Influenza is an infectious disease that primarily attacks the respiratory system. Innate immunity provides both a very early defense to influenza virus invasion and an effective control of viral ...growth. Previous modelling studies of virus-innate immune response interactions have focused on infection with a single virus and, while improving our understanding of viral and immune dynamics, have been unable to effectively evaluate the relative feasibility of different hypothesised mechanisms of antiviral immunity. In recent experiments, we have applied consecutive exposures to different virus strains in a ferret model, and demonstrated that viruses differed in their ability to induce a state of temporary immunity or viral interference capable of modifying the infection kinetics of the subsequent exposure. These results imply that virus-induced early immune responses may be responsible for the observed viral hierarchy. Here we introduce and analyse a family of within-host models of re-infection viral kinetics which allow for different viruses to stimulate the innate immune response to different degrees. The proposed models differ in their hypothesised mechanisms of action of the non-specific innate immune response. We compare these alternative models in terms of their abilities to reproduce the re-exposure data. Our results show that 1) a model with viral control mediated solely by a virus-resistant state, as commonly considered in the literature, is not able to reproduce the observed viral hierarchy; 2) the synchronised and desynchronised behaviour of consecutive virus infections is highly dependent upon the interval between primary virus and challenge virus exposures and is consistent with virus-dependent stimulation of the innate immune response. Our study provides the first mechanistic explanation for the recently observed influenza viral hierarchies and demonstrates the importance of understanding the host response to multi-strain viral infections. Re-exposure experiments provide a new paradigm in which to study the immune response to influenza and its role in viral control.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Group A Streptococcus (GAS) skin infections are caused by a diverse array of strain types and are highly prevalent in disadvantaged populations. The role of strain-specific immunity in preventing GAS ...infections is poorly understood, representing a critical knowledge gap in vaccine development. A recent GAS murine challenge study showed evidence that sterilising strain-specific and enduring immunity required two skin infections by the same GAS strain within three weeks. This mechanism of developing enduring immunity may be a significant impediment to the accumulation of immunity in populations. We used an agent-based mathematical model of GAS transmission to investigate the epidemiological consequences of enduring strain-specific immunity developing only after two infections with the same strain within a specified interval. Accounting for uncertainty when correlating murine timeframes to humans, we varied this maximum inter-infection interval from 3 to 420 weeks to assess its impact on prevalence and strain diversity, and considered additional scenarios where no maximum inter-infection interval was specified. Model outputs were compared with longitudinal GAS surveillance observations from northern Australia, a region with endemic infection. We also assessed the likely impact of a targeted strain-specific multivalent vaccine in this context. Our model produced patterns of transmission consistent with observations when the maximum inter-infection interval for developing enduring immunity was 19 weeks. Our vaccine analysis suggests that the leading multivalent GAS vaccine may have limited impact on the prevalence of GAS in populations in northern Australia if strain-specific immunity requires repeated episodes of infection. Our results suggest that observed GAS epidemiology from disease endemic settings is consistent with enduring strain-specific immunity being dependent on repeated infections with the same strain, and provide additional motivation for relevant human studies to confirm the human immune response to GAS skin infection.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Models of infectious disease are increasingly utilising empirical contact data to quantify the number of potentially infectious contacts between age groups. While a growing body of data is being ...collected on contact patterns across many populations, less attention has been paid to the social contacts of young infants. We collected information on the social contacts of primary carers of young infants and investigated their potential for use as a proxy for contacts made by their infant.
We recruited primary carers of infants under one year of age residing in two geographically, demographically and socioeconomically distinct local government areas of Melbourne, Australia - Boroondara and Hume - including a sub-group of Turkish-speaking participants. Participants recorded their own contacts in a paper diary and noted whether their infant was present or absent. Information collected included times at an address; description of location; and details on people contacted at the location. Descriptive summary measures and distributions of contacts by location type, intensity, day of contact and by age are reported.
Of the 226 participants recruited, 220 completed diaries were returned. Participant contact patterns were similar across all groups, with respect to the types of locations, intensity and day of contact, with some variation in the number of unique daily contacts. The infant was present at around 85% of locations at which the primary carer contacted other individuals. The majority of contacts occurring when the infant was present were in Own Home (32%), Retail and Hospitality (18%) and Transport (18%) settings. The mean daily number of unique contacts by infants was estimated as 9.1, 8.7 and 6.5 in Boroondara, Hume (English) and Hume (Turkish), respectively, with a similar age distribution across each of our surveyed groups.
Our demonstration that contact patterns of mothers with infants are reasonably robust to socioeconomic and cultural differences is a step forward in modelling infectious disease transmission. With infants spending most of their time in the company of their mother, contact patterns of mothers are a useful proxy measure of infant contact patterns. The age distribution of contacts made by infants estimated in this study may be used to supplement population-wide contact information commonly used in infectious disease transmission models.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Recent studies have used Bayesian methods to predict timing of influenza epidemics many weeks in advance, but there is no documented evaluation of how such forecasts might support the day‐to‐day ...operations of public health staff.
During the 2015 influenza season in Melbourne, Australia, weekly forecasts were presented at Health Department surveillance unit meetings, where they were evaluated and updated in light of expert opinion to improve their accuracy and usefulness.
Predictive capacity of the model was substantially limited by delays in reporting and processing arising from an unprecedented number of notifications, disproportionate to seasonal intensity. Adjustment of the predictive algorithm to account for these delays and increased reporting propensity improved both current situational awareness and forecasting accuracy.
Collaborative engagement with public health practitioners in model development improved understanding of the context and limitations of emerging surveillance data. Incorporation of these insights in a quantitative model resulted in more robust estimates of disease activity for public health use.
In addition to predicting future disease trends, forecasting methods can quantify the impact of delays in data availability and variable reporting practice on the accuracy of current epidemic assessment. Such evidence supports investment in systems capacity.
Australian states and territories used test–trace–isolate–quarantine (TTIQ) systems extensively in their response to the COVID-19 pandemic in 2020-2021. We report on an analysis of Australian case ...data to estimate the impact of test–trace–isolate–quarantine systems on SARS-CoV-2 transmission.
Our analysis uses a novel mathematical modelling framework and detailed surveillance data on COVID-19 cases including dates of infection and dates of isolation. First, we directly translate an empirical distribution of times from infection to isolation into reductions in potential for onward transmission during periods of relatively low caseloads (tens to hundreds of reported cases per day). We then apply a simulation approach, validated against case data, to assess the impact of case-initiated contact tracing on transmission during a period of relatively higher caseloads and system stress (up to thousands of cases per day).
We estimate that under relatively low caseloads in the state of New South Wales (tens of cases per day), TTIQ contributed to a 54% reduction in transmission. Under higher caseloads 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 (thousands of cases per day).
Contact tracing systems for COVID-19 in Australia were highly effective and adaptable in supporting the national suppression strategy from 2020–21, prior to the emergence of the Omicron variant in November 2021. TTIQ systems were critical to the maintenance of the strong suppression strategy and were more effective when caseloads were (relatively) low.
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.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Surveillance data indicate that most circulating A(H1N1)pdm09 influenza viruses have remained antigenically similar since they emerged in humans in 2009. However, antigenic drift is likely to occur ...in the future in response to increasing population immunity induced by infection or vaccination. In this study, sequential passaging of A(H1N1)pdm09 virus by contact transmission through two independent series of suboptimally vaccinated ferrets resulted in selection of variant viruses with an amino acid substitution (N156K, H1 numbering without signal peptide; N159K, H3 numbering without signal peptide; N173K, H1 numbering from first methionine) in a known antigenic site of the viral HA. The N156K HA variant replicated and transmitted efficiently between naïve ferrets and outgrew wildtype virus in vivo in ferrets in the presence and absence of immune pressure. In vitro, in a range of cell culture systems, the N156K variant rapidly adapted, acquiring additional mutations in the viral HA that also potentially affected antigenic properties. The N156K escape mutant was antigenically distinct from wildtype virus as shown by binding of HA-specific antibodies. Glycan binding assays demonstrated the N156K escape mutant had altered receptor binding preferences compared to wildtype virus, which was supported by computational modeling predictions. The N156K substitution, and culture adaptations, have been detected in human A(H1N1)pdm09 viruses with N156K preferentially reported in sequences from original clinical samples rather than cultured isolates. This study demonstrates the ability of the A(H1N1)pdm09 virus to undergo rapid antigenic change to evade a low level vaccine response, while remaining fit in a ferret transmission model of immunization and infection. Furthermore, the potential changes in receptor binding properties that accompany antigenic changes highlight the importance of routine characterization of clinical samples in human A(H1N1)pdm09 influenza surveillance.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
During the early stages of an emerging disease outbreak, governments are required to make critical decisions on how to respond, 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. Here we describe a rapid risk assessment framework that was developed in February 2020 to support time-critical decisions on the risk of SARS-CoV-2 importation into Australia. We briefly describe the context in which our framework was developed, the framework itself, and provide an example of the type of decision support provided to the Australian government. We then report a critical evaluation of the modelling choices made in February 2020, assessing the impact of our assumptions on estimated rates of importation, and provide a summary of “lessons learned”. The framework presented and evaluated here provides a flexible approach to rapid assessment of importation risk, of relevance to current and future pandemic scenarios.
•Rapid decision making is needed during emerging disease outbreaks.•We describe a flexible framework used for rapid risk assessment of importation risk.•Our framework was used to provide timely and transparent advice about SARS-CoV-2.•We evaluate assumptions made by our framework as a guide to future use.
Background Impetigo or skin sores are estimated to affect >162 million people worldwide. Detailed descriptions of the anatomical location of skin sores are lacking. Methods 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. Results 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 x 10.sup.-5 ). Sores from which only Staphylococcus aureus was cultured differed in distribution to those with only Streptococcus pyogenes cultured (p = 3 x 10.sup.-4 ) and were more commonly found on the upper posterior lower limbs. Conclusions 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.
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