RESUMO
Surveillance studies of the influenza viruses circulating in Europe and other countries in 2007 and 2008 have revealed rates of resistance to oseltamivir of up to 67% among H1N1 viruses. In the present study, we examined 202 clinical samples obtained from patients infected with H1N1 virus in Japan in 2007 and 2008 for oseltamivir resistance and found that three were oseltamivir resistant (1.5%). The 50% inhibitory concentrations (IC(50)s), as measured by a sialidase inhibition assay with these drug-resistant viruses, were >100-fold higher than those of the nonresistant viruses (median IC(50), 12.6 nmol/liter). The His274Tyr (strain N2 numbering) mutation of the neuraminidase protein, which is known to confer oseltamivir resistance, was detected in these three isolates. Phylogenetic analysis showed that one virus belonged to a lineage that is composed of drug-resistant viruses isolated in Europe and North America and that the other two viruses independently emerged in Japan. Continued surveillance studies are necessary to observe whether these viruses will persist.
Assuntos
Antivirais/farmacologia , Farmacorresistência Viral , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Influenza Humana/virologia , Oseltamivir/farmacologia , Substituição de Aminoácidos/genética , Análise por Conglomerados , Humanos , Vírus da Influenza A Subtipo H1N1/classificação , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Concentração Inibidora 50 , Japão , Mutação de Sentido Incorreto , Neuraminidase/genética , Filogenia , Homologia de Sequência , Proteínas Virais/genéticaRESUMO
We investigated the effectiveness of oseltamivir treatment against influenza virus infection in children. We treated 131 patients (mean age, 5.8 +/- 3.6 years) with oseltamivir (4 mg/kg/day for 5 days) during the 2001-2002 epidemic. All of the patients had been diagnosed with influenza using a rapid diagnosis kit. When treatment was initiated within 48 hours of the onset of fever, 44% of the patients became afebrile (< 37.5 degrees C) within one day, and 86% of them recovered within two days. The average duration of fever after the initiation of oseltamivir treatment was 1.7 days. Oseltamivir was equally effective against both influenza type A and type B. No differences in the effectiveness of oseltamivir treatment were observed between young children (< 4 years of age) and school-aged children (> 6 years of age). No obvious side effects were observed.