Doherty Institute - Research Publications
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ItemNo Preview AvailableLongitudinal Analysis of Group A Streptococcus emm Types and emm Clusters in a High-Prevalence Setting: Relationship between Past and Future Infections.(Oxford University Press (OUP), 2020-05-01)Group A Streptococcus is a pathogen of global importance, but despite the ubiquity of group A Streptococcus infections, the relationship between infection, colonization, and immunity is still not completely understood. The M protein, encoded by the emm gene, is a major virulence factor and vaccine candidate and forms the basis of a number of classification systems. Longitudinal patterns of emm types collected from 457 Fijian schoolchildren over a 10-month period were analyzed. No evidence of tissue tropism was observed, and there was no apparent selective pressure or constraint of emm types. Patterns of emm type acquisition suggest limited, if any, modification of future infection based on infection history. Where impetigo is the dominant mode of transmission, circulating emm types either may not be constrained by ecological niches or population immunity to the M protein, or they may require several infections over a longer period of time to induce such immunity.
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ItemModelling the household-level impact of a maternal respiratory syncytial virus (RSV) vaccine in a high-income setting(BMC, 2020-11-12)BACKGROUND: Respiratory syncytial virus (RSV) infects almost all children by the age of 2 years, with the risk of hospitalisation highest in the first 6 months of life. Development and licensure of a vaccine to prevent severe RSV illness in infants is a public health priority. A recent phase 3 clinical trial estimated the efficacy of maternal vaccination at 39% over the first 90 days of life. Households play a key role in RSV transmission; however, few estimates of population-level RSV vaccine impact account for household structure. METHODS: We simulated RSV transmission within a stochastic, individual-based model framework, using an existing demographic model, structured by age and household and parameterised with Australian data, as an exemplar of a high-income country. We modelled vaccination by immunising pregnant women and explicitly linked the immune status of each mother-infant pair. We quantified the impact on children for a range of vaccine properties and uptake levels. RESULTS: We found that a maternal immunisation strategy would have the most substantial impact in infants younger than 3 months, reducing RSV infection incidence in this age group by 16.6% at 70% vaccination coverage. In children aged 3-6 months, RSV infection was reduced by 5.3%. Over the first 6 months of life, the incidence rate for infants born to unvaccinated mothers was 1.26 times that of infants born to vaccinated mothers. The impact in older age groups was more modest, with evidence of infections being delayed to the second year of life. CONCLUSIONS: Our findings show that while individual benefit from maternal RSV vaccination could be substantial, population-level reductions may be more modest. Vaccination impact was sensitive to the extent that vaccination prevented infection, highlighting the need for more vaccine trial data.
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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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ItemEstimation of the force of infection and infectious period of skin sores in remote Australian communities using interval-censored data(Public Library of Science (PLoS), 2020-10-01)Prevalence of impetigo (skin sores) remains high in remote Australian Aboriginal communities, Fiji, and other areas of socio-economic disadvantage. Skin sore infections, driven primarily in these settings by Group A Streptococcus (GAS) contribute substantially to the disease burden in these areas. Despite this, estimates for the force of infection, infectious period and basic reproductive ratio—all necessary for the construction of dynamic transmission models—have not been obtained. By utilising three datasets each containing longitudinal infection information on individuals, we estimate each of these epidemiologically important parameters. With an eye to future study design, we also quantify the optimal sampling intervals for obtaining information about these parameters. We verify the estimation method through a simulation estimation study, and test each dataset to ensure suitability to the estimation method. We find that the force of infection differs by population prevalence, and the infectious period is estimated to be between 12 and 20 days. We also find that optimal sampling interval depends on setting, with an optimal sampling interval between 9 and 11 days in a high prevalence setting, and 21 and 27 days for a lower prevalence setting. These estimates unlock future model-based investigations on the transmission dynamics of skin sores.
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ItemInfection-acquired versus vaccine-acquired immunity in an SIRWS model(KEAI PUBLISHING LTD, 2018)In some disease systems, the process of waning immunity can be subtle, involving a complex relationship between the duration of immunity-acquired either through natural infection or vaccination-and subsequent boosting of immunity through asymptomatic re-exposure. We present and analyse a model of infectious disease transmission where primary and secondary infections are distinguished to examine the interplay between infection and immunity. Additionally we allow the duration of infection-acquired immunity to differ from that of vaccine-acquired immunity to explore the impact on long-term disease patterns and prevalence of infection in the presence of immune boosting. Our model demonstrates that vaccination may induce cyclic behaviour, and the ability of vaccinations to reduce primary infections may not lead to decreased transmission. Where the boosting of vaccine-acquired immunity delays a primary infection, the driver of transmission largely remains primary infections. In contrast, if the immune boosting bypasses a primary infection, secondary infections become the main driver of transmission under a sufficiently long duration of immunity. Our results show that the epidemiological patterns of an infectious disease may change considerably when the duration of vaccine-acquired immunity differs from that of infection-acquired immunity. Our study highlights that for any particular disease and associated vaccine, a detailed understanding of the waning and boosting of immunity and how the duration of protection is influenced by infection prevalence are important as we seek to optimise vaccination strategies.
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ItemQuantity or quality? Assessing relationships between perceived social connectedness and recorded encounters(PUBLIC LIBRARY SCIENCE, 2018-11-29)INTRODUCTION: Higher levels of social connectedness are associated with better physical and mental health outcomes, but measures of connectedness are often study specific. Prior research has distinguished between perceived and received (quantifiable) measures of social connectedness, with differing impacts on health, sometimes mediated by place of residence. This analysis investigated the relationship between perceptions of social support/connection and quantifiable measures of social encounters, by neighbourhood, to inform understanding of place-based differences in connectedness and health outcomes. METHODS: Negative binomial regression models were used to determine associations between perceptions of social connectedness (perceived community connections and social involvement) and the number of recorded daily social encounters as a proxy for received support/connectedness. Analyses were undertaken across two Local Government Areas (LGAs) in Melbourne with disparate socio-economic profiles to examine potential modification of social connectedness measures by neighbourhood of residence. RESULTS: Two measures of perceived connectedness had a clear relationship with recorded daily social encounters-feeling a sense of community belonging (RR 1.20 (1.04, 1.37), p = 0.010) and having family or friends close by (RR 1.30 (1.10,1.54), p = 0.002 "neither" compared to "disagree", (RR 1.15 (1.04, 1.26), p = 0.006 "agree" compared to "disagree"). Involvement in a local church, sporting or social club was associated with a greater number of daily social encounters for respondents who participated a few times a year (RR 1.17 (1.05,1.32), p = 0.006) or often (RR 1.23 (1.12,1.36), p<0.001) compared to never. In the less affluent LGA, active contributions to neighbours and community through assistance and volunteering were a frequent driver of social connection. Differences in patterns between the two areas were found with some measures of perception showing stronger relationships with recorded daily encounters in one area but not the other. CONCLUSIONS: These results indicate substantial complexity in the relationship between perceptions of social connectedness and recorded daily social encounters/received connectedness, meaning that one cannot be reliably extrapolated from the other. Drivers of individuals' social connections also varied by area of residence. These findings offer new insights into potential mediators of the association between connectedness and wellbeing.
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ItemScabies and risk of skin sores in remote Australian Aboriginal communities: A self-controlled case series study(PUBLIC LIBRARY SCIENCE, 2018-07)BACKGROUND: Skin sores caused by Group A streptococcus (GAS) infection are a major public health problem in remote Aboriginal communities. Skin sores are often associated with scabies, which is evident in scabies intervention programs where a significant reduction of skin sores is seen after focusing solely on scabies control. Our study quantifies the strength of association between skin sores and scabies among Aboriginal children from the East Arnhem region in the Northern Territory. METHODS AND RESULTS: Pre-existing datasets from three published studies, which were conducted as part of the East Arnhem Healthy Skin Project (EAHSP), were analysed. Aboriginal children were followed from birth up to 4.5 years of age. Self-controlled case series design was used to determine the risks, within individuals, of developing skin sores when infected with scabies versus when there was no scabies infection. Participants were 11.9 times more likely to develop skin sores when infected with scabies compared with times when no scabies infection was evident (Incidence Rate Ratio (IRR) 11.9; 95% CI 10.3-13.7; p<0.001), and this was similar across the five Aboriginal communities. Children had lower risk of developing skin sores at age ≤1 year compared to at age >1 year (IRR 0.8; 95% CI 0.7-0.9). CONCLUSION: The association between scabies and skin sores is highly significant and indicates a causal relationship. The public health importance of scabies in northern Australia is underappreciated and a concerted approach is required to recognise and eliminate scabies as an important precursor of skin sores.
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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.
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ItemIndigenous Australian household structure: a simple data collection tool and implications for close contact transmission of communicable diseases(PEERJ INC, 2017-10-26)Households are an important location for the transmission of communicable diseases. Social contact between household members is typically more frequent, of greater intensity, and is more likely to involve people of different age groups than contact occurring in the general community. Understanding household structure in different populations is therefore fundamental to explaining patterns of disease transmission in these populations. Indigenous populations in Australia tend to live in larger households than non-Indigenous populations, but limited data are available on the structure of these households, and how they differ between remote and urban communities. We have developed a novel approach to the collection of household structure data, suitable for use in a variety of contexts, which provides a detailed view of age, gender, and room occupancy patterns in remote and urban Australian Indigenous households. Here we report analysis of data collected using this tool, which quantifies the extent of crowding in Indigenous households, particularly in remote areas. We use these data to generate matrices of age-specific contact rates, as used by mathematical models of infectious disease transmission. To demonstrate the impact of household structure, we use a mathematical model to simulate an influenza-like illness in different populations. Our simulations suggest that outbreaks in remote populations are likely to spread more rapidly and to a greater extent than outbreaks in non-Indigenous populations.
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ItemDetermining the Best Strategies for Maternally Targeted Pertussis Vaccination Using an Individual-Based Model(OXFORD UNIV PRESS INC, 2017-07-01)Rising pertussis incidence has prompted a number of countries to implement maternally targeted vaccination strategies to protect vulnerable infants, but questions remain about the optimal design of such strategies. We simulated pertussis transmission within an individual-based model parameterized to match Australian conditions, explicitly linking infants and their mothers to estimate the effectiveness of alternative maternally targeted vaccination strategies (antenatal delivery vs. postnatal delivery) and the benefit of revaccination over the course of multiple pregnancies. For firstborn infants aged less than 2 months, antenatal immunization reduced annual pertussis incidence by 60%, from 780 per 100,000 firstborn children under age 2 months (interquartile range (IQR), 682-862) to 315 per 100,000 (IQR, 260-370), while postnatal vaccination produced a minimal reduction, with an incidence of 728 per 100,000 (IQR, 628-789). Subsequent infants obtained limited protection from a single antenatal dose, but revaccinating mothers during every pregnancy decreased incidence for these infants by 58%, from 1,878 per 100,000 subsequent children under age 2 months (IQR, 1,712-2,076) to 791 per 100,000 (IQR, 683-915). Subsequent infants also benefited from household-level herd immunity when antenatal vaccination for every pregnancy was combined with a toddler booster dose at age 18 months; incidence was reduced to 626 per 100,000 (IQR, 548-691). Our approach provides useful information to aid consideration of alternative maternally targeted vaccination strategies and can inform development of outcome measures for program evaluation.