Tamiflu
[Effect of post-exposure prophylaxis with oseltamivir for those in contacts with influenza patients in pediatric wards]

[Article in Japanese]

Shinjoh M, Sato S, Sugaya N, Mitamura K, Takeuchi Y, Kosaki K, Takahashi T.

Department of Pediatrics, School of Medicine, Keio University.

During the influenza season, outbreaks of influenza may occur in the pediatric wards due to spread from the patients hospitalized with influenza, or from those hospitalized during the latency period and develop influenza afterwards. Post-exposure prophylaxis with neuraminidase inhibitors has been reported to be effective in preventing outbreaks among household members and nursing home residents. However, for nosocomial spread, its effectiveness and possible adverse effects are to be determined. During the 2002/2003 influenza season, we experienced a total of 3 nosocomial outbreaks of influenza in the pediatric wards in two hospitals in the Kanto district, Japan. Since the number of contacts who developed influenza had been increasing despite the isolation precaution implemented, post-exposure prophylaxis with oseltamivir (2 mg/kg/dose, maximum 75 mg/dose, once a day for 7-10 days) was implemented with a permission from the parents to terminate the outbreaks. In the outbreaks (one with influenza A, two with influenza B), a total of 29 inpatients had contact with influenza patients: among those 29, 13 were given post-exposure prophylaxis, 16 were not. Out of 16 patients who did not receive post-exposure prophylaxis, 11 (69%) developed influenza: out of 13 with post-exposure prophylaxis, none developed influenza. Those patients who developed influenza were given oseltamivir (2 mg/kg/dose, maximum 75 mg/dose, twice a day for 5 days) and accommodated in a private room or a room with other patients with influenza of the same type. No significant adverse effects due to oseltamivir were observed among those who were enrolled in this study.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15103909&dopt=Abstract oseltamivir Tamiflu



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Skin reactions in patients with influenza treated with oseltamivir: a retrospective cohort study.

Nordstrom BL, Oh K, Sacks ST, L'Italien GJ.

Ingenix Epidemiology, Auburndale, Mass., USA. bnordstrom epidemiology.com

Oseltamivir phosphate is an FDA-approved treatment for influenza that has been available for prescription use in the USA since 1999. The present report describes findings from a post-marketing safety study of skin reactions associated with oseltamivir use. All patients in the claims-derived Ingenix Research Database with a physician diagnosis of influenza and/or a dispensing of oseltamivir between 1 December 1999 and 31 March 2002 were identified. Cohort eligibility criteria included minimum baseline enrolment duration of 3 months, age of at least 1 year and no influenza vaccination on the date of influenza diagnosis or oseltamivir dispensing. Patients were classified into two primary cohorts, influenza diagnosis and oseltamivir dispensing on the same day, and influenza diagnosis but no oseltamivir at any time, and a cohort included for secondary analyses comprising patients who received an oseltamivir dispensing without an influenza diagnosis on the same day. Outcomes included general skin reactions and several specific skin reactions. Events occurring during the 30 days following the date of influenza diagnosis or oseltamivir dispensing were examined using Cox proportional hazards models. Model covariates included age, use of another influenza drug, month and year of index date, and use of antitussives. Adjusted rate ratios for the general class of skin reactions among the primary cohort of oseltamivir users versus non-users were 1.05 (95% CI: 0.88-1.24) for incident cases and 0.98 (95% CI: 0.77-1.24) among patients with a history of a skin reaction. Similar results were seen for the other skin reaction categories, and secondary analyses investigating the oseltamivir users without influenza revealed no elevation in risk. It is concluded that oseltamivir use does not appear to be associated with an increased risk of skin reactions.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15134180&dopt=Abstract oseltamivir Tamiflu



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Surveillance of influenza isolates for susceptibility to neuraminidase inhibitors during the 2000-2002 influenza seasons.

Mungall BA, Xu X, Klimov A.

Influenza Branch, Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, Mailstop G-16, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30333, USA.

Neuraminidase (NA) inhibitors (NI) have recently been licensed for the prophylaxis and treatment of influenza virus infection in humans. This study has utilized a new chemiluminescent (CL) neuraminidase assay to routinely monitor more than a thousand influenza field isolates collected worldwide during the 2000-2002 seasons for susceptibility to both licensed NIs, zanamivir, and oseltamivir by determining the 50% inhibitory concentration (IC50). Our data demonstrated that influenza A viruses of the N2 subtype were less susceptible to zanamivir, but not oseltamivir, than those of the N1 subtype such that 41 of 45 confirmed H1N2 isolates could be reliably differentiated from H1N1 viruses based on their zanamivir susceptibility. Pre-titration of influenza A viruses appeared to have no effect on IC50 determined for either NI, while pre-titration of influenza B viruses significantly reduced oseltamivir IC50 and increased zanamivir IC50. Influenza B viruses were less susceptible to either compound than type A isolates. The CL assay is a rapid and reliable method for screening large numbers of influenza isolates for NI susceptibility. Reassortant viruses of the H1N2 subtype that started to circulate worldwide during the 2001-2002 season can be reliably separated from H1N1 viruses based on their zanamivir susceptibility, enabling large scale screening of H1 isolates for determining the prevalence of such reassortants.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15163509&dopt=Abstract oseltamivir Tamiflu



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Molecular mechanisms of influenza virus resistance to neuraminidase inhibitors.

Gubareva LV.

Department of Internal Medicine, University of Virginia Health Sciences Center, P.O. Box 800473, Charlottesville, VA, USA. lvg9b virginia.edu

A wide use of inhibitors of influenza virus neuraminidase (NAIs) to control influenza in humans demands a better understanding of the mechanisms involved in the resistance emergence. In vitro studies demonstrate that both neuraminidase (NA) and hemagglutinin (HA) influence virus susceptibility to NAIs. Drug resistance conferred due to changes in the NA could be monitored in the NA inhibition assays. Zanamivir-selected viruses acquired the NA substitutions at residues 119 and 292; oseltamivir-selected--at 274 and 292; peramivir-selected--at 292; and A-315675-selected--at 119. The HA binding efficiency and therefore susceptibility to NAIs are affected by the amino acids forming the HA receptor-binding site, the location and number of oligosaccharide chains, and structure of the neuraminic acid-containing cellular receptors. The lack of suitable cell culture-based assays hampers the assessment of virus susceptibility in humans. Emergence of the viruses with the NAI-induced substitutions in the NA is uncommon in drug-treated humans, however a compromised state of the immune system promotes emergence of drug resistance. In vivo, the zanamivir-selected mutant contained a substitution at 152 (B/NA); the oseltamivir-selected mutants-at residues 119 (A/N2), 198 (B/NA), 274 (A/N1), and 292 (A/N2). Substitutions in the NA were often accompanied by impairment of virus infectivity and virulence in animal models. Because of complexity of mechanisms of virus resistance, further analysis of the viruses recovered from the drug-treated humans is warranted.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15163510&dopt=Abstract oseltamivir Tamiflu