concept is that FRI throat samples are collected and frozen in liquid nitrogen or –70°C freezers and shipped to NRDL for laboratory diagnosis upon return to port. If more rapid testing is warranted, arrangements are made to transport samples to NRDL as soon as possible. In addition to influenza surveillance, the find- ings would help define the relative importance of pathogens responsible for FRI, describe shipboard transmission, lead to appropriate preventive measures, and help maintain ship readiness. The fleet has requested that NRDL assist in expanding shipboard di- agnostic capability, both with polymerase chain reaction (PCR) technology and new, validated rapid tests, particularly for avian influenza. Achieving this goal presents numerous challenges, including the competency levels of technical staff on board ship, competition from other duties, the need to train staff, staff turnover, available laboratory space, and, especially, access to simple and reliable technology. NRDL continues to evaluate promising technology, with considerable attention given to quality assurance. The Centers for Disease Control and Prevention (CDC) Laboratory Response Network (LRN) H5 test is a possible candidate. Complicating shipboard surveillance—and to a lesser extent recruit surveillance—is the potential interpretation that such programs represent research and thus require informed consent. As the number of fleet com- mands, ship commanders, and institutional review boards increases, com- pleting the protocol review and informed-consent requirements become increasingly more time consuming. Longer and more complicated consent forms are a disincentive to both staff and patient for sample collection and enrollment in FRI surveillance. 

NAVAL HEALTH RESEARCH CENTER SAN DIEGO 173 Conclusions Shipboard FRI surveillance is a valuable augmentation to global influ- enza surveillance efforts. The IOM committee commends NRDL staff on their commitment and their caution in responding to the requests of the command to introduce rapid-testing capability on ship for avian influenza. NRDL’s heavy investment into quality control for the program is consistent with the recognized challenges of operating complex equipment and inter- preting results in the shipboard environment. RECOMMENDATION 8-2. The services should explore interpretation of the syndromic surveillance mandate to include laboratory diagnos- tic testing of clinically ill subjects in order to facilitate crucial febrile respiratory illness and other infectious disease surveillance in military populations. California-Mexico Border FRI Surveillance Surveillance among the cross-border civilian population began in 2004 as a collaborative effort with the CDC, the San Ysidro Health Center (San Diego Co.), and Clinicas de Salud del Pueblo, Calexico (Imperial Co.) (Faix, 2006). The project is funded through CDC. The clinic population, many of whom are largely unimmunized against influenza, includes people of different age groups with a variety of respiratory pathogens. NRDL tests all samples for influenza A and adenoviruses with PCR and tests for all other agents with viral culture and bacteriology techniques. These samples provide a valuable resource for evaluating promising rapid-test systems. Simultaneous evaluation of the commercially available point-of-collection influenza test in this population proved that the performance of that test was suboptimal (Faix, 2006). Conclusions NRDL’s collaboration in this border surveillance program is valuable for NRDL and for the region. Its participation enhances the collaborative relationship with CDC and local agencies, makes possible surveillance in a binational population that may have interaction with the large number of military in the area, and provides a high yield of beneficial samples at low cost. 

174 REVIEW OF THE DOD-GEIS INFLUENZA PROGRAMS Expanded Surveillance Capacity NRDL is collaborating with the U.S. Naval Hospital in Yokosuka, Japan, to establish a Pacific Rim surveillance hub (NHRC, 2006a). The rationale for establishing this hub stems from the number of shipboard influenza clusters that have occurred after port stops in the Pacific Rim area, the presence of avian influenza in the area, and the absence of capac- ity in the region for sample collection, testing, and shipment. Permission to proceed has been granted by the Seventh Fleet command, the hospital, and the hospital laboratory director. Office and laboratory space has been made available in the hospital, a LightCycler has been purchased, and a research assistant has been hired to organize the activity. A search for a qualified study coordinator is underway. NRDL is also assisting the Air Force Insti- tute for Operational Health (AFIOH) in increasing sample collection and processing at its five base sentinel sites in Japan and is interfacing with Seventh Fleet preventive medicine personnel to provide FRI surveillance for upcoming deployment and exercises. Conclusions Establishment of the Pacific Rim surveillance hub is a logical exten- sion of current NRDL surveillance activities. NRDL personnel on site will greatly strengthen surveillance in the area. LABORATORY The NRDL currently has a fully operational biosafety level 2 (BSL-2) influenza diagnostic laboratory, and a BSL-3E laboratory is under construc- tion (NHRC, 2006a). Virus detection, identification, and sub-typing are performed in the molecular biology laboratory (PCR, subtyping, and gene sequencing) and followed by culture of positive samples and selected nega- tives in the virology division (culture, identification via direct or indirect immunofluorescence, and hemagglutination inhibition serotyping) of the microbiology laboratory. The supplemental funding for avian influenza/pandemic influenza (AI/ PI) has been allocated to expanding or enhancing physical structure and laboratory capacity in several important ways. First, it has been used to in- crease the laboratory surge capacity, allowing for the collection of a greater number of specimens than was previously possible. This has been accom- plished through the use of reverse transcriptase PCR (RT-PCR) screening of samples in a high throughput format. Currently, these samples are handled in the BSL-2 facilities. Second, a BSL-3E facility is under construction that will, when it is 

NAVAL HEALTH RESEARCH CENTER SAN DIEGO 175 completed, enhance the capabilities of the DoD in the Pacific Rim region to safely manage human pathogens of high consequence. BSL-3E facilities staffed and equipped to work with influenza A viruses of high consequence are in short supply in California. Additionally, in the Pacific Rim region, there are no other existing DoD BSL-3E facilities. The BSL-3E facility will add new challenges that may not yet have been fully anticipated. The regu- latory requirements for containment facilities are shifting and will continue to change in the future. Funding for the annual maintenance and required upgrades of the BSL-3E facility is critical to maintain its functional use, and a functioning facility is a critical need for the DoD-GEIS program. Third, personnel who add substantial expertise to the laboratory have been hired. These individuals have been able to explore cutting-edge bio- technology that can increase capacity and improve data quality and the rapid identification of the viruses detected. Fourth, laboratories have been added in the surveillance network, in- cluding shipboard efforts and one overseas hospital (Yokosuka). Finally, additional freezers have been purchased so that samples can be archived appropriately. With a median time of seven days, cell culture methods for influenza A and B viruses seem to be overly time-consuming. The NHRC team has sought to overcome this time lag by directly sequencing positive samples, but challenges remain. Quality control is a significant priority at NHRC. There are a number of checks that have been instituted internally to monitor the validity of find- ings, in addition to those checks prescribed by CAP and CLIP. Additionally, a full-time position has been added to oversee issues of quality assurance. Conclusions The NHRC team has thought through the testing and reporting of each sample that is received. Although the completeness of these planning efforts has led to the laboratories, staff, and management being highly effective in achieving the goals of the current surveillance efforts as well as in anticipat- ing future needs, the time-consuming cell culture methods for influenza A and B viruses are a challenge that can and should be overcome. RESPONSE CAPACITY In terms of the three pillars of the National Strategy for Pandemic Influenza—preparedness and communication, surveillance and detection, and response and containment—NRDL interprets its mandate as the sec- ond. Supplemental 2006 funding greatly enhanced capacity for influenza surveillance and detection. Laboratory surge capacity has been increased, 

176 REVIEW OF THE DOD-GEIS INFLUENZA PROGRAMS high-capacity cutting-edge diagnostics have been introduced, the Pacific Rim surveillance hub has been established, shipboard surveillance has been expanded, and a BSL-3E laboratory is under construction. Rigorous valida- tion tests are under way on multiple novel procedures to identify influenza strains with high strain-specific sensitivity using original specimens. Outbreak Response NHRC is well positioned to assist in the response to infectious disease outbreaks in the San Diego area as well as in relevant military personnel populations. The following are a few outbreaks in which NHRC contrib- uted to the response and investigation: • NHRC identified an early season cluster of influenza A at Marine Corps Recruit Depot (MCRD) San Diego in August 2006. Laboratory staff quickly determined that an H1N1 strain was responsible and that none of the cases had been vaccinated. Information was immediately shared with MCRD San Diego, GEIS headquarters, CDC, and local public heath of- ficials. FRI surveillance was intensified at this site for several weeks until it was determined that transmission had ceased. Training operations at the base were allowed to continue uninterrupted, in large part due to the epidemiological data provided by NHRC. • Four separate outbreaks of Group A streptococcal illness among basic trainees occurred during fiscal year 2006, and NHRC provided labo- ratory and epidemiological support for all. In all four outbreaks, emm type 5 Streptococcus pyogenes was the predominant subtype isolated. • An outbreak of severe pneumonia that required hospitalization of some patients occurred among Navy SEAL trainees in March 2006. NHRC was notified and worked with the Navy Environmental and Preven- tive Medicine Unit No. 5 to obtain and test specimens from the outbreak; Streptococcus pneumoniae (type 31) was identified as the etiologic agent, and appropriate treatment and prophylaxis were initiated. • NHRC also provided laboratory support for 11 fatal or severe re- spiratory illness cases during fiscal year 2006. Most of these were referred through the mortality surveillance program at the Armed Forces Institute of Pathology (AFIP). Key findings included determination that emm type 5 Streptococcus pyogenes was isolated in two fatal cases among active-duty service members in Texas and that Streptococcus pneumoniae was associ- ated with another fatal case. • NHRC provided weekly updates that included influenza and FRI rate data to surveillance partners throughout the year. • NHRC provided rapid laboratory confirmation of adenoviral eti- ology during FRI rate spikes that were identified by the FRI surveillance 

NAVAL HEALTH RESEARCH CENTER SAN DIEGO 177 program. These spikes occurred at six of eight camps under surveillance during fiscal year 2006. Surge Capacity NRDL performs routine molecular screening on approximately 168 samples per week. Samples are extracted in a 96-well format (two plates) that includes a total of 12 internally placed positive and negative controls per plate (NHRC, 2007) (see Table 8-1). NRDL would initially be able to alter its current testing algorithm to test for only influenza A first and then H5 if positive. This would allow the screening of an additional 504 samples per week, for a total of 672 samples per week (NHRC, 2007). NRDL does stock supplies, but only sufficient quantities for a defined “high throughput” period of operation (see below). Further refinement of the screening process, targeting only the gene required to rule in or out the strain of interest, would allow NRDL to more than double the altered algorithm and total throughput to approximately 1,548 samples. This would require reassignment of some staff to focus on these efforts (NHRC, 2007). In an emergency situation, NRDL could transition into a 24-hour oper- ation, doubling again the number of samples processed. The best estimates of NRDL short-term surge capability would result in a throughput of 3,528 samples per week using the lab’s standard molecular capabilities (NHRC, 2007). Again, this would require reassigning staff to focus only on these activities. The limiting factor would not be the laboratory or equipment, but rather—eventually—reagents. In order to help with a surge in sample processing and rapid identifica- tion, NRDL has advanced diagnostic compatibility that would help identify type and strain of circulating influenzas. This technology would be able to process 176 samples in a 24-hour period (NHRC, 2007). Validation efforts for the College of American Pathology certification are near completion. Although the advanced diagnostic equipment may not be able to test all TABLE 8-1  Summary of Surge Capability at the NRDL, NHRC Condition PCR T-5000 Total Routine operation 168/week 168/week 336/week Altered algorithm — 672/week 440/week 1,112/week influenza A and H5 first Target only specific gene 1,548/week 440/week 1,988/week 24-hour operations 3,528/week 1,232/week 4,760/week SOURCE: NHRC, 2007. 

178 REVIEW OF THE DOD-GEIS INFLUENZA PROGRAMS positive specimens during a pandemic, testing a systematic sample of posi- tives would provide much additional information about circulating strains in much less time than traditional methods. A potential problem with high-throughput processing is the rate at which reagents and consumables are used. In the event that pandemic influenza transmission is thought to be occurring, it is likely that routine shipping sources would slow. In preparation for any 24-hour processing scenario, NRDL is now preparing stockpiles of consumables and reagents that would allow the laboratory to maintain a 24-hour operation for one month in the event of a national emergency (NHRC, 2007). NRDL will rotate reagents with new orders when received, thus maintaining the surge capability indefinitely and without additional cost or risk of wasted reagents. Conclusions NRDL is a highly focused operation with well-qualified staff dedicated to its mission. This laboratory is poised to play a valuable leadership role in identifying and responding to a potential influenza pandemic. COLLABORATION AND COORDINATION NHRC has established a number of strategically advantageous relation- ships with U.S. government agencies (including those within the DoD) as well as academic and private organizations. NRDL works closely with the CDC in sharing influenza isolates and with Lawrence Livermore National Laboratory and multiple manufacturers in the evaluation of rapid diag- nostic tests for installation and field (shipboard) applications. NRDL and AFIOH collaborated on quality-control testing and in exercises designed to facilitate testing backup in the event one or the other laboratory was overwhelmed with influenza samples. Ties are close with training sites, fleet commands, and each of the overseas laboratories. By design there are no direct collaborations with foreign governments or international organiza- tions; NHRC relies instead on the naval medical research units and fleet bases to provide those channels. Contacts with the U.S. Department of Agriculture are through certification for importation of animal isolates, and contacts with CDC are through importation of human samples. Addi- tionally, NRDL collaborates with CDC and local health authorities on the cross-border project. Collaborations should be explored with local health departments and relevant university departments as well as the local veteri- nary community to promote and increase communication and information sharing within the region. 

NAVAL HEALTH RESEARCH CENTER SAN DIEGO 179 References Faix, D. 2006. Febrile respiratory illness surveillance and research at Naval Health Research Center: Evaluating unique populations. PowerPoint presentation at first meeting of the IOM Committee for the Assessment of DoD-GEIS, December 19, Washington, DC. NHRC (Naval Health Research Center). 2006a. NHRC project titles and descriptions. (unpublished). NHRC. 2006b. FY06 annual summary report (Unpublished). NHRC. 2007. Laboratory surge capacity. (unpublished). Russell K. L., Ryan M. A. , Hawksworth A., Freed N. E., Irvine M., Daum L.T. 2005. Ef- fectiveness of the 2003-2004 influenza vaccine among U.S. military basic trainees: A year of suboptimal match between vaccine and circulating strain. Vaccine Mar 14; 23(16):1981-1985. 

180 REVIEW OF THE DOD-GEIS INFLUENZA PROGRAMS List of Contacts DoD-GEIS NHRC Assessment: San Diego, California Lt. Cmdr. Dennis Faix, Naval Health Research Center, San Diego, California Julie Fuller, Naval Health Research Center, San Diego, California Tony Hawksworth, Naval Health Research Center, San Diego, California Marina Irvine, Naval Health Research Center, San Diego, California Dr. Pete Kammerer, Naval Health Research Center, San Diego, California Dr. David Metzgar, Naval Health Research Center, San Diego, California Dr. Chris Myers, Naval Health Research Center, San Diego, California Miguel Angel Osuna, Naval Health Research Center, San Diego, California Cmdr. Kevin Russell, Naval Health Research Center, San Diego, California Margaret Ryan, Naval Health Research Center, San Diego, California Schedule of Events DoD-GEIS NHRC Assessment San Diego, California Participants: Dr. Carol J. Cardona Dr. Walter R. Dowdle Kimberly Weingarten March 26-27, 2007 Monday, March 26, 2007 0800-0830 Breakfast 0830-0840 Welcome remarks 0840-0900 Introduction to Naval Respiratory Disease Laboratory activities Cmdr. Kevin Russell 0900-0940 Discussion about febrile respiratory illness surveillance in U.S. military basic training centers Tony Hawksworth 0940-1010 Discussion about global naval shipboard surveillance Cmdr. Kevin Russell 1040-1040 Discussion about Pacific Rim surveillance hub Dr. Peter Kammerer 1100-1100 Break 

NAVAL HEALTH RESEARCH CENTER SAN DIEGO 181 1100-1130 Discussion about surveillance in the United States- Mexico border region Tony Hawksworth 1200-1200 Discussion on DoD support Lt. Cmdr. Dennis Faix 1200-1330 Lunch 1330-1430 Tour of U.S. Navy ship 1500-1600 Tour of branch medical clinic at Marine Corps Recruit Depot Tuesday, March 27, 2007 0800-0830 Breakfast 0830-0850 Welcome remarks and introduction to MRDL research projects Cmdr. Kevin Russell 0850-0920 Discussion about laboratory testing Miguel Angel Osuna 0920-1000 Discussion about the sequencing of 100 percent of influenza isolates Dr. Chris Myers 1000-1020 Break 1020-1100 Discussion about the influenza differentiation between wild type and vaccine (FluMist©) Dr. Dave Metzgar 1100-1130 Evaluations of advanced diagnostic platforms Cmdr. Kevin Russell 1130-1200 Discussion about expanding capabilities through technology-transfer training or an advanced diagnostic laboratory Lt. Cmdr. Dennis Faix 1200-1230 Discussion about BSL-3E laboratory Julie Fuller 1330-1330 Lunch 1500-1500 Tour of NRDL facilities 1600-1600 Final discussion, farewells 1600- Departure