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29 December 2011 - Increase in oseltamivir-resistant pH1N1 in Australia
Researchers in Australia have reported an increase in transmission of oseltamivir-resistant pH1N1 in a new South Wales community during the previous southern hemisphere influenza season.  In the letter published in the New England Journal of Medicine, 29 (16%) out of 182 viruses analysed from the period May to August were found to carry the H275Y mutation conferring oseltamivir resistance.  The viruses were also resistant to the adamantane class of drugs, but sensitive to zanamivir.  Genetic analysis of the viruses showed that they were similar to the vaccine strain and closely related, suggesting transmission of a single variant.  Only one of the patients had been treated with oseltamivir, and all lived within a 30 mile radius of Newcastle in the Hunter New England region. Some were household contacts or shared a short car ride.  The report can be accessed at:
19 December 2011 - Low-level community transmission of oseltamivir-resistant influenza A(H1N1), USA
Researchers from the US Centers for Disease Control and Prevention (CDC) have published the results of oseltamivir-resistance testing of influenza A(H1N1) viruses from the 2010-11 influenza season.  Whilst only 1% (35/3,652) viruses tested carried the H275Y mutation conferring oseltamivir resistance, there was an increase in the proportion of people who had not been exposed to oseltamivir, compared to during the pandemic months.  Two siblings from the same household were infected with the resistant strain, although neither of them had received oseltamivir.  The authors note that the United Kingdom also found a higher proportion of oseltamivir-resistant infections in the 2010-11 season, suggesting that the increase in resistant viruses in the two years preceding the pandemic represented a worrisome pattern.  The viruses were also resistant to the adamantane class of drugs, but sensitive to zanamivir.  The report can be accessed at:
19 December 2011 - Recommendations for the treatment and management of oseltamivir-resistant influenza virus infection

A group of experts who advise the World Health Organisation (WHO) on issues relating to antiviral resistance in influenza A(H1N1) have expressed concerns about the community-spread of the oseltamivir-resistant strain, and have made recommendations for testing, reporting cases and managing infected patients.  Since April 2009, data on more than 27,000 samples which have been tested for neuraminidase sensitivity have been reported to WHO.  Of these, 447 oseltamivir-resistant viruses have been detected. Most resistant viruses were detected in patients undergoing oseltamivir treatment, including those who are immunocompromised, but a small number (14%) were detected in patients who had not been treated with oseltamivir and had no known contact with patients who were.  The authors recommend that countries that routinely use antiviral medication should establish baseline susceptibility monitoring.  The authors also called for a global database to allow researchers to rapidly share information on current and newly detected mutations associated with reduced susceptibility to oseltamivir.  The report abstract can be accessed at:

18 November 2011 - Mutations I117V and I117M and oseltamivir sensitivity of pandemic viruses
Researchers in Australia and Singapore have reported the results of a study to investigate the role of the I117M and I117V mutations in conferring oseltamivir resistance.  The researchers generated recombinant viruses and assessed neuraminidase inhibition activity using a fluorescence-based assay.  Analysis demonstrated that the I117V mutation alone resulted in a mild reduction in oseltamivir sensitivity, but this was not expected to be clinically relevant.  When combined with the H275Y mutation, however, there was a synergistic effect on oseltamivir resistance greater than that of H275Y alone, which was likely to be clinically relevant.  The I117M mutation did not confer significant resistance in combination with H275Y.  The publication can be accessed ahead of print at:
20 October 2011 - Antiviral treatment before and during the 2009 pandemic, USA
Researchers in the USA have reported that the use of antiviral drugs for the treatment of hospitalised patients increased following the publication of guidance during the 2009 H1N1 pandemic.  The researchers compared medical records for the four previous flu seasons with the first 8 months of the pandemic in 2009 .  During the prepandemic seasons, 54% of patients hospitalized with flu received antiviral medication, but this increased to 82% during the pandemic.  Prior to the pandemic, only 22% of pregnant women received antivirals, but this increased to 86% during the pandemic.  The abstract can be accessed at:
26 August 2011 - Australia reports oseltamivir-resistant 2009 H1N1 cluster
Australian health officials have reported a cluster of oseltamivir-resistant influenza A H1N1 cases in the Hunter New England region of New South Wales.  Between May and August 2011, 26 of 184 cases (14%) have shown reduced sensitivity to oseltamivir due the H275Y mutation.  Of the 16 patients interviewed to date, none have been treated with the drug.  The initial report can be accessed via ProMed at:,F2400_P1001_PUB_MAIL_ID:1000,89966
17 August 2011 - Study shows little benefit of IV zanamivir use in critically ill patients with H1N1
A retrospective study of intravenous (IV) zanamivir (Relenza) treatment in Dutch patients who were severely ill with influenza H1N1 infection and admitted to intensive care units has found that the drug had limited benefits.  Of 26 patients who were treated with IV zanamivir, 13 met the study inclusion criteria.  Whilst there was a sustained reduction in viral load in 6 of 13 cases, this did not affect mortality, as 3 of the 6 patients with sustained reduction died.  The response to IV zanamivir could have been influenced by the high proportion of immunocompromised patients and the poor response to oral oseltamivir.  The abstract of the paper published online in the Journal of Infectious Diseases can be found at:
02 August 2011 - Oseltamivir resistant pandemic influenza virus infection in England and Scotland, 2009-10
Researchers in the UK have reported the results of a case-control study to determine risk factors for the emergence of oseltamivir resistance and severe infection during the 2009-10 pandemic.  The authors identified 34patients with oseltamivir-resistant infections (cases) and 346 with oseltamivir sensitive strains (controls). Of those cases for whom information was available, 21 were immunocompromised and most had received antiviral drugs before a sample was taken.  Analysis indicated that cases remained significantly more likely to be immunocompromised, with selective drug pressure a likely explanation for the emergence of resistance in this group.  The full paper can be found at:
16 June 2011 - Meta-analysis shows that oseltamivir reduces risk of influenza complications by 37%
Researchers at Harvard university have undertaken a meta-analysis of 11 randomized clinical trials and shown in patients with confirmed influenza, oseltamivir reduces the risk of lower respiratory complications requiring antibiotics by 37% .  In patients with influenza-like illness, there is a 28% reduction in risk of complications.  The abstract can be found at:
09 June 2011 - Detection of influenza A(H1N1)2009 variant with S247N mutation
Researchers from Australia and Singapore have reported the increased detection of an influenza A(H1N1)2009 variant with reduced oseltamivir and zanamivir sensitivity due to an S247N neuraminidase mutation.  The variant has been detected in approximately 10% of community derived specimens in Singapore, and more than 30% of specimens from Northern Australia during the first few months of 2001.  When combined with the H275Y mutation, as detected in an oseltamivir-treated patient, the dual S247N and H275Y mutation had extremely high oseltamivir resistance. The full paper can be found at:
25 May 2011 - Early administration of prophylactic antivirals during pandemic reduced secondary attack rates
Results of an observational cohort study undertaken in the UK during the pandemic showed that early administration of antiviral prophylaxis reduced the secondary attack rate of pandemic influenza A(H1N1)2009 from 10.6% to 4.5%.  Researchers followed 285 confirmed influenza cases in 259 households with 761 contacts during a period when antiviral drugs were administered to both patients and their close contacts.  The confirmed secondary attack rate at 2 weeks was assessed. The full paper can be found at:
31 March 2011 - US awards contract for long-acting neuraminidase inhibitor, laninamivir
The United States Government has awarded $231 million to an Australian company, Biota Scientific Management Pty. Ltd., for the development of a single-dose long-acting neuraminidase inhibitor drug.  The drug, known generically as laninamivir, requires only one dose for full treatment, compared to 5 days of twice-daily dosing of oseltamivir or zanamivir.  The contract calls for Biota to establish US manufacturing, optimize its manufacturing processes, and conduct clinical trials of the drug in adults and children in preparation for applying for US licensing of the drug.  The full statement can be found at:
30 March 2011 - Influenza B viruses with lower antiviral sensitivity reported
Health officials in North Carolina, USA, have detected a number of influenza B virus isolates with reduced sensitivity to oseltamivir.  Of 92 viruses from North Carolina tested by the Centers for Disease Control (CDC), 32 showed reduced sensitivity, although not full resistance, to oseltamivir.  The viruses remain susceptible to zanamivir.  Most of the patients infected with the reduced-sensitivity viruses had typical 'flu symptoms and recovered after several days, although one patient with 'severe underlying immune problems' died shortly after being diagnosed with flu.  The full statement from North Carolina health officials can be found at:
03 March 2011 - IV peramivir well tolerated during H1N1 2009 pandemic
Analysis of data on 41 patients in the USA treated with IV peramivir during the 2009 influenza H1N1 pandemic show that the drug was well tolerated and that most patients recovered.  The study authors report data from 20 adults and 11 children who received the drug under an Emergency Investigational New Drug authorisation between April and October 2009 due to rapidly progressing, radiologically confirmed pneumonia with respiratory failure.  In most cases the illness had progressed despite oseltamivir treatment.  Peramivir was administered from 1 to 14 days, with a median of 10 days; the 14-day, 28-day, and 56-day survival rates were 76.7%, 66.7%, and 59.0%, respectively.  The report and accompanying editorial can be found at:
22 February 2011 - Japan reports peramivir-resistant H1N1 flu case
The National Institute of Infectious Diseases (NIID) in Japan has reported the first detected case of resistance to the antiviral drug peramivir, which was licensed in the country last year.  The influenza A H1N1 virus that contained a genetic mutation conferring resistance was detected in a child aged 5 years.  The virus was also resistant to oseltamivir, but remained sensitive to zanamivir and laninamivir.  The news report can be found at:

07 February 2011 - Monitoring & characterisation of oseltamivir-resistant influenza H1N1 viruses, Japan, 2009-10
A study published online in the journal Emerging Infectious Diseases provides details of oseltamivir-resistant influenza viruses detected in Japan during 2009/10.  Of 4,307 clinical specimens analysed, 61 were resistant to oseltamivir.  Of these, 55 (90%) had received the drug, either for treatment (45) or prevention (10).  There was no evidence of sustained transmission of the resistant viruses, however two suspected incidents of human-to-human transmission were reported.  The paper can be found at at:
07 February 2011 - Compensatory role of I222V mutation in oseltamivir-resistant influenza A(H3N2) E119V mutant
A short report provides details of oseltamivir-resistant influenza A(H3N2) isolates both with and without the E119V and I222V neuraminidase (NA) mutation that were recovered from an immunocompromised patient.  Characterisation of the viruses demonstrated that the impaired viral fitness of the E119V mutation was partially restored by the I222V NA mutation.  The full report can be found online in the Journal of Clinical Microbiology:
04 February 2011 - Emergence and changing epidemiology of oseltamivir-resistant influenza H1N1, United Kingdom
A report published online in Eurosurveillance provides a detailed account of 27 oseltamivir-resistant cases of influenza A(H1N1)2009 detected in the UK during the winter 2010/11.  Resistance was mainly detected in severely immunocompromised individuals or patients sampled post-treatment, although three cases were in community settings with no known exposure to oseltamivir, suggesting possible onward transmission of resistant strains.  The paper can be found at at:
31 January 2011 - Influenza experts report that opportunities were missed to use antiviral drugs during influenza H1N1 pandemic 
Influenza experts attending a meeting of the Infectious Diseases Society of America (IDSA) said that antiviral drugs could have been used more widely during the pandemic and opportunities to learn from their use were missed.   Some antiviral treatment opportunities were missed as rapid diagnostic tests yielded false-negative results, and formal clinical trials of antiviral effectiveness were hindered due to delays in gaining the necessary approval.  Presentations and expert panel discussion on antiviral usage focused on oseltamivir (Tamiflu) and zanamivir (Relenza) that were used during the pandemic.  The ISDA seasonal and pandemic influenza webcast site can be found at:
21 January 2011 - Recommendations on antiviral agents for the treatment and chemoprophylaxis of influenza

The Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP) has published updated recommendations regarding the use of antiviral agents for the prevention and treatment of influenza.   The report contains information on treatment and chemoprophylaxis of influenza virus infection and provides a summary of the effectiveness and safety of antiviral treatment medications.  The report can be found at:

20 January 2011 - Report on advantages of zanamivir treatment in children

A study undertaken by a research group in Japan has found that zanamivir may be a better treatment than oseltamivir for influenza virus infection in children.   The study of 144 paediatric patients was undertaken between 2005 and 2009.  The researchers found that resistance to zanamivir, an inhaled drug, was reported less frequently than with oseltamivir, which is taken orally.  They also concluded that zanamivir was more efficient than oseltamivir at reducing the virus-shedding period. An early online edition of the report can be found at:

19 January 2011 - GSK announces phase III study of IV zanamivir for hospitalised patients

GlaxoSmithKline (GSK) has announced that a phase III clinical trial of intravenous zanamivir for the treatment of hospitalised patients with influenza has begun.  The study, which will compare IV zanamivir to oral oseltamivir, aims to recruit 462 patients across 20 countries.  The primary endpoint is time to clinical response in patients with confirmed influenza.  Details of the trial can be found at:

14 January 2011 - Characteristics of patients with oseltamivir resistant pandemic influenza

A report has been published in the journal Emerging Infectious Diseases which provides a detailed account of 37 patients in whom oseltamivir resistant influenza viruses were detected.   The surveillance data were collected by the Centers for Disease Control and Prevention (CDC) during the period April 2009 to June 2010.  All resistant viruses had the H275Y mutation conferring oseltamivir resistance, but were sensitive to zanamivir. The authors describe the characteristics of the patients who were mainly hospitalised, had a severe immunocompromising condition or had been exposed to oseltamivir before collection of the specimen.  The full report can be found at:

13 January 2011 - CDC updates guidance on use of flu antivirals in pregnant women
The Centers for Disease Control and Prevention (CDC) has recently updated its guidance on the use of antivirals in pregnant and postpartum women during the current influenza season.   Because pregnancy increases the risk of severe flu complications, the CDC recommends antiviral treatment in women during pregnancy and up to 2 weeks postpartum if they have suspected or confirmed flu, with oseltamivir (Tamiflu) as the currently preferred drug.  The full guidance can be found at:

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