title: Neuraminidase inhibitor susceptibility testing in human influenza viruses: a laboratory surveillance perspective.
abstract: Neuraminidase inhibitors (NAIs) are vital in managing seasonal and pandemic influenza infections. NAI susceptibilities of virus isolates (n = 5540) collected during the 2008-2009 influenza season were assessed in the chemiluminescent neuraminidase inhibition (NI) assay. Box-and-whisker plot analyses of log-transformed IC(50)s were performed for each virus type/subtype and NAI to identify outliers which were characterized based on a statistical cutoff of IC(50) >3 interquartile ranges (IQR) from the 75(th) percentile. Among 1533 seasonal H1N1 viruses tested, 1431 (93.3%) were outliers for oseltamivir; they all harbored the H275Y mutation in the neuraminidase (NA) and were reported as oseltamivir-resistant. Only 15 (0.7%) of pandemic 2009 H1N1 viruses tested (n = 2259) were resistant to oseltamivir. All influenza A(H3N2) (n = 834) and B (n = 914) viruses were sensitive to oseltamivir, except for one A(H3N2) and one B virus, with D151V and D197E (D198E in N2 numbering) mutations in the NA, respectively. All viruses tested were sensitive to zanamivir, except for six seasonal A(H1N1) and several A(H3N2) outliers (n = 22) which exhibited cell culture induced mutations at residue D151 of the NA. A subset of viruses (n = 1058) tested for peramivir were sensitive to the drug, with exception of H275Y variants that exhibited reduced susceptibility to this NAI. This study summarizes baseline susceptibility patterns of seasonal and pandemic influenza viruses, and seeks to contribute towards criteria for defining NAI resistance.
authors: Virus Surveillance and Diagnosis Branch, Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Rd NE, Mailstop G16, Atlanta, GA 30333, USA.
authors: Margaret
authors: M
authors: Okomo-Adhiambo
authors: Virus Surveillance and Diagnosis Branch, Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Rd NE, Mailstop G16, Atlanta, GA 30333, USA.
authors: Katrina
authors: K
authors: Sleeman
authors: Virus Surveillance and Diagnosis Branch, Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Rd NE, Mailstop G16, Atlanta, GA 30333, USA.
authors: Kristina
authors: K
authors: Ballenger
authors: Virus Surveillance and Diagnosis Branch, Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Rd NE, Mailstop G16, Atlanta, GA 30333, USA.|Atlanta Research and Education Foundation, 1670 Clairmont Rd, 151F, Decatur, GA 30033, USA.
authors: Ha T
authors: HT
authors: Nguyen
authors: Virus Surveillance and Diagnosis Branch, Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Rd NE, Mailstop G16, Atlanta, GA 30333, USA.
authors: Vasiliy P
authors: VP
authors: Mishin
authors: Virus Surveillance and Diagnosis Branch, Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Rd NE, Mailstop G16, Atlanta, GA 30333, USA.|Battelle, Century Plaza 1, 2987 Clairmont Rd, Suite 450, Atlanta, GA 30329, USA.
authors: Tiffany G
authors: TG
authors: Sheu
authors: Virus Surveillance and Diagnosis Branch, Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Rd NE, Mailstop G16, Atlanta, GA 30333, USA.|Oak Ridge Institute for Science and Education, MC-100-22, P.O. Box 117, Oak Ridge, TN 37831, USA.
authors: James
authors: J
authors: Smagala
authors: Influenza and Respiratory Viruses Section, National Microbiology Laboratory, Public Health Agency of Canada, 1015 Arlington St., Suite H4050, Winnipeg, MB, R3E 3R2, Canada.
authors: Yan
authors: Y
authors: Li
authors: Virus Surveillance and Diagnosis Branch, Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Rd NE, Mailstop G16, Atlanta, GA 30333, USA.
authors: Alexander I
authors: AI
authors: Klimov
authors: Virus Surveillance and Diagnosis Branch, Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Rd NE, Mailstop G16, Atlanta, GA 30333, USA.
authors: Larisa V
authors: LV
authors: Gubareva