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Sullivan S.G.,University of California at Los Angeles | Sullivan S.G.,Collaborating Center for Reference and Research on Influenza | Greenland S.,University of California at Los Angeles
International Journal of Epidemiology | Year: 2013

Bayesian methods have been found to have clear utility in epidemiologic analyses involving sparse-data bias or considerable background information. Easily implemented methods for conducting Bayesian analyses by data augmentation have been previously described but remain in scant use. Thus, we provide guidance on how to do these analyses with ordinary regression software. We describe in detail and provide code for the implementation of data augmentation for Bayesian and semi-Bayes regression in SAS ® software, and illustrate their use in a real logistic-regression analysis. For comparison, the same model was fitted using the Markov-chain Monte Carlo (MCMC) procedure. The two methods required a similar number of steps and yielded similar results, although for the main example, data augmentation ran in about 0.5% of the time required for MCMC. We also provide online appendices with details and examples for conditional logistic, Poisson and Cox proportional-hazards regression. © The Author 2012; all rights reserved. Source

Kelly H.A.,Victorian Infectious Diseases Reference Laboratory | Kelly H.A.,Australian National University | Sullivan S.G.,Collaborating Center for Reference and Research on Influenza | Grant K.A.,Victorian Infectious Diseases Reference Laboratory | And 2 more authors.
Influenza and other Respiratory Viruses | Year: 2013

Background: Influenza vaccines are licensed annually based on immunogenicity studies. We used five sequential years of data to estimate influenza vaccine effectiveness (VE), the critical outcome in the field. Methods Between 2007 and 2011, we performed annual prospective test-negative design case-control studies among adults aged 20-64years recruited from sentinel general practices in the Australian state of Victoria. We used PCR-confirmed influenza as the endpoint to estimate influenza VE for all years. We compared annual VE estimates with the match between circulating and vaccine strains, determined by haemagglutination inhibition assays. Results The adjusted VE estimate for all years (excluding 2009) was 62% (95% CI 43, 75). By type and subtype, the point estimates of VE by year ranged between 31% for seasonal influenza A(H1N1) and 88% for influenza A(H1N1)pdm09. In 2007, when circulating strains were assessed as incompletely matched, the point estimate of the adjusted VE against all influenza was 58%. The point estimate was 59% in 2011 when all strains were assessed as well matched. Conclusion Trivalent inactivated vaccines provided moderate protection against laboratory-confirmed influenza in adults of working age, although VE estimates were sensitive to the model used. VE estimates correlated poorly with circulating strain match, as assessed by haemagglutination inhibition assays, suggesting a need for VE studies that incorporate antigenic characterization data. © 2012 John Wiley & Sons Ltd. Source

Londrigan S.L.,University of Melbourne | Tate M.D.,University of Melbourne | Tate M.D.,Monash Institute of Medical Research | Brooks A.G.,University of Melbourne | And 2 more authors.
Journal of Leukocyte Biology | Year: 2012

Airway MFF{cyrillic} and DCs are important components of innate host defense and can play a critical role in limiting the severity of influenza virus infection. Although it has been well established that cell-surface SA acts as a primary attachment receptor for IAV, the particular receptors) or coreceptor(s) that mediate IAV entry into any cell, including MFF{cyrillic} and DC, have not been clearly defined. Identifying which receptors are involved in attachment and entry of IAV into immune cells may have important implications in regard to understanding IAV tropism and pathogenesis. Recent evidence suggests that specialized receptors on MFF{cyrillic} and DCs, namely CLRs, can act as capture and/or entry receptors for many viral pathogens, including IAV. Herein, we review the early stages of infection of MFF{cyrillic} and DC by IAV. Specifically, we examine the potential role of CLRs expressed on MFF{cyrillic} and DC to act as attachment and/or entry receptors for IAV. © Society for Leukocyte Biology. Source

Hurt A.C.,Collaborating Center for Reference and Research on Influenza
Current Opinion in Virology | Year: 2014

Significant changes in the circulation of antiviral-resistant influenza viruses have occurred over the last decade. The emergence and continued circulation of adamantane-resistant A(H3N2) and A(H1N1)pdm09 viruses mean that the adamantanes are no longer recommended for use. Resistance to the newer class of drugs, the neuraminidase inhibitors, is typically associated with poorer viral replication and transmission. But 'permissive' mutations, that compensated for impairment of viral function in A(H1N1) viruses during 2007/2008, enabled them to acquire the H275Y NA resistance mutation without fitness loss, resulting in their rapid global spread. Permissive mutations now appear to be present in A(H1N1)pdm09 viruses thereby increasing the risk that oseltamivir-resistant A(H1N1)pdm09 viruses may also spread globally, a concerning scenario given that oseltamivir is the most widely used influenza antiviral. Source

Tate M.D.,University of Melbourne | Ioannidis L.J.,University of Melbourne | Croker B.,Walter and Eliza Hall Institute of Medical Research | Brown L.E.,University of Melbourne | And 3 more authors.
PLoS ONE | Year: 2011

Neutrophils have been implicated in both protective and pathological responses following influenza virus infections. We have used mAb 1A8 (anti-Ly6G) to specifically deplete LyG6high neutrophils and induce neutropenia in mice infected with virus strains known to differ in virulence. Mice were also treated with mAb RB6-8C5 (anti-Ly6C/G or anti-Gr-1), a mAb widely used to investigate the role of neutrophils in mice that has been shown to bind and deplete additional leukocyte subsets. Using mAb 1A8, we confirm the beneficial role of neutrophils in mice infected with virus strains of intermediate (HKx31; H3N2) or high (PR8; H1N1) virulence whereas treatment of mice infected with an avirulent strain (BJx109; H3N2) did not affect disease or virus replication. Treatment of BJx109-infected mice with mAb RB6-8C5 was, however, associated with significant weight loss and enhanced virus replication indicating that other Gr-1+ cells, not neutrophils, limit disease severity during mild influenza infections. © 2011 Tate et al. Source

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