Comparing the transmission potential from sequence and surveillance data of 2009 North American influenza pandemic waves

Abstract

Technological advancements in phylodynamic modeling coupled with the accessibility of real-time pathogen genetic data are increasingly important for understanding the infectious disease transmission dynamics. In this study, we compare the transmission potentials of North American influenza A(H1N1)pdm09 derived from sequence data to that derived from surveillance data. The impact of the choice of tree-priors, informative epidemiological priors, and evolutionary parameters on the transmission potential estimation is evaluated. North American Influenza A(H1N1)pdm09 hemagglutinin (HA) gene sequences are analyzed using the coalescent and birth-death tree prior models to estimate the basic reproduction number (R ₀ ). Epidemiological priors gathered from published literature are used to simulate the birth-death skyline models. Path-sampling marginal likelihood estimation is conducted to assess model fit. A bibliographic search to gather surveillance-based R ₀ values were consistently lower (mean ≤ 1.2) when estimated by coalescent models than by the birth-death models with informative priors on the duration of infectiousness (mean ≥ 1.3 to ≤2.88 days). The user-defined informative priors for use in the birth-death model shift the directionality of epidemiological and evolutionary parameters compared to non-informative estimates. While there was no certain impact of clock rate and tree height on the R ₀ estimation, an opposite relationship was observed between coalescent and birth-death tree priors. There was no significant difference (p = 0.46) between the birth-death model and surveillance R ₀ estimates. This study concludes that tree-prior methodological differences may have a substantial impact on the transmission potential estimation as well as the evolutionary parameters. The study also reports a consensus between the sequence-based R ₀ estimation and surveillance-based R ₀ estimates. Altogether, these outcomes shed light on the potential role of phylodynamic modeling to augment existing surveillance and epidemiological activities to better assess and respond to emerging infectious diseases.

Keywords: Birth-death models; Coalescent growth models; Pandemic 2009 H1N1; Pathogen sequence data; Phylodynamics; Public health; Reproduction number.

Fig. 1

Epidemiological parameter estimates from coalescent and BDSKY models across 2009 pandemic waves and North American geographic regions. A. Transmission potential (R₀ or R_e) and B. Become non-infectiousness (δ). BDSKY: Birth-Death Skyline, CE & CL: Coalescent exponential growth and coalescent logistic growth models. Empty plot: no data available.

Fig. 2

Relationship of coalescent tree prior's clock rate and tree height on the estimation of transmission potential (R₀). A. Clock rate, and B. Tree height. BDSKY: Birth-Death Skyline, CE & CL: Coalescent exponential and coalescent logistic; and Empty plot: no data available. Data points are posterior results from each model.

Fig. 3

Relationship of birth-death tree-prior's clock rate and tree height on the estimation of transmission potential (R₀). A. Clock rate, and B. Tree height. BDSKY: Birth-Death Skyline, CE & CL: Coalescent exponential and coalescent logistic; and Empty plot: no data available. Data points are posterior results from each model.

Fig. 4

Correlation of R₀ estimated from sequence and surveillance data. Both CE (coalescent exponential growth) and CL (coalescent logistic growth) are coalescent models. BDSKY: birth-death skyline model; coalescent and BDSKY models were used to estimate R₀ from the HA sequences; surveillance represents published R₀ estimates from the 2009 pandemic H1N1 incidence data.