Extension of disease burden modeling from seasonal influenza to 2009 pandemic influenza

Abstract

Reliable quantification of disease burden associated with influenza is critical to formulating proper public health prevention and intervention strategies. Direct counting of influenza infections on laboratory-test results, hospitalization records or death certificates grossly underestimates the true disease burden because of under-ascertainment and underreporting of influenza cases. To tackle the limitation of counting approach, statistical modeling approach utilizing routine public health surveillance data has been developed rapidly since last decade. However, few studies have properly discussed on how to adequately adjust for confounders in influenza disease burden modeling, such as in the Poisson model. Therefore, I conducted a simulation study to assess the performance of four model selection criteria in selecting the best Poisson model with adequate adjustment for Reliable quantification of disease burden associated with influenza is critical to formulating proper public health prevention and intervention strategies. Direct counting of influenza infections on laboratory-test results, hospitalization records or death certificates grossly underestimates the true disease burden because of under-ascertainment and underreporting of influenza cases. To tackle the limitation of counting approach, statistical modeling approach utilizing routine public health surveillance data has been developed rapidly since last decade. However, few studies have properly discussed on how to adequately adjust for confounders in influenza disease burden modeling, such as in the Poisson model. Therefore, I conducted a simulation study to assess the performance of four model selection criteria in selecting the best Poisson model with adequate adjustment for confounders. Generalized cross-validation (GCV) criterion was selected as the best criterion as it consistently provided the smallest bias and root-mean-square error in estimating disease burden of seasonal influenza. The Poisson model has been validated to provide reliable estimates for disease burden of seasonal influenza, but whether it could be extended to pandemic influenza remains unclear given that the epidemiological profiles of pandemic strains usually differ from the seasonal viruses. In this thesis, I extended the Poisson model from seasonal influenza to the 2009 pandemic influenza with proper adjustment for changes of hospital admission thresholds. The Poisson model estimated that in Hong Kong there were 10,377 excess hospitalizations for acute respiratory disease (subcategory: 7,204 for pneumonia and influenza), 1,676 for cardiovascular disease (subcategories: 848 for ischemic heart disease and 359 for stroke) and 1,550 for diabetes associated with the 2009 pandemic influenza. Compared with those of seasonal viruses, the hospitalization burden of pandemic strain clearly shifted towards children and young adults. By combining the influenza disease burden modeling with previous serology studies, the hospitalization risk of the 2009 pandemic cases was the highest in people aged 60 years or older (17.5%). Stratified by age and gender, influenza disease burden modeling revealed statistically significant gender difference of excess hospitalization for A(H3N2) in children and adolescents, but not in other age-virus categories. Influenza vaccination remains the most effective way to prevent influenza infection. The influenza vaccination rates increased dramatically from 1998–2010 in Hong Kong, but the pneumonia and influenza (P&I) hospitalization rate did not go downward correspondingly but nearly doubled. Therefore, an age-period-cohort analysis was conducted to assess the impact of influenza vaccination on P&I hospitalization risks. The relative risks of P&I hospitalization for those born in the first decade of the 21st century decreased rapidly, which suggested that the subsidized influenza vaccination scheme since 2008 in Hong Kong might have effectively reduced the P&I hospitalization risk in children. Taken together, GCV criterion is recommended in selecting the Poisson model to estimate disease burden of seasonal influenza. Poisson model could be extended from seasonal influenza to pandemic influenza in estimation of disease burden, assessment of severity and identification of vulnerable subgroups. Influenza vaccination schemes may be effective in lowering risks of P&I hospitalization.