Clinical effectiveness of oseltamivir for influenza A(H1N1) virus with H274Y neuraminidase mutation.
OBJECTIVE
To evaluate the clinical effectiveness of oseltamivir therapy started within 48h of the onset for influenza A(H1N1) virus with H274Y neuraminidase (NA) mutation.


METHODS
Virus was isolated before and four to six days after starting oseltamivir treatment from 73 outpatients with influenza A(H1N1) virus in the 2007-2008 and 2008-2009 seasons. NA inhibition assays (IC(50)) and sequence analyses were done using influenza viruses isolated from these patients. Body temperature was evaluated before and on the second, third, and fourth days after starting treatment.


RESULTS
H274Y mutation was not shown in the 2007-2008 season (44 patients) and shown in all 29 patients in the 2008-2009 season by NA sequence analyses. The mean IC(50) before oseltamivir treatment was significantly higher in 2008-2009 (319.3+/-185.4 nM) than in 2007-2008 (1.5+/-0.8 nM; p<.001). Patients < or =15 years with oseltamivir-resistant virus infection had a higher ratio of patients persisted virus after oseltamivir treatment than patients >15 years (50% and 11.8%, respectively, p=0.038), and a significant higher body temperature during oseltamivir treatment, compared to patients < or =15 years treated for oseltamivir-sensitive virus infection.


CONCLUSIONS
The clinical effectiveness of oseltamivir for the A(H1N1) virus was reduced in the 2008-2009 season compared with the previous season, especially in children, probably due to the H274Y mutation. Oseltamivir seems to be not recommended for children and patients with high-risk underlying diseases infected with H274Y mutated A(H1N1) virus.
Kawai
Naoki
N
Japan Physicians Association, Tokyo Medical Association Building 3F, 2-5 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062, Japan. nkawai@city.gifu.med.or.jp
Ikematsu
Hideyuki
H
Iwaki
Norio
N
Kondou
Kunio
K
Hirotsu
Nobuo
N
Kawashima
Takashi
T
Maeda
Tetsunari
T
Tanaka
Osame
O
Doniwa
Ken-Ichi
K
Kashiwagi
Seizaburo
S
D000293:Adolescent; D000328:Adult; D019943:Amino Acid Substitution; D000998:Antiviral Agents / Q000627:therapeutic use*; D001831:Body Temperature; D002648:Child; D002675:Child, Preschool; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D007251:Influenza, Human / Q000188:drug therapy* / Q000453:epidemiology; D008875:Middle Aged; D009154:Mutation; D009439:Neuraminidase / Q000037:antagonists & inhibitors / Q000235:genetics*; D053139:Oseltamivir / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
D000998:Antiviral Agents; D053139:Oseltamivir; D009439:Neuraminidase