ABSTRACT
BACKGROUND: In recent years several reports of influenza vaccine effectiveness (VE) have been made early for public health decision. The majority of these studies use the case test-negative control design (TND), which has been showed to provide, under certain conditions, unbiased estimates of influenza VE. Nevertheless, discussions have been taken on the best influenza negative control group to use. The present study aims to contribute to the knowledge on this field by comparing influenza VE estimates using three test-negative controls: all influenza negative, non-influenza respiratory virus and pan-negative. METHODS: Incident ILI patients were prospectively selected and swabbed by a sample of general practitioners. Cases were ILI patients tested positive for influenza and controls ILI patients tested negative for influenza. The influenza negative control group was divided into non-influenza virus control group and pan-negative control group. Data were collected on vaccination status and confounding factors. Influenza VE was estimated as one minus the odds ratio of been vaccinated in cases versus controls adjusted for confounding effect by logistic regression. RESULTS: Confounder adjusted influenza VE against medically attended laboratory-confirmed influenza was 68.4% (95% CI: 20.7-87.4%) using all influenza negatives controls, 82.1% (95% CI: 47.6-93.9%) using non-influenza controls and 49.4% (95% CI: -44.7% to 82.3%) using pan-negative controls. CONCLUSIONS: Influenza VE estimates differed according to the influenza negative control group used. These results are in accordance with the expected under the hypothesis of differential viral interference between influenza vaccinated and unvaccinated individuals. Given the wide importance of TND study further studies should be conducted in order to clarify the observed differences.