title: Outcomes and Susceptibility to Neuraminidase Inhibitors in Individuals Infected With Different Influenza B Lineages: The Influenza Resistance Information Study.
abstract: BACKGROUND
  Little is known about how influenza infections caused by B/Victoria and B/Yamagata virus lineages compare with respect to disease course and susceptibility to antiviral therapy.
  
  
  METHODS
  Data from patients with influenza B infections from the first 5 years (2009-2013) of the prospective Influenza Resistance Information Study (IRIS, NCT00884117) were evaluated. Cultured viruses were phenotypically tested for neuraminidase inhibitor (NAI) sensitivity, and sequenced to determine virus lineage (B/Victoria or B/Yamagata). Differences in clinical outcomes (viral clearance and symptom resolution) between virus lineages were assessed using Kaplan-Meier analysis.
  
  
  RESULTS
  In all, 914 patients were positive for influenza B by reverse transcriptase polymerase chain reaction (
  B/Victoria, 586; B/Yamagata, 289; not subtyped, 39); 474 were treated with antivirals. No phenotypic resistance to oseltamivir or zanamivir was found in B/Victoria or B/Yamagata viruses. Of 15 predefined resistance mutations, 2 were detected by neuraminidase sequencing: I221T had reduced sensitivity to oseltamivir, and I221V was sensitive to NAI inhibition. No consistent differences between virus lineages in times to viral clearance or to symptom or fever resolution were found in adults and adolescents or in children.
  
  
  CONCLUSIONS
  Influenza B virus lineage had no notable effect on disease outcomes or antiviral susceptibility in this population.
authors.affiliation: Department of Virosciences, Erasmus Medical Center, Erasmus University, Rotterdam, The Netherlands.
authors.forename: Erhard
authors.initials: E
authors.lastname: van der Vries
authors.affiliation: School of Public Health, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Dennis K M
authors.initials: DK
authors.lastname: Ip
authors.affiliation: School of Public Health, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Cowling
authors.affiliation: Department of Pharmaceutical Sciences, Translational Technologies and Bioinformatics, Roche Innovation Center Basel, Switzerland.
authors.forename: Jitao D
authors.initials: JD
authors.lastname: Zhang
authors.affiliation: Infectious Diseases Discovery, Hoffmann-La Roche, Nutley, New Jersey.
authors.forename: Xiao
authors.initials: X
authors.lastname: Tong
authors.affiliation: Micron Research Ltd, Ely, United Kingdom.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Wojtowicz
authors.affiliation: Department of Virosciences, Erasmus Medical Center, Erasmus University, Rotterdam, The Netherlands.
authors.forename: Martin
authors.initials: M
authors.lastname: Schutten
authors.affiliation: Department of Virosciences, Erasmus Medical Center, Erasmus University, Rotterdam, The Netherlands.
authors.forename: Charles A
authors.initials: CA
authors.lastname: Boucher
mesh_terms: D000293:Adolescent; D000328:Adult; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D024882:Drug Resistance, Viral / Q000235:genetics; D006801:Humans; D007223:Infant; D009981:Influenza B virus / Q000145:classification / Q000187:drug effects / Q000235:genetics*; D007251:Influenza, Human / Q000188:drug therapy / Q000821:virology*; D008875:Middle Aged; D009439:Neuraminidase / Q000037:antagonists & inhibitors* / Q000145:classification; D053139:Oseltamivir / Q000494:pharmacology* / Q000627:therapeutic use; D055815:Young Adult; D053243:Zanamivir / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000998:Antiviral Agents; D053139:Oseltamivir; D009439:Neuraminidase; D053243:Zanamivir
keywords: IC50; Victoria; Yamagata; antiviral; influenza B; lineage; neuraminidase inhibitor; outcomes; resistance; susceptibility