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2013

11th December 2013 - Influenza A(H7N9) neuraminidase resistance without loss of in vivo virulence or transmissibility
Researchers from the Icahn School of Medicine at Mount Sinai have reported that oseltamivir-resistant strains of influenza A(H7N9) transmit and cause disease as efficiently as strains that are sensitive to the neuraminidase inhibitor class of drugs. The report raises concern as antiviral medication is a key treatment and prevention measure in the absence of a vaccine against the novel strain. The full paper can be accessed at: http://www.nature.com/ncomms/2013/131210/ncomms3854/full/ncomms3854.html
 
17th July 2013 - Study outlines difficulties in detecting H7N9 antiviral resistance 
Research published in the journal mBio, the online journal of the American Society for Microbiology (ASM), provides further data on cases of influenza A(H7N9) antiviral resistance detected in Shanghai in May 2013.
The researchers undertook detailed characterisation of an isolate obtained from the first confirmed human case of infection in China, two days after Oseltamivir treatment had been commenced. They found that whilst the clinical isolate exhibited a phenotype of sensitivity to NA-inhibitors using the enzyme-based NA inhibition assay, genetic analysis revealed a mixture of H7N9 variants. One of the variants, K292, was resistant to the neuraminidase inhibitor class of antiviral drugs, including oseltamivir, zanamivir and peramivir.
The authors conclude that resistance to NA inhibitors conferred by the R292K mutation in a human H7N9 isolate can be masked by a mixed R/K viral population, and this should be taken into consideration when monitoring antiviral resistance in patients with H7N9 infection.
The full paper can be accessed at: http://mbio.asm.org/content/4/4/e00396-13.full
 
 
28th May 2013 - First clinical confirmation of H7N9 viruses resistant to Tamiflu 

Research published today in the Lancet documents the first clinical cases of resistance to Tamiflu (Oseltamivir) and similar neuraminidase inhibitor drugs in people infected with influenza A(H7N9) infection.
Researchers analysed the viral load of 14 patients throughout the course of their illness and found that for most, treatment with neuraminidase inhibitor drugs resulted in a reduction in the viral load found on throat swabs and was associated with clinical recovery. However, for three patients who became severely ill, antiviral treatment did not reduce their viral load. The researchers found a genetic mutation characteristic of resistance to neuraminidase inhibitors (Arg292Lys). In one of the patients this mutation appears to have arisen as a result of treatment with Tamiflu, leading to concerns that it might arise in response to treatment with neuraminidase inhibitors.
The paper can be accessed at:
http://download.thelancet.com/flatcontentassets/pdfs/S0140673613611253.pdf

 
12th April 2013 - Antiviral susceptibility of influenza A(H7N9) viruses
Genetic analysis of influenza A(H7N9) viruses isolated from patients in China predict that the viruses are susceptible to the neuraminidase inhibitor class of drugs, except for one sample from Shanghai which has an R294K mutation in the NA protein which has been linked to resistance in N2 and N9 flu subtypes.  The results of the analysis can be found here.  The sequences of the influenza viruses characterised are available in the GISAID database

3rd April 2013 - Human infection with avian influenza A(H7N9) in China
Information about human infection with avian influenza A(H7N9) in China is available on the news pages of the main isirv site.

2 April 2013 - The value of neuraminidase inhibitors for the prevention and treatment of seasonal influenza: a systematic review of systematic reviews
A systematic review has been published in the online journal PLOS ONE which evaluates previously published systematic reviews of the benefits and disadvantages of neuraminidase inhibitors (NIs) (oseltamivir and zanamivir) compared to placebos for the prophylaxis and treatment of seasonal influenza. 

The authors found that the efficacy of NIs in prophylaxis ranged from 64% (16–85) to 92% (37–99); the absolute risk reduction ranged from 1.2% to 12.1%. Clinically relevant treatment benefits of NIs were small in healthy adults and children suffering from influenza-like illness. No evidence was available on the treatment benefits of NIs in elderly and at-risk groups and their effects on hospitalization and mortality. They conclude that the combination of diagnostic uncertainty, the risk for virus strain resistance, possible side effects and financial cost outweigh the small benefits of oseltamivir or zanamivir for the prophylaxis and treatment of healthy individuals. No relevant benefits of these NIs on complications in at-risk individuals have been established.

The full review is available at: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0060348

26 February 2013 - Mechanism-based covalent neuraminidase inhibitors with broad spectrum influenza antiviral activity
Researchers from Australia have published data in the journal Science on a new class of specific, mechanism-based, anti-influenza drugs that function via the formation of a stabilised covalent intermediate in the influenza neuraminidase enzyme.  The mode of action has been confirmed via structural and mechanistic studies.  The report abstract can be accessed at:  http://www.sciencemag.org/content/early/2013/02/20/science.1232552

18 January 2013 - Oseltamivir and fetal health

A study reported in the American Journal of Obstetrics and Gynecology has found no association between oseltamivir use during pregnancy and fetal outcome.  The retrospective cohort study of 55,355 women in Canada included 1,237 (2.2%) who had received oseltamivir for the treatment or prevention of influenza during pregnancy.

The researchers found no association between oseltamivir use and being small for gestational age (SGA) on 3rd percentile, preterm birth, very preterm birth or low Agpar score. 
The report abstract can be accessed at:
http://www.sciencedirect.com/science/article/pii/S0002937813000513

11 January 2013 - Study of resistance to neuraminidase inhibitors, 2008 to 2011
The first three years of data from the Influenza Resistance Information Study that began in 2008 have been published in a report in the journal Clinical Infectious Diseases. The data show that resistance to the neuraminidase inhibitor (NI) class of drugs was 2.2% overall and mostly found in patients aged 1 to 5 years.  The study of 1,799 laboratory-confirmed influenza cases detected 1281 influenza A (47 seasonal H1N1; 335 H3N2; 899 H1N1 pdm2009) and 518 influenza B. All 47 of the seasonal influenza A(H1N1) viruses tested were resistant to the NI drug oseltamivir (Tamiflu). No resistance was detected amongst any of the other viral subtypes. 
The report abstract can be accessed at:
http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD008965.pub3/abstract

January 2013 - Special issue of 'Influenza and Other Respiratory Viruses' journal on Influenza Antivirals: Efficacy and Resistance
The isirv journal 'Influenza and Other Respiratory Viruses' has published a supplement edition 'Influenza Antivirals: Efficacy and Resistance'. The Conference Proceedings are from the first isirv Antiviral Group conference held in Rio de Janeiro, Brazil, from 8-10 November 2011. The full supplement edition can be found at:
http://onlinelibrary.wiley.com/doi/10.1111/irv.2012.7.issue-s1/issuetoc

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