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Sheryl L. Chang

Publications and source records attributed to Sheryl L. Chang.

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Multi-scale phylodynamic modelling of rapid punctuated pathogen evolution

Computational multi-scale pandemic modelling remains a major and timely challenge. Here we identify specific requirements for a new class of models simulating pandemics across three scales: (1) pathogen evolution, often punctuated by the rapid emergence of new variants, (2) human interactions within a heterogeneous population, and (3) public health responses which constrain individual actions to control the disease transmission. We then present a pandemic modelling framework satisfying these requirements and capable of simulating feedback loops between dynamics unfolding at these different scales. The developed framework comprises a stochastic agent-based model of pandemic spread, coupled with a phylodynamic model that incorporates within-host pathogen evolution. It is validated with a case study, modelling the punctuated evolution of SARS-CoV-2, based on global and contemporary genomic surveillance data, which captures a large heterogeneous population. We demonstrate that the model replicates the essential features of the COVID-19 pandemic and virus evolution, while retaining computational tractability and scalability.

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Impact of opinion dynamics on recurrent pandemic waves: balancing risk aversion and peer pressure

Recurrent waves which are often observed during long pandemics typically form as a result of several interrelated dynamics including public health interventions, population mobility and behaviour, varying disease transmissibility due to pathogen mutations, and changes in host immunity due to recency of vaccination or previous infections. Complex nonlinear dependencies among these dynamics, including feedback between disease incidence and the opinion-driven adoption of social distancing behaviour, remain poorly understood, particularly in scenarios involving heterogeneous population, partial and waning immunity, and rapidly changing public opinions. This study addressed this challenge by proposing an opinion dynamics model that accounts for changes in social distancing behaviour (i.e., whether to adopt social distancing) by modelling both individual risk perception and peer pressure. The opinion dynamics model was integrated and validated within a large-scale agent-based COVID-19 pandemic simulation that modelled the spread of the Omicron variant of SARS-CoV-2 between December 2021 and June 2022 in Australia. Our study revealed that the fluctuating adoption of social distancing, shaped by individual risk aversion and social peer pressure from both household and workplace environments, may explain the observed pattern of recurrent waves of infections.

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Measuring unequal distribution of pandemic severity across census years, variants of concern and interventions

Diverse and complex intervention policies deployed over the last years have shown varied effectiveness in controlling the COVID-19 pandemic. However, a systematic analysis and modelling of the combined effects of different viral lineages and complex intervention policies remains a challenge. Using large-scale agent-based modelling and a high-resolution computational simulation matching census-based demographics of Australia, we carried out a systematic comparative analysis of several COVID-19 pandemic scenarios. The scenarios covered two most recent Australian census years (2016 and 2021), three variants of concern (ancestral, Delta and Omicron), and five representative intervention policies. In addition, we introduced pandemic Lorenz curves measuring an unequal distribution of the pandemic severity across local areas. We quantified nonlinear effects of population heterogeneity on the pandemic severity, highlighting that (i) the population growth amplifies pandemic peaks, (ii) the changes in population size amplify the peak incidence more than the changes in density, and (iii) the pandemic severity is distributed unequally across local areas. We also examined and delineated the effects of urbanisation on the incidence bimodality, distinguishing between urban and regional pandemic waves. Finally, we quantified and examined the impact of school closures, complemented by partial interventions, and identified the conditions when inclusion of school closures may decisively control the transmission. Our results suggest that (a) public health response to long-lasting pandemics must be frequently reviewed and adapted to demographic changes, (b) in order to control recurrent waves, mass-vaccination rollouts need to be complemented by partial NPIs, and (c) healthcare and vaccination resources need to be prioritised towards the localities and regions with high population growth and/or high density.

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Persistence of the Omicron variant of SARS-CoV-2 in Australia: The impact of fluctuating social distancing

We modelled emergence and spread of the Omicron variant of SARS-CoV-2 in Australia between December 2021 and June 2022. This pandemic stage exhibited a diverse epidemiological profile with emergence of co-circulating sub-lineages of Omicron, further complicated by differences in social distancing behaviour which varied over time. Our study delineated distinct phases of the Omicron-associated pandemic stage, and retrospectively quantified the adoption of social distancing measures, fluctuating over different time periods in response to the observable incidence dynamics. We also modelled the corresponding disease burden, in terms of hospitalisations, intensive care unit occupancy, and mortality. Supported by good agreement between simulated and actual health data, our study revealed that the nonlinear dynamics observed in the daily incidence and disease burden were determined not only by introduction of sub-lineages of Omicron, but also by the fluctuating adoption of social distancing measures. Our high-resolution model can be used in design and evaluation of public health interventions during future crises.

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Simulating transmission scenarios of the Delta variant of SARS-CoV-2 in Australia

An outbreak of the Delta (B.1.617.2) variant of SARS-CoV-2 that began around mid-June 2021 in Sydney, Australia, quickly developed into a nation-wide epidemic. The ongoing epidemic is of major concern as the Delta variant is more infectious than previous variants that circulated in Australia in 2020. Using a re-calibrated agent-based model, we explored a feasible range of non-pharmaceutical interventions, including case isolation, home quarantine, school closures, and stay-at-home restrictions (i.e., "social distancing"). Our modelling indicated that the levels of reduced interactions in workplaces and across communities attained in Sydney and other parts of the nation were inadequate for controlling the outbreak. A counter-factual analysis suggested that if 70% of the population followed tight stay-at-home restrictions, then at least 45 days would have been needed for new daily cases to fall from their peak to below ten per day. Our model predicted that, under a progressive vaccination rollout, if 40-50% of the Australian population follow stay-at-home restrictions, the incidence will peak by mid-October 2021: the peak in incidence across the nation was indeed observed in mid-October. We also quantified an expected burden on the healthcare system and potential fatalities across Australia.

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Genome-wide networks reveal emergence of epidemic strains of Salmonella Enteritidis

Objectives: To enhance monitoring of high-burden foodborne pathogens, there is opportunity to combine pangenome data with network analysis. Methods: Salmonella enterica subspecies Enterica serovar Enteritidis isolates were referred to the New South Wales (NSW) Enteric Reference Laboratory between August 2015 and December 2019 (1033 isolates in total), inclusive of a confirmed outbreak. All isolates underwent whole genome sequencing. Distances between genomes were quantified by in silico MLVA as well as core SNPs, which informed construction of undirected networks. Prevalence-centrality spaces were generated from the undirected networks. Components on the undirected SNP network were considered alongside a phylogenetic tree representation. Results: Outbreak isolates were identifiable as distinct components on the MLVA and SNP networks. The MLVA network based centrality/prevalence space did not delineate the outbreak, whereas the outbreak was clearly delineated in the SNP network based centrality/prevalence space. Components on the undirected SNP network showed a high concordance to the SNP clusters based on phylogenetic analysis. Conclusions: Bacterial whole genome data in network based analysis can improve the resolution of population analysis. High concordance of network components and SNP clusters is promising for rapid population analyses of foodborne Salmonella spp. due to the low overhead of network analysis.

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How will mass-vaccination change COVID-19 lockdown requirements in Australia?

Background: To prevent future outbreaks of COVID-19, Australia is pursuing a mass-vaccination approach in which a targeted group of the population comprising healthcare workers, aged-care residents and other individuals at increased risk of exposure will receive a highly effective priority vaccine. The rest of the population will instead have access to a less effective vaccine. Methods: We apply a large-scale agent-based model of COVID-19 in Australia to investigate the possible implications of this hybrid approach to mass-vaccination. The model is calibrated to recent epidemiological and demographic data available in Australia, and accounts for several components of vaccine efficacy. Findings: Within a feasible range of vaccine efficacy values, our model supports the assertion that complete herd immunity due to vaccination is not likely in the Australian context. For realistic scenarios in which herd immunity is not achieved, we simulate the effects of mass-vaccination on epidemic growth rate, and investigate the requirements of lockdown measures applied to curb subsequent outbreaks. In our simulations, Australia's vaccination strategy can feasibly reduce required lockdown intensity and initial epidemic growth rate by 43% and 52%, respectively. The severity of epidemics, as measured by the peak number of daily new cases, decreases by up to two orders of magnitude under plausible mass-vaccination and lockdown strategies. Interpretation: The study presents a strong argument for a large-scale vaccination campaign in Australia, which would substantially reduce both the intensity of future outbreaks and the stringency of non-pharmaceutical interventions required for their suppression.

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Modelling transmission and control of the COVID-19 pandemic in Australia

There is a continuing debate on relative benefits of various mitigation and suppression strategies aimed to control the spread of COVID-19. Here we report the results of agent-based modelling using a fine-grained computational simulation of the ongoing COVID-19 pandemic in Australia. This model is calibrated to match key characteristics of COVID-19 transmission. An important calibration outcome is the age-dependent fraction of symptomatic cases, with this fraction for children found to be one-fifth of such fraction for adults. We apply the model to compare several intervention strategies, including restrictions on international air travel, case isolation, home quarantine, social distancing with varying levels of compliance, and school closures. School closures are not found to bring decisive benefits, unless coupled with high level of social distancing compliance. We report several trade-offs, and an important transition across the levels of social distancing compliance, in the range between 70% and 80% levels, with compliance at the 90% level found to control the disease within 13--14 weeks, when coupled with effective case isolation and international travel restrictions.

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Impact of network assortativity on epidemic and vaccination behaviour

The resurgence of measles is largely attributed to the decline in vaccine adoption and the increase in mobility. Although the vaccine for measles is readily available and highly successful, its current adoption is not adequate to prevent epidemics. Vaccine adoption is directly affected by individual vaccination decisions, and has a complex interplay with the spatial spread of disease shaped by an underlying mobility (travelling) network. In this paper, we model the travelling connectivity as a scale-free network, and investigate dependencies between the network's assortativity and the resultant epidemic and vaccination dynamics. In doing so we extend an SIR-network model with game-theoretic components, capturing the imitation dynamics under a voluntary vaccination scheme. Our results show a correlation between the epidemic dynamics and the network's assortativity, highlighting that networks with high assortativity tend to suppress epidemics under certain conditions. In highly assortative networks, the suppression is sustained producing an early convergence to equilibrium. In highly disassortative networks, however, the suppression effect diminishes over time due to scattering of non-vaccinating nodes, and frequent switching between the predominantly vaccinating and non-vaccinating phases of the dynamics.

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The effects of imitation dynamics on vaccination behaviours in SIR-network model

We present a series of SIR-network models, extended with a game-theoretic treatment of imitation dynamics which result from regular population mobility across residential and work areas and the ensuing interactions. Each considered SIR-network model captures a class of vaccination behaviours influenced by epidemic characteristics, interaction topology, and imitation dynamics. Our focus is the eventual vaccination coverage, produced under voluntary vaccination schemes, in response to these varying factors. Using the next generation matrix method, we analytically derive and compare expressions for the basic reproduction number $R_0$ for the proposed SIR-network models. Furthermore, we simulate the epidemic dynamics over time for the considered models, and show that if individuals are sufficiently responsive towards the changes in the disease prevalence, then the more expansive travelling patterns encourage convergence to the endemic, mixed equilibria. On the contrary, if individuals are insensitive to changes in the disease prevalence, we find that they tend to remain unvaccinated in all the studied models. Our results concur with earlier studies in showing that residents from highly connected residential areas are more likely to get vaccinated. We also show that the existence of the individuals committed to receiving vaccination reduces $R_0$ and delays the disease prevalence, and thus is essential to containing epidemics.

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Game theoretic modelling of infectious disease dynamics and intervention methods: a mini-review

We review research papers which use game theory to model the decision making of individuals during an epidemic, attempting to classify the literature and identify the emerging trends in this field. We show that the literature can be classified based on (i) type of population modelling (compartmental or network-based), (ii) frequency of the game (non-iterative or iterative), and (iii) type of strategy adoption (self-evaluation or imitation). We highlight that the choice of model depends on many factors such as the type of immunity the disease confers, the type of immunity the vaccine confers, and size of population and level of mixing therein. We show that while early studies used compartmental modelling with self-evaluation based strategy adoption, the recent trend is to use network-based modelling with imitation-based strategy adoption. Our review indicates that game theory continues to be an effective tool to model intervention (vaccination or social distancing) decision-making by individuals.

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