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A New Framework for Influenza – Rational Use of Antiviral Therapy and Vaccines


efficacy in younger age cohorts and should be the preferred vaccine for that age group.29


administered the high-dose formulation, indicate that its greater efficacy may make it the preferred vaccine for that age group.30


Likewise, immunogenicity studies in the elderly, The intradermal


version of the vaccine includes a lower antigen dose and is administered with a shorter needle.28


Virulence Enhancing Features of Influenza Several virulence-enhancing features of influenza have been identified and are known to increase morbidity and mortality from influenza. They are summarised in Table 4.31–33


. Adjunctive Therapies


Given the current interest in immunomodulatory therapy, several different immunomodulatory drugs have been considered for use in influenza. Though there are no randomised human clinical trials to support their use, HMG-CoA reductase inhibitors (‘statins’), cycloxygenase-2 inhibitors (celecoxib), and peroxisome proliferator-activated receptor (PPAR) agonists (metformin, pioglitazone, gemfibrozil) have been advocated as adjuncts to standard therapy to restrict the inflammatory response from influenza.34


There also may be some benefit to the administration of intravenous immunoglobulin (IVIG) or convalescent sera as well.35,36


Strategies for Optimising Treatment of Concomitant Bacterial Pneumonia During the 2009 H1N1 pandemic bacterial pneumonia complicated up to 55 % of cases of influenza necessitating the use of antibacterial therapy.37


Table 4: Virulence-enhancing Features of Influenza PB1-F230,31


A pro-apoptic toxin produced from an alternate open reading frame of the PB1 gene; present in most avian and human isolates; absent from 2009 H1N1


Polybasic Amino Cleavage Site of Viral Haemagglutinin31,32 Proteolytic cleavage site of viral haemagglutin that, when containing basic amino acids at site, allows for greater organ tropism owing to ability to be cleaved by alternative protease; seen in highly pathogenic avian influenza viruses (e.g. H5, H7)


D225G32,33


Mutation in haemagglutinin that confers the ability of an influenza virus to bind to the alpha 2,3-sialic acid containing cells in the lower respiratory tract


pathway, enhance inflammation. The use of combination therapy including azithromycin, even in the setting of azithromycin resistance, may be useful in quieting inflammation. Also, animal data suggest that clindamycin may have a lesser – but still significant – benefit.38


Conclusion


New data are emerging – from animal models – that choosing antibacterial agents that have some immunomodulatory properties may be beneficial. Data suggest that the use of cell-wall active agents alone releases inflammatory molecules that, through a TLR-2 dependent


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Adept management of seasonal influenza, employing the latest technologies and clinical thinking, carries almost 100 % applicability to a pandemic situation, where the efforts would be scaled up to a nationwide level. Implementation of widespread influenza testing, typing and informed antiviral prescribing will create an environment much more resilient and adept at managing influenza, rendering a pandemic influenza virus spread much more difficult. The expertise and competence engendered by a programme, to increase clinical and laboratory acumen with seasonal influenza, will add to the confidence with which pandemics are approached and will supplement pandemic readiness measurably. n


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