Tamiflu
Surveillance for neuraminidase inhibitor resistance in human influenza viruses from Australia.

Hurt AC, Barr IG, Durrant CJ, Shaw RP, Sjogren HM, Hampson AW.

WHO Collaborating Centre for Reference and Research on Influenza, Melbourne, Australia. Aeron_Hurt csl.com.au

Two hundred and forty-five human influenza A and B viruses isolated in Australia between 1996 and 2003 were tested for their sensitivity to the NA inhibitor drugs, zanamivir and oseltamivir using a fluorescence-based neuraminidase inhibition assay. Based on mean IC50 values, influenza A viruses (with neuraminidase subtypes N1 and N2) were more sensitive to both the NA inhibitors than were influenza B strains. Influenza A viruses with a N1 subtype and influenza B strains both demonstrated a greater sensitivity to zanamivir than to oseltamivir carboxylate, whereas influenza A strains with a N2 subtype were more susceptible to oseltamivir carboxylate. A comparison of IC50 values for viruses isolated before and after the release of the NA inhibitors in Australia, found there was no significant difference in the sensitivity of strains to either neuraminidase inhibitor and none of the isolates tested showed clinically significant resistance.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15508516&dopt=Abstract oseltamivir Tamiflu



Tamiflu
Treatment of mannan-enhanced influenza B virus infections in mice with oseltamivir, ribavirin and viramidine.

Smee DF, Wandersee MK, Wong MH, Bailey KW, Sidwell RW.

Institute for Antiviral Research, Department of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, UT, USA. dsmee cc.usu.edu

Mannan, a polysaccharide preparation from Saccharomyces cerevisiae, has previously been shown to enhance influenza virus replication in mice by inhibiting host defense collectins. The use of mannan in infections may serve to broaden the types of influenza viruses that can be studied in rodent infection models. When mannan was co-administered with influenza B/Sichuan/379/99 virus to mice, the animals died from the infection, whereas mice infected with only virus survived. Three types of influenza A (H1N1) and another influenza B (Hong Kong/330/01) virus infection were also enhanced by mannan, but not four types of influenza A (H3N2) viruses. Mannan was used at 0.16 or 0.5 mg/mouse for optimal disease-enhancing activity using influenza B/Sichuan/379/99 virus. Using this model, influenza B/Sichuan/379/99 infections were treated with oseltamivir, ribavirin or viramidine (the carboxamidine derivative of ribavirin). When oral gavage treatments started 4 h before virus and mannan challenge, oseltamivir was effective at 2.5, 5 and 10 mg/kg/day. Ribavirin was active at 20, 40 and 80 mg/kg/day. Viramidine was effective at 80 and 160 mg/kg/day but not at 40 mg/kg/day. Active drug doses improved lung consolidation scores and lung weights, with decreases in lung virus titres also noted. Arterial oxygen saturation values in treated groups were significantly better than those of the placebo group on days 7-11 of the infection. Oseltamivir (5 mg/kg/day) and ribavirin (40 mg/kg/day) were used alone and in combination to determine how late after infection they could be beneficially administered. Ribavirin alone was very effective (90-100% survival of mice) when treatments started as late as 3 days after infection. Forty percent survival was evident even when treatments started 4 days post-infection. Oseltamivir was active starting treatments 1 day after virus exposure, but lost considerable efficacy when treatments began after that time. The combination of ribavirin and oseltamivir appeared to be no better than ribavirin alone, due to the stronger beneficial effect of ribavirin in this model. The overall results demonstrate that mannan can be used to enhance certain non-lethal influenza virus infections sufficiently to allow antiviral studies.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15535048&dopt=Abstract oseltamivir Tamiflu



Tamiflu
Adverse effects of amantadine and oseltamivir used during respiratory outbreaks in a center for developmentally disabled adults.

McGeer AJ, Lee W, Loeb M, Simor AE, McArthur M, Green K, Benjamin JH, Gardner C.

Department of Microbiology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.

BACKGROUND AND OBJECTIVES: Antiviral prophylaxis is recommended for the control of institutional influenza A outbreaks. In long-term-care institutions other than nursing homes, neither the seriousness of influenza nor the risks and benefits of antiviral prophylaxis is clearly understood. We studied the severity of illness due to influenza among adults residing in a center for the developmentally disabled and assessed adverse reactions to amantadine and oseltamivir prophylaxis. METHODS: Data were collected from the charts of consenting residents. Complications of upper respiratory tract illness were recorded. Potential adverse events were documented during amantadine and oseltamivir therapy, and during a baseline period with neither medication. RESULTS: The median age of the 287 participants was 46.4 years. Only 15 (5%) were older than 65 years, and 69 (24%) had chronic underlying medical illness placing them at high risk for influenza. Of the 122 residents with an upper respiratory tract infection, 16 (13%) developed pneumonia, 12 (9.8%) were hospitalized, and 5 (4%) died. Twenty-eight (25%) of 112 residents had an adverse neurologic event while receiving amantadine prophylaxis, compared with 3 (2.7%) receiving no antiviral medication and 5 (4.5%) receiving oseltamivir (P < .001). Sixteen percent of the residents discontinued amantadine due to adverse events; in contrast, adverse events were identified in 2.9% of the residents prescribed oseltamivir, and none discontinued therapy. CONCLUSIONS: Viral respiratory tract infections are associated with a high risk of complications in this population. The rate of adverse neurologic events associated with amantadine was significantly higher than that associated with oseltamivir.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15566030&dopt=Abstract oseltamivir Tamiflu



Tamiflu
Antiviral prophylaxis in the management of an influenza outbreak in an aged care facility.

Bush KA, McAnulty J, McPhie K, Reynolds R, Boomer M, Clarkson LM, Quaine J, Dwyer DE; Southern New South Wales Public Health Unit.

Southern New South Wales Public Health Unit, Goulburn. kym.bush sahs.nsw.gov.au

Influenza in persons aged > or = 65 years is associated with an increased risk of severe complications. Residents in aged care facilities have a higher proportion of chronic illnesses and within closed settings there is an increased risk of transmission. In July 2002, a 50 bed aged care facility reported an influenza-like illness (ILI) among residents and staff despite over 90 per cent influenza vaccine coverage among residents. A total of 17 of 49 residents and 9 of 43 staff met the case definition for ILI with onset on or after 26 June 2002. Seven people required hospitalisation and two died. Nasopharyngeal swabs were collected from symptomatic residents and staff, and influenza A was detected in six residents and two staff. Five unimmunised residents and 33 unimmunised staff were offered influenza vaccine and all residents and staff were offered oseltamivir prophylaxis of 75mg daily for 10 days. Subsequently, of 41 residents tested, seven demonstrated a fourfold or greater rise in antibody titres specific to H3N2 yet reported no symptoms. All seven had been immunised at least eight weeks previously, and had taken oseltamivir prophylaxis. This outbreak was characterised by a high attack rate of ILI in a well-immunised community. The ability to access rapid diagnostic testing enabled the prompt initiation of antiviral prophylaxis, which may have a role in controlling influenza in this setting.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15574064&dopt=Abstract oseltamivir Tamiflu



Tamiflu
Cooperative Anti-Influenza Activities of Respiratory Innate Immune Proteins and Neuraminidase Inhibitor.

White MR, Crouch E, van Eijk M, Hartshorn M, Pemberton L, Tornoe I, Holmskov U, Hartshorn KL.

Department of Medicine, Section Hematology/Oncology, Boston University School of Medicine, Boston, MA, USA.

The surfactant collectins, surfactant proteins A and D (SP-A and D) and scavenger receptor rich glycoprotein gp-340 (gp-340) inhibit influenza A virus (IAV) in the following order of potency: SP-D>gp-340>SP-A. SP-D binds in a calcium-dependent manner to carbohydrate attachments on the viral hemagglutinin (HA) and neuraminidase (NA). By contrast, gp-340 and SP-A act like mucins in that they provide sialic acid ligands which bind to the viral HA. In this study, SP-D, SP-A and gp-340 showed cooperative antiviral interactions. These cooperative effects were most evident in viral aggregation, but were also observed in at least some hemagglutination inhibition and viral neutralization assays. The mechanism of binding between gp-340 and SP-D was further characterized using monoclonal antibodies. Although gp-340 can bind to SP-D at a site distinct from the mannan-binding site, binding of gp-340 to SP-D did not contribute to cooperative antiviral interactions. SP-D and mucin showed cooperative interactions, apparently dependent on NA inhibition by SP-D. The commercial NA inhibitor, oseltamivir, had a similar effect and also enhanced the neutralizing activity of SP-A and bronchoalveolar lavage (BAL) fluid. Hence, oseltamivir collaborates with innate immune proteins in inhibiting the initial infection of epithelial cells.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15608147&dopt=Abstract oseltamivir Tamiflu