Doherty Institute - Research Publications

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    Longitudinal Analysis of Group A Streptococcus emm Types and emm Clusters in a High-Prevalence Setting: Relationship between Past and Future Infections.
    Campbell, PT ; Tong, SYC ; Geard, N ; Davies, MR ; Worthing, KA ; Lacey, JA ; Smeesters, PR ; Batzloff, MR ; Kado, J ; Jenney, AWJ ; Mcvernon, J ; Steer, AC (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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    A model of population dynamics with complex household structure and mobility: implications for transmission and control of communicable diseases
    Chisholm, RH ; Crammond, B ; Wu, Y ; Bowen, AC ; Campbell, PT ; Tong, SYC ; McVernon, J ; Geard, N (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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    Estimation of the force of infection and infectious period of skin sores in remote Australian communities using interval-censored data
    Lydeamore, MJ ; Campbell, PT ; Price, DJ ; Wu, Y ; Marcato, AJ ; Cuningham, W ; Carapetis, JR ; Andrews, RM ; McDonald, M ; McVernon, J ; Tong, SYC ; McCaw, JM ; Kouyos, RD (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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    Inhibition of Influenza A Virus by Human Infant Saliva
    Gilbertson, B ; Edenborough, K ; McVernon, J ; Brown, LE (MDPI, 2019-08-01)
    Innate antiviral factors in saliva play a role in protection against respiratory infections. We tested the anti-influenza virus activities of saliva samples taken from human infants, 1-12 months old, with no history of prior exposure to influenza. In contrast to the inhibitory activity we observed in mouse and ferret saliva, the activity of human infant saliva was complex, with both sialic acid-dependent and independent components, the proportion of which differed between individuals. Taken as a whole, we showed that the major anti-influenza activity of infant saliva is acquired over the first year of life and is associated with sialic acid-containing molecules. The activity of sialic acid-independent inhibitors was lower overall, more variable between individuals, and less dependent on age. The results show that the saliva of very young infants can provide a degree of protection against influenza, which may be critical in the absence of adaptive immunity.
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    Prior exposure to immunogenic peptides found in human influenza A viruses may influence the age distribution of cases with avian influenza H5N1 and H7N9 virus infections
    Komadina, N ; Sullivan, SG ; Kedzierska, K ; Quinones-Parra, SM ; Leder, K ; McVernon, J (CAMBRIDGE UNIV PRESS, 2019-01-01)
    The epidemiology of H5N1 and H7N9 avian viruses of humans infected in China differs despite both viruses being avian reassortants that have inherited six internal genes from a common ancestor, H9N2. The median age of infected populations is substantially younger for H5N1 virus (26 years) compared with H7N9 virus (63 years). Population susceptibility to infection with seasonal influenza is understood to be influenced by cross-reactive CD8+ T cells directed towards immunogenic peptides derived from internal viral proteins which may provide some level of protection against further influenza infection. Prior exposure to seasonal influenza peptides may influence the age-related infection patterns observed for H5N1 and H7N9 viruses. A comparison of relatedness of immunogenic peptides between historical human strains and the two avian emerged viruses was undertaken for a possible explanation in the differences in age incidence observed. There appeared to be some relationship between past exposure to related peptides and the lower number of H5N1 virus cases in older populations, however the relationship between prior exposure and older populations among H7N9 virus patients was less clear.
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    Infectious disease pandemic planning and response: Incorporating decision analysis
    Shearer, FM ; Moss, R ; McVernon, J ; Ross, JV ; McCaw, JM (PUBLIC LIBRARY SCIENCE, 2020-01-01)
    Freya Shearer and co-authors discuss the use of decision analysis in planning for infectious disease pandemics.
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    Insights from mathematical modelling on the proposed WHO 2030 goals for scabies.
    Marks, M ; McVernon, J ; Engelman, D ; Kaldor, J ; Steer, A (F1000 Research Ltd, 2019)
    Scabies was adopted by the World Health Organization (WHO) as a Neglected Tropical Disease in 2017. There is currently no formal global scabies control programmes or existing WHO guidelines on scabies control although at least two countries, Fiji and Ethiopia, have adopted national approaches to scabies control. In February 2019 WHO held a first Informal Consultation on a Framework for Scabies Control, in part as a response to multiple national requests for guidance on public health management in high disease burden areas. Below we outline control strategies proposed at this meeting and summarise the role that modelling can play in supporting the development of evidence to translate these proposals into formal WHO recommendations and national and global control programmes. Provisional proposals discussed at the WHO Informal Consultation for a scabies control programme include the use of mass drug administration when the community prevalence of scabies is ≥ 10% (generally considered to reflect a childhood prevalence of at least 20%) and the use of intensified case management when the prevalence is below 10%.
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    Early analysis of the Australian COVID-19 epidemic
    Price, DJ ; Shearer, FM ; Meehan, MT ; McBryde, E ; Moss, R ; Golding, N ; Conway, EJ ; Dawson, P ; Cromer, D ; Wood, J ; Abbott, S ; McVernon, J ; McCaw, JM (eLIFE SCIENCES PUBL LTD, 2020-08-13)
    As of 1 May 2020, there had been 6808 confirmed cases of COVID-19 in Australia. Of these, 98 had died from the disease. The epidemic had been in decline since mid-March, with 308 cases confirmed nationally since 14 April. This suggests that the collective actions of the Australian public and government authorities in response to COVID-19 were sufficiently early and assiduous to avert a public health crisis - for now. Analysing factors that contribute to individual country experiences of COVID-19, such as the intensity and timing of public health interventions, will assist in the next stage of response planning globally. We describe how the epidemic and public health response unfolded in Australia up to 13 April. We estimate that the effective reproduction number was likely below one in each Australian state since mid-March and forecast that clinical demand would remain below capacity thresholds over the forecast period (from mid-to-late April).
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    Antimicrobial stewardship in remote primary healthcare across northern Australia
    Cuningham, W ; Anderson, L ; Bowen, AC ; Buising, K ; Connors, C ; Daveson, K ; Martin, J ; McNamara, S ; Patel, B ; James, R ; Shanks, J ; Wright, K ; Yarwood, T ; Tong, SYC ; McVernon, J (PEERJ INC, 2020-07-22)
    BACKGROUND: The high burden of infectious disease and associated antimicrobial use likely contribute to the emergence of antimicrobial resistance in remote Australian Aboriginal communities. We aimed to develop and apply context-specific tools to audit antimicrobial use in the remote primary healthcare setting. METHODS: We adapted the General Practice version of the National Antimicrobial Prescribing Survey (GP NAPS) tool to audit antimicrobial use over 2-3 weeks in 15 remote primary healthcare clinics across the Kimberley region of Western Australia (03/2018-06/2018), Top End of the Northern Territory (08/2017-09/2017) and far north Queensland (05/2018-06/2018). At each clinic we reviewed consecutive clinic presentations until 30 presentations where antimicrobials had been used were included in the audit. Data recorded included the antimicrobials used, indications and treating health professional. We assessed the appropriateness of antimicrobial use and functionality of the tool. RESULTS: We audited the use of 668 antimicrobials. Skin and soft tissue infections were the dominant treatment indications (WA: 35%; NT: 29%; QLD: 40%). Compared with other settings in Australia, narrow spectrum antimicrobials like benzathine benzylpenicillin were commonly given and the appropriateness of use was high (WA: 91%; NT: 82%; QLD: 65%). While the audit was informative, non-integration with practice software made the process manually intensive. CONCLUSIONS: Patterns of antimicrobial use in remote primary care are different from other settings in Australia. The adapted GP NAPS tool functioned well in this pilot study and has the potential for integration into clinical care. Regular stewardship audits would be facilitated by improved data extraction systems.
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    Impact of Emerging Antiviral Drug Resistance on Influenza Containment and Spread: Influence of Subclinical Infection and Strategic Use of a Stockpile Containing One or Two Drugs
    McCaw, JM ; Wood, JG ; McCaw, CT ; McVernon, J ; Montgomery, JM (PUBLIC LIBRARY SCIENCE, 2008-06-04)
    BACKGROUND: Wide-scale use of antiviral agents in the event of an influenza pandemic is likely to promote the emergence of drug resistance, with potentially deleterious effects for outbreak control. We explored factors promoting resistance within a dynamic infection model, and considered ways in which one or two drugs might be distributed to delay the spread of resistant strains or mitigate their impact. METHODS AND FINDINGS: We have previously developed a novel deterministic model of influenza transmission that simulates treatment and targeted contact prophylaxis, using a limited stockpile of antiviral agents. This model was extended to incorporate subclinical infections, and the emergence of resistant virus strains under the selective pressure imposed by various uses of one or two antiviral agents. For a fixed clinical attack rate, R(0) rises with the proportion of subclinical infections thus reducing the number of infections amenable to treatment or prophylaxis. In consequence, outbreak control is more difficult, but emergence of drug resistance is relatively uncommon. Where an epidemic may be constrained by use of a single antiviral agent, strategies that combine treatment and prophylaxis are most effective at controlling transmission, at the cost of facilitating the spread of resistant viruses. If two drugs are available, using one drug for treatment and the other for prophylaxis is more effective at preventing propagation of mutant strains than either random allocation or drug cycling strategies. Our model is relatively straightforward, and of necessity makes a number of simplifying assumptions. Our results are, however, consistent with the wider body of work in this area and are able to place related research in context while extending the analysis of resistance emergence and optimal drug use within the constraints of a finite drug stockpile. CONCLUSIONS: Combined treatment and prophylaxis represents optimal use of antiviral agents to control transmission, at the cost of drug resistance. Where two drugs are available, allocating different drugs to cases and contacts is likely to be most effective at constraining resistance emergence in a pandemic scenario.