Replicating superspreader dynamics with compartmental models.

Infectious disease outbreaks often exhibit superspreader dynamics, where most infected people generate no, or few secondary cases, and only a small fraction of individuals are responsible for a large proportion of transmission. Although capturing this heterogeneity is critical for estimating outbreak risk and the effectiveness of group-specific interventions, it is typically neglected in compartmental models of infectious disease transmission-which constitute the most common transmission dynamic modeling framework. In this study we propose different classes of compartmental epidemic models that incorporate transmission heterogeneity, fit them to a number of real outbreak datasets, and benchmark their performance against the canonical superspreader model (i.e., the negative binomial branching process model). We find that properly constructed compartmental models can capably reproduce observed superspreader dynamics and we provide the pathogen-specific parameter settings required to do so. As a consequence, we also show that compartmental models parameterized according to a binary clinical classification have limited support.

Sustaining effective COVID-19 control in Malaysia through large-scale vaccination.

INTRODUCTION: As of 3rd June 2021, Malaysia is experiencing a resurgence of COVID-19 cases. In response, the federal government has implemented various non-pharmaceutical interventions (NPIs) under a series of Movement Control Orders and, more recently, a vaccination campaign to regain epidemic control. In this study, we assessed the potential for the vaccination campaign to control the epidemic in Malaysia and four high-burden regions of interest, under various public health response scenarios. METHODS: A modified susceptible-exposed-infectious-recovered compartmental model was developed that included two sequential incubation and infectious periods, with stratification by clinical state. The model was further stratified by age and incorporated population mobility to capture NPIs and micro-distancing (behaviour changes not captured through population mobility). Emerging variants of concern (VoC) were included as an additional strain competing with the existing wild-type strain. Several scenarios that included different vaccination strategies (i.e. vaccines that reduce disease severity and/or prevent infection, vaccination coverage) and mobility restrictions were implemented. RESULTS: The national model and the regional models all fit well to notification data but underestimated ICU occupancy and deaths in recent weeks, which may be attributable to increased severity of VoC or saturation of case detection. However, the true case detection proportion showed wide credible intervals, highlighting incomplete understanding of the true epidemic size. The scenario projections suggested that under current vaccination rates complete relaxation of all NPIs would trigger a major epidemic. The results emphasise the importance of micro-distancing, maintaining mobility restrictions during vaccination roll-out and accelerating the pace of vaccination for future control. Malaysia is particularly susceptible to a major COVID-19 resurgence resulting from its limited population immunity due to the country's historical success in maintaining control throughout much of 2020.

Modelling direct and herd protection effects of vaccination against the SARS-CoV-2 Delta variant in Australia.

OBJECTIVES: To analyse the outcomes of COVID-19 vaccination by vaccine type, age group eligibility, vaccination strategy, and population coverage. DESIGN: Epidemiologic modelling to assess the final size of a COVID-19 epidemic in Australia, with vaccination program (Pfizer, AstraZeneca, mixed), vaccination strategy (vulnerable first, transmitters first, untargeted), age group eligibility threshold (5 or 15 years), population coverage, and pre-vaccination effective reproduction number ( Reffv¯ ) for the SARS-CoV-2 Delta variant as factors. MAIN OUTCOME MEASURES: Numbers of SARS-CoV-2 infections; cumulative hospitalisations, deaths, and years of life lost. RESULTS: Assuming Reffv¯ = 5, the current mixed vaccination program (vaccinating people aged 60 or more with the AstraZeneca vaccine and people under 60 with the Pfizer vaccine) will not achieve herd protection unless population vaccination coverage reaches 85% by lowering the vaccination eligibility age to 5 years. At Reffv¯ = 3, the mixed program could achieve herd protection at 60-70% population coverage and without vaccinating 5-15-year-old children. At Reffv¯ = 7, herd protection is unlikely to be achieved with currently available vaccines, but they would still reduce the number of COVID-19-related deaths by 85%. CONCLUSION: Vaccinating vulnerable people first is the optimal policy when population vaccination coverage is low, but vaccinating more socially active people becomes more important as the Reffv¯ declines and vaccination coverage increases. Assuming the most plausible Reffv¯ of 5, vaccinating more than 85% of the population, including children, would be needed to achieve herd protection. Even without herd protection, vaccines are highly effective in reducing the number of deaths.

Influencing public health policy with data-informed mathematical models of infectious diseases: Recent developments and new challenges.

Modern data and computational resources, coupled with algorithmic and theoretical advances to exploit these, allow disease dynamic models to be parameterised with increasing detail and accuracy. While this enhances models' usefulness in prediction and policy, major challenges remain. In particular, lack of identifiability of a model's parameters may limit the usefulness of the model. While lack of parameter identifiability may be resolved through incorporation into an inference procedure of prior knowledge, formulating such knowledge is often difficult. Furthermore, there are practical challenges associated with acquiring data of sufficient quantity and quality. Here, we discuss recent progress on these issues.

Modelling the in-host dynamics of Neisseria gonorrhoeae infection.

The bacterial species Neisseria gonorrhoeae (NG) has evolved to replicate effectively and exclusively in human epithelia, with its survival dependent on complex interactions between bacteria, host cells and antimicrobial agents. A better understanding of these interactions is needed to inform development of new approaches to gonorrhoea treatment and prevention but empirical studies have proven difficult, suggesting a role for mathematical modelling. Here, we describe an in-host model of progression of untreated male symptomatic urethral infection, including NG growth and interactions with epithelial cells and neutrophils, informed by in vivo and in vitro studies. The model reproduces key observations on bacterial load and clearance and we use multivariate sensitivity analysis to refine plausible ranges for model parameters. Model variants are also shown to describe mouse infection dynamics with altered parameter ranges that correspond to observed differences between human and mouse infection. Our results highlight the importance of NG internalisation, particularly within neutrophils, in sustaining infection in the human model, with ∼80% of the total NG population internalised from day 25 on. This new mechanistic model of in-host NG infection dynamics should also provide a platform for future studies relating to antimicrobial treatment and resistance and infection at other anatomical sites.