Doherty Institute - Research Publications
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ItemA model of population dynamics with complex household structure and mobility: implications for transmission and control of communicable diseases(PEERJ INC, 2020-11-03)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 individual dwellings changing rapidly over time. In this study, we developed an individual-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.
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ItemEpidemiological consequences of enduring strain-specific immunity requiring repeated episodes of infection(PUBLIC LIBRARY SCIENCE, 2020-06)Group A Streptococcus (GAS) skin infections are caused by a diverse array of strain types and are highly prevalent in 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 an agent-based 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 diversity, and considered additional scenarios where no maximum inter-infection interval was specified. 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.
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ItemImplications of asymptomatic carriers for infectious disease transmission and control(ROYAL SOC, 2018-02)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.