Background: The aim of the present study was to estimate the effectiveness of the MF59TM-adjuvanted influenza A(H1N1)pdm09 vaccine against medically attended influenza-like illness and RT-PCR confirmed influenza in the at-risk population and persons over 60 in the Netherlands. Methods: We conducted a retrospective cohort study in a Dutch based GP medical record database between 30 November 2009 and 1 March 2010 to estimate the vaccine effectiveness against influenza-like illness. Within the cohort we nested a test negative case-control study to estimate the effectiveness against laboratory confirmed influenza. Results: The crude effectiveness in preventing diagnosed or possible influenza-like illness was 17.3 % (95%CI:28.5%–36.9%). Of the measured covariates, age, the severity of disease and health seeking behaviour through devised proxies confounded the association between vaccination and influenza-like illness. The adjusted vaccine effectiveness was 20.8 % (95%CI:25.4%, 40.5%) and varied significantly by age, being highest in adults up to 50 years (59%, 95%CI: 23%, 78%), and non-detectable in adults over 50 years. The number of cases in the nested case control study was too limited to validly estimate the VE against confirmed influenza. Conclusions: With our study we demonstrated that the approach of combining a cohort study in a primary health car
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