ORCID Profile
0000-0001-9774-1961
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Research Topics
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.
Top 5 Research Topics
ANZSRC Field of Research (FoR)
Public Health and Health Services | Epidemiology | Biostatistics | Phylogeny and Comparative Analysis | Community Planning | Medical Microbiology | Family and Household Studies | Medical Virology | Epidemiology | Veterinary Epidemiology | Evolutionary Biology | Population Trends and Policies | Social and Community Psychology | Global Change Biology
ANZSRC Socio-Economic Objective (SEO)
Social Structure and Health | Disease Distribution and Transmission (incl. Surveillance and Response) | Expanding Knowledge through Studies of Human Society | Infectious diseases | Expanding Knowledge in the Agricultural and Veterinary Sciences | Expanding Knowledge in the Biological Sciences | Diagnostic methods | Expanding Knowledge in the Mathematical Sciences |
Related Links
Publications
Learnings from the Australian first few X household transmission project for COVID-19
Publisher: Elsevier BV
Date: 11-2022
Epidemiological consequences of enduring strain-specific immunity requiring repeated episodes of infection
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.
Rapid assessment of the risk of SARS-CoV-2 importation: case study and lessons learned
Publisher: Elsevier BV
Date: 03-2022
Antimicrobial stewardship in remote primary healthcare across northern Australia.
Publisher: PeerJ
Date: 22-07-2020
DOI: 10.7717/PEERJ.9409
Abstract: 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. 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. 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. 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.
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
Publisher: Public Library of Science (PLoS)
Date: 04-06-2008
Antibody Persistence in Australian Adolescents Following Meningococcal C Conjugate Vaccination
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2015
Evaluation of the effectiveness of mass drug administration strategies for reducing scabies burden in Monrovia, Liberia: An agent-based modelling approach
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.
Comparison of three methods for ascertainment of contact information relevant to respiratory pathogen transmission in encounter networks
Publisher: Springer Science and Business Media LLC
Date: 10-06-2010
Epidemiological consequences of enduring strain-specific immunity requiring repeated episodes of infection
Publisher: Public Library of Science (PLoS)
Date: 05-06-2020
Modelling strategic use of the national antiviral stockpile during the CONTAIN and SUSTAIN phases of an Australian pandemic influenza response
Publisher: Elsevier BV
Date: 04-2010
DOI: 10.1111/J.1753-6405.2010.00493.X
Abstract: To define optimum use of the national antiviral stockpile during the early phases of the response to pandemic influenza in Australia, to inform the 2008 revision of the Australian Health Management Plan for Pandemic Influenza. A mathematical model was used to compare strategic uses of antiviral agents for treatment and post-exposure prophylaxis to limit transmission until availability of a strain-specific vaccine. The impact of provision of pre-exposure prophylaxis to healthcare workers (HCWs) on the ability to control the epidemic was also assessed. Optimal constraint of epidemic growth was achieved by intensive ascertainment of contacts of cases for post-exposure prophylaxis for as long as feasible. While pre-exposure prophylaxis of healthcare workers utilised a substantial proportion of the stockpile, this did not impede disease control or the ability to treat cases. Absolute delays to outbreak depended on both the intervention strategy and the growth rate of the epidemic. As vaccination was only effective when introduced before explosive growth, this timing was critical to success. Liberal distribution of antiviral drugs to limit disease spread for as long as is feasible represents optimal use of these agents to constrain epidemic growth. In reality, additional non-pharmaceutical control measures are likely to be required to control transmission until vaccines can definitively contain pandemic influenza outbreaks.
Prior immunity helps to explain wave-like behaviour of pandemic influenza in 1918-9
Publisher: Springer Science and Business Media LLC
Date: 25-05-2010
A model of population dynamics with complex household structure and mobility: implications for transmission and control of communicable diseases
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.
Incorporating population dynamics into household models of infectious disease transmission
Publisher: Elsevier BV
Date: 09-2011
DOI: 10.1016/J.EPIDEM.2011.05.001
Abstract: Most household models of disease transmission assume static household distributions. Although this is a reasonable simplification for assessing vaccination strategies at a single point in time or over the course of an outbreak, it has considerable drawbacks for assessing long term vaccination policies or for predicting future changes in immunity. We demonstrate that household models that include births, deaths and movement between households can show dramatically different patterns of infection and immunity to static population models. When immunity is assumed to be life-long, the pattern of births by household size is the key driver of infection, suggesting that the influx of susceptibles has most impact on infection risk in the household. In a comparison of 12 countries, we show that both the crude birth rate and the mean household size affect the risk of infection in households.
Immunogenicity and Safety of an Investigational Combined Haemophilus influenzae Type B-Neisseria meningitidis Serogroups C and Y-Tetanus Toxoid Conjugate Vaccine
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2011
COVID-19 in low-tolerance border quarantine systems: Impact of the Delta variant of SARS-CoV-2
Publisher: American Association for the Advancement of Science (AAAS)
Date: 08-04-2022
Abstract: In controlling transmission of coronavirus disease 2019 (COVID-19), the effectiveness of border quarantine strategies is a key concern for jurisdictions in which the local prevalence of disease and immunity is low. In settings like this such as China, Australia, and New Zealand, rare outbreak events can lead to escalating epidemics and trigger the imposition of large-scale lockdown policies. Here, we develop and apply an in idual-based model of COVID-19 to simulate case importation from managed quarantine under various vaccination scenarios. We then use the output of the in idual-based model as input to a branching process model to assess community transmission risk. For parameters corresponding to the Delta variant, our results demonstrate that vaccination effectively counteracts the pathogen’s increased infectiousness. To prevent outbreaks, heightened vaccination in border quarantine systems must be combined with mass vaccination. The ultimate success of these programs will depend sensitively on the efficacy of vaccines against viral transmission.
Assessing the risk of spread of COVID-19 to the Asia Pacific region
Publisher: Cold Spring Harbor Laboratory
Date: 11-04-2020
DOI: 10.1101/2020.04.09.20057257
Abstract: During the early stages of an emerging disease outbreak, governments are required to make critical decisions on how to respond appropriately, despite limited data being available to inform these decisions. Analytical risk assessment is a valuable approach to guide decision-making on travel restrictions and border measures during the early phase of an outbreak, when transmission is primarily contained within a source country. Here we introduce a modular framework for estimating the importation risk of an emerging disease when the direct travel route is restricted and the risk stems from indirect importation via intermediary countries. This was the situation for Australia in February 2020. The framework was specifically developed to assess the importation risk of COVID-19 into Australia during the early stages of the outbreak from late January to mid-February 2020. The dominant importation risk to Australia at the time of analysis was directly from China, as the only country reporting uncontained transmission. However, with travel restrictions from mainland China to Australia imposed from February 1, our framework was designed to consider the importation risk from China into Australia via potential intermediary countries in the Asia Pacific region. The framework was successfully used to contribute to the evidence base for decisions on border measures and case definitions in the Australian context during the early phase of COVID-19 emergence and is adaptable to other contexts for future outbreak response.
Long-term impact of vaccination on Haemophilus influenzae type b (Hib) carriage in the United Kingdom
Publisher: Cambridge University Press (CUP)
Date: 09-07-2004
DOI: 10.1017/S0950268804002122
Abstract: A recent resurgence in serious infections due to Haemophilus influenzae type b (Hib) has been observed in the United Kingdom. More information on Hib transmission in the population is required in order to better understand the mechanism of this increase. The Public Health Laboratory Service (subsumed into the Health Protection Agency since April 2004) conducted four cross-sectional studies of asymptomatic oropharyngeal Hib carriage in children attending day-care nurseries in England and Wales in 1992, 1994, 1997 and 2002. These demonstrated a marked reduction in the prevalence of Hib colonization over time since vaccine introduction (3·98% in 1992 0·70% in 1994 0% in 1997 0% in 2002), which did not explain the increase in invasive disease reports from 1999 onwards. We believe that a reduction in antibody levels over the first 5 years of life in immunized children in recent years has fuelled the rise in reported cases in the absence of an obvious increase in transmission.
Reducing Uncertainty in Within-Host Parameter Estimates of Influenza Infection by Measuring Both Infectious and Total Viral Load
Publisher: Public Library of Science (PLoS)
Date: 15-05-2013
The efficacy of sampling strategies for estimating scabies prevalence
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.
Detection of a divergent Parainfluenza 4 virus in an adult patient with influenza like illness using next-generation sequencing
Publisher: Springer Science and Business Media LLC
Date: 19-05-2014
Forecasting COVID-19 activity in Australia to support pandemic response: May to October 2020
Publisher: Cold Spring Harbor Laboratory
Date: 06-08-2022
DOI: 10.1101/2022.08.04.22278391
Abstract: As of January 2021, Australia had effectively controlled local transmission of COVID-19 despite a steady influx of imported cases and several local, but contained, outbreaks in 2020. Throughout 2020, state and territory public health responses were informed by weekly situational reports that included an ensemble forecast for each jurisdiction. We present here an analysis of one forecasting model included in this ensemble across the variety of scenarios experienced by each jurisdiction from May to October 2020. We examine how successfully the forecasts characterised future case incidence, subject to variations in data timeliness and completeness, showcase how we adapted these forecasts to support decisions of public health priority in rapidly-evolving situations, evaluate the impact of key model features on forecast skill, and demonstrate how to assess forecast skill in real-time before the ground truth is known. Conditioning the model on the most recent, but incomplete, data improved the forecast skill, emphasising the importance of developing strong quantitative models of surveillance system characteristics, such as ascertainment delay distributions. Forecast skill was highest when there were at least 10 reported cases per day, the circumstances in which authorities were most in need of forecasts to aid in planning and response.
A model of population dynamics with complex household structure and mobility: implications for transmission and control of communicable diseases
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.
A Historical Perspective of Influenza A(H1N2) Virus
Publisher: Centers for Disease Control and Prevention (CDC)
Date: 2014
Rapid prototyping of models for COVID-19 outbreak detection in workplaces
Publisher: Cold Spring Harbor Laboratory
Date: 07-02-2023
DOI: 10.1101/2023.02.05.23285483
Abstract: Early case detection is critical to preventing onward transmission of COVID-19 by enabling prompt isolation of index infections, and identification and quarantining of contacts. Timeliness and completeness of ascertainment depend on the surveillance strategy employed. We use rapid prototype modelling to quickly investigate the effectiveness of testing strategies, to aid decision making. Models are developed with a focus on providing relevant results to policy makers, and these models are continually updated and improved as new questions are posed. The implementation of testing strategies in high risk settings in Australia was supported using models to explore the effects of test frequency and sensitivity on outbreak detection. An exponential growth model is firstly used to demonstrate how outbreak detection changes with varying growth rate, test frequency and sensitivity. From this model we see that low sensitivity tests can be compensated for by high frequency testing. This model is then updated to an Agent Based Model, which was used to test the robustness of the results from the exponential model, and to extend it to include intermittent workplace scheduling. These models help our fundamental understanding of disease detectability through routine surveillance in workplaces and evaluate the impact of testing strategies and workplace characteristics on the effectiveness of surveillance. This analysis highlights the risks of particular work patterns while also identifying key testing strategies to best improve outbreak detection in high risk workplaces.
Estimating the transmissibility of SARS-CoV-2 during periods of high, low and zero case incidence
Publisher: Cold Spring Harbor Laboratory
Date: 29-11-2021
DOI: 10.1101/2021.11.28.21264509
Abstract: Against a backdrop of widespread global transmission, a number of countries have successfully brought large outbreaks of COVID-19 under control and maintained near-elimination status. A key element of epidemic response is the tracking of disease transmissibility in near real-time. During major outbreaks, the reproduction rate can be estimated from a time-series of case, hospitalisation or death counts. In low or zero incidence settings, knowing the potential for the virus to spread is a response priority. Absence of case data means that this potential cannot be estimated directly. We present a semi-mechanistic modelling framework that draws on time-series of both behavioural data and case data (when disease activity is present) to estimate the transmissibility of SARS-CoV-2 from periods of high to low – or zero – case incidence, with a coherent transition in interpretation across the changing epidemiological situations. Of note, during periods of epidemic activity, our analysis recovers the effective reproduction number, while during periods of low – or zero – case incidence, it provides an estimate of transmission risk. This enables tracking and planning of progress towards the control of large outbreaks, maintenance of virus suppression, and monitoring the risk posed by re-introduction of the virus. We demonstrate the value of our methods by reporting on their use throughout 2020 in Australia, where they have become a central component of the national COVID-19 response.
Host and environmental factors associated with Hib in England, 1998-2002
Publisher: BMJ
Date: 08-2008
Abstract: Declining effectiveness of the UK's Hib vaccine programme was observed between 1998 and 2002. To provide insight into non-vaccine factors contributing to ongoing Hib disease in England after immunisation. Postal questionnaire study, matched case-control design. Health Protection Agency Centre for Infections, England. Cases were children born after 1 January 1993 presenting with confirmed Hib infection in England between the start of 1998 and end of 2002, regardless of vaccination status. Controls were matched by date of birth and region. Odds ratios were calculated to assess the impact of host and environmental variables on disease risk. Increased disease risk was noted among children with frequent antibiotic use (adjusted OR (AOR) (trend) 1.51 (95% CI 1.06 to 2.13) p = 0.02) and from sole-parent households (AOR 2.56 (95% CI 1.24 to 5.29) p = 0.01). These two risk factors were further related to each other, consistent with previously reported associations between infection and social deprivation. In fully immunised children, receipt of all three doses of the primary course as an acellular pertussis-containing combination vaccine (DTaP-Hib) increased the risk of vaccine failure (OR 2.88 (95% CI 0.99 to 8.37), p = 0.01). Day care attendance between 2 and 5 years of age was linked with a dose-dependent reduction in risk (AOR (trend) 0.79 (95% CI 0.66 to 0.93) p = 0.01), possibly because of natural boosting of immunity. The association noted between invasive infection and social deprivation in this and other studies is concerning and merits further investigation. The importance of ongoing surveillance of vaccine-preventable diseases to allow nested studies of this kind was reinforced.
A randomized trial to assess safety and immunogenicity of alternative formulations of a quadrivalent meningococcal (A, C, Y, and W-135) tetanus protein conjugate vaccine in toddlers.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2012
Safety and tolerability of a 2009 trivalent inactivated split-virion influenza vaccine in infants, children and adolescents.
Publisher: Wiley
Date: 08-2022
DOI: 10.1111/IRV.12107
The dynamical consequences of seasonal forcing, immune boosting and demographic change in a model of disease transmission
Publisher: Elsevier BV
Date: 11-2014
DOI: 10.1016/J.JTBI.2014.07.028
Abstract: The impact of seasonal effects on the time course of an infectious disease can be dramatic. Seasonal fluctuations in the transmission rate for an infectious disease are known mathematically to induce cyclical behaviour and drive the onset of multistable and chaotic dynamics. These properties of forced dynamical systems have previously been used to explain observed changes in the period of outbreaks of infections such as measles, varicella (chickenpox), rubella and pertussis (whooping cough). Here, we examine in detail the dynamical properties of a seasonally forced extension of a model of infection previously used to study pertussis. The model is novel in that it includes a non-linear feedback term capturing the interaction between exposure and the duration of protection against re-infection. We show that the presence of limit cycles and multistability in the unforced system give rise to complex and intricate behaviour as seasonal forcing is introduced. Through a mixture of numerical simulation and bifurcation analysis, we identify and explain the origins of chaotic regions of parameter space. Furthermore, we identify regions where saddle node lines and period-doubling cascades of different orbital periods overlap, suggesting that the system is particularly sensitive to small perturbations in its parameters and prone to multistable behaviour. From a public health point of view - framed through the 'demographic transition' whereby a population׳s birth rate drops over time (and life-expectancy commensurately increases) - we argue that even weak levels of seasonal-forcing and immune boosting may contribute to the myriad of complex and unexpected epidemiological behaviours observed for diseases such as pertussis. Our approach helps to contextualise these epidemiological observations and provides guidance on how to consider the potential impact of vaccination programs.
Virus detection and its association with symptoms during influenza-like illness in a sample of healthy adults enrolled in a randomised controlled vaccine trial.
Publisher: Wiley
Date: 19-06-2012
Recommendations for and compliance with social restrictions during implementation of school closures in the early phase of the influenza A (H1N1) 2009 outbreak in Melbourne, Australia
Publisher: Springer Science and Business Media LLC
Date: 30-09-2011
Understanding influenza transmission, immunity and pandemic threats
Publisher: Wiley
Date: 15-06-2009
Immunogenicity of a monovalent 2009 influenza A(H1N1) vaccine in infants and children: a randomized trial.
Publisher: American Medical Association (AMA)
Date: 06-01-2009
Abstract: In the ongoing influenza pandemic, a safe and effective vaccine against 2009 influenza A(H1N1) is needed for infants and children. To assess the immunogenicity and safety of a 2009 influenza A(H1N1) vaccine in children. Randomized, observer-blind, age-stratified, parallel group study assessing 2 doses of an inactivated, split-virus 2009 influenza A(H1N1) vaccine in 370 healthy infants and children aged 6 months to less than 9 years living in Australia. Intramuscular injection of 15 microg or 30 microg of hemagglutinin antigen dose of monovalent, unadjuvanted 2009 influenza A(H1N1) vaccine in a 2-dose regimen, administered 21 days apart. Hemagglutination inhibition assay to estimate the proportion of participants with antibody titers of 1:40 or greater, seroconversion, or a significant antibody titer increase, and factor increase in geometric mean titer. Assessments of solicited adverse events during 7 days and unsolicited adverse events for 21 days after each vaccination. Following the first dose of vaccine, antibody titers of 1:40 or greater were observed in 161 of 174 infants and children in the 15-microg group (92.5% 95% confidence interval [CI], 87.6%-95.6%) and in 168 of 172 infants and children in the 30-microg group (97.7% 95% CI, 94.2%-99.1%). Corresponding seroconversion rates were 86.8% (95% CI, 80.9%-91.0%) and 94.2% (95% CI, 89.6%-96.8%), and factor increases in geometric mean titer were 13.6 (95% CI, 11.8-15.6) and 18.3 (95% CI, 15.7-21.4). All participants demonstrated antibody titers of 1:40 or greater after the second vaccine dose. Immune responses were robust regardless of age, baseline serostatus, or seasonal influenza vaccination status. The majority of adverse events were mild to moderate in severity. One 15-microg dose of vaccine was immunogenic in infants and children starting at 6 months of age and vaccine-associated reactions were mild to moderate in severity. clinicaltrials.gov Identifier: NCT00940108.
Recommendations for the prevention of secondary Haemophilus influenzae type b (Hib) disease
Publisher: Elsevier BV
Date: 2009
DOI: 10.1016/J.JINF.2008.10.007
Abstract: Haemophilus influenzae serotype b (Hib) can cause severe life threatening disease in healthy in iduals, with over 80% of cases in the pre-vaccine era occurring in children under five years of age. The introduction of Hib conjugate vaccine into routine childhood immunisation programmes has resulted in a dramatic reduction in the incidence of invasive Hib disease across all age groups. The objective of this paper is to update existing UK guidelines on the prevention of Hib disease among contacts of an index case by reviewing the original literature and the current epidemiology of Hib carriage and invasive disease. Household contacts of in iduals who develop invasive Hib disease are at higher risk of developing secondary Hib infection themselves, particularly if the contact is a young child or is immunosuppressed. Pre-school contacts of young children with invasive Hib disease are also at higher risk of developing secondary Hib infection. Rif icin at a dose of 20mg/kg/day for 4 days is highly effective in eradicating pharyngeal carriage of Hib and reducing the risk of invasive Hib disease among household and pre-school contacts. Children under 10 years of age who develop invasive Hib disease should also receive rif icin chemoprophylaxis to eliminate carriage and have Hib antibody levels tested around four weeks after infection. Hib vaccine failure cases should additionally have immunoglobulin concentrations measured and be assessed for evidence of an immune deficiency. If there is a vulnerable in idual (child younger than 10 years or an immunosuppressed or asplenic in idual of any age) among the household contacts of a case, all members of that household, including the index case, should receive chemoprophylaxis. All children younger than 10 years in the household should be appropriately vaccinated against Hib. Where more than one case occurs in a pre-school or primary school setting, chemoprophylaxis should be offered to all room contacts (including staff), and unimmunised and partially immunised children younger than 10 years should complete their primary immunisations, including a booster dose, as soon as possible. Families of children attending the same pre-school or primary school as an index case should be advised to seek medical advice if their child becomes unwell.
H1N1 influenza and the Australian macroeconomy
Publisher: Informa UK Limited
Date: 02-2012
Immunogenicity and safety of measles-mumps-rubella and varicella vaccines coadministered with a fourth dose of Haemophilus influenzae type b and Neisseria meningitidis serogroups C and Y-tetanus toxoid conjugate vaccine in toddlers: a pooled analysis of randomized trials.
Publisher: Informa UK Limited
Date: 08-2012
DOI: 10.4161/HV.20357
Impact of human movement between hypo- and hyperendemic areas on sustainability of elimination ofOnchocerca volvulustransmission
Publisher: Cold Spring Harbor Laboratory
Date: 22-01-2023
DOI: 10.1101/2023.01.20.23284850
Abstract: Onchocerciasis is a vector-borne disease caused by the filarial nematode Onchocerca volvulus . Endemic countries target elimination of parasite transmission using primarily annual ivermectin mass administration. Elimination is particularly challenging in sub-Saharan Africa, where there are large contiguous areas with varying levels of endemicity and intervention history. We examined one challenge to elimination that has received little attention to date: movement of people between areas. We extended one of the commonly used onchocerciasis transmission models, EPIONCHO, to allow modelling the effect of movement of people and/or flies between areas (“patches”). We explored the impact of humans travelling between a hypoendemic area (i.e., with low vector biting rates) with no history of interventions and a hyperendemic area (high vector biting rates) that stopped intervention (ivermectin mass administration) after infection prevalence decreased below 1.4%. Our results suggest that human travel in either direction will accelerate recrudescence in the hyperendemic area to pre-intervention levels, relative to recrudescence without travel, and can reduce the annual biting rate required for parasite transmission within hypoendemic areas. Our results emphasize the importance of decisions on which hypoendemic areas to include in interventions and suggest that transmission mediated by human movement needs to be considered when planning (a) the geographic areas and s ling density for evaluations for decisions on when and where to stop interventions, (b) where, how often, and for how long to conduct post-intervention surveillance for verification of elimination of transmission and (c) where and how frequently to conduct post-elimination surveillance. Given the cost implications of stopping interventions too early or later than necessary, we encourage the development of models such as the one presented here for quantitating the impact of human and vector movement between areas on the risk and timeframe of recrudescence after interventions are stopped to inform economic analyses. Onchocerciasis is an infectious parasitic disease that causes significant morbidity, from incessant skin itching to blindness. Onchocerciasis has also been implicated as the cause of high epilepsy rates. Efforts are underway to eliminate the parasite. Mathematical models for parasite transmission between humans via blackflies can be used to explore how interventions (e.g., mass drug administration or blackfly control) impact the percentage of people infected (infection prevalence). We extended a commonly used model to explore how people travelling between areas that differ in blackfly abundance, infection prevalence, and past interventions affects infection prevalence. We found that people travelling between an area with few blackflies (hypoendemic), low infection prevalence, and no interventions and an area with many blackflies (hyperendemic) but very low infection prevalence thanks to many years of mass drug administration which was then stopped will accelerate the increase in infection prevalence in the hyperendemic area compared to a situation where no people travel between these areas. This means that strategies for onchocerciasis elimination need to consider the effect of humans travelling.
Risk of vaccine failure after Haemophilus influenzae type b (Hib) combination vaccines with acellular pertussis
Publisher: Elsevier BV
Date: 05-2003
DOI: 10.1016/S0140-6736(03)13171-6
Abstract: An increase in invasive Hib disease incidence in the UK has coincided with the distribution of combination vaccines that contain acellular pertussis (DTaP-Hib). These vaccines have been associated with reduced immunogenicity of the Hib component, although there is little agreement on the clinical relevance of this finding. We retrospectively compared vaccine formulations given to fully vaccinated Hib cases with those administered to fully immunised age-matched controls using conditional logistic regression. More cases than controls received all three doses of their infant primary course as DTaP-Hib, compared with two or three doses of another Hib vaccine (conditional odds ratio 6.77 [95% CI 3.26-14.07]).
Diagnosis and Antiviral Intervention Strategies for Mitigating an Influenza Epidemic
Publisher: Public Library of Science (PLoS)
Date: 04-02-2011
Optimal allocation of PCR tests to minimise disease transmission through contact tracing and quarantine
Publisher: Cold Spring Harbor Laboratory
Date: 26-03-2021
DOI: 10.1101/2021.03.23.21254148
Abstract: PCR testing is a crucial capability for managing disease outbreaks, but it is also a limited resource and must be used carefully to ensure the information gain from testing is valuable. Testing has two broad uses, namely to track epidemic dynamics and to reduce transmission by identifying and managing cases. In this work we develop a modelling framework to examine the effects of test allocation in an epidemic, with a focus on using testing to minimise transmission. Using the COVID-19 pandemic as an ex le, we examine how the number of tests conducted per day relates to reduction in disease transmission, in the context of logistical constraints on the testing system. We show that if daily testing is above the routine capacity of a testing system, which can cause delays, then those delays can undermine efforts to reduce transmission through contact tracing and quarantine. This work highlights that the two goals of aiming to reduce transmission and aiming to identify all cases are different, and it is possible that focusing on one may undermine achieving the other. To develop an effective strategy, the goals must be clear and performance metrics must match the goals of the testing strategy. If metrics do not match the objectives of the strategy, then those metrics may incentivise actions that undermine achieving the objectives.
Leave entitlements, time off work and the household financial impacts of quarantine compliance during an H1N1 outbreak.
Publisher: Springer Science and Business Media LLC
Date: 20-11-2012
A Small Community Model for the Transmission of Infectious Diseases: Comparison of School Closure as an Intervention in Individual-Based Models of an Influenza Pandemic
Publisher: Public Library of Science (PLoS)
Date: 23-12-2008
Three-year antibody persistence and safety after a single dose of combined haemophilus influenzae type b (Hib)-Neisseria meningitidis serogroup C-tetanus toxoid conjugate vaccine in Hib-primed toddlers.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2013
Hib vaccination in infants born prematurely
Publisher: BMJ
Date: 03-2003
DOI: 10.1136/ADC.88.3.206
Abstract: To document the immunogenicity and persistence of antibody to polyribosyl-ribitol phosphate (PRP) as well as the clinical protection against invasive Haemophilus influenzae type b (Hib) disease in premature infants immunised at the routine schedule. Blood was obtained at 2, 5, 12, and 64 months of age from a cohort of prematurely born infants (<or=32 weeks gestation). Anti-PRP antibody concentrations were compared with those of a control cohort of infants born at full term and vaccinated at the same schedule. Hib vaccine failures occurring between October 1992 and October 2000 were reported by paediatricians through an active, prospective, national survey in the UK and Republic of Ireland. The number of prematurely born children with vaccine failure was compared with the corresponding number born at term. Twenty seven prematurely born infants were followed to 5 years of age. Compared with term infants they had a significantly lower geometric mean concentration of anti-PRP antibody and/or a significantly lower proportion above one or both of the conventional protective antibody concentrations (0.15 and 1.0 micro g/ml) at all ages. A total of 165 cases of invasive Hib disease were identified over eight years of national surveillance. Eighteen were premature (<37 weeks) approximately 12 would be expected. The relative risk of UK premature infants developing disease compared with term infants was 1.5 (95% CI 0.9 to 2.6). Premature infants develop lower antibody concentrations than term infants following Hib conjugate vaccination. Premature infants may also have an increased risk of clinical vaccine failure, but interpretation is limited by the small number of premature infants developing invasive Hib disease over eight years of national surveillance. Overall, vaccination with Hib conjugate vaccines affords a high level of protection to premature babies.
Immunologic memory in Haemophilus influenzae type b conjugate vaccine failure
Publisher: BMJ
Date: 05-2003
DOI: 10.1136/ADC.88.5.379
Abstract: To compare the convalescent antibody response to invasive Haemophilus influenzae type b (Hib) disease between conjugate vaccine immunised and unimmunised children, to look for evidence of priming for immunologic memory. Unmatched case-control study in the UK and Eire 1992-2001 and Victoria, Australia 1988-1990. A total of 93 children were identified as having invasive Hib disease following three doses of conjugate vaccine in infancy through post licensure surveillance throughout the UK and Eire 92 unvaccinated children admitted to an Australian paediatric hospital with invasive Hib disease were used as historical controls. Convalescent serum was taken for measurement of Hib antibody concentration, and clinical information relating to potential disease risk factors was collected. The geometric mean concentrations of convalescent Hib antibodies were compared between immunised and unimmunised children, using raw and adjusted data. Hib conjugate vaccine immunised children had higher serum Hib antibody responses to disease (geometric mean concentration (GMC) 10.81 microg/ml (95% CI 6.62 to 17.66) than unimmunised children (1.06 microg/ml (0.61 to 1.84)) (p < 0.0001). However, following adjustment for the significant confounding influences of age at presentation and timing of serum collection, a difference persisted only in children presenting with meningitis (vaccinated GMC 3.78 microg/ml (2.78 to 5.15) unvaccinated GMC 1.48 microg/ml (0.90 to 2.21) p = 0.003). Higher antibody responses to invasive Hib disease in vaccinated children with meningitis reflect priming for immunologic memory by the vaccine. Although a majority of children in the UK are protected from Hib disease by immunisation, the relative roles of immunologic memory and other immune mechanisms in conferring protection remain unclear.
Influence of contact definitions in assessment of the relative importance of social settings in disease transmission risk
Publisher: Public Library of Science (PLoS)
Date: 16-02-2012
Learnings from the Australian First Few X Household Transmission Project for COVID-19
Publisher: Cold Spring Harbor Laboratory
Date: 25-01-2022
DOI: 10.1101/2022.01.23.22269031
Abstract: First Few “X” (FFX) studies provide a platform to collect the required epidemiological, clinical and virological data to help address emerging information needs about the COVID-19 pandemic. We adapted the WHO FFX protocol for COVID-19 to understand severity and household transmission dynamics in the early stages of the pandemic in Australia. Implementation strategies were developed for participating sites all household members provided baseline epidemiological data and were followed for 14 days from case identification. Household contacts completed symptom diaries and had respiratory swabs taken at baseline, day 7 and day 14, and day 28 where applicable. We modelled the spread of COVID-19 within households using a susceptible-exposed-infectious-recovered-type model, and calculated the household secondary attack rate and key epidemiological parameters. 96 households with 101 cases and 286 household contacts were recruited into the study between April–October 2020. Forty household contacts tested positive for SARS-CoV-2 in the study follow-up period. Our model estimated the household secondary attack rate to be 15% (95% CI 8–25%), which scaled up with increasing household size. Children were less infectious than their adult counterparts but were also more susceptible to infection. Our study provides important baseline data characterising the transmission of early SARS-CoV-2 strains from children and adults in Australia, against which properties of variants of concern can be benchmarked. We encountered many challenges with respect to logistics, ethics, governance and data management that may have led to biases in our study. Continued efforts to invest in preparedness research will help to test, refine and further develop Australian FFX study protocols in advance of future outbreaks. Australian Government Department of Health The emergence of SARS-CoV-2 was initially characterised by uncertainty over key epidemiological, clinical and virological characteristics of the pathogen. We conducted a prospective household transmission study of confirmed cases of COVID-19 and their household contacts to collect data to understand severity and household transmission dynamics in Australia and add to the emerging evidence base for decision making. Large systematic reviews and meta-analyses of severity and transmission dynamics of SARS-CoV-2 in households have since been published, although estimates vary by setting. This is the first multi-jurisdictional prospective household transmission study of its kind for SARS-CoV-2 in Australia. Australia experienced low epidemic activity during the study period in 2020 due to robust public health and social measures including extensive PCR testing of symptomatic persons and isolation of all known contacts of confirmed cases. Hence, we describe the transmission dynamics in our cohort, i.e. in a low incidence setting and provide estimates of the household secondary attack rate, the relative susceptibility of children compared to adults, and transmission from children compared to adults. Our findings describe the epidemiology of COVID-19 in Australian households in 2020, and demonstrate the effectiveness of public health measures to limit transmission in this setting. Comparisons to other household transmission studies must be interpreted in light of the local epidemiology and context including study design, and s ling methods. Additional research is needed to incorporate genomic and serological data to further study transmission dynamics in our cohort. Continued development of the FFX study platform in Australia will enable integration into surveillance systems and help inform targetted public health responses to future infectious disease emergencies.
Estimating Haemophilus influenzae type b vaccine effectiveness in England and Wales by use of the screening method
Publisher: Oxford University Press (OUP)
Date: 15-08-2003
DOI: 10.1086/376997
Abstract: In October 1992, Haemophilus influenzae type b (Hib) conjugate vaccine was introduced to infants in the United Kingdom with a "catch-up" program for those aged <4 years. Initially, the rate of invasive Hib disease decreased dramatically but has been increasing since 1999. To determine possible reasons for this increase, the effectiveness of Hib conjugate vaccine was estimated by use of the screening method. Between October 1993 and December 2001, a total of 443 cases of Hib infection occurred in children eligible for vaccination 363 (82%) were fully vaccinated. Vaccine effectiveness was estimated to be 56.7% (95% confidence interval, 42.5-67.4). Effectiveness was lower in children vaccinated during infancy, compared with those who were vaccinated during the catch-up c aign (P=.0033), declined with time since vaccination (P=.0008), and was lower in children born during 2000-2002, compared with other children scheduled for infant vaccination (P=.0041). Use of a catch-up vaccination program enhanced the control of Hib infection in England and Wales. Since 1999, however, low effectiveness in infants, declining effectiveness with age, and the use of lower-efficacy vaccines have contributed to increased rates of Hib infection. The potential role of boosters needs to be considered.
Safety and immunogenicity of a prototype adjuvanted inactivated split-virus influenza A (H5N1) vaccine in infants and children.
Publisher: Elsevier BV
Date: 11-2008
DOI: 10.1016/J.VACCINE.2008.08.046
Abstract: Highly pathogenic avian influenza A virus (H5N1) is a leading candidate for the next influenza pandemic, and infants and children may play an important role in transmission in a pandemic. Our objective was to evaluate the safety and immunogenicity of a prototype inactivated, aluminium adjuvanted, split-virus, clade 1 H5N1 vaccine (A/Vietnam/1194/2004/NIBRG-14) in infants and children aged > or =6 months to or =1:20) and HI assays (95-100% > or =1:32), with 80-87% of children having MN antibody persistence (> or =1:20) up to 6 months post-vaccination. Additionally, robust cross-clade HI antibody responses were elicited following two doses. Two doses of prototype 30 microg or 45 microg aluminium-adjuvanted, H5N1 vaccines were highly immunogenic and well-tolerated, with considerable antibody persistence 6 months after the primary vaccination course. Additional cross-clade HI antibody responses and an acceptable safety and tolerability profile support the use of the either candidate vaccine formulations in infants and children in the event of a pandemic.
Intranasal administration of the TLR2 agonist pam2Cys provides rapid protection against influenza in mice
Publisher: American Chemical Society (ACS)
Date: 03-08-2012
DOI: 10.1021/MP300257X
Abstract: The protective role played by the innate immune system during early stages of infection suggests that compounds which stimulate innate responses could be used as antimicrobial or antiviral agents. In this study, we demonstrate that the Toll-like receptor-2 agonist Pam2Cys, when administered intranasally, triggers a cascade of inflammatory and innate immune signals, acting as an immunostimulant by attracting neutrophils and macrophages and inducing secretion of IL-2, IL-6, IL-10, IFN-γ, MCP-1 and TNF-α. These changes provide increased resistance against influenza A virus challenge and also reduce the potential for transmission of infection. Pam2Cys treatment also reduced weight loss and lethality associated with virulent influenza virus infection in a Toll-like receptor-2-dependent manner. Treatment did not affect the animals' ability to generate an adaptive immune response, measured by the induction of functional influenza A virus-specific CD8(+) T cells following exposure to virus. Because this compound demonstrates efficacy against distinct strains of influenza, it could be a candidate for development as an agent against influenza and possibly other respiratory pathogens.
Insights into breeding history, hotspot regions of selection, and untapped allelic diversity for bread wheat breeding
Publisher: Wiley
Date: 11-2022
DOI: 10.1111/TPJ.15952
Abstract: Breeding has increasingly altered the genetics of crop plants since the domestication of their wild progenitors. It is postulated that the genetic ersity of elite wheat breeding pools is too narrow to cope with future challenges. In contrast, plant genetic resources (PGRs) of wheat stored in genebanks are valuable sources of unexploited genetic ersity. Therefore, to ensure breeding progress in the future, it is of prime importance to identify the useful allelic ersity available in PGRs and to transfer it into elite breeding pools. Here, a erse collection consisting of modern winter wheat cultivars and genebank accessions was investigated based on reduced‐representation genomic sequencing and an iSelect single nucleotide polymorphism (SNP) chip array. Analyses of these datasets provided detailed insights into population structure, levels of genetic ersity, sources of new allelic ersity, and genomic regions affected by breeding activities. We identified 57 regions representing genomic signatures of selection and 827 regions representing private alleles associated exclusively with genebank accessions. The presence of known functional wheat genes, quantitative trait loci, and large chromosomal modifications, i.e., introgressions from wheat wild relatives, provided initial evidence for putative traits associated within these identified regions. These findings were supported by the results of ontology enrichment analyses. The results reported here will stimulate further research and promote breeding in the future by allowing for the targeted introduction of novel allelic ersity into elite wheat breeding pools.
Estimating age‐specific cumulative incidence for the 2009 influenza pandemic: a meta‐analysis of A (H 1N 1)pdm09 serological studies from 19 countries
Publisher: Wiley
Date: 21-01-2013
DOI: 10.1111/IRV.12074
Prophylaxis or treatment? Optimal use of an antiviral stockpile during an influenza pandemic
Publisher: Elsevier BV
Date: 10-2007
DOI: 10.1016/J.MBS.2007.02.003
Abstract: We introduce a novel mathematical model that effectively incorporates contact tracing in a realistic distribution mechanism for antiviral drugs in an influenza pandemic scenario. A strategy focused on targeted provision of post-exposure prophylaxis, rather than treatment, will provide the greatest chance of minimising the impact of an influenza pandemic. Targeted post-exposure prophylaxis delays the onset of the pandemic and for a wide range of parameter values, a delay of the order of 6-18 months may be achievable. This may provide enough time to develop and distribute a vaccine. In contrast, a treatment based strategy typically does not delay the onset of a pandemic by an appreciable amount and, in general, is not capable of significantly reducing the attack rate from baseline.
Increased Population Prevalence of Low Pertussis Toxin Antibody Levels in Young Children Preceding a Record Pertussis Epidemic in Australia
Publisher: Public Library of Science (PLoS)
Date: 27-04-2012
Transmission of SARS‐CoV‐2 in standardised first few X cases and household transmission investigations: A systematic review and meta‐analysis
Publisher: Wiley
Date: 16-06-2022
DOI: 10.1111/IRV.13002
Abstract: We aimed to estimate the household secondary infection attack rate (hSAR) of SARS‐CoV‐2 in investigations aligned with the WHO Unity Studies Household Transmission Investigations (HHTI) protocol. We conducted a systematic review and meta‐analysis according to PRISMA 2020 guidelines. We searched Medline, Embase, Web of Science, Scopus and medRxiv/bioRxiv for “Unity‐aligned” First Few X cases (FFX) and HHTIs published 1 December 2019 to 26 July 2021. Standardised early results were shared by WHO Unity Studies collaborators (to 1 October 2021). We used a bespoke tool to assess investigation methodological quality. Values for hSAR and 95% confidence intervals (CIs) were extracted or calculated from crude data. Heterogeneity was assessed by visually inspecting overlap of CIs on forest plots and quantified in meta‐analyses. Of 9988 records retrieved, 80 articles (64 from databases 16 provided by Unity Studies collaborators) were retained in the systematic review 62 were included in the primary meta‐analysis. hSAR point estimates ranged from 2% to 90% (95% prediction interval: 3%–71% I 2 = 99.7%) I 2 values remained % in subgroup analyses, indicating high, unexplained heterogeneity and leading to a decision not to report pooled hSAR estimates. FFX and HHTI remain critical epidemiological tools for early and ongoing characterisation of novel infectious pathogens. The large, unexplained variance in hSAR estimates emphasises the need to further support standardisation in planning, conduct and analysis, and for clear and comprehensive reporting of FFX and HHTIs in time and place, to guide evidence‐based pandemic preparedness and response efforts for SARS‐CoV‐2, influenza and future novel respiratory viruses.
Structured water in polyelectrolyte dendrimers: Understanding small angle neutron scattering results through atomistic simulation
Publisher: AIP Publishing
Date: 11-04-2012
DOI: 10.1063/1.3697479
Abstract: Based on atomistic molecular dynamics (MD) simulations, the small angle neutron scattering (SANS) intensity behavior of a single generation-4 polyelectrolyte polyamidoamine starburst dendrimer is investigated at different levels of molecular protonation. The SANS form factor, P(Q), and Debye autocorrelation function, γ(r), are calculated from the equilibrium MD trajectory based on a mathematical approach proposed in this work. The consistency found in comparison against previously published experimental findings (W.-R. Chen, L. Porcar, Y. Liu, P. D. Butler, and L. J. Magid, Macromolecules 40, 5887 (2007)) leads to a link between the neutron scattering experiment and MD computation, and fresh perspectives. The simulations enable scattering calculations of not only the hydrocarbons but also the contribution from the scattering length density fluctuations caused by structured, confined water within the dendrimer. Based on our computational results, we explore the validity of using radius of gyration RG for microstructure characterization of a polyelectrolyte dendrimer from the scattering perspective.
Changes in the epidemiology of epiglottitis following introduction of Haemophilus influenzae type b (Hib) conjugate vaccines in England: a comparison of two data sources
Publisher: Cambridge University Press (CUP)
Date: 17-11-2006
DOI: 10.1017/S0950268805005546
Abstract: Paediatric cases of epiglottitis declined markedly in England following the introduction of safe effective immunization against Haemophilus influenzae type b (Hib). With the recently described resurgence in Hib infections, a corresponding rise in the number of presentations of clinical epiglottitis in children was observed, although numbers were still well below those reported prior to vaccine availability. This was seen both in microbiology reports and hospital admissions data for England. In keeping with the more erse aetiology of epiglottitis in adults, Hib vaccination had minimal impact on hospital presentations with upper airway infections in those aged 15 years and over, which showed an overall increasing trend over 10 years. The need for a high index of suspicion to allow early diagnosis of this life-threatening clinical presentation is reinforced.
Quantifying differences in the epidemic curves from three influenza surveillance systems: a nonlinear regression analysis
Publisher: Cambridge University Press (CUP)
Date: 23-04-2014
DOI: 10.1017/S0950268814000764
Abstract: Influenza surveillance enables systematic collection of data on spatially and demographically heterogeneous epidemics. Different data collection mechanisms record different aspects of the underlying epidemic with varying bias and noise. We aimed to characterize key differences in weekly incidence data from three influenza surveillance systems in Melbourne, Australia, from 2009 to 2012: laboratory-confirmed influenza notified to the Victorian Department of Health, influenza-like illness (ILI) reported through the Victorian General Practice Sentinel Surveillance scheme, and ILI cases presenting to the Melbourne Medical Deputising Service. Using nonlinear regression, we found that after adjusting for the effects of geographical region and age group, characteristics of the epidemic curve (including season length, timing of peak incidence and constant baseline activity) varied across the systems. We conclude that unmeasured factors endogenous to each surveillance system cause differences in the disease patterns recorded. Future research, particularly data synthesis studies, could benefit from accounting for these differences.
Quantifying spatial heterogeneity of malaria in the endemic Papua region of Indonesia: analysis of epidemiological surveillance data
Publisher: Cold Spring Harbor Laboratory
Date: 19-04-2022
DOI: 10.1101/2022.04.18.22273950
Abstract: As control efforts progress towards elimination, malaria is likely to become more spatially concentrated in few local areas. The purpose of this study was to quantify and characterise spatial heterogeneity in malaria transmission-intensity across highly endemic Indonesian Papua. We analysed in idual-level malaria surveillance data for nearly half a million cases (2019–2020) reported in the Papua and West Papua provinces and adapted the Gini index approach to quantify spatial heterogeneity at the district and health-unit levels. We showed malaria incidence trends and the spatial and temporal distribution of sociodemographic characteristics and aetiological parasites among cases. While Papua province accounted for the majority of malaria cases reported in the region and had seen a rise in transmission since 2015, West Papua province had maintained a comparatively low incidence. We observed that Gini index estimates were high, particularly when the lower spatial scale of health units was evaluated. The Gini index appears to be inversely associated to annual parasite-incidence, as well as the proportions of vivax malaria, male sex, and adults. This study suggests that areas with varying levels of transmission-intensities exhibited distinct characteristics. Malaria was distributed in a markedly disproportionate manner throughout the region, emphasising the need for spatially targeted interventions. Periodic quantification and characterisation of risk heterogeneity at various spatial levels using routine malaria surveillance data may aid in tracking progress towards elimination and guiding evidence-informed prioritisation of resource allocation. Strengthening Preparedness in the Asia-Pacific Region through Knowledge (SPARK) project. We searched PubMed up to and including November 19, 2021, for relevant articles on the spatial distribution of malaria in the Papua region of Indonesia, using the terms (“malaria”) AND (“distribution” OR “variation” OR “heterogeneity” OR “cluster” OR “aggregation”) AND (“Papua”) AND (“Indonesia”). Despite the region’s mostly stable transmission areas, there has been considerable variation in transmission intensity across the region. According to community surveys conducted up to 2010, estimates of parasite prevalence of Plasmodium falciparum and Plasmodium vivax were highly variable, ranging from 0% to at least 40% and from 0% to at least 7%, respectively, across the region. Similarly, when the Papuan subset of the 2007 National Basic Health Research data was used, the degree of spatial heterogeneity in malaria risk among Papuan districts remained apparent even after sociodemographic were adjusted. Current evidence that is more representative of the current situation, including an easily interpretable and comparable measure of spatial heterogeneity across space and time, is limited. Our analysis of large-scale and routinely collected malaria surveillance data from January 2019 to December 2020 revealed significant spatial heterogeneity across the Papua region, as measured by the Gini index. Complementing conventional approaches using geospatial maps and risk tables, the Gini index can be used to provide a single, and sensitive numerical indicator summarising the degree of transmission heterogeneity at a specified spatial level of interest. Along with the previously recognised high spatial heterogeneity among districts, this study revealed a greater degree of intra-district heterogeneity at the health-unit level. That is, within the districts, there were also few health centres and hospitals with a disproportionately higher malaria burden. We observed distinct characteristics of in iduals who contracted malaria in districts with varying levels of incidence. The higher transmission magnitude was associated with a lower Gini index, as well as with lower proportions of vivax malaria, male sex, and adults among the cases. This study provides contemporary empirical evidence for the spatial heterogeneity of malaria distribution across the Papua region of Indonesia, particularly at the lower spatial resolution of health units. Evaluating spatial heterogeneity at a lower spatial scale is likely essential to refine and update local malaria control strategic planning. The combination of comprehensive, routine malaria surveillance data and the Gini index may enable policymakers to assess the magnitude and characteristics of spatial heterogeneity with increased frequency, interpretability, and comparability, allowing for the rapid identification of transmission foci and the deployment of public health measures. Effective control of parasite reservoirs associated with intense transmission may further shrink the risk of infection in adjacent areas with a lower degree of malaria exposure.
Drivers and consequences of influenza antiviral resistant-strain emergence in a capacity-constrained pandemic response
Publisher: Elsevier BV
Date: 12-2012
DOI: 10.1016/J.EPIDEM.2012.12.002
Abstract: Antiviral agents remain a key component of most pandemic influenza preparedness plans, but there is considerable uncertainty regarding their optimal use. In particular, concerns exist regarding the likelihood of wide-scale distribution to select for drug-resistant variants. We used a model that considers the influence of logistical constraints on diagnosis and drug delivery to consider achievable 'reach' of alternative antiviral intervention strategies targeted at cases of varying severity, with or without pre-exposure prophylaxis of contacts. To identify key drivers of epidemic mitigation and resistance emergence, we used Latin hypercube s ling to explore plausible ranges of parameters describing characteristics of wild type and resistant viruses, along with intervention efficacy, target coverage and distribution capacity. Within our model framework, 'real world' constraints substantially reduced achievable drug coverage below stated targets as the epidemic progressed. In consequence, predictions of both intervention impact and selection for resistance were more modest than earlier work that did not consider such limitations. Definitive containment of transmission was unlikely but, where observed, achieved through early liberal post-exposure prophylaxis of known contacts of treated cases. Predictors of resistant strain dominance were high intrinsic fitness relative to the wild type virus, and early emergence in the course of the epidemic into a largely susceptible population, even when drug use was restricted to severe case treatment. Our work demonstrates the importance of consideration of 'real world' constraints in scenario analysis modeling, and highlights the utility of models to guide surveillance activities in preparedness and response.
Household transmission of respiratory viruses - assessment of viral, individual and household characteristics in a population study of healthy Australian adults.
Publisher: Springer Science and Business Media LLC
Date: 12-2012
Optimal timing of influenza vaccine during pregnancy: A systematic review and meta-analysis.
Publisher: Wiley
Date: 05-06-2019
DOI: 10.1111/IRV.12649
Deep sequence characterisation of a divergent HPIV-4a from an adult with prolonged influenza-like illness
Publisher: Elsevier BV
Date: 12-2015
A Biological Model for Influenza Transmission: Pandemic Planning Implications of Asymptomatic Infection and Immunity
Publisher: Public Library of Science (PLoS)
Date: 28-11-2007
Infectious disease pandemic planning and response: Incorporating decision analysis
Publisher: Public Library of Science (PLoS)
Date: 09-01-2020
Modelling the impact of hybrid immunity on future COVID-19 epidemic waves
Publisher: Cold Spring Harbor Laboratory
Date: 17-03-2023
DOI: 10.1101/2023.03.12.23287174
Abstract: Since the emergence of SARS-CoV-2 (COVID-19), there have been multiple waves of infection and multiple rounds of vaccination rollouts. Both prior infection and vaccination can prevent future infection and reduce severity of outcomes, combining to form hybrid immunity against COVID-19 at the in idual and population level. Here, we explore how different combinations of hybrid immunity affect the size and severity of near-future Omicron waves. To investigate the role of hybrid immunity, we use an agent-based model of COVID-19 transmission with waning immunity to simulate outbreaks in populations with varied past attack rates and past vaccine coverages, basing the demographics and past histories on the World Health Organization (WHO) Western Pacific Region (WPR). We find that if the past infection immunity is high but vaccination levels are low, then the secondary outbreak with the same variant can occur within a few months after the first outbreak meanwhile, high vaccination levels can suppress near-term outbreaks and delay the second wave. Additionally, hybrid immunity has limited impact on future COVID-19 waves with immune-escape variants. Enhanced understanding of the interplay between infection and vaccine exposure can aid anticipation of future epidemic activity due to current and emergent variants, including the likely impact of responsive vaccine interventions.
Development of an influenza pandemic decision support tool linking situational analytics to national response policy
Publisher: Elsevier BV
Date: 09-2021
Safety and immunogenicity of an inactivated thimerosal-free influenza vaccine in infants and children.
Publisher: Wiley
Date: 22-10-2009
Immediate and longer term immunogenicity of a single dose of the combined haemophilus influenzae type B-Neisseria meningitidis serogroup C-tetanus toxoid conjugate vaccine in primed toddlers 12 to 18 months of age.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2011
Sources, perceived usefulness and understanding of information disseminated to families who entered home quarantine during the H1N1 pandemic in Victoria, Australia: A cross-sectional study
Publisher: Springer Science and Business Media LLC
Date: 04-01-2011
The influence of changing host immunity on 1918–19 pandemic dynamics
Publisher: Elsevier BV
Date: 09-2014
DOI: 10.1016/J.EPIDEM.2014.07.004
Abstract: The sociological and biological factors which gave rise to the three pandemic waves of Spanish influenza in England during 1918-19 are still poorly understood. Symptom reporting data available for a limited set of locations in England indicates that reinfection in multiple waves occurred, suggesting a role for loss of infection-acquired immunity. Here we explore the role that changes in host immunity, driven by a combination of within-host factors and viral evolution, may play in explaining weekly mortality data and wave-by-wave symptomatic attack-rates available for a subset of English cities. Our results indicate that changes in the phenotype of the pandemic virus are likely required to explain the closely spaced waves of infection, but distinguishing between the detailed contributions of viral evolution and changing adaptive immune responses to transmission rates is difficult given the dearth of sero-epidemiological and virological data available even for more contemporary pandemics. We find that a dynamical model in which pre-pandemic protection in older "influenza-experienced" cohorts is lost rapidly prior to the second wave provides the best fit to the mortality and symptom reporting data. Best fitting parameter estimates for such a model indicate that post-infection protection lasted of order months, while other statistical analyses indicate that population-age was inversely correlated with overall mortality during the herald wave. Our results suggest that severe secondary waves of pandemic influenza may be triggered by viral escape from pre-pandemic immunity, and thus that understanding the role of heterosubtypic or cross-protective immune responses to pandemic influenza may be key to controlling the severity of future influenza pandemics.
Understanding mortality in the 1918–1919 influenza pandemic in England and Wales
Publisher: Wiley
Date: 03-11-2010
Pandemic controllability: A concept to guide a proportionate and flexible operational response to future influenza pandemics
Publisher: Oxford University Press (OUP)
Date: 03-06-2014
Outbreak of Haemophilus influenzae type b disease among fully vaccinated children in a day-care center
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2004
Body distribution of impetigo and association with host and pathogen factors
Publisher: PeerJ
Date: 12-10-2022
DOI: 10.7717/PEERJ.14154
Abstract: Impetigo or skin sores are estimated to affect million people worldwide. Detailed descriptions of the anatomical location of skin sores are lacking. We used prospectively collected data from a randomised control trial of treatments for impetigo in Aboriginal children in Australia. We generated heat-map distributions of skin sores on the human body from 56 predefined anatomical locations and stratified skin sore distribution by sex, age, causative pathogen and co-infection with scabies, tinea and head lice. We compared the distribution of sores between males and females, between sores with only Streptococcus pyogenes and sores with only Staphylococcus aureus and across age groups with a Fisher’s exact test. There were 663 episodes of impetigo infections among 508 children enrolled in the trial. For all 663 episodes, the lower limbs were the most affected body sites followed by the distal upper limbs, face and scalp. On the anterior surface of the body, the pre-tibial region was the most affected while on the posterior surface, the dorsum of the hands and calves predominated. There was no observable difference between males and females in distribution of sores. Children up to 3 years of age were more likely to have sores on the upper posterior lower limbs and scalp than older age groups, with the distribution of sores differing across age groups ( p = 3 × 10 −5 ). Sores from which only Staphylococcus aureus was cultured differed in distribution to those with only Streptococcus pyogenes cultured ( p = 3 × 10 −4 ) and were more commonly found on the upper posterior lower limbs. Skin sores were predominantly found on exposed regions of the lower leg and distal upper limbs. The distribution of sores varied by age group and pathogen. These results highlight key areas of the body for clinicians to pay attention to when examining children for skin sores.
A Mathematical Framework for Estimating Pathogen Transmission Fitness and Inoculum Size Using Data from a Competitive Mixtures Animal Model
Publisher: Public Library of Science (PLoS)
Date: 28-04-2011
Likely effectiveness of pharmaceutical and non-pharmaceutical interventions for mitigating influenza virus transmission in Mongolia
Publisher: WHO Press
Date: 04-2012
Transmission of SARS-CoV-2 in standardised First Few X cases and household transmission investigations: a systematic review and meta-analysis
Publisher: Cold Spring Harbor Laboratory
Date: 03-04-2022
DOI: 10.1101/2022.04.01.22273107
Abstract: We aimed to estimate the household secondary infection attack rate (hSAR) of SARS-CoV-2 in investigations aligned with the WHO Unity Studies Household Transmission Investigations (HHTI) protocol. We conducted a systematic review and meta-analysis according to PRISMA 2020 guidelines. We searched Medline, Embase, Web of Science, Scopus and medRxiv/bioRxiv for ‘Unity-aligned’ First Few X cases (FFX) and HHTIs published between 1 December 2019 and 26 July 2021. Standardised early results were shared by WHO Unity Studies collaborators (to 1 October 2021). We used a bespoke tool to assess investigation methodological quality. Values for hSAR and 95% confidence intervals (CIs) were extracted or calculated from crude data. Heterogeneity was assessed by visually inspecting overlap of CIs on forest plots and quantified in meta-analyses. Of 9988 records retrieved, 80 articles (64 from databases 16 provided by Unity Studies collaborators) were retained in the systematic review and 62 were included in the primary meta-analysis. hSAR point estimates ranged from 2%–90% (95% prediction interval: 3%–71% I 2 =99.7%) I 2 values remained % in subgroup analyses, indicating high, unexplained heterogeneity and leading to a decision not to report pooled hSAR estimates. FFX and HHTI remain critical epidemiological tools for early and ongoing characterisation of novel infectious pathogens. The large, unexplained variance in hSAR estimates emphasises the need to further support standardisation in planning, conduct and analysis, and for clear and comprehensive reporting of FFX and HHTIs in time and place, to guide evidence-based pandemic preparedness and response efforts for SARS-CoV-2, influenza and future novel respiratory viruses.
Estimation of the force of infection and infectious period of skin sores in remote Australian communities using interval-censored data
Publisher: Public Library of Science (PLoS)
Date: 05-10-2020
Estimating the impact of test-trace-isolate-quarantine systems on SARS-CoV-2 transmission in Australia
Publisher: Cold Spring Harbor Laboratory
Date: 11-01-2023
DOI: 10.1101/2023.01.10.23284209
Abstract: We report on an analysis of Australian COVID-19 case data to estimate the impact of TTIQ systems on SARS-CoV-2 transmission in 2020–21. We estimate that in a low prevalence period in the state of New South Wales (tens of cases per day), TTIQ contributed to a 54% reduction in transmission. In a higher prevalence period in the state of Victoria (hundreds of cases per day), TTIQ contributed to a 42% reduction in transmission. Our results also suggest that case-initiated contact tracing can support timely quarantine in times of system stress. Contact tracing systems for COVID-19 in Australia were highly effective and adaptable in supporting the national suppression strategy through 2020 and 2021.
COVID-19 vaccine coverage targets to inform reopening plans in a low incidence setting
Publisher: Cold Spring Harbor Laboratory
Date: 06-12-2022
DOI: 10.1101/2022.12.04.22282996
Abstract: Since the emergence of SARS-CoV-2 in 2019 through to mid-2021, much of the Australian population lived in a COVID-19 free environment. This followed the broadly successful implementation of a strong suppression strategy, including international border closures. With the availability of COVID-19 vaccines in early 2021, the national government sought to transition from a state of minimal incidence and strong suppression activities to one of high vaccine coverage and reduced restrictions but with still-manageable transmission. This transition is articulated in the national “re-opening” plan released in July 2021. Here we report on the dynamic modelling study that directly informed policies within the national re-opening plan including the identification of priority age groups for vaccination, target vaccine coverage thresholds and the anticipated requirements for continued public health measures — assuming circulation of the Delta SARS-CoV-2 variant. Our findings demonstrated that adult vaccine coverage needed to be at least 70% to minimise public health and clinical impacts following the establishment of community transmission. They also supported the need for continued application of test-trace-isolate-quarantine and social measures during the vaccine roll-out phase and beyond.
Related Organisations
No related organisations have been discovered for Jodie McVernon.
Related Funding Activities
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