This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Calfee, D. P.
Right arrow Articles by Hayden, F. G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Calfee, D. P.
Right arrow Articles by Hayden, F. G.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, July 1999, p. 1616-1620, Vol. 43, No. 7
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Safety and Efficacy of Intravenous Zanamivir in Preventing Experimental Human Influenza A Virus Infection

David P. Calfee,1 Amy W. Peng,2 Lindsey M. Cass,2 Monica Lobo,1 and Frederick G. Hayden1,3,*

Departments of Internal Medicine1 and Pathology,3 University of Virginia Health Sciences Center, Charlottesville, Virginia, and Glaxo Wellcome, Inc., Research Triangle Park, North Carolina2

Received 23 December 1998/Returned for modification 24 February 1999/Accepted 26 April 1999

Zanamivir is a potent inhibitor of influenza A and B virus neuraminidases and is active topically in experimental and natural human influenza. We conducted this double-blinded, placebo-controlled study to evaluate the safety and efficacy of intravenously administered zanamivir. Susceptible volunteers were randomized to receive either saline or zanamivir (600 mg) intravenously twice daily for 5 days beginning 4 h prior to intranasal inoculation with ~105 50% tissue culture infectious doses (TCID50) of influenza A/Texas/36/91 (H1N1) virus. Reductions in the frequency of viral shedding (0% versus 100% in placebo, P < 0.005) and seroconversion (14% versus 100% in placebo, P < 0.005) and decreases in viral titer areas under the curve (0 versus 11.6 [median] log10 TCID50 · day/ml in placebo, P < 0.005) were observed in the zanamivir group, as were reductions in fever (14% versus 88% in placebo, P < 0.05), upper respiratory tract illness (0% versus 100% in placebo, P < 0.005), total symptom scores (1 versus 44 [median] in placebo, P < 0.005), and nasal-discharge weight (3.9 g versus 17.5 g [median] in placebo, P < 0.005). Zanamivir was detectable in nasal lavage samples collected on days 2 and 4 (unadjusted median concentrations, 10.5 and 12.0 ng/ml of nasal wash, respectively). This study demonstrates that intravenously administered zanamivir is distributed to the respiratory mucosa and is protective against infection and illness following experimental human influenza A virus inoculation.

* Corresponding author. Mailing address: University of Virginia Health Sciences Center, Box 473, Charlottesville, VA 22908. Phone: (804) 924-5059. Fax: (804) 924-9065. E-mail: fgh{at}avery.med.virginia.edu.

Antimicrobial Agents and Chemotherapy, July 1999, p. 1616-1620, Vol. 43, No. 7
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Carrat, F., Vergu, E., Ferguson, N. M., Lemaitre, M., Cauchemez, S., Leach, S., Valleron, A.-J. (2008). Time Lines of Infection and Disease in Human Influenza: A Review of Volunteer Challenge Studies. Am J Epidemiol 167: 775-785 [Abstract] [Full Text]  
  • Carroll, T. D., Matzinger, S. R., Genesca, M., Fritts, L., Colon, R., McChesney, M. B., Miller, C. J. (2008). Interferon-Induced Expression of MxA in the Respiratory Tract of Rhesus Macaques Is Suppressed by Influenza Virus Replication. J. Immunol. 180: 2385-2395 [Abstract] [Full Text]  
  • Vynnycky, E., Trindall, A., Mangtani, P. (2007). Estimates of the reproduction numbers of Spanish influenza using morbidity data. Int J Epidemiol 36: 881-889 [Abstract] [Full Text]  
  • Peiris, J. S. M., de Jong, M. D., Guan, Y. (2007). Avian Influenza Virus (H5N1): a Threat to Human Health. Clin. Microbiol. Rev. 20: 243-267 [Abstract] [Full Text]  
  • Thomas, J. K., Noppenberger, J. (2007). Avian influenza: A review. Am J Health Syst Pharm 64: 149-165 [Abstract] [Full Text]  
  • Gupta, R. K., Nguyen-Van-Tam, J. S., de Jong, M. D., Hien, T. T., Farrar, J. (2006). Oseltamivir resistance in influenza A (H5N1) infection.. NEJM 354: 1423-1424 [Full Text]  
  • Wong, S. S. Y., Yuen, K.-y. (2006). Avian Influenza Virus Infections in Humans. Chest 129: 156-168 [Abstract] [Full Text]  
  • McSharry, J. J., McDonough, A. C., Olson, B. A., Drusano, G. L. (2004). Phenotypic Drug Susceptibility Assay for Influenza Virus Neuraminidase Inhibitors. CVI 11: 21-28 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»