Burden and control of influenza viruses

Abstract

Human influenza viruses contribute to considerable morbidity and mortality worldwide. This thesis sets out to enhance understanding of key issues relating to influenza vaccination, and the burden caused by human influenza virus infections in China to inform future control strategies. Influenza vaccination is the best prevention tool available in the fight against influenza virus infections and associated complications. Over the past decade, the effectiveness of influenza vaccination has been monitored using a type of observational study – the test-negative design – which is a variant of the case-control study. The increasing application of this study design has stimulated questions about the methodological underpinnings that influence the estimates and interpretations of vaccine effectiveness. In this research, I used two approaches to assess a crucial underlying assumption, i.e., whether the choice of controls is independent of exposure. I analysed influenza surveillance data from the United States and reviewed articles reporting vaccine effectiveness by the choice of control groups, and I did not find evidence that the choice of control group is associated with influenza vaccination. Moreover, since sources of bias of the test-negative design are likely to differ by study setting, I compared the vaccine effectiveness of inpatient and outpatient settings in a systematic review and meta-analysis, and identified comparable vaccine effectiveness estimates. The duration of vaccine-generated immune responses is of great interest and importance for public health, especially for regions with year-round influenza activity. I analysed data from test-negative design studies collected for children from Hong Kong hospitals in order to estimate the waning rate of vaccine effectiveness since vaccination. Based on over 15,000 children, I estimated a waning rate of 2–5 percent points per month since vaccination by influenza type/subtype, confirming the importance of annual vaccination. Understanding the burden caused by human influenza virus infections plays a key role in enabling us to achieve a comprehensive understanding of vaccine impact. In this thesis, I estimated the influenza-associated outpatient burden in China across 30 provinces over a 10-year period. The findings suggest that vaccination programmes are likely to benefit from incorporating children as a target group. Future studies could further evaluate influenza-associated hospitalisations and mortality, and the cost-effectiveness of influenza vaccination based on disease burden and vaccine effectiveness.