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2012

10 December 2012 - Oseltamivir pharmacokinetics, dosing, and resistance in children from birth to two years of age with influenza
A paper published by the National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group presents the results of an evaluation of oseltamivir in infants from birth to age 2 years of age.  A study of 87 subjects enrolled between 2006 and 2010 recommended that the appropriate daily dose for infants from birth to 8-months of age is 3.0mg/kg while the dose for infants from 9-11months is 3.5mg/kg.  
Six of ten subjects 12 through 23 months of age receiving the FDA-approved unit dose for this age group of 30mg had oseltamivir carboxylate exposures below the target range. Virus from three subjects developed oseltamivir resistance during antiviral treatment.  The abstract and link to the pdf publication can be found at: http://jid.oxfordjournals.org/content/early/2012/12/10/infdis.jis765.short

10 December 2012 - A cluster of patients infected with I221V influenza B virus variants with reduced oseltamivir susceptibility  - North Carolina and South Carolina 2010-2011 
During 2010-2011, the prevalence of the novel neuraminidase substitution, I221V, was evaluated in influenza B virus isolates submitted to the United States Centers for Disease Control and Prevention (CDC) for antiviral resistance surveillance.  I221V was detected in 45 (22%) of influenza B viruses from North Carolina and 8 (10%) of 82 B viruses from South Carolina.  The novel substitution was detected in only three (0.3%) of 881 B viruses tested from 45 other states.

Infection with the B/I221V was not associated with differences in underlying conditions or disease severity compared with wild type infection.  No patients with I221V received oseltamivir prior to specimen collection.  Those with I221V who completed oseltamivir reported a longer illness duration until illness resolution (5 versus 3 days); p=0.002
The report highlights the importance of global surveillance for I221V.  The abstract and link to the pdf publication can be found at: http://jid.oxfordjournals.org/content/early/2012/12/13/infdis.jis776.short
30 November 2012 - Evaluation of influenza virus antiviral susceptibility testing in Europe: results of the first EQA exercise

A paper summarising the results of the first EQA exercise for antiviral susceptibility testing in  Europe has been published in the Journal of Clinical Virology.  The exercise was undertaken during the 2010/11 winter by the Community Network of Reference Laboratories for Human Influenza in Europe (CNRL), under the auspices of ECDC.


An EQA panel containing ten specimens of inactivated influenza A and B viruses with reduced susceptibility to neuraminidase inhibitors (NAI) and adamantanes was evaluated by 24 laboratories from 19 member states in the WHO European region.  Whilst detection of NA-H275Y in A(H1N1) viruses was achieved by most laboratories, IC50 values and interpretation thereof varied for a sensitive/resistant virus mixture and for influenza B virus. The full report and results of the EQA can be found at:

http://www.sciencedirect.com/science/article/pii/S1386653212004040
 

29 November 2012 - Impact of neuraminidase inhibitor treatment on outcomes of public health importance during the 2009-10 influenza A(H1N1) pandemic: a systematic review and meta-analysis in hospitalised patients

A paper in the Journal of Infectious Diseases reports that a meta-analysis of 90 observational studies involving 34,895 patients, of whom 85% had laboratory-confirmed pandemic 2009 H1N1 influenza virus, shows that antiviral therapy (principally oseltamivir), intiated within 48 hours of symptom onset, reduced the likelihood of severe outcomes, namely admission to a critical care unit or death, by 49 to 65%. The full report and accompanying editorial can be found at:

http://jid.oxfordjournals.org/content/early/2012/11/28/infdis.jis726.long
http://jid.oxfordjournals.org/content/early/2012/11/28/infdis.jis727.long 
 

28 September 2012 - Report from the WHO working group on surveillance of influenza antiviral susceptibility

A report summarising the activities to date of the WHO expert working group on surveillance of influenza antiviral susceptibility (AVWG) has been published in the WHO Weekly Epidemiological Record (WER).  Since its formation in 2011, the group have reviewed the scope of antiviral surveillance performed by the Global Influenza Surveillance and Response System (GISRS), the distribution of antiviral testing capacity, the laboratory methodologies available and the necessary level of surveillance.  In 2012, the group have moved towards addressing the issues of interpretation of antiviral susceptibility data, reporting, practical guidance for laboratories seeking to implement antiviral surveillance, and the most appropriate means to monitor quality in laboratories.  The full report can be found at: 
http://www.who.int/wer/2012/wer8739.pdf
 

2 July 2012 - Study finds high mortality rates in H1N1 patients treated with Peramivir

Researchers have reported that 29 (51%) of 57 critically ill patients who received intravenous peramivir during the 2009 H1N1 influenza pandemic died, raising questions about the safety and efficacy of the drug.  The study, reported in PLoS One, looked at 1,684 California residents who were admitted to intensive care units (ICUs) and received antiviral treatment during the pandemic.  The 57 patients who received peramivir were significantly more likely to be diagnosed as having pneumonia and acute respiratory distress syndrome or sepsis, require mechanical ventilation and to die compared to those who did not receive peramivir.  The authors state that 'the high mortality could be due to the pre-existing clinical severity of cases prior to request for peramivir, but also raises questions about peramivir safety and effectiveness in hospitalised and critically ill patients'.  
The full report can be found at: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0040261
 

31 May 2012 - Scientists develop influenza inhibitors using 'deep sequencing' methodology

A paper published in the journal Nature Biotechnology describes a technique to design influenza proteins which act as potent antivirals against an array of flu strains.  The proteins were optimised using a technique of 'DNA deep sequencing' to identify beneficial mutations.  The most potent of these, a 51-residue protein, is broadly cross-reactive against all influenza group 1 haemagglutinins, including human H2, and neutralises human H1N1 viruses with a potency similar to several human monoclonal antibodies. The abstract can be found at:
http://www.nature.com/nbt/journal/vaop/ncurrent/full/nbt.2214.html 
 

4 May 2012 - Characteristics of widespread community cluster of oseltamivir resistant influenza
A report and commentary published in the Journal of Infectious Diseases describes the widespread community transmission of oseltamivir resistant influenza A(H1N1)pdm09 in Australia.  Twenty-nine (15%) of 191 viruses collected between May and September 2011 contained the H275Y neuraminidase substitution conferring oseltamivir resistance.  Only one patient had received oseltamivir before specimen collection.  The resistant strains were closely genetically related, suggesting spread of a single variant.
The full report and accompanying commentary can be accessed at:
http://jid.oxfordjournals.org/content/early/2012/05/04/infdis.jis337.short
http://jid.oxfordjournals.org/content/early/2012/05/04/infdis.jis338.short

6 April 2012 - Emergency use authorisation of intravenous peramivir during 2009 pandemic
A report and commentary published in the journal Clinical Infectious Diseases suggests that the impact and safety profile of the intravenous antiviral, Peramivir, remain unclear following its use in nearly 1,300 severely ill patients during the 2009 pandemic, partly due to patchy data collection.
The Centers for Disease Control and Prevention (CDC) estimate that of 1,274 patients that received the IV drug under an Emergency Use Authorisation, and the Food and Drug Administration (FDA) estimate that approximately 16% of these died, which is within the range of fatality rates reported for hospitalised patients generally.  
Many adverse events were reported, but these were mainly attributed to their already severe illness at the time of treatment, plus other factors.  Rashes were the only adverse reaction directly attributed to the drug, but the overall safety data were incomplete due to gaps in data collection.  The full report and commentary can be accessed at: 
http://cid.oxfordjournals.org/content/early/2012/04/05/cid.cis351.short
http://cid.oxfordjournals.org/content/early/2012/04/05/cid.cis365.full.pdf+html
3 April 2012 - Systematic Review and Meta-Analysis of Antivirals for the Treatment of Influenza

A systematic review of observational studies for benefits and harms of oseltamivir, zanamivir, amantadine and rimantadine in the treatment of influenza has been published in the Annals of Internal Medicine.  The review of 74 studies concluded that treatment with oral oseltamivir or zanamivir may provide a net benefit over no treatment of influenza.  Only one study of amantadine was included; there were no studies of rimantadine included in the analysis.  The full report can be found at:
http://www.annals.org/content/156/7/512.full.pdf+html
 

29 March 2012 - Oseltamivir shown to cross placental barrier to newborn
In a letter published today in the journal Clinical Infectious Diseases, researchers in the Netherlands report that significant levels of Oseltamivir were detected in umbilical cord blood after a woman with a severe case of pandemic influenza 2009 H1N1(pH1N1) infection was treated with high doses of the drug, suggesting that the drug can cross the placental barrier in humans.  The 29-year old woman who was 29 weeks pregnant was treated in ICU for respiratory failure requiring artifical respiration, and pneumonia. She received antibiotics and 75mg oseltamivir three times a day, which was doubled after 3 days.  Following delivery by caesarean section, test results showed oseltamivir and oseltamivir carboxylate exceeding 90% inhibitory concentration in cord blood taken after cord clamping.  The letter can be found at:
http://cid.oxfordjournals.org/content/early/2012/03/24/cid.cis265.extract  
 
29 March 2012 - Combination Antiviral Therapy for Influenza: Predictions from Modeling of Human Infections
Researchers in the USA have published a paper which uses a probabilistic model to predict the benefits of combination antiviral therapy to reduce the risk of antiviral resistance emergence in seasonal and pandemic influenza viruses.  The authors argue that a triple combination regimen would markedly reduce the risk of antiviral resistance emergence.  The paper can be found at:
http://jid.oxfordjournals.org/content/early/2012/03/22/infdis.jis265.full.pdf+html
 
15 February 2012 - Efficient transmission of pandemic H1N1 with high-level oseltamivir resistance

A report published in the Journal of Virology provides data on the transmission characteristics of highly oseltamivir-resistant viruses encoding both the S274N and H275Y neuraminidase mutations in an animal model.  Whilst the viruses conferring both mutations were found to transmit less efficiently by respiratory droplet transmission than those with just the H275Y mutation, the authors note that it is a concern that viruses conferring high-level oseltamivir resistance are still able to transmit with efficiency.The full report can be found at: 
http://jvi.asm.org/content/86/9/5386.long

19 January 2012 - Cochrane review of neuraminidase inhibitors for preventing and treating influenza

The Cochrane Library has published an updated Cochrane Review of neuraminidase inhibitors (oseltamivir and zanamivir) for the prevention and treatment of influenza in adults and children.  Using methods which have been updated to address the risk of reporting bias, the analysis questions the effectiveness of oseltamivir, stating that whilst it shortens flu symptoms by about a day, there is no evidence that it reduces hospital admissions.  The researchers also conclude that they were not able to gather enough data to conclude whether oseltamivir reduces flu complications and transmission.  The authors also question the safety of oseltamivir, saying that some reports of adverse events were not included in the published reports of clinical trials. Roche, the manufacturers of oseltamivir, say that clinical trials and medical experience have shown that oseltamivir is effective and usually well tolerated, but the authors say in the report that the company withheld some data that they requested. 
The report abstract and accompanying editorial can be accessed at:
http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD008965.pub3/abstract
http://www.thecochranelibrary.com/details/editorial/1442857/Neuraminidase-inhibitors-for-influenza-methods-change-principles-dont.html

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