title: Clinical importance and impact on the households of oseltamivir-resistant seasonal A/H1N1 influenza virus in healthy children in Italy.
abstract: A resistance of A/H1N1 influenza viruses to oseltamivir has recently emerged in a number of countries. However, the clinical and socioeconomic importance of this resistance has not been precisely defined. As children have the highest incidence of influenza infection and are at high risk of severe disease, the aim of this study was to evaluate the clinical importance and the impact on the households of oseltamivir-resistant seasonal A/H1N1 influenza virus in an otherwise healthy pediatric population. A total of 4,726 healthy children younger than 15 years with influenza-like illness were tested for influenza viruses by real-time polymerase chain reaction in the winters of 2007-2008 and 2008-2009 in Italy. The influenza A virus-positive samples underwent neuraminidase gene analysis using pyrosequencing to identify mutations H275Y and N294 S in A/H1N1, and E119V, R292K, and N294 S in A/H3N2. Among the A/H1N1 subtypes, the H275Y mutation was found in 2/126 samples taken in 2007-2008 (1.6%) and in all 17 samples (100%; p < 0.0001) taken in 2008-2009. No other mutation was identified in any of the A/H1N1 or A/H3N2 influenza viruses. No significant differences were found in terms of clinical importance or impact on the households between the children with oseltamivir-resistant seasonal A/H1N1 influenza virus and those with the wild-type. The spread of H275Y-mutated A/H1N1 seasonal influenza virus is a common phenomenon and the clinical importance and impact on the households of the mutated virus is similar to that of the wild-type in an otherwise healthy pediatric population.
authors.affiliation: Department of Maternal and Pediatric Sciences, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Susanna
authors.initials: S
authors.lastname: Esposito
authors.forename: Claudio Giuseppe
authors.initials: CG
authors.lastname: Molteni
authors.forename: Cristina
authors.initials: C
authors.lastname: Daleno
authors.forename: Antonia
authors.initials: A
authors.lastname: Valzano
authors.forename: Emilio
authors.initials: E
authors.lastname: Fossali
authors.forename: Liviana
authors.initials: L
authors.lastname: Da Dalt
authors.forename: Valerio
authors.initials: V
authors.lastname: Cecinati
authors.forename: Eugenia
authors.initials: E
authors.lastname: Bruzzese
authors.forename: Raffaella
authors.initials: R
authors.lastname: Giacchino
authors.forename: Carlo
authors.initials: C
authors.lastname: Giaquinto
authors.forename: Carlotta
authors.initials: C
authors.lastname: Galeone
authors.forename: Angie
authors.initials: A
authors.lastname: Lackenby
authors.forename: Nicola
authors.initials: N
authors.lastname: Principi
mesh_terms: D000293:Adolescent; D019943:Amino Acid Substitution / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D024882:Drug Resistance, Viral; D005192:Family Health; D005260:Female; D006801:Humans; D007223:Infant; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity; D007251:Influenza, Human / Q000453:epidemiology* / Q000821:virology*; D007558:Italy / Q000453:epidemiology; D008297:Male; D020125:Mutation, Missense; D009439:Neuraminidase / Q000235:genetics; D053139:Oseltamivir / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D014764:Viral Proteins / Q000235:genetics
chemical_list: D014764:Viral Proteins; D053139:Oseltamivir; C487630:NA protein, influenza A virus; D009439:Neuraminidase