title: Molecular characterization of respiratory syncytial viruses infecting children reported to have received palivizumab immunoprophylaxis.
abstract: BACKGROUND
  Respiratory syncytial virus (RSV) is a major cause of respiratory infections in children. Palivizumab (PZ) is the only RSV-specific immunoprophylaxis approved by the U.S. Food and Drug Administration. Mutations leading to amino acid substitutions in the PZ binding site of the RSV F protein have been associated with breakthrough RSV infections in patients receiving PZ.
  
  
  OBJECTIVE
  To detect PZ resistance conferring mutations in RSV strains from children who received PZ.
  
  
  METHODS
  Children aged ≤ 24 months on October 31 who were hospitalized or had outpatient visits for respiratory illness and/or fever during October-May 2001-2008 in 3 US counties were included. PZ receipt was obtained from parent interviews and medical records among children subsequently infected with RSV. Archived nasal/throat swab specimens were tested for RSV by real-time RT-PCR. The coding region of the PZ binding site of the RSV F protein was sequenced using both Sanger and pyrosequencing methods.
  
  
  RESULTS
  Of 8762 enrolled children, 375 (4.3%) were tested for RSV and had a history of PZ receipt, of which 56 (14.9%) were RSV-positive and 45 of these had available archived specimens. Molecular typing identified 42 partial F gene sequences in specimens from 39 children: 19 single RSV subgroup A, 17 subgroup B and 3 mixed infections. Nucleotide substitutions were identified in 12/42 (28.6%) RSV strains. PZ resistance mutations were identified in 4 (10.2%) of the 39 children, of which one had documented PZ receipt.
  
  
  CONCLUSIONS
  Although RSV PZ resistance mutations were infrequent, most RSV-associated illnesses in children with a history of PZ receipt were not due to strain resistance.
authors.affiliation: Institute of Biomedical Science, University of São Paulo, Brazil.
authors.forename: Danielle B L
authors.initials: DB
authors.lastname: Oliveira
authors.affiliation: Division of Viral Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Marika K
authors.initials: MK
authors.lastname: Iwane
authors.affiliation: Division of Viral Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Mila M
authors.initials: MM
authors.lastname: Prill
authors.affiliation: University of Rochester School of Medicine, Rochester, NY, USA.
authors.forename: Geoffrey A
authors.initials: GA
authors.lastname: Weinberg
authors.affiliation: Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: John V
authors.initials: JV
authors.lastname: Williams
authors.affiliation: Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Marie R
authors.initials: MR
authors.lastname: Griffin
authors.affiliation: University of Rochester School of Medicine, Rochester, NY, USA.
authors.forename: Peter G
authors.initials: PG
authors.lastname: Szilagyi
authors.affiliation: Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Edwards
authors.affiliation: Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: Mary A
authors.initials: MA
authors.lastname: Staat
authors.affiliation: University of Rochester School of Medicine, Rochester, NY, USA.
authors.forename: Caroline B
authors.initials: CB
authors.lastname: Hall
authors.affiliation: Institute of Biomedical Science, University of São Paulo, Brazil.
authors.forename: Edison L
authors.initials: EL
authors.lastname: Durigon
authors.affiliation: Division of Viral Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA. Electronic address: dde1@cdc.gov.
authors.forename: Dean D
authors.initials: DD
authors.lastname: Erdman
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D000069455:Palivizumab / Q000494:pharmacology / Q000627:therapeutic use*; D018357:Respiratory Syncytial Virus Infections / Q000517:prevention & control* / Q000821:virology*; D012136:Respiratory Syncytial Viruses / Q000187:drug effects* / Q000235:genetics*; D017422:Sequence Analysis, DNA; D013997:Time Factors; D014481:United States
chemical_list: D000998:Antiviral Agents; D000069455:Palivizumab
keywords: Palivizumab resistance; Pyrosequencing; Respiratory syncytial virus