eBriefing

Flu Preparedness: Lessons Learned, Action Plans & New Directions

Flu Preparedness
Reported by
Marilynn Larkin

Posted February 23, 2007

Overview

Will the avian influenza virus H5N1 cause the next human pandemic? We don't know, but we must be prepared nonetheless, stressed experts participating in a briefing on influenza preparedness sponsored by the Emerging Infectious Diseases Discussion Group and held at the New York Academy of Sciences on October 23, 2006.

The prospect of an influenza pandemic is daunting, but there is some reason for optimism. Studies of the 1918 pandemic virus suggest it is sensitive to currently available vaccines and antiviral therapy. And lessons learned from that pandemic suggest that, even in the face of vaccine and antiviral shortages, a variety of nondrug interventions, from social distancing to hand washing, can help control a pandemic and limit its spread. Moreover, if H5N1 is, indeed, the culprit, humans may have partial immunity because of prior exposure to H1N1 viruses.

These themes were echoed throughout the meeting, with each speaker providing data and insights from different perspectives.

Web Sites

New York City Department of Health and Mental Hygiene
The Bureau of Communicable Disease at the New York City Department of Health and Mental Hygiene maintains a web site with information about New York City's efforts to prepare for avian flu and pandemic flu.

FAO's Animal Production and Health Division
The Food and Agriculture Organization of the United Nations's Animal Production and Health Division is working to educate and monitor poultry handlers worldwide in an effort to contain avian flu.

Epidemic and Pandemic Alert and Response (EPR) Site at The World Health Organization
The EPR site contains a wealth of information about international efforts to detect and contain epidemics. It has an avian influenza page that discusses the evolving situation and provides access to both technical guidelines, including the WHO global influenza preparedness plan, and information useful for the general public.

UN System Influenza Coordination (UNSIC)
The UN System Influenza Coordination (UNSIC) has been created within the UN Development Group to help ensure that the UN system responds to national, regional and global challenges in relation to influenza. Their web site contains maps showing global avian flu incidence, links to various plans for preparing for a pandemic, and other resources.

PandemicFlu.gov
Advertised as "One-stop access to U.S. Government avian and pandemic flu information," and managed by the Department of Health and Human Services, this Web site contains plans for preparing for a pandemic from the national level to the individual and family level You can also download the February 1, 2007, CDC report on nonpharmaceutical interventions against pandemic here.

Avian Influenza information from UNICEF
This Web site outlines UNICEF's efforts to use its extensive network to help control bird flu and prepare for a possible pandemic.


Books

Department of Health and Human Services, Centers for Disease Control. 2007. Interim Pre-pandemic Planning Guidance: Community Strategy for Pandemic Influenza Mitigation in the United States - Early Targeted Layered use of Non-Pharmaceutical Interventions. FULL TEXT (PDF, 10.2 MB)

Holtz TH, Leighton J, Balter S, et al. 2003. The public health response to the World Trade Center disaster, New York City. In Sidel VW, Levy BS, eds. Terrorism and Public Health. Oxford University Press, New York.
Amazon | Barnes & Noble

Homeland Security Council. 2006. Homeland Security Council. National Strategy for Pandemic Influenza Implementation Plan. Full Text

Morse SS, ed. 1993. Emerging Viruses. Oxford University Press, New York.
Amazon | Barnes & Noble


Journal Articles

Influenza and Influenza Viruses: An Introduction

Falcón AM, Fernandez-Sesma Y, Nakaya T, et al. 2005. Attenuation and immunogenicity in mice of temperature-sensitive influenza viruses expressing truncated NS1 proteins. J. Gen. Virol. 86: 2817-2821. Full Text

Kopecky-Bromberg SA, Martinez-Sobrido L, Friedman M, et al. 2007. Severe acute respiratory syndrome coronavirus open reading frame (ORF) 3B, ORF 6, and nucleocapsid proteins function as interferon antagonists. J Virol. 8: 548-557.

Lowen AC, Mubareka S, Tumpey TM, et al. 2006. The guinea pig as a transmission model for human influenza viruses. Proc. Natl. Acad. Sci. USA 103: 9988-9992. Full Text

Palese P. 2006. Making better influenza virus vaccines? Emerg. Infect. Dis. 12: 61-65.

Park MS, Steel J, García-Sastre A, et al. 2006. Engineered viral vaccine constructs with dual specificity: avian influenza and Newcastle disease. Proc. Natl. Acad. Sci. USA 103: 8203-8208. Full Text

Tumpey TM, Basler CF, Aguilar PV, et al. 2005. Characterization of the reconstructed 1918 Spanish influenza pandemic virus. Science 310: 77-80.

Zamarin D, García-Sastre A, Xiao X, et al. 2005. Influenza virus PB1-F2 protein induces cell death through mitochondrial ANT3 and VDAC1. PLoS Pathog. 1: e4. Full Text

Zamarin D, Ortigoza MB, Palese P. 2006. Influenza A virus PB1-F2 protein contributes to viral pathogenesis in mice. J Virol. Aug; 80: 7976-7983. Full Text

Can Vaccines Stop the Next Influenza Virus Pandemic? A Virologist's Perspective

Basler CF, García-Sastre A. 2002. Viruses and the type I interferon antiviral system: induction and evasion. Int. Rev. Immunol. 21: 305-337.

Fernandez A, Marukian S, Ebersole BJ, et al. 2006. Influenza virus evades innate and adaptive immunity via the NS1 protein. J. Virol. 80: 6295-6304. Full Text

Fodor E, Devenish OG, Engelhardt P, et al. 1999. Rescue of influenza A virus from recombinant DNA. J. Virol. 73: 9679-9682. Full Text

García-Sastre A, Egorov A, Matassov D, et al. 1998. Influenza A virus lacking the NS1 gene replicates in interferon-deficient systems. Virology 252: 324-330.

García-Sastre A, Biron CB. 2006. Type 1 interferon and the virus-host relationship: A lesson in détente. Science, 312, 879-882.

Nakaya T, Cros J, Park M-S, et al, 2001. Recombinant Newcastle disease virus as a vaccine vector. J. Virol. 75: 11868-11873. Full Text

Palese P, García-Sastre A. 2002. Influenza vaccines: present and future. J. Clin. Invest. 110: 9-13. Full Text

Park M-S, Steel J, García-Sastre A, et al. 2006. Engineered viral vaccine constructs with dual specificity: Avian influenza and Newcastle disease. Proc. Natl. Acad. Sci. USA 103: 8203-8208. Full Text

Quinlivan M, Zamarin D, García-Sastre A, et al. 2005. Attenuation of equine influenza viruses through truncations of the NS1 protein. J. Virol. 79: 8431-8439. Full Text

Richt JA, Lekcharoensuk P, Lager KM, et al. 2006. Vaccination of pigs against swine influenza viruses using an NS1-truncated modified live virus vaccine. J. Virol. 80: 11009-11018.

Schickli JH, Flandorfer A, Nakaya T, et al. 2001. Plasmid-only rescue of influenza A virus vaccine candidates. Philos. Trans. R. Soc. Lond. B. Biol. Sci. 356: 1965-1973.

Solórzano A, Webby RJ, Lager KM, et al. 2005. Mutations in the NS1 protein of swine influenza virus impair anti-interferon activity and confer attenuation in pigs. J. Virol. 79: 7535-7543. Full Text

Swayne DE, Suarez DL, Schultz-Cherry S, et al. 2003. Recombinant paramyxovirus type 1 avian influenza H7 virus as a vaccine for protection of chickens against influenza and Newcastle disease. Avian Dis. 47: 1047-1050.

Talon J, Salvatore M, O'Neill RE, et al. 2000. Influenza A and B viruses expressing altered NS1 proteins: a vaccine approach. Proc. Natl. Acad. Sci. USA 97: 4309-4314. Full Text

Waiting for the Vaccine to Arrive: Nonpharmaceutical Interventions

Ash C, Roberts L. 2006. Influenza: the state of our ignorance. Science 312: 379. Special issue on influenza.

Enserink M. 2006. Oseltamivir becomes plentiful—but still not cheap. Science 312: 382-383.

Kaiser J. 2006. A one-size-fits-all flu vaccine? Science 312: 380-382.

Kuiken T, Holmes EC, McCauley J, et al. 2006. Host species barriers to influenza virus infections. Science 312: 394-397.

Lu PS. 2006. Early diagnosis of avian influenza. Science 312: 337.

Morse SS. 1995. Factors in the emergence of infectious diseases. Emerg. Infect. Dis. 1: 7-15.

Morse SS, Garwin, RL, Olsiewski PJ. 2006. Next flu pandemic: What to do until the vaccine arrives? Science 314: 929.

Olsen B, Munste VJr, Wallensten A, et al. 2006. Global patterns of influenza A virus in wild birds. Science 312: 384-388.

Olson DR, Simonsen L, Edelson PJ, Morse SS. 2005. Epidemiological evidence of an early wave of the 1918 influenza pandemic in New York City. Proc. Natl. Acad. Sci. USA 102: 11059-11063. Full Text

Regoes RR, Bonhoeffer S. 2006. Emergence of drug-resistant influenza virus: population dynamical considerations. Science 312: 389-391.

Smith DJ. 2006. Predictability and preparedness in influenza control. Science 312: 392-394.

Stevens S, Blixt O, Tumpey TM, et al. 2006. Structure and receptor specificity of the hemagglutinin from an H5N1 influenza virus. Science 312: 404-410.

van Riel D, Munster VJ, de Wit E, et al. 2006. H5N1 virus attachment to lower respiratory tract. Science 312: 399.

Viboud C, Bjørnstad ON, Smith DL, et al. 2006. Synchrony, waves, and spatial hierarchies in the spread of influenza. Science 312: 447-451.

Pandemic Flu Planning in New York City

Jernigan DB, Raghunathan PL, Bell BP, et al. 2002. Investigation of bioterrorism related anthrax, United States, 2001: epidemiologic findings. Emerg. Infect. Dis. 8: 1019-1028.

Weisfuse IB, Berg D, Gasner R, et al. 2006. Pandemic influenza planning in New York City. J. Urban Health 83: 351-354.

Human Infections with Influenza H5N1 Virus: Observations from Vietnam

Beigel JH, Farrar J, Han AM, et al. 2005. Avian influenza A (H5N1) infection in humans. N. Engl. J. Med. 353: 1374-1385. Erratum in: N. Engl. J. Med. 354: 884. Full Text

de Jong MD, Bach VC, Phan TQ, et al. 2005. Fatal avian influenza A (H5N1) in a child presenting with diarrhea followed by coma. N. Engl. J. Med. 352: 686-691.

de Jong MD, Hien TT. 2006. Avian influenza A (H5N1). J. Clin. Virol. 35: 2-13.

de Jong MD, Simmons CP, Thanh TT, et al. 2006. Fatal outcome of human influenza A (H5N1) is associated with high viral load and hypercytokinemia. Nat. Med. 12: 1203-1207.

Hien TT, de Jong M, Farrar J. 2004. Avian influenza—a challenge to global health care structures. N. Engl. J. Med. 351: 2363-2365.

Schultsz C, Dong VC, Chau NV, et al. 2005. Avian influenza H5N1 and healthcare workers. Emerg. Infect. Dis. 11: 1158-1159.

Tran TH, Nguyen TL, Nguyen TD, et al. 2004. Avian influenza A (H5N1) in 10 patients in Vietnam. N. Engl. J. Med. 350: 1179-1188. Full Text

Additional journal articles

Kilpatrick AM, Chmura AA, Gibbons DW, et al. 2006. Predicting the global spread of H5N1 avian influenza. Proc. Natl. Acad. Sci. USA 103: 19215-19216. Full Text

Webster RG, Govorkova EA. 2006. H5N1 Influenza—Continuing Evolution and Spread. N. Engl. J. Med. Vol. 355: 2174-2177 Full Text

Speakers

Peter Palese, PhD

Mount Sinai School of Medicine
e-mail | web site | publications

Peter Palese is a professor of microbiology and chair of the Department of Microbiology at the Mount Sinai School of Medicine in New York. He has over 200 scientific publications that include research on the replication of RNA-containing viruses with a special emphasis on influenza viruses, which are negative-strand RNA viruses. Specifically, he established the first genetic maps for influenza A, B and C viruses, identified the function of several viral genes, and defined the mechanism of neuraminidase inhibitors (which are now FDA-approved antivirals).

Palese also pioneered the field of reverse genetics for negative strand RNA viruses, which allows the introduction of site-specific mutations into the genomes of these viruses. This technique is crucial for the study of the structure/function relationships of viral genes, for investigation of viral pathogenicity and for development of novel vaccines.

Palese's group was also involved in the reconstruction and the study of viruses containing genes of the highly virulent but extinct 1918 pandemic influenza virus. His recent work in collaboration with García-Sastre has revealed that most negative strand RNA viruses possess proteins with interferon antagonist activity, enabling them to counteract the antiviral response of the infected host. Palese was elected to the National Academy of Sciences in 2000 for his seminal studies on influenza viruses. At present he serves on the editorial board for the Proceedings of the National Academy of Sciences and as an editor for the Journal of Virology. Palese was president of the Harvey Society and the American Society for Virology in 2004.

He received his PhD in chemistry from the University of Vienna.

Adolfo García-Sastre, PhD

Mount Sinai School of Medicine
e-mail | web site | publications

Adolfo García-Sastre is professor in the Department of Microbiology of Mount Sinai School of Medicine in New York. For the past 15 years, his research interest has been focused on the molecular biology of influenza viruses and several other negative strand RNA viruses. During his postdoctoral training in the early 1990s, he developed, for the first time, novel strategies for expression of foreign antigens by a negative strand RNA virus, influenza virus. His research has resulted in more than 100 scientific publications and reviews.

Together with Charlie Rice at the Rockefeller University, García-Sastre is the leader of the basic research component on Viral Therapeutics and Pathogenesis of the North East Biodefense Center proposal, which was recently funded by NIAID and involves the collaboration of more than 20 academic institutions in New York, Connecticut and New Jersey. He is among the first members of the Vaccine Study Section of the NIH. In addition, he is member of the Editorial Board of PLOS Pathogens, Journal of Virology, Virology, Journal of General Virology, and Virus Research. He has been a coorganizer of the international course on Viral Vectors (2001), held in Heidelberg, Germany, sponsored by Federation of European Biochemical Societies (FEBS), and of the first Research Conference on Orthomyxoviruses in 2001, held in Teixel, the Netherlands, sponsored by the European Scientific Working Group on Influenza (ESWI). Recently, his publication with Palese and others in Science on the reconstruction and characterization of the pandemic influenza virus of 1918 has been awarded with the distinction of the paper of the year 2005 by Lancet.

Stephen S. Morse, PhD

Columbia University
e-mail | web site | publications

Stephen Morse is an associate professor of clinical epidemiology and founding director of the Center for Public Health Preparedness at Columbia University. His professional interests include the epidemiology of emerging infections (a concept he originated), international cooperation for infectious disease surveillance, and defense against bioterrorism. Morse returned to Columbia in 2000 after four years in government service as program manager at the Defense Advanced Research Projects Agency (DARPA), U.S. Department of Defense, where he codirected the Pathogen Countermeasures program and subsequently directed the Advanced Diagnostics program. Before coming to Columbia, he was an assistant professor (virology) at the Rockefeller University in New York, where he remains an adjunct faculty member.

Morse is the editor of two books, Emerging Viruses (Oxford University Press, 1993; paperback, 1996), which was selected by American Scientist for its list of "100 Top Science Books of the 20th Century," and The Evolutionary Biology of Viruses (Raven Press, 1994). He currently serves as a section editor of the CDC journal Emerging Infectious Diseases and was formerly editor-in-chief of the Pasteur Institute's journal Research in Virology.

Morse received his PhD from the University of Wisconsin–Madison.

Isaac B. Weisfuse, MD, MPH

New York City Department of Health and Mental Hygiene
e-mail | web site | publications

Isaac B. Weisfuse is deputy commissioner of the New York City Department of Health and Mental Hygiene. He began his public health career at the Centers for Disease Control and Prevention as an epidemic intelligence service officer. Since 1987 he has worked in public health in New York City at the Health Department. His current responsibilities include prevention and control of communicable diseases, including HIV/AIDS, TB, and STIs, as well as emergency preparedness and public health laboratory services. Weisfuse received his BA and MPH from Columbia University and his MD from the SUNY Downstate Medical Center. He is board certified in internal medicine.

David Nabarro, FRCP, BM, BCh

United Nations
e-mail | web site | publications

David Nabarro was appointed as United Nations System Senior Coordinator for Avian and Human Influenza by UN Secretary General Kofi Annan in 2005. He was seconded to this position, at the level of UN Assistant Secretary-General, by the World Health Organization. Prior to this, Nabarro served for six years at the WHO headquarters in Geneva. He started in 1999 as head of the Roll Back Malaria Program, then was promoted in 2000 to Executive Director in the Office of the then Director-General. In 2002, he led the WHO cluster on Sustainable Development and Healthy Environments. In 2003, he was made head of the newly created Health Action in Crisis group, and special representative of then Director General Lee Jong-Wook.

Nabarro qualified as a physician in 1973, then worked in the UK National Health Service. In 1976 he worked for two years as District Child Health Officer in Dhankuta District, East Nepal. He then moved to the London School of Hygiene and Tropical Medicine (LSHTM), qualifying in public health.

Menno de Jong, MD, PhD

Oxford University Clinical Research Unit, Vietnam
e-mail | web site | publications

Menno de Jong heads the virology labs at the Oxford University Clinical Research Unit at the Hospital for Tropical Diseases in Ho Chi Minh City, Vietnam. He received his MD from the Medical School at the University of Amsterdam in 1990. De Jong received his PhD in 1996 from the Academic Medical Center at the University of Amsterdam for his research on drug failure in the treatment of HIV. He stayed on there to complete medical specialist training for clinical microbiology and became a staff clinical microbiologist, first at Leiden University Medical Center and then at the Academic Medical Center at the University of Amsterdam.


Marilynn Larkin

website

Marilynn Larkin is a medical editor, journalist, and videographer based in New York City. Her work has frequently appeared in, among others, The Lancet, The Lancet Infectious Diseases, and Reuters Health's professional newswire. She is currently head of publications for the Society for Biomolecular Screening.

Ms. Larkin has served as editor of clinical publications for neurologists, anesthesiologists, HIV providers, and long-term care professionals. She also developed physician/patient education videos and continuing medical education symposia for several medical communications companies.

Prior to her work for physician audiences, she covered health, nutrition, fitness, psychology, and travel for women's and general interest magazines. She is also author of five medical books for general readers, and of Reporting on Health Risk, a handbook for journalists.

In 2004, Ms. Larkin started her own fitness consulting company (www.mlarkinfitness.com), and developed a class, Posture-cize, that helps people improve their posture, increase productivity, and reduce injury.