title: Modeling the global transmission of antiviral-resistant influenza viruses.
abstract: BACKGROUND
  The mutations that confer resistance to antiviral agents are thought to be detrimental, or at best neutral, to influenza virus fitness. The fact that resistant influenza strains can circulate and sometimes replace sensitive strains is of great public health concern.
  
  
  OBJECTIVE
  We used mathematical modeling to test various hypotheses about the transmission of antiviral-resistant influenza viruses by comparing the model's output with the observed rise in antiviral resistance of seasonal A(H1N1) influenza viruses between 2006 and 2009.
  
  
  METHODS
  We developed a mathematical model of the transmission of influenza among 321 cities around the globe. In the model, influenza strains resistant to antiviral agents competed with sensitive strains.
  
  
  CONCLUSIONS
  We found that a resistant strain of influenza could not displace the sensitive strain as rapidly as has been observed unless it was more transmissible than the sensitive strain in the general population. We believe that an antiviral-resistant strain displaced the antiviral-sensitive seasonal A(H1N1) virus by hitchhiking on an escape mutation. Because of the complex global patterns of influenza circulation, tracking the emergence and spread of antiviral resistance must be a coordinated global effort.
authors.affiliation: Center for Statistics and Quantitative Infectious Diseases, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. dchao@fhcrc.org
authors.forename: Dennis L
authors.initials: DL
authors.lastname: Chao
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D024882:Drug Resistance, Viral / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D014943:Global Health; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects* / Q000235:genetics; D007251:Influenza, Human / Q000635:transmission* / Q000821:virology; D008954:Models, Biological; D009439:Neuraminidase / Q000037:antagonists & inhibitors; D053139:Oseltamivir / Q000494:pharmacology*
chemical_list: D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D053139:Oseltamivir; D009439:Neuraminidase