Pandemic Influenza Threat

ABSTRACT
The threat of a human influenza pandemic has greatly increased over the past several years with
the emergence of highly virulent avian influenza viruses, notably H5N1 viruses, which have infected
humans in several Asian and European countries. Previous influenza pandemics have arrived with
little or no warning, but the current widespread circulation of H5N1 viruses among avian populations
and their potential for increased transmission to humans and other mammalian species may afford us
an unprecedented opportunity to prepare for the next pandemic threat. The US Department of Health
and Human Services is coordinating a national strategy to respond to an influenza pandemic that
involves multiple agencies, including the Centers for Disease Control and Prevention, the Food and
Drug Administration, and the National Institutes of Health (NIH). Within NIH, the National Institute
of Allergy and Infectious Diseases (NIAID) conducts basic and clinical research to develop new
vaccine technologies and antiviral drugs against influenza viruses. We describe recent research
progress in preparing for pandemic influenza.

References
[1] Specter M. Nature’s bioterrorist. New Yorker. 2005 Feb 28. p. 50-61.
[2] Webby RJ, Webster RG. Are we ready for pandemic influenza? Science. 2003; 302:
1519-1522.
[3] Monto AS. The threat of and an avian influenza pandemic. N Engl J Med. 2005; 352: 3
23-5.
[4] Stohr K. Avian influenza and pandemics: research needs and opportunities. N Engl J
Med. 2005; 352: 405-7.
[5] Institute of Medicine. The threat of pandemic influenza: are we ready? 2004 Nov [cited
2005 Oct 21]. Available from http://www. iom.edu/report.asp?id=23639
[6] Couch RB. An overview of serum antibody responses to influenza virus antigens. Dev
Biol (Basel). 2003; 115: 25-30.
[7] Reid AH, Taubenberger JK, Fanning TG. The 1918 Spanish influenza: integrating
history and biology. Microbes Infect. 2003; 3: 81-7.
[8] Chen H, Smith GJ, Zhang SY, Qin K, Wang J, Li KS, et al. Avian flu: H5N1 virus
outbreak in migratory water fowl. Nature. 2005; 436: 191-2.
[9] Liu J, Xiao H, Lei F, Zhu Q, Qin K, Zhang X, et al. Highly pathogenic H5N1 influenza
virus infection in migratory birds. Science. 2005; 309: 1206.
[10] Kuiken T, Rimmelzwaan G, van Riel D, van Amerongen G, Baars M, Fouchier R, et al.
Avian influenza in cats. Science. 2004; 306: 241.
[11] Keawcharoen J, Oraveerakul K, Kuiken T, Fouchier RA, Amonsin A, Payungporn S, et
al. Avian influenza in tigers and leopards. Emerg Infect Dis. 2004; 10: 2189-91.
[12] Olsen SJ, Ungchusak K, Sovann L, Uyeki TM, Dowell SF, Cox NJ, et al. Family
clustering of avian influenza A (H5N1). Emerg Infec Dis. 2005; 11: 1799-1801.
[13] Ungchusak K, Auewarakul P, Dowell SF, Kitphati R, Auwanit W, Puthhavathana P, et
al. Probable person-to-person transmission of avian influenza A (H5N1). N Engl J Med.
2005; 352: 333-40.
[14] Peiris M, Yuen KY, Leung CW, Chan KH, Ip PL, Lai RW, et al. Human infection with
influenza H9N2. Lancet. 1999; 354: 916-7.
[15] Choi YK, Ozaki H, Webby RJ, Webster RG, Peiris JS, Poon L, et al. Continuing
evolution of H9N2 influenza viruses in southeastern China. J Virol. 2004; 78: 8609-14.
[16] Guo, Y., J. Li and X. Cheng. Discovery of men infected by avian influenza A (H9N2)
virus. Chinese journal of experimental and clinical virology 13 2 (1999): 105-8
[17] Fouchier RA, Schneeburger PM, Rozendaal FW, Broekman JM, Kemink SA, Munster
V, et al. Avian influenza A virus (H7N7) associated with human conjunctivitis and a
fatal case of acute respiratory distress syndrome. Proc Natl Acad Sci U S A. 2004; 101:
1356-61.
[18] Koopmans M, Wilbrink B, Conyn M, Natrop G, van der Nat H, Vennema H, et al.
Transmission of H7N7 avian influenza A virus to human beings during a large outbreak
in commercial poultry farms in the Netherlands. Lancet. 2004; 363: 587-93.
[19] Fauci AS. Race against time. Nature. 2005; 435: 423-4.
[20] Webby RJ, Perez DR, Coleman JS, Guan Y, Knight JH, Govorkova EA, et al.
Responsiveness to a pandemic alert: use of reverse genetics for rapid development of
influenza vaccines. Lancet. 2004; 363: 1099-103.
[21] Clements ML, Betts RF, Murphy BR. Advantage of live attenuated cold-adapted
influenza A virus over inactivated vaccine for A/Washington/80 (H3N2) wild-type virus
infection. Lancet. 1984; 1: 705-8.
[22] La Montagne JR, Fauci AS. Intradermal influenza vaccination: can less be more? N
Engl J Med. 2004; 351: 2330-2.
[23] Belshe RB, Newman FK, Cannon J, Duane C, Treanor J, van Hoecke C, et al. Serum
antibody responses after intradermal vaccination against influenza. N Engl J Med. 2004;
351: 2286-94.
[24] Kenney RT, Frech SA, Muenz LR, Villar CP, Glenn GM. Dose sparing with
intradermal injection of influenza vaccine. N Engl J Med. 2004; 3 51: 2295-301.
[25] Ward P, Small I, Smith J, Suter P, Dutkowski R. Oseltamivir (Tamiflu) and its potential
for use in the event of an influenza pandemic. J Antimicrob Chemother. 2005; 55(Suppl
1): i5-21.
[26] Sloan FA, Berman S, Rosenbaum S, Chalk RA, Giffin RB. The fragility of the U.S.
vaccine supply. N Engl J Med. 2004; 351: 2443-7.
[27] Poland GA, Marcuse EK. Vaccine availability in the US: problems and solutions. Nat
Immunol. 2004; 5: 1195-8.
[28] Muller MP, McGeer A, Straus SE, Hawryluck L, Gold WL. Clinical trials and novel
pathogens: lessons learned from SARS. Emerg Infect Dis. 2004; 10: 389-94.
[29] Finlay BB, See RH, Brunham RC. Rapid response research to emerging infectious
diseases. Nat Rev Microbiol. 2004; 2: 602-7.