Beigel_edit.qxp 19/11/07 02:17 Page 33
Medical Options in the Event of an Influenza Pandemic
that peramivir remains tightly bound to the neuraminidase (t
1
⁄ 2
>24 hours), mouse model.
30
The disadvantage of monoclonal antibodies is the
whereas zanamivir and oseltamivir carboxylate dissociate rapidly from the possibility that viral mutations would render a monoclonal antibody
enzyme (t
1
⁄ 2
= 1.25 hours).
26
A single IM dose of peramivir up to 48 hours ineffective, and clinical studies to develop polyclonal immune globulin are
post-infection gave complete protection against a lethal dose of influenza currently under way.
in mouse models.
26
T-705 is a pyrazine derivative similar to ribavirin and is a potent inhibitor
Other antiviral agents are in
of RNA synthesis. Unlike the currently licensed anti-influenza agents, this
compound has activity against influenza A, B, and C viruses.
27
T-705 development, and offer intriguing
given up to 96 hours after infection was 89% protective against H5N1 in
insights into antiviral therapy in the
mouse models.
28
future, although currently their use
should be limited to controlled
…combination therapy with oseltamivir
clinical trials.
and amantadine in a mouse model
increased the survival rate compared
Lastly, borrowing the paradigm of combination therapy from other
with single-drug therapy with either
infectious diseases, combination therapy with oseltamivir and amantadine
in a mouse model increased the survival rate compared with single-drug
drug alone.
therapy with either drug alone.
2
Recommendations
Early administration of convalescent blood products in the 1918 pandemic Based on currently available antivirals, oseltamivir at standard doses would
was shown to halve the mortality from 37% among controls to 16% be the primary treatment in the event of an influenza pandemic.
19
Zanamivir
among treated patients.
29
As these were poorly designed studies, it is could be tried, with recognition of its limitations as discussed above.
unclear whether the perceived benefit was due to antibodies in the plasma Rimantidine and amantadine would generally not be used for pandemic
or other factors. influenza unless the circulating strain was known to be susceptible or other
antivirals were not available.
19
Other antiviral agents are in development,
Several monoclonal antibodies demonstrated 100% efficacy in preventing and offer intriguing insights into antiviral therapy in the future, although
death up to 72 hours after infection in a lethal H5N1 Vietnam 1203/04 currently their use should be limited to controlled clinical trials. ■
1. Springer GF, Schwick HG, Fletcher MA, The relationship of the 12. Clark IA, The advent of the cytokine storm, Immunol Cell Biol, 22. Treanor JJ, Hayden FG, Vrooman PS, et al., Efficacy and safety of
influenza virus inhibitory activity of glycoproteins to their 2007;85(4):271–3. the oral neuraminidase inhibitor oseltamivir in treating acute
molecular size and sialic acid content, Proc Natl Acad Sci U S A, 13. La Gruta NL, Kedzierska K, Stambas J, Doherty PC, A question of influenza: a randomized controlled trial. US Oral Neuraminidase
1969;64(2):634–41. self-preservation: immunopathology in influenza virus infection, Study Group, JAMA, 2000;283(8):1016–24.
2. Ilyushina NA, Hoffmann E, Solomon R, et al., Amantadine- Immunol Cell Biol, 2007;85(2):85–92. 23. Tran TH, Nguyen TL, Nguyen TD, et al., Avian influenza A (H5N1) in
oseltamivir combination therapy for H5N1 influenza virus infection 14. Salomon R, Hoffmann E, Webster RG, Inhibition of the cytokine 10 patients in Vietnam, N Engl J Med, 2004;350(12):1179–88.
in mice, Antivir Ther, 2007;12(3):363–70. response does not protect against lethal H5N1 influenza infection, 24. Cass LM, Efthymiopoulos C, Bye A, Pharmacokinetics of zanamivir
3. Suzuki Y, Ito T, Suzuki T, et al., Sialic acid species as a determinant Proc Natl Acad Sci U S A, 2007;104(30):12479–81. after intravenous, oral, inhaled or intranasal administration to
of the host range of influenza A viruses, J Virol, 2000;74(24): 15. Szretter KJ, Gangappa S, Lu X, et al., Role of host cytokine healthy volunteers, Clin Pharmacokinet, 1999;36(Suppl. 1):1–11.
11825–31. responses in the pathogenesis of avian H5N1 influenza viruses in 25. Gubareva LV, Webster RG, Hayden FG, Comparison of the activities
4. Shinya K, Ebina M, Yamada S, et al., Avian flu: influenza virus mice, J Virol, 2007;81(6):2736–44. of zanamivir, oseltamivir, and RWJ-270201 against clinical isolates
receptors in the human airway, Nature, 2006;440(7083):435–6. 16. de Jong MD, Tran TT, Truong HK, et al., Oseltamivir resistance of influenza virus and neuraminidase inhibitor-resistant variants,
5. van Riel D, Munster VJ, de Wit E, et al., H5N1 virus attachment to during treatment of influenza A (H5N1) infection, N Engl J Med, Antimicrob Agents Chemother, 2001;45(12):3403–8.
lower respiratory tract, Science, 2006;312(5772):399. 2005;353(25):2667–72. 26. Bantia S, Parker CD, Ananth SL, et al., Comparison of the anti-
6. Adamson IY, Bowden DH, The type 2 cell as progenitor of alveolar 17. Bright RA, Shay DK, Shu B, et al., Adamantane resistance among influenza virus activity of RWJ-270201 with those of oseltamivir
epithelial regeneration. A cytodynamic study in mice after influenza A viruses isolated early during the 2005–2006 influenza and zanamivir, Antimicrob Agents Chemother, 2001;45(4):1162–7.
exposure to oxygen, Lab Invest, 1974;30(1):35–42. season in the United States, JAMA, 2006;295(8):891–4. 27. Furuta Y, Takahashi K, Fukuda Y, et al., In vitro and in vivo
7. Evans MJ, Cabral LJ, Stephens RJ, Freeman G, Transformation of 18. Hurt AC, Selleck P, Komadina N, et al., Susceptibility of highly activities of anti-influenza virus compound T-705, Antimicrob
alveolar type 2 cells to type 1 cells following exposure to NO
2
, pathogenic A(H5N1) avian influenza viruses to the neuraminidase Agents Chemother, 2002;46(4):977–81.
Exp Mol Pathol, 1975;22(1):142–50. inhibitors and adamantanes, Antiviral Res, 2007;73(3):228–31. 28. Sidwell RW, Barnard DL, Day CW, et al., Efficacy of orally
8. Evans MJ, Stephens RJ, Freeman G, Effects of nitrogen dioxide on 19. Schunemann HJ, Hill SR, Kakad M, et al., WHO Rapid Advice administered T-705 on lethal avian influenza A (H5N1) virus
cell renewal in the rat lung, Arch Intern Med, 1971;128(1):57–60. Guidelines for pharmacological management of sporadic human infections in mice, Antimicrob Agents Chemother, 2007;51(3):
9. Beigel JH, Farrar J, Han AM, et al., Avian influenza A (H5N1) infection with avian influenza A (H5N1) virus, Lancet Infect Dis, 845–51.
infection in humans, N Engl J Med, 2005;353(13):1374–85. 2007;7(1):21–31. 29. Luke TC, Kilbane EM, Jackson JL, Hoffman SL, Meta-analysis:
10. de Jong MD, Simmons CP, Thanh TT, et al., Fatal outcome of 20. Hayden FG, Osterhaus AD, Treanor JJ, et al., Efficacy and safety of convalescent blood products for Spanish influenza pneumonia: a
human influenza A (H5N1) is associated with high viral load and the neuraminidase inhibitor zanamivir in the treatment of future H5N1 treatment?, Ann Intern Med, 2006;145(8):599–609.
hypercytokinemia, Nat Med, 2006;12(10):1203–7. influenza virus infections. GG167 Influenza Study Group, N Engl J 30. Simmons CP, Bernasconi NL, Suguitan AL, et al., Prophylactic and
11. Uiprasertkul M, Puthavathana P, Sangsiriwut K, et al., Influenza A Med, 1997;337(13):874–80. therapeutic efficacy of human monoclonal antibodies against
H5N1 replication sites in humans, Emerg Infect Dis, 2005;11(7): 21. Nicholson K, Webster RG, Hay AJ, Textbook of Influenza,Blackwell H5N1 influenza, PLoS Med, 2007;4(5):e178.
1036–41. Science, 1998.
US INFECTIOUS DISEASE 2007 33
Page 1  |  Page 2  |  Page 3  |  Page 4  |  Page 5  |  Page 6  |  Page 7  |  Page 8  |  Page 9  |  Page 10  |  Page 11  |  Page 12  |  Page 13  |  Page 14  |  Page 15  |  Page 16  |  Page 17  |  Page 18  |  Page 19  |  Page 20  |  Page 21  |  Page 22  |  Page 23  |  Page 24  |  Page 25  |  Page 26  |  Page 27  |  Page 28  |  Page 29  |  Page 30  |  Page 31  |  Page 32  |  Page 33  |  Page 34  |  Page 35  |  Page 36  |  Page 37  |  Page 38  |  Page 39  |  Page 40  |  Page 41  |  Page 42  |  Page 43  |  Page 44  |  Page 45  |  Page 46  |  Page 47  |  Page 48  |  Page 49  |  Page 50  |  Page 51  |  Page 52  |  Page 53  |  Page 54  |  Page 55  |  Page 56  |  Page 57  |  Page 58  |  Page 59  |  Page 60  |  Page 61  |  Page 62  |  Page 63  |  Page 64  |  Page 65  |  Page 66  |  Page 67  |  Page 68