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

Autor: Peter G. Szilagyi, Mary Allen Staat, Dean D. Erdman, Danielle Bruna Leal Oliveira, John V. Williams, Edison Luiz Durigon, Marika K. Iwane, Geoffrey A. Weinberg, Mila M. Prill, Marie R. Griffin, Caroline B. Hall, Kathryn M. Edwards
Rok vydání: 2015
Předmět:
Zdroj: Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual)
Universidade de São Paulo (USP)
instacron:USP
Journal of Clinical Virology
ISSN: 1386-6532
DOI: 10.1016/j.jcv.2015.01.016
Popis: Highlights • Palivizumab (PZ) immunoprophylaxis of high-risk children reduces RSV hospitalizations. • PZ resistance mutations can result in RSV breakthrough infections in PZ recipients. • PZ resistance mutations were identified in 10.2% of children reportedly receiving PZ. • PZ resistance mutations did not account for the majority of PZ failures.
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.
Databáze: OpenAIRE
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