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

Chapter: 7 Naval Medical Research Center Detachment Peru Avian and Pandemic Influenza Activities

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Suggested Citation:"7 Naval Medical Research Center Detachment Peru Avian and Pandemic Influenza Activities." Institute of Medicine. 2008. Review of the DoD-GEIS Influenza Programs: Strengthening Global Surveillance and Response. Washington, DC: The National Academies Press. doi: 10.17226/11974.
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Suggested Citation:"7 Naval Medical Research Center Detachment Peru Avian and Pandemic Influenza Activities." Institute of Medicine. 2008. Review of the DoD-GEIS Influenza Programs: Strengthening Global Surveillance and Response. Washington, DC: The National Academies Press. doi: 10.17226/11974.
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Suggested Citation:"7 Naval Medical Research Center Detachment Peru Avian and Pandemic Influenza Activities." Institute of Medicine. 2008. Review of the DoD-GEIS Influenza Programs: Strengthening Global Surveillance and Response. Washington, DC: The National Academies Press. doi: 10.17226/11974.
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Suggested Citation:"7 Naval Medical Research Center Detachment Peru Avian and Pandemic Influenza Activities." Institute of Medicine. 2008. Review of the DoD-GEIS Influenza Programs: Strengthening Global Surveillance and Response. Washington, DC: The National Academies Press. doi: 10.17226/11974.
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Suggested Citation:"7 Naval Medical Research Center Detachment Peru Avian and Pandemic Influenza Activities." Institute of Medicine. 2008. Review of the DoD-GEIS Influenza Programs: Strengthening Global Surveillance and Response. Washington, DC: The National Academies Press. doi: 10.17226/11974.
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Suggested Citation:"7 Naval Medical Research Center Detachment Peru Avian and Pandemic Influenza Activities." Institute of Medicine. 2008. Review of the DoD-GEIS Influenza Programs: Strengthening Global Surveillance and Response. Washington, DC: The National Academies Press. doi: 10.17226/11974.
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Suggested Citation:"7 Naval Medical Research Center Detachment Peru Avian and Pandemic Influenza Activities." Institute of Medicine. 2008. Review of the DoD-GEIS Influenza Programs: Strengthening Global Surveillance and Response. Washington, DC: The National Academies Press. doi: 10.17226/11974.
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Suggested Citation:"7 Naval Medical Research Center Detachment Peru Avian and Pandemic Influenza Activities." Institute of Medicine. 2008. Review of the DoD-GEIS Influenza Programs: Strengthening Global Surveillance and Response. Washington, DC: The National Academies Press. doi: 10.17226/11974.
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Suggested Citation:"7 Naval Medical Research Center Detachment Peru Avian and Pandemic Influenza Activities." Institute of Medicine. 2008. Review of the DoD-GEIS Influenza Programs: Strengthening Global Surveillance and Response. Washington, DC: The National Academies Press. doi: 10.17226/11974.
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Suggested Citation:"7 Naval Medical Research Center Detachment Peru Avian and Pandemic Influenza Activities." Institute of Medicine. 2008. Review of the DoD-GEIS Influenza Programs: Strengthening Global Surveillance and Response. Washington, DC: The National Academies Press. doi: 10.17226/11974.
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Suggested Citation:"7 Naval Medical Research Center Detachment Peru Avian and Pandemic Influenza Activities." Institute of Medicine. 2008. Review of the DoD-GEIS Influenza Programs: Strengthening Global Surveillance and Response. Washington, DC: The National Academies Press. doi: 10.17226/11974.
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Suggested Citation:"7 Naval Medical Research Center Detachment Peru Avian and Pandemic Influenza Activities." Institute of Medicine. 2008. Review of the DoD-GEIS Influenza Programs: Strengthening Global Surveillance and Response. Washington, DC: The National Academies Press. doi: 10.17226/11974.
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Suggested Citation:"7 Naval Medical Research Center Detachment Peru Avian and Pandemic Influenza Activities." Institute of Medicine. 2008. Review of the DoD-GEIS Influenza Programs: Strengthening Global Surveillance and Response. Washington, DC: The National Academies Press. doi: 10.17226/11974.
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Suggested Citation:"7 Naval Medical Research Center Detachment Peru Avian and Pandemic Influenza Activities." Institute of Medicine. 2008. Review of the DoD-GEIS Influenza Programs: Strengthening Global Surveillance and Response. Washington, DC: The National Academies Press. doi: 10.17226/11974.
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Suggested Citation:"7 Naval Medical Research Center Detachment Peru Avian and Pandemic Influenza Activities." Institute of Medicine. 2008. Review of the DoD-GEIS Influenza Programs: Strengthening Global Surveillance and Response. Washington, DC: The National Academies Press. doi: 10.17226/11974.
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Suggested Citation:"7 Naval Medical Research Center Detachment Peru Avian and Pandemic Influenza Activities." Institute of Medicine. 2008. Review of the DoD-GEIS Influenza Programs: Strengthening Global Surveillance and Response. Washington, DC: The National Academies Press. doi: 10.17226/11974.
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Suggested Citation:"7 Naval Medical Research Center Detachment Peru Avian and Pandemic Influenza Activities." Institute of Medicine. 2008. Review of the DoD-GEIS Influenza Programs: Strengthening Global Surveillance and Response. Washington, DC: The National Academies Press. doi: 10.17226/11974.
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Suggested Citation:"7 Naval Medical Research Center Detachment Peru Avian and Pandemic Influenza Activities." Institute of Medicine. 2008. Review of the DoD-GEIS Influenza Programs: Strengthening Global Surveillance and Response. Washington, DC: The National Academies Press. doi: 10.17226/11974.
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Suggested Citation:"7 Naval Medical Research Center Detachment Peru Avian and Pandemic Influenza Activities." Institute of Medicine. 2008. Review of the DoD-GEIS Influenza Programs: Strengthening Global Surveillance and Response. Washington, DC: The National Academies Press. doi: 10.17226/11974.
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Suggested Citation:"7 Naval Medical Research Center Detachment Peru Avian and Pandemic Influenza Activities." Institute of Medicine. 2008. Review of the DoD-GEIS Influenza Programs: Strengthening Global Surveillance and Response. Washington, DC: The National Academies Press. doi: 10.17226/11974.
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7 Naval Medical Research Center Detachment Peru Avian and Pandemic Influenza Activities T he Naval Medical Research Center Detachment Peru (NMRCD), for- merly known as the Naval Medical Research Institute Detachment, was established in Lima in 1983 through an agreement between the surgeons general of the Peruvian and U.S. navies, with the concurrence of the U.S. Department of State and the Peruvian Ministry of Foreign Affairs (IOM, 2001). The agreement established a cooperative medical research program to study infectious diseases of interest to both parties. NMRCD is a field detachment of its parent command, the Naval Medical Research Center (NMRC) in Forest Glen, Maryland. Historically, NMRCD has fo- cused on applied research in support of its medical mission. Its past research focus provides a strong framework for the U.S. Department of the Defense Global Emerging Infections Surveillance and Response System (DoD-GEIS) focus on surveillance and response capacity. NMRCD projects receive funding from numerous sources, including the Military Infectious Disease Research Program, the U.S. Department of Defense Southern Command (SOUTHCOM), and DoD-GEIS. NMRCD is the sole DoD overseas medical research unit in the Western Hemisphere, and it serves a critical role in the DoD-GEIS global network of surveillance and response for emerging infectious diseases. Peru’s relative proximity to the continental United States and the frequent commerce and travel between North and South America give this unit an important role in infectious diseases surveillance, particularly as it relates to the biosecurity of the United States (IOM, 2001). NMRCD now has 230 staff members (15 U.S. military and civilian 147

148 REVIEW OF THE DOD-GEIS INFLUENZA PROGRAMS FIGURE 7-1  DoD’s regional presence in influenza surveillance (Latin America), 2007. Source: DoD-GEIS, 2007b. employees and contractors, 207 Peruvians, and 8 Venezuelans and Boliv- ians). Most staff are based at a 37,000-square-foot laboratory and animal care facility on the Peruvian naval hospital compound in metropolitan Lima fig 7-1 (DoD-GEIS, 2007a). This facility contains three biosafety level 3 (BSL-3) laboratories, including one dedicated to animal investigations. NMRCD Revised also has a new 5,000-square-foot facility on the base of the Peruvian Navy clinic in Iquitos, Peru. The mission of the detachment includes support for vaccine and drug development, evaluation of rapid diagnostics, and surveil- lance of emerging and re-emerging infectious diseases. The programs and collaborations of NMRCD extend through most of the countries of South and Central America (see Figure 7-1). The DoD-GEIS program at NMRCD is in alignment with the strategic goals of the overall DoD-GEIS mission as described in the recent five-year plan for the years 2005-2009. DoD-GEIS has identified the following goals as integral to its mission in South America: outbreak response preparation, detection, investigation, microbial agent identification, and communicable

NAVAL MEDICAL RESEARCH CENTER DETACHMENT PERU 149 disease control and prevention. NMRCD has addressed these goals with its fiscal year 2006 projects, including influenza surveillance and detection, response and readiness, systems research, development and integration, public health capacity building, and training. A site visit team of the Institute of Medicine (IOM) Committee for the Assessment of DoD-GEIS Influenza Surveillance and Response Programs visited NMRCD from March 4-9, 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 Staffing In addition to the administrative sections and the standard research laboratory operating committees, the organization of the laboratory in- cludes seven programmatic science sections: bacteriology, emerging infec- tious diseases, entomology, parasitology, virology, training, and the Iquitos lab. The leadership is provided by the 13 U.S. scientists, administrators, and technicians, including three Navy physicians, one Army veterinarian, five Navy Ph.D. scientists, one Ph.D. Public Health Service epidemiologist from the Centers for Disease Control and Prevention (CDC), one civilian epide- miologist, and one entomologist. The Peruvian staff includes many highly trained professionals, including physicians, scientists, a veterinarian, and technicians. These Peruvian scientists and administrators provide a large measure of continuity. While the U.S. staff members tend to turn over every several years, many of the civilian staff have been employed at NMRCD for multiple rotations of U.S. staff. This continuity serves a critical role in allowing sustainable programming, especially for ongoing projects which cannot be completed within the tour of a U.S. principal investigator. A hallmark of NMRCD is that there is extensive cross-disciplinary col- laboration between the various science sections. DoD-GEIS appears to be fully integrated across the scientific directorates within the unit. Fieldwork done by the emerging infections section is complemented by the laboratory capabilities of the virology section, and personnel from the training section strengthen the capability for fieldwork. A recent Fogarty International Cen- ter training grant benefited not only NMRCD but also many of its external collaborators. A representative from CDC has brought to NMRCD his extensive experience as a field epidemiologist in outbreak investigation. His tight   Prior to the committee’s visit to NMRCD, the laboratory staff provided the committee with detailed background information on NMRCD and the pandemic/avian influenza activities they were supporting. These materials are available from the IOM in the Public Access File.

150 REVIEW OF THE DOD-GEIS INFLUENZA PROGRAMS links with CDC experts also facilitate strong interagency communications. Although this CDC representative leads the outbreak investigation section, he also plays a central role in influenza surveillance and associated forms of outreach to Peruvian collaborators. The influenza surveillance program also makes good use of the technical field expertise of a staff veterinarian. Technology and Information Management NMRCD employs state-of-the-art tools for communications and in- formation management. In addition to a well-organized in-house data processing center, NMRCD has pioneered in Latin America several inno- vative information technology systems; one example is ALERTA, which is used for reportable disease surveillance of Peruvian military populations, including virtually all elements of the Peruvian Navy. Employing an effec- tive mix of appropriate technologies including cell phones, radios, and the Internet, this system allows rapid surveillance from remote jungle areas and Pacific-based ships. The system’s suitability has been well evaluated according to CDC-recommended criteria. NMRCD has also adapted the NAMRU-2 Early Warning Outbreak Response System (EWORS) for syn- dromic surveillance in Peru. The detachment has also been able to make use of current U.S. military remote-sensing mapping photos in the course of outbreak investigations. NMRCD is also efficiently connected to collaborators through excellent Internet connectivity, cell phones, and personal digital assistants. As one might imagine, connectivity is less robust for some partner organizations in Peru. In particular, the Ministry of Health Directorate of General Epi- demiology (DGE) noted a serious need for an integrated real-time national public health information-management system to foster hierarchical com- munications between the local, regional, and national epidemiology and public health laboratory authorities. The DGE has a slower hierarchical system of reportable disease reporting called NOTI. NMRCD may be able to make a valuable contribution in helping to transfer insights from U.S. public health information-management systems. In addition, through its extensive regional collaborations, NMRCD may also be able to identify the best approaches to information management and foster exchange of relevant information-management system tools from other countries in the region. Perhaps through partnerships with the U.S. Agency for International Development (USAID), Pan American Health Organization (PAHO), and other technical and donor organizations, NMRCD and DoD-GEIS can play a useful role in fostering the development of the type of an effective real-time information system that will save critical time in an outbreak. It would seem that individual “home grown” information-management sys- tems would not be the most effective or cost-effective way of implementing

NAVAL MEDICAL RESEARCH CENTER DETACHMENT PERU 151 the type of communication tools central to multi-agency outbreak detection and response. In addition, NMRCD is developing a Web-based software program to provide real-time surveillance data to the DoD, the wider U.S. government, and the global public health community. Conclusions Communication with the DoD-GEIS Headquarters in Silver Spring has been effective, and at the time of the IOM team visit it had recently increased. The addition of strong, experienced staff at DoD-GEIS in Silver Spring has been clearly of benefit. Regularly scheduled telephone or video conferences with these DoD-GEIS partners would help to exchange infor- mation and experiences with respect to pandemic influenza preparedness. RECOMMENDATION 7-1. NMRCD should continue to work to increase information sharing with both the DoD-GEIS headquarters staff and staff at other overseas laboratories. While the site visit team found the avian influenza/pandemic influenza (AI/PI) activities being conducted at NMRCD to be well planned and ex- ecuted, NMRCD could contribute more significantly to the evaluation of national influenza preparedness. For example, tabletop simulations may help NMRCD, the U.S. Department of Health and Human Services (HHS), and the U.S. Department of Agriculture (USDA) direct future investments of pandemic preparedness funding for Peru. RECOMMENDATION 7-2. NMRCD should support additional table- top simulation exercises in which NMRCD has the potential to identify areas of the Peruvian plan that need strengthening. SURVEILLANCE Human Surveillance The DoD-GEIS-sponsored ALERTA surveillance system for monitoring reportable diseases in the Peruvian Navy has been extended to the Peruvian Army. The Navy now has 50 reporting units covering 97.5 percent of the Navy. An ALERTA training program has conducted 47 courses and has trained a total of 877 persons, and ALERTA reports increased from 3,700 in 2003 to approximately 25,000 in 2005 (NMRCD, 2006). There are plans to use SOUTHCOM funding to extend this surveillance system to the Colombian military. It would be desirable to establish a link between ALERTA clinical reports and laboratory-based surveillance reports.

152 REVIEW OF THE DOD-GEIS INFLUENZA PROGRAMS The NAMRU-2 EWORS syndromic surveillance system has been suc- cessfully implemented in Lima and Tumbes. These electronic surveillance systems have identified two recent influenza B outbreaks involving ap- proximately 80 people (NMRCD, 2006). The head of the surveillance unit presented an excellent systematic evaluation of these systems using the CDC-recommended schema for the evaluation of surveillance systems. NMRCD has a long-standing febrile syndrome surveillance protocol under DoD-GEIS. NMRCD’s surveillance study, performed primarily with the General Office of Epidemiology in Lima and the National Institute of Health in Lima, is supported by approximately 10 additional collaborat- ing institutions in Peru and the U.S. This prospective observational study of febrile disease syndromes in Peru began in May 2000 and will end in 2008. Involved in this study are approximately 20,400 subjects, including the 10,000 individuals who were enrolled in the study’s first five years, an additional 2,000 individuals being recruited through active surveillance and 7,200 by passive surveillance, as well as 1,200 Peruvian military personnel. As described in their May 2006 protocol, the sample size was calculated to study about 400 patients per study site per year, for a total of about 30 patients per month at each of the sites. Currently about 64 clinics and hospitals (military and civilian) participate in febrile syndrome surveillance, and all can provide rapid diagnosis for influenza. The protocol focuses on patients presenting to selected health services or detected during the active surveillance with fever (oral) greater or equal to 38°C, 7 days or less in duration, accompanied by one or more of the following: headache, muscle, ocular and/or joint pain, generalized fatigue, cough, nausea/vomiting, sore throat, rhinnorhea, difficulty breathing, diar- rhea, bloody stools, jaundiced, dizziness, disoriented, stiff neck, petechiae, ecchymoses, bleeding gum and/or nose. Only individuals five years of age or older are included, unless hemorrhagic manifestations are present. Acute and convalescent blood specimens are drawn, and a throat swab is obtained from individuals presenting with an influenza-like illness characterized pri- marily by a fever, generalized fatigue, sore throat and rhinorrhea. With the help of AI/PI funds this long-standing surveillance protocol has been successfully adapted to incorporate influenza surveillance. This surveillance approach is now being extended to the Colombian Army, Na- tional Police, and Navy as well as to two Army sites in Ecuador. NMRCD provides salaries for approximately ten physicians to operate this network (NMRCD, 2006). The influenza surveillance capabilities include isola- tion from nasopharyngeal swabs, polymerase chain reaction (PCR), and sequencing at NMRCD. Good primers are in hand for human influenza, but more effective primers for avian influenza need to be identified. With the AI/PI funding, diagnostic capacity has been extended to include a wider range of respiratory agents. Some sites send weekly shipments to Lima,

NAVAL MEDICAL RESEARCH CENTER DETACHMENT PERU 153 and other locations forward samples on a monthly basis. Reporting to the ministries of health, participating physicians, and the Air Force Institute for Operational Health (AFIOH) in San Antonio, Texas, takes place on a monthly basis (AFIOH, 2004). Critical results are reported directly after sequence confirmation. Continued expansion of diagnostic capabilities is planned and will include coronaviruses. Avian virus surveillance will also be expanded. Consideration is being given to expanding efforts to other countries such as Suriname. Screening for antiviral resistance is not a cur- rent capability. The fiscal year 2006 AI/PI funding allowed the addition of about 40 new surveillance sites. The NMRCD scope of activities covers a wide range, including mo- lecular biology, descriptive epidemiology, and social science efforts. The social science-oriented surveillance has tracked knowledge, attitude, and behavior concerning influenza among occupationally at-risk workers. A Peruvian social scientist will be involved in addressing risk communica- tion issues. NMRCD collaborates with many partners, including the CDC, MoH, USAID, PAHO, DGE, and the Instituto Nacional de Salud. Capacity building is central to the program. Animal Surveillance In addition to human surveillance, the NMRCD program extends to avian influenza. It is a participant in the Global Avian Influenza Network Surveillance, managed by the World Wildlife Conservation Society at the Bronx Zoo (NMRCD, 2006). This network focuses on surveillance of dead and dying birds in coastal areas as well as on droppings from closely observed migratory birds along coastal lagoons. The self-assessment of NMRCD is that their efforts are weakest in the area of animal surveillance. One of the surveillance initiatives planned to address this deficit is active surveillance of influenza-like illness in chicken farm workers using an electronic surveillance approach. Surveillance of workers in the large mixed live bird markets of Lima is also under consid- eration. Both of these activities were deemed to be of value to establishing current influenza patterns. Another plan is to study different strategies to optimize reporting within electronic surveillance systems. Conclusions The site visit team found that NMRCD has a suite of innovative sur- veillance systems that benefit from not only DoD-GEIS AI/PI funds but also DoD-GEIS core funding as well as leveraging from associations with CDC, the Fogarty International Center, USAID, and SOUTHCOM.

154 REVIEW OF THE DOD-GEIS INFLUENZA PROGRAMS RECOMMENDATION 7-3. NMRCD should consider expanding its surveillance activities to include populations at high risk of contract- ing avian influenza, including poultry farm workers, live bird market workers, and recruits in military training camps. LABORATORY NMRCD possesses three BSL-3 containment laboratories. Two are located in the main laboratory complex, and a third is located in the ani- mal care facility laboratory. If required, this latter unit could be modified into two separate BSL-3 laboratories rather easily. For influenza testing the laboratory has both conventional and real-time PCR capability as well as the ability to do immunofluroescence testing. Conventional virus culture is done using various cell lines that are maintained in the laboratory. All labo- ratories are inspected twice annually and a Peruvian technologist trained in the United States certifies safety hoods annually. Renovations and upgrades to the laboratory are being made on a continuing basis to enhance its ca- pability and efficiency. The ability to operate at the BSL-3 enhanced level could be achieved by adding shower-out facilities. The NMRCD virology program has the necessary human influenza A primers to identify any isolated virus, including the full complement of hemagglutinins, key neuraminidases, and matrix protein. The laboratory is collaborating with the CDC to increase its complement of primers for avian influenza. This should hopefully reduce some of the delays that have been experienced in the characterizing of avian influenza types. The laboratory currently has two sequencers, a 16-column and a 4- column unit. Consideration is currently being given to trading the 4-column unit up to another 16-column unit to increase sequencing capacity. While the current sequencing capacity is generally adequate for the present work- load, two 16-column units would provide a significant enhancement in surge capacity. The laboratory role of NMRCD in AI/PI surveillance in Peru and the Andean Region is of crucial importance. From 1999-2004 AFIOH per- formed all influenza virus identifications. While the technical and scientific support provided by AFIOH was excellent, the current ability of NMRCD to perform in-house testing has greatly decreased the turnaround time required to report test results to submitters. This in turn has encouraged clinical sites to place much greater value on participation in surveillance activities. At the present time NMRCD does not have separate laboratory suites for the testing and identification of avian and human influenza isolates. The current laboratory layout will allow for necropsy of dead birds and specimen collection in the BSL-3 unit in the animal care facility laboratory.

NAVAL MEDICAL RESEARCH CENTER DETACHMENT PERU 155 Specimens then are tested by immunofluorescence (IF) and PCR in the same area used for the testing of human isolates located in the main laboratory complex. As the World Health Organization (WHO) recommends that clinical specimens from humans and from swine or birds should never be processed in the same laboratory, consideration should be given to how this might be best accomplished (WHO, 2007). At a minimum, any option chosen to separate human and animal isolations would require the devel- opment of additional IF/PCR capability in which only AI specimens would be tested, either at NMRCD or possibly at another collaborating Peruvian sites, such as the Servicio Nacional de Sanidad Agraria (SENASA). It is recommended that NMRCD propose this additional capability in future funding requests. Conclusions The site visit team found NMRCD’s plans to improve the laboratory worthwhile. These plans included the extension of diagnostic capabilities and avian influenza surveillance, the addition of capability for coronavi- ruses and non-H5N1 avian viruses, and the expansion of surveillance ef- forts to additional countries. RECOMMENDATION 7-4. 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. RESPONSE CAPACITY Outbreak Investigation Outbreak response has been central to NMRCD. NMRCD is well positioned to respond to influenza outbreaks, as evidenced from its experi- ences in 2006-2007 when it responded to outbreaks of plague, yellow fever, diarrhea, cyclospora, undifferentiated febrile syndrome, Venezuelan equine encephalitis, mumps, dengue, rabies, and influenza. The recent posting of a representative from CDC extends this capacity considerably. NMRCD is building a considerable network and capacity for both surveillance of and response to outbreaks. The training unit has sponsored 33 iterations of the NMRCD outbreak- investigation course. Since 2002 an avian influenza case study has been included in the course. Over 1,300 trainees from 14 countries have been trained over the past five years. Other institutions in Latin American have

156 REVIEW OF THE DOD-GEIS INFLUENZA PROGRAMS been adapting the course to local needs. These courses have been conducted in collaboration with PAHO, CDC, and USAID. Reports have been received on 248 outbreaks. Surge Capacity As part of the committee’s data gathering, NMRCD was asked to es- timate the number of samples it would be able to process in the following four scenarios: routine operation (baseline); an altered algorithm, testing only for influenza A and H5; PCR testing to amplify only one specific gene from H5; and, finally, not only making these other modifications but also arranging to perform tests 24 hours per day, seven days a week. According to information provided to the committee, NMRCD rou- tinely does cell culture isolation on all respiratory specimens. The influenza isolates are typed as A or B by this process and are then genotyped by reverse transcription polymerase chain reaction (RT-PCR) and sequencing. Under normal conditions approximately 100 specimens per week are pro- cessed by cell culture isolation. Specimens in transport media are not usu- ally screened by RT-PCR because the sensitivity of RT-PCR is slightly less than that of cell culture isolation. Under normal conditions, 200 specimens per week can be processed by RT-PCR (NMRCD, 2007). Under 24-hours–a-day, seven-days-a-week conditions at NMRCD, 300 specimens per week can be processed by cell culture isolation and 1,000 specimens per week can be processed by RT-PCR (NMRCD, 2007). Conclusions Although there have not been any reported cases of H5 highly patho- genic avian influenza in Peru or South America in general, NMRCD does have experience in infectious disease outbreak investigations as well as a surge capacity plan in the event that an avian outbreak does occur. CAPACITY BUILDING NMRCD Laboratory Capacity NMRCD has been doing respiratory disease surveillance since 1996, but AI supplemental funds have allowed for the expansion and improve- ment of these programs. In the past, NMRCD relied on AFIOH to conduct the viral isolation and identification of samples collected in Peru, which led to delays of several months in receiving the results. Using supplemen- tal funds NMRCD has increased its capacity to detect influenza with cell culture, real-time PCR, and gene-sequencing capabilities. This capacity al-

NAVAL MEDICAL RESEARCH CENTER DETACHMENT PERU 157 lows NMRCD to return results to providers quickly, keeping collaborators engaged and patients satisfied with the results. In addition to the NMRCD laboratory capability having been in- creased, the number of sites from which NMRCD actively collects respira- tory specimens has increased as well. Samples are collected from sites in 10 countries throughout South and Central America. Peru has the most active sites with 25; other sites are located in Argentina, Bolivia, Colombia, Ecua- dor, El Salvador, Honduras, Nicaragua, Paraguay, and Venezuela. NMRCD Training Activities NMRCD puts a strong emphasis on training. The training unit has sponsored 33 iterations of the NMRCD outbreak investigation course. Since 2002 an avian influenza case study has been included in the course. Over 1,300 trainees from 14 countries have been trained over the past five years. Other institutions in Latin America have been adapting the course to local needs. These courses have been conducted in collaboration with PAHO, CDC, and USAID. NMRCD also has a Fogarty Center Training grant that funds Peruvians from NMRCD and other organizations to at- tend the Johns Hopkins Bloomberg School of Public Health summer session (two per year), to attend the one-year MPH program at the Uniformed Services University of the Health Sciences (USUHS), and to obtain doctoral training in the United States. The grant will also be used to help initiate a master’s level program at Cayetano-Heredia University. NMRCD has also made a commitment to offering training seminars through the download of webcasts from the United States and has sponsored a number of very well attended sessions on various laboratory practices. In addition to outbreak training, NMRCD has provided a number of courses in the conduct of research, bioethics, data analysis, and epidemiol- ogy. Students from many institutions based in the United States have been rotating regularly through NMRCD. These include USUHS, the University of Washington, the University of Iowa, Johns Hopkins University, Emory University, Tulane University, Kansas State University, and the State Univer- sity of New York at Stony Brook. Considering the demand for training at NMRCD, the successes to date, and the need for wider and deeper human networks to address emerging infections including AI/PI, further investment in physical classroom and teaching laboratory facilities as well as human infrastructure to support training is encouraged. NMRCD is clearly a suit- able focal point for U.S. investments in epidemiological and laboratory capacity building in Latin America.

158 REVIEW OF THE DOD-GEIS INFLUENZA PROGRAMS Conclusions NMRCD’s track record for pre-service and in-service training to U.S. and Peruvian students and practitioners is impressive. It has developed a well-received outbreak investigation course that has built a wide network of contacts across Peru and Latin America. RECOMMENDATION 7-5. NMRCD should continue to support in- house and webcast training in epidemiological surveillance and labora- tory methods. Outbreak response should receive additional emphasis, including Peru’s Field Epidemiology Training Program. COLLABORATION AND COORDINATION Host Country Government NMRCD is clearly engaged with a wide range of national and regional influenza-related committees and organizations involved with avian and human influenza surveillance and response. NMRCD’s network is active and wide, encompassing not only the ministries of health and agriculture but also Peruvian Army and Navy medical surveillance channels. The NMRCD influenza program has established substantial networks with relevant entities in the Peruvian government, including the Insti- tuto Nacional de Salud (INS), the Directorate de Epidemiologia General, and ­ SENASA. Peru manages its national influenza-preparedness program through three committees: an executive committee chaired by the Vice Minister of Health, a committee of technical support, and a national multi­ sectoral committee. NMRCD is a recognized advisor to these entities. Ironi- cally, the detachment may also help serve as a bridge between human and animal health-oriented elements of the Peruvian government, which don’t seem to have yet established close communications on influenza ­issues. Peru has a detailed and thoughtful pandemic influenza-preparedness plan on paper based on 1999 and 2005 WHO guidance. It would appear, however, that the plan is not well-resourced. Issues such as the ability to diagnose cases and institute effective infection control in the face of a pandemic are of concern. The Ministry of Agriculture’s laboratory, SENASA, has a mandate from the Food and Agricultural Organization and the World Organi­zation for Animal Health to do animal surveillance for influenza, but resources to conduct this surveillance are quite limited. Resources are also limited for the INS influenza laboratory, staffed by only three persons, to process more than a handful of the specimens that NMRCD shares with it. Independent collection of specimens by the INS influenza laboratory is compromised in a number of locations around Peru by issues ­surrounding

NAVAL MEDICAL RESEARCH CENTER DETACHMENT PERU 159 the cold chain, the series of low-temperature facilities used for storing samples. These limitations have prompted the INS to focus on surveillance in intensive care units, whereas the NMRCD collects specimens primar- ily from primary care settings. A unified national influenza-surveillance database combining data from the NMRCD and Peruvian government laboratories would seem desirable. As noted above, NMRCD collaborates with a number of Peruvian government agencies on influenza surveillance. These agencies lack re- sources in many cases. Though they have willing professionals, obstacles such as unreliable cold chains hinder the amount of work that can be done. NMRCD laboratory space and other resources are available to the INS to support influenza virus isolation. The laboratory leadership appeared to understand and be sensitive to the potential challenges associated with the large resource gap for influenza between NMRCD and the INS. In order to strengthen collective Peruvian diagnostic capacity to characterize influenza viruses, NMRCD should continue to work collaboratively with other labo- ratory resources in country, including offers of assistance, resource sharing, and a common database. Multilateral Agencies Though NMRCD has strong relationships with Peruvian government entities involved in influenza surveillance and response, it is clearly in the position to be a leading source of U.S. government assistance if AI/PI emerges as a problem in the region. NMRCD has applied in the past for designation as a WHO Collaborating Center for Emerging Infections. It is reported that despite the passage of more than a year, the application has not been forwarded from PAHO in Washington, D.C., to the WHO in Geneva. To better position NMRCD to provide expert reference-level surveillance and response assistance to other countries of South and Cen- tral America, WHO Collaborating Center status should be aggressively pursued, perhaps with the support of leadership from other U.S. govern- ment departments such as the State Department and HHS. The head of the PAHO country office in Peru suggested that NMRCD solicit the active support of ministers of health in other Andean countries to request that status for NMRCD. U.S. Government Agencies The officer-in-charge of the NMRCD is a participating member of the U.S. embassy country team under the leadership of the U.S. ambassador to Peru. It was clear that NMRCD has the strong support of the U.S. ambas- sador and that the U.S. ambassador specifically appreciates and values the

160 REVIEW OF THE DOD-GEIS INFLUENZA PROGRAMS role of the NMRDC in strengthening avian and pandemic influenza surveil- lance in Peru and the region. He has supported relevant increases in staffing levels and has, from his position, successfully encouraged Peruvian officials to address the global threat of avian and pandemic influenza. Within the embassy, NMRCD is seen as a valuable source of consultation with respect to USDA investments in controlling avian influenza in the region. NMRCD is also well connected to the USAID section at the embassy. The overall fiscal year 2006 operating budget of the detachment was $10,025,169.28. The DoD-GEIS core budget was $1.34 million. The fiscal year 2006 AI/PI supplement brought $1.74 million to the laboratory. For fiscal year 2007, the desired AI/PI budget is $2.20 million, of which $750,000 has been received to date. HHS has provided $825,000 in funding to Peru for pandemic influenza preparedness, of which 80 percent was earmarked for epidemiologic and laboratory strengthening. NMRCD has offered to help the Peruvian gov- ernment with various aspects, such as provision of a database to help with monitoring national influenza trends and improving diagnostic capacities at the INS. One of the main challenges for the Peruvian government influenza surveillance network is the cold chain needed to preserve specimens col- lected around the country. NMRCD has offered use of its ultra-low-temper- ature freezers around the country as well as assistance with biosafety issues. The detachment has also offered other electronic surveillance technologies to supplement those of the government. NMRCD has an open relationship with the USAID program in Peru, though the USAID commitment to influenza in Peru is not major. Based on the observations of the site visit team, NMRCD is respected by USAID as an important builder of regional capacity. Perhaps surprisingly, a senior Peruvian USAID staffer said that NMRCD has brought consistency to some programs in the face of turnover in the Peruvian government. As the Peru- vian governmental health care system becomes more decentralized, USAID sees capacity building as much needed. The assignment of a representative from CDC to NMRCD illustrates that there is a serious commitment, backed by human resources, to maintain collaboration between the DoD and CDC. The representative’s tight links with CDC experts also facilitate strong interagency communications. In addition to partnering effectively with the HHS, NMRCD has lever- aged DoD humanitarian assistance funds to improve regional surveillance. A very strong working relationship was evident between NMRCD and the office of the military assistance group at the U.S. embassy.

NAVAL MEDICAL RESEARCH CENTER DETACHMENT PERU 161 Conclusions NMRCD is a critical national and regional resource for avian influ- enza/pandemic influenza surveillance and response as well as for addressing other emerging infectious diseases. It has established a strong reputation in the region and is well positioned to support emerging infections surveil- lance, response, and capacity building. It is well integrated into several governmental and multisectoral committees formed to prepare for the Pe- ruvian national response. Though perhaps less practical, it could also play a valuable role for other Andean countries. Host countries appreciate its role and for the most part trust its leaders in sensitive matters. Without a doubt many Latin American countries will turn to NMRCD for its expertise and capabilities in the face of a national emerging infections crisis, such as an outbreak of avian or epidemic influenza. A renewed drive for WHO Col- laborating Center status should be undertaken with the support of other ministers of health in the Andean Region. NMRCD has much deeper resources for influenza work than are avail- able to Peruvian government counterparts. It needs to continue to be sensi- tive to the potential unintended consequences of this resource imbalance so as to not allow the collateral weakening of Peruvian government capacities if providers preferentially turn to NMRCD for diagnostic support. RECOMMENDATION 7-6. A close working relationship, the shar- ing 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 data- base with both NMRCD and INS results would be desirable. References Air Force Institute for Operational Health (AFIOH). 2004. DoD global influenza and other respiratory viral pathogens surveillance weekly update week 14 (4 Apr–10 Apr). http:// www.geis.fhp.osd.mil/GEIS/SurveillanceActivities/Influenza/Reports/influenza_2004-04- 04.pdf (accessed September 5, 2007). DoD-GEIS (Department of Defense Global Emerging Infections System). 2007a. U.S. Naval Medical Research Center Detachment. http://www.geis.fhp.osd.mil/GEIS/Training/nmrcd. asp (accessed July 30, 2007). DoD-GEIS. 2007b. Department of Defense influenza surveillance sites worldwide, 2007 (unpublished). IOM (Institute of Medicine). 2001. Perspectives on the Department of Defense Global Emerg- ing Infections Surveillance and Response System: A program review. Washington, DC: The National Academies Press. NMRCD (U.S. Naval Medical Research Center Detachment). 2006. Influenza and disease surveillance summary (unpublished). NMRCD. 2007. Surge capacity plan (unpublished).

162 REVIEW OF THE DOD-GEIS INFLUENZA PROGRAMS WHO (World Health Organization). 2007. Recommended laboratory tests to identify avian in- fluenza A virus in specimens from humans March 2007. http://www.who.int/csr/­disease/ avian_influenza/guidelines/labtestsMarch07web.pdf (accessed August 15, 2007).

NAVAL MEDICAL RESEARCH CENTER DETACHMENT PERU 163 List of contacts DoD-GEIS NMRCD Assessment: Peru Cmdr. David Blazes, Naval Medical Research Center Detachment, Lima, Peru Lt. Cmdr. Tadeusz Kochel, Naval Medical Research Center Detachment, Lima, Peru Andres Lescano, Naval Medical Research Center Detachment, Lima, Peru Lt. Cmdr. Joel Montgomery, Naval Medical Research Center Detachment, Lima, Peru Cecilia Mundaca, Naval Medical Research Center Detachment, Lima, Peru Milagros Salazar Gross, Naval Medical Research Center Detachment, Lima, Peru Ambassador J. Curtis Struble, U.S. Embassy, Lima Peru Col. Jeffrey H. Fargo, United States Military Advisory and Assistance Group, Department of Defense, Washington, D.C. Eugene Philhower, United States Department of Agriculture, Lima, Peru Michele Russell, United States Agency for International Development, Lima, Peru Luis Seminario, United States Agency for International Development, Lima, Peru Twani Ortiz Almeida, Dirección General de Epidemiología, Lima, Peru Jorge Goméz Benavides, Dirección General de Epidemiología, Lima, Peru Paúl Pachas Chavez, Dirección General de Epidemiología, Lima, Peru José Bolarte Espinoza, Dirección General de Epidemiología, Lima, Peru Gladys Ramírez Prada, Dirección General de Epidemiología, Lima, Peru Aguiles Vilchez, Dirección General de Epidemiología, Lima, Peru Roberto Acosta, Servicio Nacional de Sanidad Agraria, Lima, Peru Roberto Antonio Acosta Galvez, Servicio Nacional de Sanidad Agraria, Lima, Peru Ysabel Montoya, Servicio Nacional de Sanidad Agraria, Lima, Peru C. Juan Raul Zegarra Valencia, Servicio Nacional de Sanidad Agraria, Lima, Peru Carolina Alvarado Dueñas, Dirección General de Salud a las Personas, Lima, Peru Maria Luz Sotomayor, Dirección General de Salud a las Personas, Lima, Peru Victor Fiestas Solorzano, Instituto Nacional de Salud, Lima, Peru Yvonne Torres, Insituto Nacional de Salud, Lima, Peru José F. Picón Gonzales, Instituto Nacional de Defensa Civil, Lima, Peru

164 REVIEW OF THE DOD-GEIS INFLUENZA PROGRAMS Armando E. Gonzalez, University San Marcos/Johns Hopkins School of Public Health Manuel Peña, Pan American Health Organization/World Health Organization, Lima, Peru Schedule of Events DoD-GEIS NMRCD Assessment Lima, Peru Participants: Dr. James M. Hughes Dr. K. Mills McNeill Dr. Patrick Kelley March 4-10, 2007 Sunday, March 4, 2007 1000-1600 Tour of the city 1900-2000 Dinner Monday, March 5, 2007 0730-0800 Drive to NMRCD 0815-0915 Review of Peruvian National Preparedness Plan  Cmdr. Joel Montgomery, USPHS, Director, Outbreak Lt. Investigation and Response Team, Emerging Diseases Program 0915-1000 Presentation on status of Emerging Infections Program Cmdr. David Blazes, Director of EDP 1000-1015 Break 1015-1100 Presentation on electronic surveillance of Influenza  Cecilia Mundaca, Electronic Surveillance Unit, Dr. Emerging Infections Program 1100-1145 Presentation on training Andres Lescano 1200-1300 Lunch 1300-1500 Presentation on virology laboratory   Cmdr. Tadeusz Kochel, MSC, USN, Director of Lt. Virology Program 1500-1630 Tour of facilities 1630-1845 Return to hotel 1845-2000 Dinner Virology Department GEIS Team 2000-2030 Return to hotel

NAVAL MEDICAL RESEARCH CENTER DETACHMENT PERU 165 Tuesday, March 6, 2007 0800-0810 Courtesy visit Eugene Philhower, Foreign Agriculture Service 0815-0845 Courtesy visit  Col. Jeffrey Fargo, Chief Military Assistance and Advisory Group 0900-0920 Courtesy visit Ambassador J. Curtis Struble 0930-1000 Courtesy visit at health office of USAID Michele Russell Luis Seminario 1000-1015 Commissary at American Embassy 1015-1200 Travel to NMRCD 1200-1330 Lunch 1330-1400 Travel to PAHO 1400-1600 Meeting Dr. Manuel Peña, PAHO/WHO Representative 1600-1630 Return to hotel Wednesday, March 7, 2007 1000-1100 Tour of SENASA 1200-1300 Lunch 1300-1315 Walk to Dirección General de Epidemiología 1330-1630  Meeting with Ministry of Health Avian Influenza Working Group Representatives of MoH, INS, DGE, SENASA 1630-1700 Return to hotel Thursday, March 8, 2007 0900-1030 Visit bird site (Pantanos de Villa, Chorrillos) Cmdr. David Blazes Lt. Cmdr. Joel Montgomery Dr. Milagros Salazar Dr. Armando Gonzales 1030-1200 Tour San Marcos Veterinary School Laboratory 1200-1600 Lunch/free time 1600-1630 Return to hotel

166 REVIEW OF THE DOD-GEIS INFLUENZA PROGRAMS Friday, March 9, 2007 0830-2130 Closeout day at NMRCD (?) 2130-2200 Drive to airport Saturday, March 10, 2007 0035- Departure

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The 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. Congress 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.

An Institute of Medicine (IOM) committee was subsequently formed to evaluate the effectiveness of these laboratory-based programs in relation to the supplemental funding, and the report that follows details the committee's findings. The committee that prepared this report, the Committee for the Assessment 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 the worth of each funded project's contribution to a comprehensive AI/PI surveillance program; the adequacy of the program in view of the evolving epidemiologic factors; responsiveness to the intent of Congress as expressed in Sec. 748, H.R.1815, Pandemic Avian Flu Preparedness; consistency with the DoD and national plans; and coordination of efforts with CDC, WHO, and local governments.
Review of the DoD-GEIS Influenza Programs: Strengthening Global Surveillance and Response reviews 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.
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