Robustly Quantifying Uncertainty in International Avian Influenza A(H5N1) Infection Fatality Ratios

Knowing the mortality rates associated with infection by a pathogen is essential for effective preparedness and response. Here, harnessing the flexibility of a Bayesian approach, we produce an estimate of the Infection Fatality Ratio (IFR) for A(H5N1) conditional on explicit assumptions, and quantify the uncertainty thereof. We also apply the method to first-wave COVID-19 data up to March 2020, demonstrating the estimates that could be obtained were the model available then. Our analysis uses World Development Indicators (WDI) from the World Bank, the A(H5N1) WHO confirmed cases and deaths tracker by country (2003-2024), and COVID-19 cases and deaths data from John Hopkins University (January and February 2020). Since infectious disease dynamics are typically influenced by local socio-economic factors rather than political borders, individual countries are placed within clusters of countries sharing similar WDIs relevant to respiratory viral diseases, with clusters derived by performing Hierarchical Clustering. To estimate the IFR, we fit a Negative Binomial Bayesian Hierarchical Model for A(H5N1) and COVID-19 separately. We explicitly modelled key unobserved parameters with informative priors from expert opinion and literature. By modelling underreporting, our analysis suggests lower fatality (15.3%) compared to WHOs Case Fatality Ratio estimate (54%) on lab-confirmed cases. However, credible intervals are wide ([0.5%, 64.2%] 95% CrI). Therefore, good preparedness for a potential A(H5N1) pandemic implies adopting scenario planning under our central estimate, as well as for IFRs as high as 70%. Our approach also returns a COVID-19 IFR estimate of 2.8% with [2.5%, 3.1%] 95% CrI which is consistent with literature. Key MessagesO_LIWe adopted a disease-agnostic and adaptable Bayesian model, embedding scientific knowledge on A(H5N1) in the priors informed by published literature, to estimate the Infection Fatality Ratio (IFR) of avian influenza A(H5N1). C_LIO_LIAccounting for underreporting of cases and deaths, we estimate the IFR of avian influenza A(H5N1) at 15.3%, albeit with wide uncertainty ([0.5%, 64.2%] 95% Credible Intervals). C_LIO_LIDue to the uncertainty in the estimate, good preparedness for a potential A(H5N1) pandemic implies adopting scenario planning under our central estimate, as well as for IFRs as high as 70%. C_LI