Virological self-sampling to monitor influenza antiviral susceptibility in a community cohort

• Published in: Journal of antimicrobial chemotherapy Vol. 68; no. 10; pp. 2324 - 2331
• Main Authors: Lackenby, Angie, Elliot, Alex J, Powers, Cassandra, Andrews, Nick, Ellis, Joanna, Bermingham, Alison, Thompson, Catherine, Galiano, Monica, Large, Shirley, Durnall, Hayley, Fleming, Douglas, Smith, Gillian, Zambon, Maria
• Format: Journal Article
• Language: English
• Published: England Oxford Publishing Limited (England) 01.10.2013; Oxford University Press
• Subjects: Adolescent; Adult; Aged; Amino acid substitution; Amino acids; Antimicrobial agents; Antiviral Agents - administration & dosage; Antiviral Agents - pharmacology; Child; Child, Preschool; Cohort Studies; Drug resistance; Drug Resistance, Viral; England; Female; Humans; Infant; Infant, Newborn; Influenza; Influenza A Virus, H1N1 Subtype - drug effects; Influenza A Virus, H1N1 Subtype - isolation & purification; Influenza A Virus, H3N2 Subtype - drug effects; Influenza A Virus, H3N2 Subtype - isolation & purification; Influenza B virus - drug effects; Influenza B virus - isolation & purification; Influenza, Human - drug therapy; Influenza, Human - virology; Male; Microbial Sensitivity Tests - methods; Middle Aged; Original Research; Oseltamivir - administration & dosage; Oseltamivir - pharmacology; Pandemics; Reverse Transcriptase Polymerase Chain Reaction; RNA, Viral - genetics; Self Administration - methods; Specimen Handling - methods; Virology; Young Adult; England; influenza virus; zanamivir; oseltamivir; surveillance; pandemic
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/dkt203

To perform antiviral susceptibility monitoring of treated individuals in the community during the 2009 influenza A(H1N1) pandemic in England. Between 200 and 400 patients were enrolled daily through the National Pandemic Flu Service (NPFS) and issued with a self-sampling kit. Initially, only persons aged 16 and over were eligible, but from 12 November (week 45), self-sampling was extended to include school-age children (5 years and older). All samples received were screened for influenza A(H1N1)pdm09 as well as seasonal influenza [A(H1N1), A(H3N2) and influenza B] by a combination of RT-PCR and virus isolation methods. Influenza A(H1N1)pdm09 RT-PCR-positive samples were screened for the oseltamivir resistance-inducing H275Y substitution, and a subset of samples also underwent phenotypic antiviral susceptibility testing by enzyme inhibition assay. We were able to detect virus by RT-PCR in self-taken samples and recovered infectious virus enabling further virological characterization. The majority of influenza A(H1N1)pdm09 RT-PCR-positive NPFS samples (n = 1273) were taken after oseltamivir treatment had begun. No reduction in phenotypic susceptibility to neuraminidase inhibitors was detected, but five cases with minority quasi-species of oseltamivir-resistant virus (an H275Y amino acid substitution in neuraminidase) were detected. Self-sampling is a useful tool for community surveillance, particularly for the follow-up of drug-treated patients. The virological study of self-taken samples from the NPFS provided a unique opportunity to evaluate the emergence of oseltamivir resistance in treated individuals with mild illness in the community, a target population that may not be captured by traditional sentinel surveillance schemes.