The association between influenza vaccination uptake and influenza and pneumonia-associated deaths in the United States.

BACKGROUND: The influenza mortality burden has remained substantial in the United States (US) despite relatively high levels of influenza vaccine uptake. This has led to questions regarding the effectiveness of the program against this outcome, particularly in the elderly. The aim of this evaluation was to develop and explore a new approach to estimating the population-level effect of influenza vaccination uptake on pneumonia and influenza (P&I) associated deaths. METHODS: Using publicly available data we examined the association between state-level influenza vaccination and all-age P&I associated deaths in the US from the 2013-2014 influenza season to the 2018-2019 season. In the main model, we evaluated influenza vaccine uptake in all those age 6 months and older. We used a mixed-effects regression analysis with generalised least squares estimation to account for within state correlation in P&I mortality. RESULTS: From 2013-2014 through 2018-2019, the total number of all-age P&I related deaths during the influenza seasons was 480,111. The mean overall cumulative influenza vaccine uptake (age 6 months and older) across the states and years considered was 46.7%, with higher uptake (64.8%) observed in those aged ≥ 65 years. We found that overall influenza vaccine uptake (6 months and older) had a statistically significant protective association with the P&I death rate. This translated to a 0.33 (95% CI: 0.20, 0.47) per 100,000 population reduction in P&I deaths in the influenza season per 1% increase in overall influenza vaccine uptake. DISCUSSION: These results using a population-level statistical approach provide additional support for the overall effectiveness of the US influenza vaccination program. This reassurance is critical given the importance of ensuring confidence in this life saving program. Future research is needed to expand on our approach using more refined data.

Modelled estimates of hospitalisations attributable to respiratory syncytial virus and influenza in Australia, 2009-2017.

BACKGROUND: Respiratory syncytial virus (RSV) and influenza are important causes of disease in children and adults. In Australia, information on the burden of RSV in adults is particularly limited. METHODS: We used time series analysis to estimate respiratory, acute respiratory infection, pneumonia and influenza, and bronchiolitis hospitalisations attributable to RSV and influenza in Australia during 2009 through 2017. RSV and influenza-coded hospitalisations in <5-year-olds were used as proxies for relative weekly viral activity. RESULTS: From 2009 to 2017, the estimated all-age average annual rates of respiratory hospitalisations attributable to RSV and seasonal influenza (excluding 2009) were 54.8 (95% confidence interval [CI]: 20.1, 88.8) and 87.8 (95% CI: 74.5, 97.7) per 100,000, respectively. The highest estimated average annual RSV-attributable respiratory hospitalisation rate per 100,000 was 464.2 (95% CI: 285.9, 641.2) in <5-year-olds. For seasonal influenza, it was 521.6 (95% CI: 420.9, 600.0) in persons aged ≥75 years. In ≥75-year-olds, modelled estimates were approximately eight and two times the coded estimates for RSV and seasonal influenza, respectively. CONCLUSIONS: RSV and influenza are major causes of hospitalisation in young children and older adults in Australia, with morbidity underestimated by hospital diagnosis codes.

Influenza-associated mortality in Australia, 2010 through 2019: High modelled estimates in 2017.

INTRODUCTION: In Australia, the 2017 and 2019 influenza seasons were severe. High-dose or adjuvanted vaccines were introduced for ≥65 year-olds in 2018. AIM: To compare influenza-associated mortality in 2017 and 2019 with the average for 2010-2019. METHODS: We used time series modelling to obtain estimates of influenza-associated death rates for influenza A(H1N1)pdm09, A(H3N2) and B in Australia, in persons of all ages and <65, 65-74 and ≥75 years. Estimates were made for pneumonia and influenza (P&I, 2010-2018), respiratory (2010-2018), and all-cause outcomes (2010-2019). RESULTS: During 2010 through 2018 (and 2019 for all-cause), influenza was estimated to be associated with an annual average of 2.1 (95% confidence interval (CI) 1.9, 2.4), 4.0 (95% CI 3.4, 4.6), and 11.6 (95% CI 8.4, 15.0) P&I, respiratory and all-cause deaths per 100,000 population, respectively. Influenza A(H1N1)pdm09 was estimated to be associated with less than one quarter of influenza-associated P&I and respiratory deaths, while A(H3N2) and B were each estimated to contribute approximately equally to the remaining influenza-associated deaths. In 2017, the respective rates were 7.8 (95% CI 7.1, 8.4), 12.3 (95% CI 10.9, 13.6) and 26.0 (95% CI 20.8, 32.0) per 100,000. In 2019, the all-cause estimate was 20.8 (95% CI 14.9, 26.7) per 100,000. CONCLUSIONS: Seasonal influenza continues to be associated with substantial mortality in Australia, with at least double the average occurring in 2017. Age-specific monitoring of vaccine effectiveness is needed in Australia to understand higher mortality seasons.

Linear conjugacy of chemical kinetic systems.

Two networks are said to be linearly conjugate if the solution of their dynamic equations can be transformed into each other by a positive linear transformation. The study on dynamical equivalence in chemical kinetic systems was initiated by Craciun and Pantea in 2008 and eventually led to the Johnston-Siegel Criterion for linear conjugacy (JSC). Several studies have applied Mixed Integer Linear Programming (MILP) approach to generate linear conjugates of MAK (mass action kinetic) systems, Bio-CRNs (which is a subset of Hill-type kinetic systems when the network is restricted to digraphs), and PL-RDK (complex factorizable power law kinetic) systems. In this study, we present a general computational solution to construct linear conjugates of any "rate constant-interaction function decomposable" (RID) chemical kinetic systems, wherein each of its rate function is the product of a rate constant and an interaction function. We generate an extension of the JSC to the complex factorizable (CF) subset of RID kinetic systems and show that any non-complex factorizable (NF) RID kinetic system can be dynamically equivalent to a CF system via transformation. We show that linear conjugacy can be generated for any RID kinetic systems by applying the JSC to any NF kinetic system that are transformed to CF kinetic system.