Oseltamivir resistance of influenza A(H1N1) viruses in young children in Finland during the 2007-08 influenza season
Session V – Heikkinen, Terho
Title of Contribution: Oseltamivir resistance of influenza A(H1N1) viruses in young children in Finland during the 2007-08 influenza season
Author(s): Santtu Heinonen, Heli Silvennoinen, Niina Ikonen, Pasi Lehtinen, Raija Vainionpää, Thedi Ziegler, Terho Heikkinen
Affiliation(s): Department of Pediatrics, Turku University Hospital; Department of Virology, University of Turku; WHO National Influenza Center, National Public Health Institute, Helsinki; Finland.
Background: During the influenza season of 2007-08, oseltamivir-resistant influenza A(H1N1) viruses emerged in several countries in Europe, North America, and Asia. Despite substantial prevalence of oseltamivir-resistant viruses, few data are available on the clinical profile of subjects infected with these viruses. As part of an ongoing randomized, double-blind, placebo-controlled trial of the efficacy of early oseltamivir treatment of influenza in young children, we assessed the prevalence of oseltamivir-resistant H1N1 viruses in our area and the clinical presentation of children infected with these viruses.
Methods: This analysis was performed during the 2007-08 influenza season in Turku, Finland. A total of 660 children aged 1-3 years were enrolled in the study cohort that was followed throughout the influenza season. The parents were asked to bring their child to the study clinic every time the child had fever and/or signs of a respiratory infection. During each visit, the child was examined by a study physician, and a nasal swab for viral detection was obtained. The signs and symptoms of the child were recorded on a structured case record form. Determination of oseltamivir resistance was based on sequencing of the neuraminidase gene of influenza A(H1N1) isolates.
Results: Among a total of 37 children with influenza A, 31 were confirmed as being infected with A(H1N1) viruses; 1 child had A(H3), and in 5 cases the virus could not be subtyped. Of the 31 H1N1 isolates, 3 (9.7%) were resistant to oseltamivir and showed the typical H274Y mutation. The children with resistant viruses were aged 1.9-3.4 years at the time of diagnosis. These children attended different day-care centers and lived in distinct parts of the city. All three infections with oseltamivir-resistant viruses occurred in different weeks of the study. All children were febrile (maximum fever 38.0-39.1oC). No differences were observed in the clinical presentation between children with oseltamivir-resistant and oseltamivir-sensitive viruses.
Conclusion: Oseltamivir-resistant A(H1N1) viruses accounted for approximately 10% of all A(H1N1) viruses circulating in young children in the Turku area in 2007-08. The resistant viruses were not clustered either temporally or geographically. Based on these limited data, the clinical presentation of oseltamivir-resistant A(H1N1) viruses in young children appears to be similar to that seen in children with oseltamivir-susceptible A(H1N1) viruses.
