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Jane M. Heffernan

Publications and source records attributed to Jane M. Heffernan.

3 recordsLinked to original sources

Joint estimation of the basic reproduction number and serial interval using Sequential Bayes

Early in an infectious disease outbreak, timely and accurate estimation of the basic reproduction number ($R_0$) and the serial interval (SI) is critical for understanding transmission dynamics and informing public health responses. While many methods estimate these quantities separately, and a small number jointly estimate them from incidence data, existing joint approaches are largely likelihood-based and do not fully exploit prior information. We propose a novel Bayesian framework for the joint estimation of $R_0$ and the serial interval using only case count data, implemented through a sequential Bayes approach. Our method assumes an SIR model and employs a mildly informative joint prior constructed by linking log-Gamma marginal distributions for $R_0$ and the SI via a Gaussian copula, explicitly accounting for their dependence. The prior is updated sequentially as new incidence data become available, allowing for real-time inference. We assess the performance of the proposed estimator through extensive simulation studies under correct model specification as well as under model misspecification, including when the true data come from an SEIR or SEAIR model, and under varying degrees of prior misspecification. Comparisons with the widely used White and Pagano likelihood-based joint estimator show that our approach yields substantially more precise and stable estimates of $R_0$, with comparable or improved bias, particularly in the early stages of an outbreak. Estimation of the SI is more sensitive to prior misspecification; however, when prior information is reasonably accurate, our method provides reliable SI estimates and remains more stable than the competing approach. We illustrate the practical utility of the proposed method using Canadian COVID-19 incidence data at both national and provincial levels.

stat.ME

Modelling cross-reactivity and memory in the cellular adaptive immune response to influenza infection in the host

The cellular adaptive immune response plays a key role in resolving influenza infection. Experiments where individuals are successively infected with different strains within a short timeframe provide insight into the underlying viral dynamics and the role of a cross-reactive immune response in resolving an acute infection. We construct a mathematical model of within-host influenza viral dynamics including three possible factors which determine the strength of the cross-reactive cellular adaptive immune response: the initial naive T cell number, the avidity of the interaction between T cells and the epitopes presented by infected cells, and the epitope abundance per infected cell. Our model explains the experimentally observed shortening of a second infection when cross-reactivity is present, and shows that memory in the cellular adaptive immune response is necessary to protect against a second infection.

q-bio.PE

On the role of $\rm CD8^+$ T cells in determining recovery time from influenza virus infection

Myriad experiments have identified an important role for $\rm CD8^+$ T cell response mechanisms in determining recovery from influenza A virus infection. Animal models of influenza infection further implicate multiple elements of the immune response in defining the dynamical characteristics of viral infection. To date, influenza virus models, while capturing particular aspects of the natural infection history, have been unable to reproduce the full gamut of observed viral kinetic behaviour in a single coherent framework. Here, we introduce a mathematical model of influenza viral dynamics incorporating all major immune components (innate, humoral and cellular) and explore its properties with a particular emphasis on the role of cellular immunity. Calibrated against a range of murine data, our model is capable of recapitulating observed viral kinetics from a multitude of experiments. Importantly, the model predicts a robust exponential relationship between the level of effector $\rm CD8^+$ T cells and recovery time, whereby recovery time rapidly decreases to a fixed minimum recovery time with an increasing level of effector $\rm CD8^+$ T cells. We find support for this relationship in recent clinical data from influenza A(H7N9) hospitalised patients. The exponential relationship implies that people with a lower level of naive $\rm CD8^+$ T cells may receive significantly more benefit from induction of additional effector $\rm CD8^+$ T cells arising from immunological memory, itself established through either previous viral infection or T cell-based vaccines.

q-bio.CB