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0000-0002-7830-793X
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In Research Link Australia (RLA), "Research Topics" refer to ANZSRC FOR and SEO codes. These topics are either sourced from ANZSRC FOR and SEO codes listed in researchers' related grants or generated by a large language model (LLM) based on their publications.
Biological Mathematics | Applied Mathematics | Stochastic Analysis and Modelling |
Expanding Knowledge in the Biological Sciences | Expanding Knowledge in the Mathematical Sciences | Infectious Diseases
Publisher: Public Library of Science (PLoS)
Date: 09-06-2022
DOI: 10.1371/JOURNAL.PNTD.0010456
Abstract: Estimating community level scabies prevalence is crucial for targeting interventions to areas of greatest need. The World Health Organisation recommends s ling at the unit of households or schools, but there is presently no standardised approach to scabies prevalence assessment. Consequently, a wide range of s ling sizes and methods have been used. As both prevalence and drivers of transmission vary across populations, there is a need to understand how s ling strategies for estimating scabies prevalence interact with local epidemiology to affect the accuracy of prevalence estimates. We used a simulation-based approach to compare the efficacy of different scabies s ling strategies. First, we generated synthetic populations broadly representative of remote Australian Indigenous communities and assigned a scabies status to in iduals to achieve a specified prevalence using different assumptions about scabies epidemiology. Second, we calculated an observed prevalence for different s ling methods and sizes. The distribution of prevalence in subpopulation groups can vary substantially when the underlying scabies assignment method changes. Across all of the scabies assignment methods combined, the simple random s ling method produces the narrowest 95% confidence interval for all s le sizes. The household s ling method introduces higher variance compared to simple random s ling when the assignment of scabies includes a household-specific component. The school s ling method overestimates community prevalence when the assignment of scabies includes an age-specific component. Our results indicate that there are interactions between transmission assumptions and surveillance strategies, emphasizing the need for understanding scabies transmission dynamics. We suggest using the simple random s ling method for estimating scabies prevalence. Our approach can be adapted to various populations and diseases.
Publisher: Cold Spring Harbor Laboratory
Date: 17-06-2019
DOI: 10.1101/674135
Abstract: Group A Streptococcus (GAS) skin infections are caused by a erse array of strain types and are highly prevalent in Indigenous and other disadvantaged populations. The role of strain-specific immunity in preventing GAS infections is poorly understood, representing a critical knowledge gap in vaccine development. A recent GAS murine challenge study showed evidence that sterilising strain-specific and enduring immunity required two skin infections by the same GAS strain within three weeks. This mechanism of developing enduring immunity may be a significant impediment to the accumulation of immunity in populations. We used a mathematical model of GAS transmission to investigate the epidemiological consequences of enduring strain-specific immunity developing only after two infections with the same strain within a specified interval. Accounting for uncertainty when correlating murine timeframes to humans, we varied this maximum inter-infection interval from 3 to 420 weeks to assess its impact on prevalence and strain ersity. Model outputs were compared with longitudinal GAS surveillance observations from northern Australia, a region with endemic infection. We also assessed the likely impact of a targeted strain-specific multivalent vaccine in this context. Our model produced patterns of transmission consistent with observations when the maximum inter-infection interval for developing enduring immunity was 19 weeks. Our vaccine analysis suggests that the leading multivalent GAS vaccine may have limited impact on the prevalence of GAS in populations in northern Australia if strain-specific immunity requires repeated episodes of infection. Our results suggest that observed GAS epidemiology from disease endemic settings is consistent with enduring strain-specific immunity being dependent on repeated infections with the same strain, and provide additional motivation for relevant human studies to confirm the human immune response to GAS skin infection. Group A Streptococcus (GAS) is a ubiquitous bacterial pathogen that exists in many distinct strains, and is a major cause of death and disability globally. Vaccines against GAS are under development, but their effective use will require better understanding of how immunity develops following infection. Evidence from an animal model of skin infection suggests that the generation of enduring strain-specific immunity requires two infections by the same strain within a short time frame. It is not clear if this mechanism of immune development operates in humans, nor how it would contribute to the persistence of GAS in populations and affect vaccine impact. We used a mathematical model of GAS transmission, calibrated to data collected in an Indigenous Australian community, to assess whether this mechanism of immune development is consistent with epidemiological observations, and to explore its implications for the impact of a vaccine. We found that it is plausible that repeat infections are required for the development of immunity in humans, and illustrate the difficulties associated with achieving sustained reductions in disease prevalence with a vaccine.
Publisher: Cold Spring Harbor Laboratory
Date: 14-11-2021
DOI: 10.1101/2021.11.13.21266293
Abstract: Estimating scabies prevalence in communities is crucial for identifying the communities with high scabies prevalence and guiding interventions. There is no standardisation of s ling strategies to estimate scabies prevalence in communities, and a wide range of s ling sizes and methods have been used. The World Health Organization recommends household s ling or, as an alternative, school s ling to estimate community-level prevalence. Due to varying prevalence across populations, there is a need to understand how s ling strategies for estimating scabies prevalence interact with scabies epidemiology to affect accuracy of prevalence estimates. We used a simulation-based approach to compare the efficacy of different s ling methods and sizes. First, we generate synthetic populations with Australian Indigenous communities’ characteristics and then, assign a scabies status to in iduals to achieve a specified prevalence using different assumptions about scabies epidemiology. Second, we calculate an observed prevalence for different s ling methods and sizes. The distribution of prevalence in population groups can vary substantially when the underlying scabies assignment method changes. Across all of the scabies assignment methods combined, the simple random s ling method produces the narrowest 95% confidence interval for all s ling percentages. The household s ling method introduces higher variance compared to simple random s ling when the assignment of scabies includes a household-specific component. The school s ling method overestimates community prevalence when the assignment of scabies includes an age-specific component. Our results indicate that there are interactions between transmission assumptions and surveillance strategies, emphasizing the need for understanding scabies transmission dynamics. We suggest using the simple random s ling method for estimating scabies prevalence. Our approach can be adapted to various populations and diseases. Scabies is a parasitic infestation that is commonly observed in underprivileged populations. A wide range of s ling sizes and methods have been used to estimate scabies prevalence. With differing key drivers of transmission and varying prevalence across populations, it can be challenging to determine an effective s ling strategy. In this study, we propose a simulation approach to compare the efficacy of different s ling methods and sizes. First, we generate synthetic populations and then assign a scabies status to in iduals to achieve a specified prevalence using different assumptions about scabies epidemiology. Second, we calculate an observed prevalence for different s ling methods and sizes. Our results indicate that there are interactions between transmission assumptions and surveillance strategies. We suggest using the simple random s ling method for estimating prevalence as it produces the narrowest 95% confidence interval for all s ling sizes. We propose guidelines for determining a s le size to achieve a desired level of precision in 95 out 100 s les, given estimates of the population size and a priori estimates of true prevalence. Our approach can be adapted to various populations, informing an appropriate s ling strategy for estimating scabies prevalence with confidence.
Publisher: Springer Science and Business Media LLC
Date: 18-12-2012
Publisher: Cold Spring Harbor Laboratory
Date: 23-02-2023
DOI: 10.1101/2023.02.18.23286135
Abstract: Interventions to mitigate the spread of infectious diseases, while succeeding in their goal, have economic and social costs associated with them. These limit the duration and intensity of the interventions. We study a class of interventions which reduce the reproduction number and find the optimal strength of the intervention which minimises the attack rate of an immunity inducing infection. The intervention works by eliminating the overshoot part of an epidemic, and avoids a second-wave of infections. We extend the framework by considering a heterogeneous population and find that the optimal intervention can pose an ethical dilemma for decision and policy makers. This ethical dilemma is shown to be analogous to the trolley problem and we discuss how the dilemma can be avoided.
Publisher: Cold Spring Harbor Laboratory
Date: 03-07-2020
DOI: 10.1101/2020.07.01.20144634
Abstract: Households are known to be high-risk locations for the transmission of communicable diseases. Numerous modelling studies have demonstrated the important role of households in sustaining both communicable diseases outbreaks and endemic transmission, and as the focus for control efforts. However, these studies typically assume that households are associated with a single dwelling and have static membership. This assumption does not appropriately reflect households in some populations, such as those in remote Australian Indigenous communities, which can be distributed across more than one physical dwelling, leading to the occupancy of in idual dwellings changing rapidly over time. In this study, we developed an in idual-based model of an infectious disease outbreak in communities with demographic and household structure reflective of a remote Australian Indigenous community. We used the model to compare the dynamics of unmitigated outbreaks, and outbreaks constrained by a household-focused prophylaxis intervention, in communities exhibiting fluid versus stable dwelling occupancy. Our findings suggest that fluid dwelling occupancy can lead to larger and faster outbreaks, interfere with the effectiveness of household-focused interventions, and may contribute to the considerable burden of communicable diseases in communities exhibiting this type of structure.
Publisher: Elsevier BV
Date: 08-2013
DOI: 10.1016/J.JPEDSURG.2012.08.034
Abstract: The gubernaculum is postulated to grow like an embryonic limb bud during inguinoscrotal descent in rodents. Recently, modelling of limb bud growth suggests the undifferentiated, distal "progress zone" provides molecular morphogenic signals, rather than cell ision, as previously thought. We aimed to develop a mathematical gubernacular growth model, hypothesising that it would mimic limb buds through evolutionary conservation. Histology was done on Sprague-Dawley rats (day 2, 8 n=7/group) to determine gubernacular length, width, cell density in distal growth centre, middle and proximal cremaster muscle. Analysis of measurements enabled gubernacular growth modelling under variable growth centre sizes/densities, assuming no apoptosis. Modelling found that gubernacular growth occurred mostly within cremaster muscle, rather than primarily in the undifferentiated mesenchymal tip, despite its higher mitotic rate. The growth centre accounted for ≤ 10% of total gubernacular enlargement/elongation. These results suggest the gubernaculum elongates by proliferation throughout cremaster muscle like a limb bud. The distal undifferentiated tip may provide signalling molecules for growth, which could be a fruitful source for causes of failed migration/elongation in cryptorchidism.
Publisher: MDPI AG
Date: 22-09-2022
Abstract: Cultural practices and development level can influence a population’s household structures and mixing patterns. Within some populations, households can be organized across multiple dwellings. This likely affects the spread of infectious disease through these communities however, current demographic data collection tools do not record these data. Methods: Between June and October 2018, the Contact And Mobility Patterns in remote Aboriginal Australian communities (CAMP-remote) pilot study recruited Aboriginal mothers with infants in a remote northern Australian community to complete a monthly iPad-based contact survey. Results: Thirteen mother–infant pairs (participants) completed 69 study visits between recruitment and the end of May 2019. Participants reported they and their other children slept in 28 dwellings during the study. The median dwelling occupancy, defined as people sleeping in the same dwelling on the previous night, was ten (range: 3.5–25). Participants who completed at least three responses (n = 8) slept in a median of three dwellings (range: 2–9). Each month, a median of 28% (range: 0–63%) of the participants travelled out of the community. Including these data in disease transmission models lified estimates of infectious disease spread in the study community, compared to models parameterized using census data. Conclusions: The lack of data on mixing patterns in populations where households can be organized across dwellings may impact the accuracy of infectious disease models for these communities and the efficacy of public health actions they inform.
Publisher: Cold Spring Harbor Laboratory
Date: 18-11-2022
DOI: 10.1101/2022.11.16.22282431
Abstract: Scabies is a parasitic infestation with high global burden. Mass drug administrations (MDAs) are recommended for communities with a scabies prevalence of %. Quantitative analyses are needed to demonstrate the likely effectiveness of MDA recommendations. In this study, we compare the effectiveness of differing MDA strategies, supported by improved treatment access, on scabies prevalence in Monrovia, Liberia. We developed an agent-based model of scabies transmission calibrated to demographic and epidemiological data from Monrovia. We used this model to compare the effectiveness of MDA scenarios for achieving scabies elimination and reducing scabies burden, as measured by time until recrudescence following delivery of an MDA and disability-adjusted-life-years (DALYs) averted. We also investigated the additional impact of improving access to scabies treatment following delivery of an MDA. Our model showed that 3 rounds of MDA delivered at 6-month intervals and reaching 80% of the population could reduce prevalence below 2% for 3 years following the final round, before recrudescence. When MDAs were followed by increased treatment uptake, prevalence was maintained below 2% indefinitely. Increasing the number of and coverage of MDA rounds increased the probability of achieving elimination and the DALYs averted. Our results suggest that acute reduction of scabies prevalence by MDA can support a transition to improved treatment access. This study demonstrates how modelling can be used to estimate the expected impact of MDAs by projecting future epidemiological dynamics and health gains under alternative scenarios. We use an agent-based model to demonstrate that mass drug administration (MDA) programs can achieve sustained reduction in scabies prevalence. However, effective MDAs must be accompanied by systemic changes that increase the rate of scabies treatment to prevent recrudescence.
Publisher: Proceedings of the National Academy of Sciences
Date: 25-07-2016
Abstract: Tuberculosis is an ancient human disease that continues to affect millions of people worldwide. A crucial component of the origins of the tuberculosis bacterium remains a mystery: What were the conditions that precipitated its emergence as an obligate transmissible human pathogen? Here, we identify a connection between the emergence of tuberculosis and another major event in human prehistory, namely the discovery of controlled fire use. Our results have serious and cautionary implications for the emergence of new infectious diseases—feedback between cultural innovation and alteration of living conditions can catalyze unexpected changes with potentially devastating consequences lasting thousands of years.
Publisher: Public Library of Science (PLoS)
Date: 05-06-2020
Publisher: Elsevier BV
Date: 12-2015
DOI: 10.1016/J.JTBI.2015.08.031
Abstract: An enduring puzzle in evolutionary biology is to understand how in iduals and populations adapt to fluctuating environments. Here we present an integro-differential model of adaptive dynamics in a phenotype-structured population whose fitness landscape evolves in time due to periodic environmental oscillations. The analytical tractability of our model allows for a systematic investigation of the relative contributions of heritable variations in gene expression, environmental changes and natural selection as drivers of phenotypic adaptation. We show that environmental fluctuations can induce the population to enter an unstable and fluctuation-driven epigenetic state. We demonstrate that this can trigger the emergence of oscillations in the size of the population, and we establish a full characterisation of such oscillations. Moreover, the results of our analyses provide a formal basis for the claim that higher rates of epimutations can bring about higher levels of intrapopulation heterogeneity, whilst intense selection pressures can deplete variation in the phenotypic pool of asexual populations. Finally, our work illustrates how the dynamics of the population size is led by a strong synergism between the rate of phenotypic variation and the frequency of environmental oscillations, and identifies possible ecological conditions that promote the maximisation of the population size in fluctuating environments.
Publisher: The Royal Society
Date: 02-2018
DOI: 10.1098/RSOS.172341
Abstract: For infectious pathogens such as Staphylococcus aureus and Streptococcus pneumoniae , some hosts may carry the pathogen and transmit it to others, yet display no symptoms themselves. These asymptomatic carriers contribute to the spread of disease but go largely undetected and can therefore undermine efforts to control transmission. Understanding the natural history of carriage and its relationship to disease is important for the design of effective interventions to control transmission. Mathematical models of infectious diseases are frequently used to inform decisions about control and should therefore accurately capture the role played by asymptomatic carriers. In practice, incorporating asymptomatic carriers into models is challenging due to the sparsity of direct evidence. This absence of data leads to uncertainty in estimates of model parameters and, more fundamentally, in the selection of an appropriate model structure. To assess the implications of this uncertainty, we systematically reviewed published models of carriage and propose a new model of disease transmission with asymptomatic carriage. Analysis of our model shows how different assumptions about the role of asymptomatic carriers can lead to different conclusions about the transmission and control of disease. Critically, selecting an inappropriate model structure, even when parameters are correctly estimated, may lead to over- or under-estimates of intervention effectiveness. Our results provide a more complete understanding of the role of asymptomatic carriers in transmission and highlight the importance of accurately incorporating carriers into models used to make decisions about disease control.
Publisher: PeerJ
Date: 03-11-2020
DOI: 10.7717/PEERJ.10203
Abstract: Households are known to be high-risk locations for the transmission of communicable diseases. Numerous modelling studies have demonstrated the important role of households in sustaining both communicable diseases outbreaks and endemic transmission, and as the focus for control efforts. However, these studies typically assume that households are associated with a single dwelling and have static membership. This assumption does not appropriately reflect households in some populations, such as those in remote Australian Aboriginal and Torres Strait Islander communities, which can be distributed across more than one physical dwelling, leading to the occupancy of in idual dwellings changing rapidly over time. In this study, we developed an in idual-based model of an infectious disease outbreak in communities with demographic and household structure reflective of a remote Australian Aboriginal community. We used the model to compare the dynamics of unmitigated outbreaks, and outbreaks constrained by a household-focused prophylaxis intervention, in communities exhibiting fluid vs. stable dwelling occupancy. We found that fluid dwelling occupancy can lead to larger and faster outbreaks in modelled scenarios, and may interfere with the effectiveness of household-focused interventions. Our findings suggest that while short-term restrictions on movement between dwellings may be beneficial during outbreaks, in the longer-term, strategies focused on reducing household crowding may be a more effective way to reduce the risk of severe outbreaks occurring in populations with fluid dwelling occupancy.
Publisher: Cold Spring Harbor Laboratory
Date: 09-10-2020
DOI: 10.1101/2020.10.07.20208819
Abstract: Remote Australian Aboriginal and Torres Strait Islander communities have potential to be severely impacted by COVID-19, with multiple factors predisposing to increased transmission and disease severity. Our modelling aims to inform optimal public health responses. An in idual-based simulation model represented communities ranging from 100 to 3,500 people, comprised of large interconnected households. A range of strategies for case finding, quarantining of contacts, testing, and lockdown were examined, following the silent introduction of a case. Multiple secondary infections are likely present by the time the first case is identified. Quarantine of close contacts, defined by extended household membership, can reduce peak infection prevalence from 60-70% to around 10%, but subsequent waves may occur when community mixing resumes. Exit testing significantly reduces ongoing transmission. Concurrent lockdown of non-quarantined households for 14 days is highly effective for epidemic control and reduces overall testing requirements peak prevalence of the initial outbreak can be constrained to less than 5%, and the final community attack rate to less than 10% in modelled scenarios. Lockdown also mitigates the effect of a delay in the initial response. Compliance with lockdown must be at least 80-90%, however, or epidemic control will be lost. A SARS-CoV-2 outbreak will spread rapidly in remote communities. Prompt case detection with quarantining of extended-household contacts and a 14-day lockdown for all other residents, combined with exit testing for all, is the most effective strategy for rapid containment. Compliance is crucial, underscoring the need for community supported, culturally sensitive responses.
Publisher: Oxford University Press (OUP)
Date: 11-07-2023
DOI: 10.1093/PNASNEXUS/PGAD227
Abstract: Several recent emerging diseases have exhibited both sexual and nonsexual transmission modes (Ebola, Zika, and mpox). In the recent mpox outbreaks, transmission through sexual contacts appears to be the dominant mode of transmission. Motivated by this, we use an SIR-like model to argue that an initially dominant sexual transmission mode can be overtaken by casual transmission at later stages, even if the basic casual reproduction number is less than one. Our results highlight the risk of intervention designs which are informed only by the early dynamics of the disease.
Publisher: American Physical Society (APS)
Date: 28-08-2014
Publisher: Springer Science and Business Media LLC
Date: 08-09-2021
DOI: 10.1186/S12879-021-06607-5
Abstract: Remote Australian Aboriginal and Torres Strait Islander communities have potential to be severely impacted by COVID-19, with multiple factors predisposing to increased transmission and disease severity. Our modelling aims to inform optimal public health responses. An in idual-based simulation model represented SARS-CoV2 transmission in communities ranging from 100 to 3500 people, comprised of large, interconnected households. A range of strategies for case finding, quarantining of contacts, testing, and lockdown were examined, following the silent introduction of a case. Multiple secondary infections are likely present by the time the first case is identified. Quarantine of close contacts, defined by extended household membership, can reduce peak infection prevalence from 60 to 70% to around 10%, but subsequent waves may occur when community mixing resumes. Exit testing significantly reduces ongoing transmission. Concurrent lockdown of non-quarantined households for 14 days is highly effective for epidemic control and reduces overall testing requirements peak prevalence of the initial outbreak can be constrained to less than 5%, and the final community attack rate to less than 10% in modelled scenarios. Lockdown also mitigates the effect of a delay in the initial response. Compliance with lockdown must be at least 80–90%, however, or epidemic control will be lost. A SARS-CoV-2 outbreak will spread rapidly in remote communities. Prompt case detection with quarantining of extended-household contacts and a 14 day lockdown for all other residents, combined with exit testing for all, is the most effective strategy for rapid containment. Compliance is crucial, underscoring the need for community supported, culturally sensitive responses.
Publisher: Elsevier BV
Date: 06-2011
DOI: 10.1016/J.JTBI.2011.02.022
Abstract: Sequential segmentation during embryogenesis involves the generation of a repeated pattern along the embryo, which is concurrently undergoing axial elongation by cell ision. Most mathematical models of sequential segmentation involve inherent cellular oscillators, acting as a segmentation clock. The cellular oscillation is assumed to be governed by the cell's physiological age or by its interaction with an external morphogen gradient. Here, we address the issue of when cellular oscillators alone are sufficient for predicting segmentation, and when a morphogen gradient is required. The key to resolving this issue lies in how cells determine positional information in the model--this is directly related to the distribution of cell isions responsible for axial elongation. Mathematical models demonstrate that if axial elongation occurs through cell isions restricted to the posterior end of the unsegmented region, a cell can obtain its positional information from its physiological age, and therefore cellular oscillators will suffice. Alternatively, if axial elongation occurs through cell isions distributed throughout the unsegmented region, then positional information can be obtained through another mechanism, such as a morphogen gradient. Two alternative ways to establish a morphogen gradient in tissue with distributed cell isions are presented--one with diffusion and the other without diffusion. Our model produces segment polarity and a distribution of segment size from the anterior-to-posterior ends, as observed in some systems. Furthermore, the model predicts segment deletions when there is an interruption in cell ision, just as seen in heat shock experiments, as well as the growth and final shrinkage of the presomitic mesoderm during somitogenesis.
Publisher: Springer Science and Business Media LLC
Date: 30-07-2016
Publisher: Oxford University Press (OUP)
Date: 07-2017
DOI: 10.1093/VE/VEX018
Publisher: Cold Spring Harbor Laboratory
Date: 29-11-2022
DOI: 10.1101/2022.11.28.22282692
Abstract: Several recent emerging diseases have exhibited both sexual and non-sexual transmission modes (Ebola, Zika and mpox). In the recent mpox outbreaks, transmission through sexual contacts appears to be the dominant mode of transmission. Motivated by this, we use an SIR-like model, to argue that an initially dominant sexual transmission mode can be overtaken by casual transmission at later stages, even if the basic casual reproduction number is less than one. Our results highlight the risk of intervention designs which are informed only by the early dynamics of the disease. The purpose of this article is to explore the risk from secondary transmission routes of diseases which spread through sexual contact. This is important because infectious diseases such as Ebola, Zika and mpox spread through both sexual transmission and other modes of transmission. Our results suggest that a secondary transmission route which is not dominant in the initial stages, can significantly alter the course of the epidemic and lead to more infections than expected in the later stages of the epidemic.
Publisher: Public Library of Science (PLoS)
Date: 30-09-2010
No related organisations have been discovered for Rebecca Chisholm.
Start Date: 04-2021
End Date: 12-2024
Amount: $390,000.00
Funder: Australian Research Council
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