title: 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.
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 (IC(50)) 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 IC(50) 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.
authors.affiliation: Japan Physicians Association, Tokyo Medical Association Building 3F, 2-5 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062, Japan. nkawai@city.gifu.med.or.jp
authors.forename: Naoki
authors.initials: N
authors.lastname: Kawai
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Ikematsu
authors.forename: Norio
authors.initials: N
authors.lastname: Iwaki
authors.forename: Kunio
authors.initials: K
authors.lastname: Kondou
authors.forename: Nobuo
authors.initials: N
authors.lastname: Hirotsu
authors.forename: Takashi
authors.initials: T
authors.lastname: Kawashima
authors.forename: Tetsunari
authors.initials: T
authors.lastname: Maeda
authors.forename: Osame
authors.initials: O
authors.lastname: Tanaka
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Doniwa
authors.forename: Osamu
authors.initials: O
authors.lastname: Iwakuni
authors.forename: Keisuke
authors.initials: K
authors.lastname: Egashira
authors.forename: Kouzaburo
authors.initials: K
authors.lastname: Yamaji
authors.forename: Seizaburo
authors.initials: S
authors.lastname: Kashiwagi
mesh_terms: D000293:Adolescent; D000328:Adult; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002648:Child; D024882:Drug Resistance, Viral / Q000187:drug effects* / Q000235:genetics; D005260:Female; D005334:Fever / Q000188:drug therapy / Q000821:virology; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification*; D007251:Influenza, Human / Q000188:drug therapy* / Q000503:physiopathology / Q000821:virology; D020128:Inhibitory Concentration 50; D007564:Japan; D008297:Male; D009154:Mutation; D053139:Oseltamivir / Q000494:pharmacology / Q000627:therapeutic use*; D058873:Pandemics; D012621:Seasons; D017422:Sequence Analysis, DNA; D016896:Treatment Outcome; D017201:Virus Shedding; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D053139:Oseltamivir