1
Introduction

BACKGROUND

The influenza pandemic of 1918 offers a warning to the world about the potential dangers of the influenza virus. Of all the influenza pandemics that have appeared in recorded history, the 1918 pandemic was particularly devastating. It killed an estimated 650,000 Americans (Tumpey et al., 2005), and for several weeks in October 1918 it was causing 5,000 to 6,000 deaths each week in the U.S. Army (Crosby, 1989).

In 2006, after a series of H5N1 avian influenza virus infections and deaths among people in Asia and Africa raised 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 of DoD domestic and overseas public health surveillance and laboratory capabilities. An Institute of Medicine (IOM) committee was subsequently formed to evaluate the effectiveness of these laboratory-based surveillance programs in relation to the supplemental funding. This report describes the committee’s findings.

Three major influenza pandemics emerged in the twentieth century, one of which—the pandemic of 1918-1919, commonly referred to as the “Spanish flu”—killed an estimated 50 million to 100 million people, thereby making it the most deadly known disease outbreak in history. The first wave of the pandemic in the United States arrived in the spring of 1918, followed by two subsequent, more deadly waves in the fall of 1918 and the



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1 Introduction BACKGROUND T he influenza pandemic of 1918 offers a warning to the world about the potential dangers of the influenza virus. Of all the influenza pan- demics that have appeared in recorded history, the 1918 pandemic was particularly devastating. It killed an estimated 650,000 Americans (Tumpey et al., 2005), and for several weeks in October 1918 it was causing 5,000 to 6,000 deaths each week in the U.S. Army (Crosby, 1989). In 2006, after a series of H5N1 avian influenza virus infections and deaths among people in Asia and Africa raised 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 of DoD domestic and overseas public health surveillance and laboratory capabilities. An Institute of Medicine (IOM) committee was subsequently formed to evaluate the effectiveness of these laboratory-based surveillance programs in relation to the supplemental funding. This report describes the committee’s findings. Three major influenza pandemics emerged in the twentieth century, one of which—the pandemic of 1918-1919, commonly referred to as the “Span- ish flu”—killed an estimated 50 million to 100 million people, thereby making it the most deadly known disease outbreak in history. The first wave of the pandemic in the United States arrived in the spring of 1918, followed by two subsequent, more deadly waves in the fall of 1918 and the 

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 REVIEW OF THE DOD-GEIS INFLUENZA PROGRAMS winter of 1918-1919 (Taubenberger and Morens, 2006). Retrospectively, the earliest cases seen in the United States appeared in the U.S. military. The strain of influenza responsible for the 1918 pandemic was particu- larly deadly, with a fatality rate of roughly 2 percent as compared with a fa- tality rate of around 0.1 percent for contemporary strains of influenza virus (IOM, 2004). The 1918 pandemic also exhibited an unprecedented excess of mortality among people from 20 to 40 years old, a population that has historically demonstrated a low influenza mortality rate, both in the years prior to 1918 and the years since (Morens and Fauci, 2007). Military popu- lations in particular were severely affected by the 1918 pandemic. The genome of the 1918 influenza virus has been recently sequenced from RNA fragments obtained from archival and frozen lung tissue of viral pneumonia victims. From that analysis the extinct pandemic strain of 1918 was identified as an influenza A virus, subtype H1N1. Studies under high- containment conditions using the reconstructed 1918 virus showed a high fatality rate in animal models 3 to 4 days after infection, a characteristic not described for any other human influenza virus (Tumpey et al., 2005). The two other major influenza pandemics of the twentieth century were milder and less devastating than the 1918 pandemic. The first of these was the Asian flu pandemic of 1957-1958 caused by subtype H2N2. The virus, first found in the Far East, was identified in the United States in June 1957, with the first outbreak occurring in September and the peak coming in October. The timing of the epidemics coincided with the opening of the winter school term (Payne, 1958). A second wave hit in early 1958. Fatali- ties occurred mainly among the very young and the very old and in total claimed the lives of roughly 1,000,000 people (Potter, 2001). The pandemic of 1968, caused by an H3N2 strain descended from H2N2 by antigenic shift (genetic reassortment), was milder than the 1957 pandemic, yet it still was estimated to have caused 500,000 deaths world- wide. The new strain was first isolated in Hong Kong in July 1968, al- though it most likely originated in nearby Guangdong Province, China. The pandemic proved less deadly in the United States than expected. Experts have suggested a variety of possible reasons: (1) antigenic overlap with the neuraminidase of the earlier H2N2 dominant strain, which would have provided a degree of cross protection; (2) the presence of preexisting an- tibodies (and protection) among the elderly born prior to 1893 as a result of the 1889-1891 pandemic; (3) the fact that the pandemic peaked around the holiday season in December, a time when most children are temporarily out of school, which would have slowed the spread of the virus; and (4) improvements in medical care and access to effective treatment (Dowdle, 1999; Kilbourne, 2006). In 1977, an H1N1 virus reemerged in the Far East, genetically closely related to strains prevalent in the late (~1950) H1N1 era (Nakajima et al.,

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 INTRODUCTION 1978). Though the origin of the virus remains in question, it met the basic criteria of a pandemic strain in that a significant percentage of the popula- tion (those people born after 1956) had no immunity and there was rapid global transmission. However, it differed from previous pandemics in that the disease was mild and most persons older than 20 years of age were pro- tected through previous immunologic experience with the H1N1 subtype. The H1N1 subtype continues to co-circulate with H3N2. The genetic iden- tity of the 1977 virus with strains from the late H1N1 era (~1950) strongly suggested that this virus had reappeared (Kendal et al., 1978; Nakajima et al., 1978). The reason for this is unexplained. In 1996 a highly pathogenic H5N1 avian influenza virus was isolated from farmed geese in Guangdong Province, China. In the following year reports from Hong Kong described outbreaks first in farm chickens and then in live poultry markets. Eighteen cases of human infection were re- ported, six of which were fatal, providing the first documented instance of a purely avian influenza virus causing respiratory disease and death in humans (Claas et al., 1998; WHO, 2007a). While the H5N1 virus of 1997 has not been detected subsequent to the culling of poultry in Hong Kong, the precursor virus found in the Guangdong geese in 1996 persisted in southern China; it has subsequently gone on to exchange various genes over time with unspecified avian influenza viruses to produce a series of highly pathogenic H5N1 descendants, some of which have spread to other parts of Asia, Europe, and northern Africa (Ducatez et al., 2006; Salzberg et al., 2007; Smith et al., 2006) (see Figure 1-1). From 2003 to writing of this report in July 2007, the WHO had confirmed a total of 319 human cases of H5N1 infection in 12 different countries, 192 of which were fatal (fatality rate around 60 percent) (WHO, 2007b). Approximately 150 million poultry have died since January 2004, either from the virus itself or as a result of culling aimed at containing the virus. H5N1 is considered endemic in poultry in China, Vietnam, Thailand, Indonesia, Egypt, Nigeria, and perhaps Cambodia and Laos (WHO, 2005; FAO, 2007). Historically, the U.S. military has played an important international role in influenza virus surveillance and vaccine development (Woodward, 1994). In 1941, on the eve of the U.S. entry into World War II, concern about a repeat of the 1918 influenza pandemic and its disastrous effects on armed forces led the U.S. military to establish a commission on influenza and place highest priority on rapid development of an effective influenza vaccine. The first successful large-scale influenza vaccine field trials any- where in the world were completed by the commission in 1943 (Francis, 1954). In 1954 the Department of Defense issued an influenza immuniza- tion policy that mandated quick pandemic risk assessment along with the formulation and provision of vaccines in order to protect military person-

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 REVIEW OF THE DOD-GEIS INFLUENZA PROGRAMS FIGURE 1-1 Nations with confirmed cases H5N1 avian influenza. SOURCE: U.S. Fish and Wildlife Service, 2007. , nel. In 1957 and again in 1968, the U.S. Military Commission on Influenza provided crucial international leadership in surveillance and risk assessment in response to reports of potential influenza pandemics emerging in the Far East. Candidate strains isolated by the military or obtained through its Figure 1-1 overseas contacts greatly accelerated production and provision of vaccines in both pandemics. In 1996, the Executive Office of the President issued the presidential decision directive NSTC-7 (NSTC is the National Science and Technology Council of the Executive Office of the President), which declared that both the international and domestic capabilities for emerging infectious disease surveillance, prevention, and response were inadequate to protect U.S. citizens from such threats (NSTC, 1996). To address that issue, NSTC-7 expanded the mission of the DoD to include support of global surveillance, training, research, and response to emerging infectious disease threats. The DoD was to “strengthen its global disease reduction efforts through central- ized coordination; improved preventive health programs and epidemiologic capabilities; and enhanced involvement with military treatment facilities and overseas laboratories” (NSTC, 1996). NSTC-7 also called for increased communication and coordination among U.S. government agencies with responsibilities for addressing emerging infectious diseases.

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 INTRODUCTION GEIS, established by the Assistant Secretary of Defense for Health Affairs in 1996 in response to NSTC-7, was tasked with “initiating and coordinating the identification, reporting and responding to emerging infec- tious disease problems” (Bancroft and Schlagel, 1997). GEIS is a tri-service program, and its activities are implemented within all three branches of the Armed Forces (Army, Navy, and Air Force), although GEIS has no direct command authority over the facilities where its activities are implemented (DoD-GEIS, 2006). The history of U.S. overseas military medical research goes back more than a century to the days of Walter Reed work on yellow fever epidemiology in Cuba at the turn of the 20th century (IOM, 2001). The current network of DoD overseas medical research units began with the establishment of the U.S. Navy Medical Research Unit in Egypt in 1942. (Gambel and Hibbs, 1996). These DoD overseas laboratories provide forward sites for GEIS activities. The DoD currently has five overseas medical research units and three domestic medical research/public health laboratories with a major focus on influenza (see Table 1-1): the U.S. Naval Medical Research No. 2 (NAMRU-2) in Jakarta, In- TABLE 1-1 Primary DoD Overseas and Domestic Laboratories Receiving DoD-GEIS AI/PI Funding Date Laboratory Location Established Naval Medical Research Unit Jakarta, Indonesia 1970 No. 2 (NAMRU-2) Armed Forces Research Institute Bangkok, Thailand 1958 of Medical Sciences (AFRIMS) Naval Medical Research Unit Cairo, Egypt 1942 No. 3 (NAMRU-3) U.S. Army Medical Research Nairobi, Kenya 1969 Unit (USAMRU-K) Naval Medical Research Center Lima, Peru 1983 Detachment (NMRCD) 1996a Naval Health Research Center San Diego, Calif. (NHRC) Air Force Institute for San Antonio, Tex. 1976 Operational Health (AFIOH) aNaval Respiratory Disease Laboratory (NRDL) was established in 1996 as one of six depart- ments of the Naval Health Research Center (NHRC). SOURCE: Adapted from: DoD-GEIS Website http://www.geis.fhp.osd.mil/. NHRC informa- tion adapted from FY06 Annual Summary Report, NHRC.

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 REVIEW OF THE DOD-GEIS INFLUENZA PROGRAMS donesia; 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; the U.S. Army Medical Research Unit-Kenya (USAMRU-K) in Nairobi; the U.S. Naval Medical Research Center Detachment (NMRCD) based in Lima, Peru; the Naval Health Research Center in San Diego (NHRC); the Air Force Institute for Operational Health in San Antonio (AFIOH); and the U.S. Army Medical Research Institute of Infectious Diseases in Fort Detrick (USAMRIID). The work of these five overseas laboratories is considerable and in- cludes basic and applied research; public health surveillance; capacity build- ing in the host countries by training scientists and developing laboratories and institutions; and, upon request, the provision of assistance to host countries during humanitarian emergencies (Gambel and Hibbs, 1996). These laboratories, varying in size and capability, have field activities that operate in other nearby countries and beyond, often with limited facilities within their regions of operation. Together with the three domestic DoD- GEIS-affiliated medical laboratories they work to address the four stated goals of GEIS: • Surveillance and detection • Response and readiness • Integration and innovation • Cooperation and capacity building In relation to these four goals, GEIS monitors all infectious diseases in military forces, with respiratory diseases, especially influenza, gastrointesti- nal infections, and febrile illness syndromes, primarily dengue and malaria, included among the priority surveillance operations. Since its formation in 1997, GEIS has maintained a focus on surveillance and respiratory diseases. The $39 million Congressional Supplement allocated in fiscal year 2006 by HR 2863 for pandemic and avian influenza—which in turn prompted the IOM evaluation detailed in this report—represented a fivefold increase in the annual GEIS budget and significantly enhanced the operations of both the GEIS-affiliated overseas and domestic laboratories (DoD-GEIS, 2006). More specifically, HR 2863 allowed DoD-GEIS to address the follow- ing goals: • Increase worldwide surveillance • Upgrade existing surveillance • Upgrade laboratory capability • Establish a surveillance information network among all elements (Erickson, 2006)

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 INTRODUCTION The worth of these overseas laboratories has been considered by a variety of related parties, and they have consistently concluded that the laboratories and the network that they form play an important role in addressing the challenges that emerging infectious diseases present to the international community, particularly those in developing countries that lack basic laboratories and epidemiologic capabilities. In a 2006 article published in Lancet Infectious Diseases, a global network of broad-based laboratories was proposed as a way to address some of these challenges, and the five DoD military overseas laboratories were offered as the model for this new network, perhaps due in part to the unique advantages and ca- pabilities they offer. “Access to the natural environments in which diseases occur is crucial if research to prevent and control infectious diseases is to progress, and if tools, such as diagnostics, vaccines, and chemoprophylactic agents . . . are to be properly tested” (Gambel and Hibbs, 1996). 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 influenza surveillance network was established to monitor host- country populations in areas where little was known about disease epidemi- ology, 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 coun- tries, including Indonesia, this DoD-GEIS network is a key way through which information on circulating influenza strains flows to the World Health Organization (WHO) (Chretien et al., 2006a). The importance of military laboratories was also noted in a 1998 WHO report, which sum- marized the findings of three surveys conducted to evaluate the possibility of including military laboratories in the WHO network and concluded that “a wealth of information is obtained by military laboratories and health- care facilities on populations at high risk for infectious diseases” (D’Amelio and Heymann, 1998). Between October 1, 2003, and February 28, 2006, the DoD-GEIS labo- ratories, working in conjunction with the 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 influenza A (H5N1) in Egypt, Indonesia, Iraq, Kazakhstan, and Turkey. Additionally, they 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). Military forces in a number of developing countries work closely with their ministries of health to help to strengthen their infectious disease sur- veillance and control programs. In turn, a number of activities performed

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 REVIEW OF THE DOD-GEIS INFLUENZA PROGRAMS by the DoD overseas laboratories are done so in collaboration with the host-country military, and two of these five laboratories are hosted by the foreign militaries: the Peruvian Navy hosts NMRCD in Lima and the Royal Thai Army (RTA) hosts AFRIMS in Bangkok. Examples of their collab- orative efforts include a unit-based surveillance system developed by RTA and AFRIMS to improve infectious disease surveillance in remote areas of Thailand along the country’s borders with Cambodia and the Lao People’s Democratic Republic and also an electronic disease surveillance system, Alerta, developed by the Peruvian Navy and NMRCD. Before the develop- ment of this system, the Peruvian Navy had relied on a time-consuming paper-based reporting system (Chretien et al., 2007). CHARGE TO THE COMMITTEE The Department of Defense requested that an IOM committee conduct an evaluation of what has been done in the Avian Influenza Surveillance and Response effort in fiscal year 2006 and fiscal year 2007 under the DoD-GEIS program. The committee was directed to provide advice on improving surveillance and response efforts in fiscal years 2006-2008 and to recommend additional surveillance and response efforts that could be un- dertaken to enhance the likelihood of early detection and timely response to an influenza pandemic. The committee was also required to provide recom- mendations for changes in support of surveillance and research related to avian influenza and pandemic influenza (AI/PI) preparedness and response. And, in addition, the committee was to perform site visits to DoD elements in receipt of DoD-GEIS AI/PI surveillance funding, including the five over- seas DoD medical research laboratories (Bangkok, Jakarta, Cairo, Nairobi, and Lima), the Air Force Institute for Operational Health (AFIOH) in San Antonio, and the Naval Health Research Center (NHRC) in San Diego. Specifically, the evaluation of the DoD-GEIS AI/PI surveillance program was to address the following: (a) The utility of each funded project’s contribution to a comprehen- sive 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, HR1815, Pandemic Avian Flu Preparedness (d) Consistency with the DoD and national plans (e) Coordination of efforts with the Centers for Disease Control and Prevention, the World Health Organization, and local governments

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 INTRODUCTION THE STUDY PROCESS At the request of GEIS management, the IOM convened a committee, the Committee for the Assessment of DoD-GEIS Influenza Surveillance and Response Programs. The study began in December 2006, with a meeting held in Washington, D.C., to familiarize the committee with GEIS, its use of the supplemental funding, its related priorities and goals, its coordination with other organizations, governments, national plans, and so forth. This committee meeting, which was open to the public, involved representatives from GEIS headquarters, NHRC and AFIOH, and a number of other in- stitutions, including CDC, the Office of the Assistant Secretary of Defense for Health Affairs, the Homeland Security Council of the White House, the Department of Infectious Diseases at St. Jude Children’s Research Hospital, and the Food and Drug Administration. Thereafter, committee members made site visits to recipients of the GEIS AI/PI supplement, including the five DoD overseas laboratories and NHRC and AFIOH. In March 2007, teams of two or three committee members each visited NMRCD in Lima; NAMRU-2 in Jakarta plus a trip to Phnom Penh, Cambodia; AFRIMS in Bangkok plus a trip to Kathmandu, Nepal; NAMRU-3 in Cairo; the USAMRU-K field site in Kisumu, Kenya plus a trip to Entebbe, Uganda; NHRC in San Diego; and AFIOH in San Antonio. Lastly, a delegation of committee members participated in a meet- ing at GEIS Headquarters in Silver Spring, MD, where they were able to discuss in detail the management and oversight roles of that office. The visits lasted approximately five days at each overseas laboratory and two days at each domestic lab. Each member of the committee partici- pated in at least one visit. During these visits, committee members toured laboratory facilities, attended briefings and presentations, and met with laboratory staff and collaborators, including representatives from CDC, WHO, national ministries of health, and local hospitals and public health laboratories. In total, eight site visits and three committee meetings (one of which was open to the public) were held during the course of the study. The committee focused its review on the development of conclusions and recommendations with long-term, program-level relevance as well as the improvement of specific DoD-GEIS projects. The committee used WHO and CDC guidelines as reference tools in conducting this review.1 In the remainder of this report, chapters 2 through 9 present the 1 Overview of WHO Framework for Monitoring & Evaluating Surveillance and Response Systems for Communicable Diseases; Updated Guidelines for Evaluating Public Health Sur- veillance Systems; Influenza Pandemic Plan: The Role of WHO and Guidelines for National and Regional Planning.

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0 REVIEW OF THE DOD-GEIS INFLUENZA PROGRAMS committee’s assessments of DoD-GEIS implementation at the DoD-GEIS headquarters, at overseas laboratories, and at sites within the military health system. These chapters include discussions of the individual DoD units’ pandemic/avian influenza activities as they relate to management and planning, surveillance, response capacity, capacity building, and collabora- tion and coordination.2 A final chapter provides summary conclusions and recommendations regarding DoD-GEIS’s AI/PI activities as a whole. REFERENCES Bancroft, W. H., and C. Schlagel. 1997. Implementation of DoD emerging infectious disease surveillance and response system. Memorandum for Commander, U.S. Army Medical Research and Materiel Command, Commanding Officer, U.S. Naval Medical Research and Development Command. Department of the Army, U.S. Department of Defense, Ft. Detrick, Md., June 9, 1997. On file with the National Academies Public Access Records Office. Canas, L. C., K. Lohman, J. A. Pavlin, T. Endy, D. L. Singh, P. Pandey, M. P. Shrestha, R. M. Scott, K. L. Russell, D. Watts, M. Hajdamowicz, I. Soriano, R. W. Douce, J. Neville, and J. C. Gaydos. 2000. The Department of Defense laboratory-based global influenza surveillance system. Military Medicine 165(7 Suppl. 2):52-56. Chretien, J. P., J. C. Gaydos, J. L. Malone, and D. L. Blazes. 2006a. Global network could avert pandemics. Nature 440(7080):25-26. Chretien, J. P., D. L. Blazes, J. C. Gaydos, S. A. Bedno, R. L. Coldren, R. C. Culpepper, D. J. Fyrauff, K. C. Earhart, M. M. Mansour, J. S. Glass, M. D. Lewis, B. L. Smoak, and J. L. . Malone, 2006b. Experience of a global laboratory network in responding to infectious disease epidemics. Lancet Infectious Diseases 6(9):538-540. Chretien, J. P., D. L. Blazes, R. L. Coldren, M. D. Lewis, J. Gaywee, K. Kana, N. Sirisopana, V. Vallejos, C. C. Mundaca, S. Montano, G. J. Martin, and J. C. Gaydos. 2007. The im- portance of militaries from developing countries in global infectious disease surveillance. Bulletin of the World Health Organization 85(3):174-180. Claas, E. C., A. D. Osterhaus, R. van Beek, J. C. De Jong, G. F. Rimmelzwaan, D. A. Senne, S. Krauss, K. F. Shortridge, and R. G. Webster. 1998. Human influenza A H5N1 virus related to a highly pathogenic avian influenza virus. Lancet 351(9101):472-477. Crosby, A. 1989. America’s forgotten pandemic. Cambridge, England: Cambridge University Press. D’Amelio, R., and D. L. Heymann. 1998. Can the military contribute to global surveillance and control of infectious diseases? Emerging Infectious Diseases 4(4):704-705. DoD-GEIS (Department of Defense Global Emerging Infections System). 2006. DoD Global Emerging Infections Surveillance and Response System annual report fiscal year 00. Silver Spring, MD: Walter Reed Army Institute for Research Dowdle, W. R. 1999. Influenza A virus recycling revisited. Bulletin of the World Health Or- ganization 77(10):820-828. Ducatez, M. F., C. M. Olinger, A. A. Owoade, S. De Landtsheer, W. Ammerlaan, H. G. Niesters, A. D. Osterhaus, R. A. Fouchier, and C. P. Muller. 2006. Multiple introductions of H5N1 in Nigeria. Nature 442(7098):37. 2 The chapters on the two domestic laboratories do not include sections on capacity building.

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 INTRODUCTION Erickson, R. L. 2006. The DoD-GEIS influenza surveillance and response programs: Charge to the IOM committee. PowerPoint presentation at first meeting of the IOM Committee for the Assessment of DoD-GEIS, December 19, Washington, D.C. FAO (Food and Agricultural Organization of the United Nations). 2007. Combining poultry vaccination with other disease control measures to combat HN. http://www.fao.org/ newsroom/en/news/2007/1000527/index.html (accessed July 27, 2007). Francis, T. 1954. Vaccination against influenza. In Influenza, a review of current research. Ed. by WHO. Geneva: World Health Organization. Pp. 125-140. Gambel, J. M. and R. G. Hibbs, Jr. 1996. U.S. military overseas medical research laboratories. Military Medicine 161(11):638-645. IOM (Institute of Medicine). 2001. Perspectives on the Department of Defense Global Emerg- ing Infections Surveillance and Response System: A program review. Washington, DC: National Academy Press. IOM. 2004. The threat of pandemic influenza: Are we ready? Washington, DC: The National Academies Press. Kendal, A. P., G. R. Noble, J. J. Skehel, and W. R. Dowdle. 1978. Antigenic similarity of in- fluenza A (H1N1) viruses from epidemics in 1977-1978 to Scandinavian strains isolated in epidemics of 1950-1951. Virology 89(2):632-636. Kilbourne, E. D. 2006. Influenza pandemics of the 20th century. Emerging Infectious Diseases 12(1):9-14. Morens, D. M., and A. S. Fauci. 2007. The 1918 influenza pandemic: Insights for the 21st century. Journal of Infectious Diseases 195(7):1018-1028. Nakajima, K., U. Desselberger, and P. Palese. 1978. Recent human influenza A (H1N1) viruses are closely related genetically to strains isolated in 1950. Nature 274(5669):334-339. NSTC (National Science and Technology Council, Executive Office of the President). 1996. Presidential decision directive NSTC-: Emerging infections. Washington, DC: National Science and Technology Council, Executive Office of the President. Payne, A. M. 1958. Some aspects of the epidemiology of the 1957 influenza pandemic. Journal of the Royal Society of Medicine. 51(12):1009-1015. Potter, C. W. 2001. A history of influenza. Journal of Applied Microbiology 91(4):572-579. Salzberg, S. L., C. Kingsford, G. Cattoli, D. J. Spiro, D. A. Janies, M. M. Aly, I. H. Brown, E. Couacy-Hymann, G. M. De Mia, H. D. Do, A. Guercio, T. Joannis, A. S. M. Ali, A. Osmani, I. Padalino, M. D. Saad, V. Savic, N. A. Sengamalay, S. Yingst, J. Zaborsky, O. Zorman-Rojs, E. Ghedin, and I. Capua. 2007. Genome analysis linking recent European and African influenza (H5N1) viruses. Emerging Infectious Diseases 13(5):713-718. Smith, G. J., X. H. Fan, J. Wang, K. S. Li, K. Qin, J. X. Zhang, D. Vijaykrishna, C. L. Cheung, K. Huang, J. M. Rayner, J. S. Peiris, H. Chen, R. G. Webster, and Y. Guan. 2006. Emer- gence and predominance of an H5N1 influenza variant in China. Proceedings of the National Academy of Science of the USA 103(45):16936-16941. Taubenberger, J. K., and D. M. Morens. 2006. 1918 influenza: The mother of all pandemics. Emerging Infectious Diseases 12(1):15-22. Tumpey, T. M., C. F. Basler, P. V. Aguilar, H. Zeng, A. Solorzano, D. E. Swayne, N. J. Cox, J. M. Katz, J. K. Taubenberger, P. Palese, and A. Garcia-Sastre. 2005. Characterization of the reconstructed 1918 Spanish influenza pandemic virus. Science 310(5745):77-80. U.S. Fish and Wildlife Service. 2007. Nations with confirmed cases HN avian influenza. http://www.pandemicflu.gov/ (accessed July 27, 2007). Woodward, T.E. 1994. The Armed Forces Epidemiological Board: The histories of the com- missions. Washington, DC: Borden Institute, Office of the Surgeon General. WHO (World Health Organization). 2005. Avian influenza frequently asked questions. http:// www.who.int/csr/disease/avian_influenza/avian_faqs/en/index.html (accessed July 27, 2007).

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 REVIEW OF THE DOD-GEIS INFLUENZA PROGRAMS WHO. 2007a. HN avian influenza: Timeline of major events. http://www.who.int/csr/ disease/avian_influenza/timeline_07_07_2007.pdf (accessed July 27, 2007). WHO. 2007b. Cumulative number of confirmed human cases of avian influenza A/(HN) reported to WHO. http://www.who.int/csr/disease/avian_influenza/country/cases_table_ 2007_07_25/en/index.html (accessed July 27, 2007).