A systematised review of seasonal influenza case-fatality risk

Case-fatality risk (CFR) is an important indicator of disease severity for influenza infection and an input to estimates of influenza burden and vaccination impact. However, CRF estimates based on laboratory-confirmed cases (cCFR) are more-highly sensitive to features of the local health-care system and surveillance. Estimates based on diagnosed-symptomatic cases (sCFR) are likely to be more consistent across health systems but are less commonly reported. We present a systematised review of sCFR for seasonal influenza to determine the availability of studies, variation across their sCFR estimates, and factors driving this variation. We identified 10 studies reporting sCFR, or primary data for its direct estimation, resulting in 40 location and season-specific point estimates (range 0.3-908 per 100,000 cases). There is considerable variation in sCFR across geographies, which was not linearly related to key socio-economic factors, but the variation can be even larger across seasons in a geography. The wide variation across studies and the lack of studies in many world regions point to the need for standardised protocols and more data collection.