Is influenza-like illness a useful concept and an appropriate test of influenza vaccine effectiveness?

PURPOSE To assess the utility of "influenza-like illness" (ILI) and whether it appropriately tests influenza vaccine effectiveness. PRINCIPAL RESULTS The WHO and CDC definitions of "influenza-like illness" are similar. However many studies use other definitions, some not specifying a temperature and requiring specific respiratory and/or systemic symptoms, making many samples non-comparable. Most ILI studies find less than 25% of cases are RT-PCR-positive, those which test for other viruses and bacteria usually find multiple other pathogens, and most identify no pathogen in about 50% of cases. ILI symptom and symptom combinations do not have high sensitivity or specificity in identifying PCR-positive influenza cases. Rapid influenza diagnostic tests are increasingly used to screen ILI cases and they have low sensitivity and high specificity when compared to RT-PCR in identifying influenza. MAIN CONCLUSIONS The working diagnosis of ILI presumes influenza may be involved until proven otherwise. Health care workers would benefit by renaming the WHO and CDC ILI symptoms and signs as "acute respiratory illness" and also using the WHO acute severe respiratory illness definition if the illness is severe and meets this criterion. This renaming would shift attention to identify the viral and bacterial pathogens in cases and epidemics, identify new pathogens, implement vaccination plans appropriate to the identified pathogens, and estimate workload during the viral season. Randomised controlled trials testing the effectiveness of influenza vaccine require all participants to be assessed by a gold standard (RT-PCR). ILI has no role in measuring influenza vaccine effectiveness. ILI is well established in the literature and in the operational definition of many surveillance databases and its imprecise definition may be inhibiting progress in research and treatment. The current ILI definition could with benefit be renamed "acute respiratory illness," with additional definitions for "severe acute respiratory illness" (SARI) with RT-PCR testing for pathogens to facilitate prevention and treatment.