Molecular characterization of respiratory syncytial viruses infecting children reported to have received palivizumab immunoprophylaxis.

Oliveira DB1, Iwane MK2, Prill MM2, Weinberg GA3, Williams JV4, Griffin MR4, Szilagyi PG3, Edwards KM4, Staat MA5, Hall CB3, Durigon EL1, Erdman DD6.

Author information

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.

STUDY DESIGN:

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.

Published by Elsevier B.V.