Persistence of pandemic influenza H1N1 virus in young patients after oseltamivir therapy in the 2009–2010 season: a comparison with seasonal H1N1 with or without H275Y mutation

• Published in: Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy Vol. 18; no. 2; pp. 180 - 186
• Main Authors: Kawai, Naoki, Ikematsu, Hideyuki, Iwaki, Norio, Kondou, Kunio, Hirotsu, Nobuo, Kawashima, Takashi, Maeda, Tetsunari, Tanaka, Osame, Doniwa, Ken-ichi, Iwakuni, Osamu, Egashira, Keisuke, Yamaji, Kouzaburo, Kashiwagi, Seizaburo
• Format: Journal Article
• Language: English
• Published: Japan Elsevier Ltd 01-04-2012; Springer Japan
• Subjects: Adolescent; Adult; Antiviral Agents - pharmacology; Antiviral Agents - therapeutic use; Child; Children; Drug Resistance, Viral - drug effects; Drug Resistance, Viral - genetics; Female; Fever; Fever - drug therapy; Fever - virology; H275Y mutation; Hematology, Oncology and Palliative Medicine; Humans; IC50; Infectious Diseases; Influenza; Influenza A Virus, H1N1 Subtype - drug effects; Influenza A Virus, H1N1 Subtype - genetics; Influenza A Virus, H1N1 Subtype - isolation & purification; Influenza A(H1N1); Influenza, Human - drug therapy; Influenza, Human - physiopathology; Influenza, Human - virology; Inhibitory Concentration 50; Japan; Male; Medical Microbiology; Medicine; Medicine & Public Health; Mutation; Original Article; Oseltamivir; Oseltamivir - pharmacology; Oseltamivir - therapeutic use; Pandemics; Seasons; Sequence Analysis, DNA; Treatment Outcome; Viral shedding; Virology; Virus Shedding; Young Adult; Japan; Influenza A(H1N1); Oseltamivir; H275Y mutation; IC 50; Viral shedding; IC50; IC
• ISSN: 1341-321X; 1437-7780
• DOI: 10.1007/s10156-011-0314-2

Abstract Comparison of the viral persistence of pandemic H1N1 (H1N1pdm) and seasonal H1N1 with or without H275Y mutation after oseltamivir therapy has not been adequately done. Virus was isolated before and on days 4–6 from the start of oseltamivir treatment for 158 cases of seasonal (2007–2008 and 2008–2009 seasons) or pandemic (2009–2010 season) H1N1 influenza. Sequence analysis was done for each season and NA inhibition assay (IC50 ) was done in the 2009–2010 season. H275Y mutation before therapy was 0% in the 2007–2008 and 2009–2010 seasons, but 100% in the 2008–2009 season. Fever and other symptoms were noticeably prolonged after oseltamivir therapy for children with H275Y mutated seasonal H1N1 (2008–2009 season), but not in patients with seasonal H1N1 without mutation (2007–2008) or H1N1pdm (2009–2010). The viral persistence rate was significantly higher for patients 15 years or younger than for those 16 years and older with H275Y mutated seasonal H1N1 (46.2% and 10.5%, respectively) or with H1N1pdm (43.3% and 11.5%, respectively). The H275Y mutation emerged after oseltamivir treatment in 2.4% (2/82) of all patients with H1N1pdm. In two children, the H275Y mutation emerged after therapy and the IC50 increased more than 200 fold; however, the prolongation of fever was not so prominent. In conclusion, oseltamivir was effective for fever and other clinical symptoms; however, the virus persisted longer than expected after treatment in H1N1pdm influenza-infected children in the 2009–2010 season, similar to seasonal H1N1 with H275Y mutation in the 2008–2009 season.