title: Neuraminidase inhibitor susceptibility surveillance of influenza viruses circulating worldwide during the 2011 Southern Hemisphere season.
abstract: BACKGROUND
  Neuraminidase (NA) inhibitors (NAIs) are currently the only antivirals effective against influenza infections due to widespread resistance to M2 inhibitors.
  
  
  METHODS
  Influenza A and B viruses (n = 1079) collected worldwide between April 01, 2011, and September 30, 2011, were assessed for susceptibility to FDA-approved NAIs, oseltamivir and zanamivir, and investigational peramivir, using the fluorescent-based NA-Fluor™ Influenza Neuraminidase Assay Kit. A subset of viruses (n = 98) were tested for susceptibility to the investigational NAI, laninamivir.
  
  
  RESULTS
  Influenza A(H1N1)pdm09 viruses (n = 326) were sensitive to all NAIs, except for two (0.6%) with H275Y (N1 numbering; H274Y in N2 numbering) substitution, which exhibited elevated IC50 s for oseltamivir and peramivir, and a third with previously unreported N325K substitution, exhibiting reduced susceptibility to oseltamivir. Influenza A(H3N2) viruses (n = 407) were sensitive to all NAIs. Influenza B viruses (n = 346) were sensitive to all NAIs, except two (0.6%) with H273Y (N1 numbering; H274Y in N2 numbering) substitution, exhibiting reduced susceptibility to oseltamivir and peramivir, and one with previously unreported G140R and N144K substitutions, exhibiting reduced susceptibility to oseltamivir, zanamivir, and peramivir. All influenza A and B viruses were sensitive to laninamivir. It is unknown whether substitutions N325K, G140R, and N144K were present in the virus prior to culturing because clinical specimens were unavailable for testing.
  
  
  CONCLUSIONS
  This study summarizes NAI susceptibility of influenza viruses circulating worldwide during the 2011 Southern Hemisphere (SH) season, assessed using the NA-Fluor™ Kit. Despite low resistance to NAIs among tested influenza viruses, constant surveillance of influenza virus susceptibility to NAIs should be emphasized.
authors.affiliation: Virus Surveillance and Diagnosis Branch, Influenza Division, National Center for Immunization and Respiratory Diseases, WHO Collaborating Center for Surveillance, Epidemiology and Control of Influenza, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Margaret
authors.initials: M
authors.lastname: Okomo-Adhiambo
authors.forename: Katrina
authors.initials: K
authors.lastname: Sleeman
authors.forename: Colleen
authors.initials: C
authors.lastname: Lysén
authors.forename: Ha T
authors.initials: HT
authors.lastname: Nguyen
authors.forename: Xiyan
authors.initials: X
authors.lastname: Xu
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Alexander I
authors.initials: AI
authors.lastname: Klimov
authors.forename: Larisa V
authors.initials: LV
authors.lastname: Gubareva
mesh_terms: D000146:Acids, Carbocyclic; D000349:Africa; D000998:Antiviral Agents / Q000494:pharmacology*; D003517:Cyclopentanes / Q000494:pharmacology; D024882:Drug Resistance, Viral; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D014943:Global Health; D006146:Guanidines / Q000494:pharmacology; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D053122:Influenza A Virus, H3N2 Subtype / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D009981:Influenza B virus / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D007251:Influenza, Human / Q000188:drug therapy / Q000821:virology*; D009439:Neuraminidase / Q000037:antagonists & inhibitors*; D044349:Oceania; D053139:Oseltamivir / Q000494:pharmacology; D011714:Pyrans; D012621:Seasons; D018571:Sentinel Surveillance; D012794:Sialic Acids; D013020:South America; D053243:Zanamivir / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D000146:Acids, Carbocyclic; D000998:Antiviral Agents; D003517:Cyclopentanes; D004791:Enzyme Inhibitors; D006146:Guanidines; D011714:Pyrans; D012794:Sialic Acids; D053139:Oseltamivir; C546918:laninamivir; D009439:Neuraminidase; D053243:Zanamivir; C414210:peramivir
keywords: Influenza; Southern Hemisphere; neuraminidase inhibitor; oseltamivir; peramivir; zanamivir