Estimating Total Number of Influenza Cases From Reported Hospitalizations: A Multi-Country Comparison of the Multiplier Method

OBJECTIVES: Sentinel data on influenza hospitalizations represent a fraction of total disease burden. The US Centers for Disease Control and Prevention (CDC) methodology applies numeric multipliers to the numbers of influenza-associated hospitalizations to estimate the number of all symptomatic influenza cases. The methodology’s applicability in other countries is unclear. This analysis assessed the practical implications of estimating total influenza burden using the multiplier method in select countries with robust influenza surveillance systems.

METHODS: The number of influenza-associated hospitalizations for the 2018-2019 season was obtained from the CDC, Public Health Agency of Canada, and Public Health England. The CDC defines “total influenza” as all symptomatic illnesses in a season. A targeted literature search was conducted to identify multipliers used by the CDC and the analogous multipliers from Canada and England. Country-specific multipliers were compared, and cross-applicability was examined.

RESULTS: Differences in surveillance systems and data availability made obtaining multipliers challenging. The multiplier for under-reporting of influenza-associated hospitalizations was lower for Canada than the US (1.3 vs 3.5), partly because it does not account for test sensitivity; in England, no analogous multiplier was found. Both age-specific multipliers (range: 11-365) and age distribution among cases determined the composite symptomatic case-to-hospitalization ratio for the US (77) in the 2018-2019 season, which can vary in seasons with different case-age distribution. In Canada, only the number of all laboratory-confirmed rather than symptomatic cases were obtainable, using a single multiplier for all ages (~5). In England, the symptomatic case-to-hospitalization ratio was obtained by a product of 2 multipliers, influenza visit-to-hospitalization ratio (~41) and symptomatic case-to-visit ratio (~2.75).

CONCLUSIONS: While the multiplier approach could theoretically estimate overall influenza burden, it remains subject to variability and uncertainty. Implementing this approach in different countries requires targeted data collection and understanding of surveillance systems, population structures, and care-seeking behaviors.