Influenza virus susceptibility and resistance to oseltamivir.
Identifieur interne : 001373 ( Main/Exploration ); précédent : 001372; suivant : 001374Influenza virus susceptibility and resistance to oseltamivir.
Auteurs : Fred Y. Aoki [Canada] ; Guy Boivin ; Noel RobertsSource :
- Antiviral therapy [ 1359-6535 ] ; 2007.
Descripteurs français
- KwdFr :
- Adolescent, Adulte, Adulte d'âge moyen, Antienzymes (pharmacologie), Antiviraux (pharmacologie), Enfant, Enfant d'âge préscolaire, Grippe humaine (virologie), Grippe humaine (épidémiologie), Humains, Mutation, Nourrisson, Oséltamivir (pharmacologie), Résistance virale aux médicaments (génétique), Sialidase (antagonistes et inhibiteurs), Sous-type H1N1 du virus de la grippe A (), Sous-type H2N2 du virus de la grippe A (), Sous-type H3N2 du virus de la grippe A (), Sujet âgé, Tests de sensibilité microbienne, Virus de la grippe A (), Virus influenza B ().
- MESH :
- antagonistes et inhibiteurs : Sialidase.
- génétique : Résistance virale aux médicaments.
- pharmacologie : Antienzymes, Antiviraux, Oséltamivir.
- virologie : Grippe humaine.
- épidémiologie : Grippe humaine.
- Adolescent, Adulte, Adulte d'âge moyen, Enfant, Enfant d'âge préscolaire, Humains, Mutation, Nourrisson, Sous-type H1N1 du virus de la grippe A, Sous-type H2N2 du virus de la grippe A, Sous-type H3N2 du virus de la grippe A, Sujet âgé, Tests de sensibilité microbienne, Virus de la grippe A, Virus influenza B.
English descriptors
- KwdEn :
- Adolescent, Adult, Aged, Antiviral Agents (pharmacology), Child, Child, Preschool, Drug Resistance, Viral (genetics), Enzyme Inhibitors (pharmacology), Humans, Infant, Influenza A Virus, H1N1 Subtype (drug effects), Influenza A Virus, H2N2 Subtype (drug effects), Influenza A Virus, H3N2 Subtype (drug effects), Influenza A virus (drug effects), Influenza B virus (drug effects), Influenza, Human (epidemiology), Influenza, Human (virology), Microbial Sensitivity Tests, Middle Aged, Mutation, Neuraminidase (antagonists & inhibitors), Oseltamivir (pharmacology).
- MESH :
- chemical , antagonists & inhibitors : Neuraminidase.
- chemical , pharmacology : Antiviral Agents, Enzyme Inhibitors, Oseltamivir.
- drug effects : Influenza A Virus, H1N1 Subtype, Influenza A Virus, H2N2 Subtype, Influenza A Virus, H3N2 Subtype, Influenza A virus, Influenza B virus.
- epidemiology : Influenza, Human.
- genetics : Drug Resistance, Viral.
- virology : Influenza, Human.
- Adolescent, Adult, Aged, Child, Child, Preschool, Humans, Infant, Microbial Sensitivity Tests, Middle Aged, Mutation.
Abstract
Oseltamivir phosphate is a prodrug of oseltamivir carboxylate, a highly specific inhibitor of influenza virus neuraminidases. Given that oseltamivir carboxylate binds to highly conserved, essential amino acids in the catalytic site of the enzyme, and that the activity of neuraminidase is critical for virus release from infected cells and subsequent virus spread, the drug was expected to have a low propensity to select for viable resistant mutants. Indeed, viruses with neuraminidase (and haemagglutinin) substitutions conferring reduced susceptibility to oseltamivir have been generated with difficulty in vitro, and these mutants generally have reduced infectivity and transmissibility compared with wild-type virus in animal models. Studies of seasonal influenza isolates collected before the introduction of oseltamivir show an absence of naturally occurring resistance. Few resistant mutants have arisen during clinical trials of oseltamivir in seasonal influenza, with cumulative data from all Roche-sponsored studies indicating an incidence of resistance of 0.32% in adults (0.4%, including low-level mutants detected by genotyping alone in mixed virus populations) and 4.1% (5.4%) in children. Higher incidences of resistance were observed in two small Japanese studies, in which children received a different dosing schedule from their Western counterparts. In summary, the overall incidence of influenza virus resistance associated with the seasonal use of oseltamivir is currently low and resistant viruses might be of little clinical significance, except perhaps in immunocompromised individuals. However, continued vigilance, especially of emerging avian H5N1 strains, combined with careful, systematic laboratory-based monitoring, is essential.
PubMed: 17944268
Affiliations:
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Le document en format XML
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influenza B</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Oseltamivir phosphate is a prodrug of oseltamivir carboxylate, a highly specific inhibitor of influenza virus neuraminidases. Given that oseltamivir carboxylate binds to highly conserved, essential amino acids in the catalytic site of the enzyme, and that the activity of neuraminidase is critical for virus release from infected cells and subsequent virus spread, the drug was expected to have a low propensity to select for viable resistant mutants. Indeed, viruses with neuraminidase (and haemagglutinin) substitutions conferring reduced susceptibility to oseltamivir have been generated with difficulty in vitro, and these mutants generally have reduced infectivity and transmissibility compared with wild-type virus in animal models. Studies of seasonal influenza isolates collected before the introduction of oseltamivir show an absence of naturally occurring resistance. Few resistant mutants have arisen during clinical trials of oseltamivir in seasonal influenza, with cumulative data from all Roche-sponsored studies indicating an incidence of resistance of 0.32% in adults (0.4%, including low-level mutants detected by genotyping alone in mixed virus populations) and 4.1% (5.4%) in children. Higher incidences of resistance were observed in two small Japanese studies, in which children received a different dosing schedule from their Western counterparts. In summary, the overall incidence of influenza virus resistance associated with the seasonal use of oseltamivir is currently low and resistant viruses might be of little clinical significance, except perhaps in immunocompromised individuals. However, continued vigilance, especially of emerging avian H5N1 strains, combined with careful, systematic laboratory-based monitoring, is essential.</div></front></TEI><affiliations><list><country><li>Canada</li></country><region><li>Manitoba</li></region><settlement><li>Winnipeg</li></settlement><orgName><li>Université du Manitoba</li></orgName></list><tree><noCountry><name sortKey="Boivin, Guy" sort="Boivin, Guy" uniqKey="Boivin G" first="Guy" last="Boivin">Guy Boivin</name><name sortKey="Roberts, Noel" sort="Roberts, Noel" uniqKey="Roberts N" first="Noel" last="Roberts">Noel Roberts</name></noCountry><country name="Canada"><region name="Manitoba"><name sortKey="Aoki, Fred Y" sort="Aoki, Fred Y" uniqKey="Aoki F" first="Fred Y" last="Aoki">Fred Y. Aoki</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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