The associations between invasive group A streptococcal disease and infection with influenza, varicella, or hepatitis C viruses: A data linkage study, Victoria, Australia.

OBJECTIVES: To quantify the associations between invasive group A streptococcal disease (iGAS) incidence and influenza, varicella, and chronic hepatitis C virus (HCV). METHODS: We used individual-level linked data of iGAS cases from Victoria, Australia (2007-2017) to assess associations between these viral infections and iGAS. A self-controlled case series method was used to estimate the relative incidence of iGAS following an influenza or varicella infection, while the relative incidence of iGAS among HCV cases, and HCV cases who inject drugs, was estimated using population-level data and a negative binomial regression model. RESULTS: Of the 1949 individuals with at least one iGAS diagnosis, 82 were diagnosed with influenza at least once, 30 with varicella, and 118 with HCV during the study period. The relative incidence of iGAS increased substantially following infection with influenza (incidence rate ratio [IRR]: 34.5, 95% confidence interval [CI]: 21.3-55.8) or varicella (IRR: 22.4, 95% CI: 10.3-48.8). iGAS incidence was higher among HCV cases (IRR: 5.7, 95% CI: 4.4-7.3) compared to individuals without HCV. iGAS incidence was also higher among HCV cases who inject drugs (IRR: 17.9, 95% CI: 13.0-24.4) compared to individuals without HCV who did not inject drugs. CONCLUSIONS: We found a significantly higher risk of iGAS following an influenza or varicella infection and for chronic HCV cases, particularly those who inject drugs. These findings are relevant to public health practice and support the timely identification of iGAS cases.

Modelling mass drug administration strategies for reducing scabies burden in Monrovia, Liberia.

Scabies is a parasitic infestation with high global burden. Mass drug administrations (MDAs) are recommended for communities with a scabies prevalence of >10%. Quantitative analyses are needed to demonstrate the likely effectiveness of MDA recommendations. In this study, 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. Our model showed that three rounds of MDA delivered at six-month intervals and reaching 80% of the population could reduce prevalence below 2% for three 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 number of 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.

The epidemiology of invasive group A streptococcal disease in Victoria, 2007-2017: an analysis of linked datasets.

OBJECTIVE: To describe the incidence and severity of invasive group A streptococcal disease (iGAS) in Victoria, Australia. METHODS: Retrospective analysis of iGAS cases identified in linked datasets, 2007-2017: laboratory data from the Victorian Hospital Pathogen Surveillance Scheme; hospitalisation data from the Victorian Admitted Episodes Dataset; and deaths reported by the Australian Coordinating Registry. RESULTS: There were 1,369 confirmed and 610 probable cases of iGAS identified from 2007 to 2017 in Victoria, Australia. The median annual incidence was 3.1 (range 2.4-5.2) per 100,000 population. The incidence was highest in 2017, with 5.2 (95%CI: 4.6-5.8) cases per 100,000 population. The median length of stay in hospital was 10 days, with 33.1% (578/1,744) of cases admitted to the intensive care unit, of whom 49.5% (286/578) were mechanically ventilated. The case fatality rate was 5.6% (110/1,979), reaching 13.5% (51/378) among those aged 75 years or older. CONCLUSIONS: There was an increased incidence of iGAS in 2017 in Victoria, with substantial healthcare utilisation and a high case fatality rate among older Victorians. IMPLICATIONS FOR PUBLIC HEALTH: These data support mandatory notification of iGAS, which will enable better characterisation of the disease, rapid identification of changes in epidemiology and targeted public health responses.

The efficacy of sampling strategies for estimating scabies prevalence.

BACKGROUND: Estimating community level scabies prevalence is crucial for targeting interventions to areas of greatest need. The World Health Organisation recommends sampling at the unit of households or schools, but there is presently no standardised approach to scabies prevalence assessment. Consequently, a wide range of sampling sizes and methods have been used. As both prevalence and drivers of transmission vary across populations, there is a need to understand how sampling strategies for estimating scabies prevalence interact with local epidemiology to affect the accuracy of prevalence estimates. METHODS: We used a simulation-based approach to compare the efficacy of different scabies sampling strategies. First, we generated synthetic populations broadly representative of remote Australian Indigenous communities and assigned a scabies status to individuals to achieve a specified prevalence using different assumptions about scabies epidemiology. Second, we calculated an observed prevalence for different sampling methods and sizes. RESULTS: The distribution of prevalence in subpopulation groups can vary substantially when the underlying scabies assignment method changes. Across all of the scabies assignment methods combined, the simple random sampling method produces the narrowest 95% confidence interval for all sample sizes. The household sampling method introduces higher variance compared to simple random sampling when the assignment of scabies includes a household-specific component. The school sampling method overestimates community prevalence when the assignment of scabies includes an age-specific component. DISCUSSION: 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 sampling method for estimating scabies prevalence. Our approach can be adapted to various populations and diseases.

Longitudinal Analysis of Group A Streptococcus emm Types and emm Clusters in a High-Prevalence Setting: Relationship between Past and Future Infections.

Group A Streptococcus is a pathogen of global importance, but despite the ubiquity of group A Streptococcus infections, the relationship between infection, colonization, and immunity is still not completely understood. The M protein, encoded by the emm gene, is a major virulence factor and vaccine candidate and forms the basis of a number of classification systems. Longitudinal patterns of emm types collected from 457 Fijian schoolchildren over a 10-month period were analyzed. No evidence of tissue tropism was observed, and there was no apparent selective pressure or constraint of emm types. Patterns of emm type acquisition suggest limited, if any, modification of future infection based on infection history. Where impetigo is the dominant mode of transmission, circulating emm types either may not be constrained by ecological niches or population immunity to the M protein, or they may require several infections over a longer period of time to induce such immunity.

Quantity or quality? Assessing relationships between perceived social connectedness and recorded encounters.

INTRODUCTION: Higher levels of social connectedness are associated with better physical and mental health outcomes, but measures of connectedness are often study specific. Prior research has distinguished between perceived and received (quantifiable) measures of social connectedness, with differing impacts on health, sometimes mediated by place of residence. This analysis investigated the relationship between perceptions of social support/connection and quantifiable measures of social encounters, by neighbourhood, to inform understanding of place-based differences in connectedness and health outcomes. METHODS: Negative binomial regression models were used to determine associations between perceptions of social connectedness (perceived community connections and social involvement) and the number of recorded daily social encounters as a proxy for received support/connectedness. Analyses were undertaken across two Local Government Areas (LGAs) in Melbourne with disparate socio-economic profiles to examine potential modification of social connectedness measures by neighbourhood of residence. RESULTS: Two measures of perceived connectedness had a clear relationship with recorded daily social encounters-feeling a sense of community belonging (RR 1.20 (1.04, 1.37), p = 0.010) and having family or friends close by (RR 1.30 (1.10,1.54), p = 0.002 "neither" compared to "disagree", (RR 1.15 (1.04, 1.26), p = 0.006 "agree" compared to "disagree"). Involvement in a local church, sporting or social club was associated with a greater number of daily social encounters for respondents who participated a few times a year (RR 1.17 (1.05,1.32), p = 0.006) or often (RR 1.23 (1.12,1.36), p<0.001) compared to never. In the less affluent LGA, active contributions to neighbours and community through assistance and volunteering were a frequent driver of social connection. Differences in patterns between the two areas were found with some measures of perception showing stronger relationships with recorded daily encounters in one area but not the other. CONCLUSIONS: These results indicate substantial complexity in the relationship between perceptions of social connectedness and recorded daily social encounters/received connectedness, meaning that one cannot be reliably extrapolated from the other. Drivers of individuals' social connections also varied by area of residence. These findings offer new insights into potential mediators of the association between connectedness and wellbeing.

Investigation of group A Streptococcus immune responses in an endemic setting, with a particular focus on J8.

Sustained control of group A Streptococcus (GAS) infections in settings of poverty has proven to be challenging, and an effective vaccine may be the most practical long-term strategy to reduce GAS-related disease burden. Candidate GAS vaccines based on the J8 peptide have demonstrated promising immunogenicity in mice, however, less is known about the role of J8 antibodies in the human immune response to GAS infection. We analysed the stimulation of J8 antibodies in response to infection, and the role of existing J8 antibodies in protection against subsequent infection, using data collected in the Fijian population: (1) cross sectional population serosurvey; (2) paired serum collection for assessment of M-specific and J8 antibody responses; and (3) longitudinal assessment of GAS infection and immunity. Median J8 antibody concentrations peaked in the 5-14 year age group, but there was no sustained increase with age. J8 antibody concentration was neither a significant predictor of time to next infection, nor did it show any relationship to the time since last recorded skin infection. Similarly, J8 antibody fold changes over a defined period were associated neither with the time since last skin infection, nor the number of intervening skin infections. While strong M-specific antibody responses were observed for skin infection, similarly strong J8 antibody responses were not observed. There is no indication that antibodies to the J8 antigen would be useful as either a marker of GAS infection or a measure of population immunity, with J8 antibody responses to infection fleeting, if existent at all.

Scabies and risk of skin sores in remote Australian Aboriginal communities: A self-controlled case series study.

BACKGROUND: Skin sores caused by Group A streptococcus (GAS) infection are a major public health problem in remote Aboriginal communities. Skin sores are often associated with scabies, which is evident in scabies intervention programs where a significant reduction of skin sores is seen after focusing solely on scabies control. Our study quantifies the strength of association between skin sores and scabies among Aboriginal children from the East Arnhem region in the Northern Territory. METHODS AND RESULTS: Pre-existing datasets from three published studies, which were conducted as part of the East Arnhem Healthy Skin Project (EAHSP), were analysed. Aboriginal children were followed from birth up to 4.5 years of age. Self-controlled case series design was used to determine the risks, within individuals, of developing skin sores when infected with scabies versus when there was no scabies infection. Participants were 11.9 times more likely to develop skin sores when infected with scabies compared with times when no scabies infection was evident (Incidence Rate Ratio (IRR) 11.9; 95% CI 10.3-13.7; p<0.001), and this was similar across the five Aboriginal communities. Children had lower risk of developing skin sores at age ≤1 year compared to at age >1 year (IRR 0.8; 95% CI 0.7-0.9). CONCLUSION: The association between scabies and skin sores is highly significant and indicates a causal relationship. The public health importance of scabies in northern Australia is underappreciated and a concerted approach is required to recognise and eliminate scabies as an important precursor of skin sores.

Who's holding the baby? A prospective diary study of the contact patterns of mothers with an infant.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Determining the Best Strategies for Maternally Targeted Pertussis Vaccination Using an Individual-Based Model.

Rising pertussis incidence has prompted a number of countries to implement maternally targeted vaccination strategies to protect vulnerable infants, but questions remain about the optimal design of such strategies. We simulated pertussis transmission within an individual-based model parameterized to match Australian conditions, explicitly linking infants and their mothers to estimate the effectiveness of alternative maternally targeted vaccination strategies (antenatal delivery vs. postnatal delivery) and the benefit of revaccination over the course of multiple pregnancies. For firstborn infants aged less than 2 months, antenatal immunization reduced annual pertussis incidence by 60%, from 780 per 100,000 firstborn children under age 2 months (interquartile range (IQR), 682-862) to 315 per 100,000 (IQR, 260-370), while postnatal vaccination produced a minimal reduction, with an incidence of 728 per 100,000 (IQR, 628-789). Subsequent infants obtained limited protection from a single antenatal dose, but revaccinating mothers during every pregnancy decreased incidence for these infants by 58%, from 1,878 per 100,000 subsequent children under age 2 months (IQR, 1,712-2,076) to 791 per 100,000 (IQR, 683-915). Subsequent infants also benefited from household-level herd immunity when antenatal vaccination for every pregnancy was combined with a toddler booster dose at age 18 months; incidence was reduced to 626 per 100,000 (IQR, 548-691). Our approach provides useful information to aid consideration of alternative maternally targeted vaccination strategies and can inform development of outcome measures for program evaluation.

Influence of Population Demography and Immunization History on the Impact of an Antenatal Pertussis Program.

BACKGROUND: Antenatal pertussis vaccination is being considered as a means to reduce the burden of infant pertussis in low- and middle-income countries (LMICs), but its likely impact in such settings is yet to be quantified. METHODS: An individual-based model was used to simulate the demographic structure and dynamics of a population with characteristics similar to those of LMICs. Transmission of pertussis within this population was simulated to capture the incidence of infection in (1) the absence of vaccination; (2) with a primary course only (three doses of diphtheria, tetanus, and pertussis vaccines [DTP3] commencing in 1985, 1995, or 2005 at 20%, 50%, or 80% coverage); and (3) with the addition of an antenatal pertussis program. RESULTS: Modeled annual incidence averaged over the period 2015-2024 reduced with increasing DTP3 coverage, regardless of the year childhood vaccination commenced. Over the same period, the proportion of infants born with passive protection did not change substantially compared with the prevaccination situation, regardless of DTP3 coverage and start year. We found minimal impact of antenatal vaccination on infection in all infants when mothers were eligible for a single antenatal dose. When mothers were eligible for multiple antenatal doses, incidence in infants aged 0-2 months was reduced by around 30%. This result did not hold for the full 0- to 1-year age group, for whom antenatal vaccination did not reduce infection levels. CONCLUSIONS: While antenatal vaccination could potentially reduce infant mortality in LMICs, broader gains at the population level are likely to be achieved by focusing efforts on increasing DTP3 coverage.

Defining long-term drivers of pertussis resurgence, and optimal vaccine control strategies.

Pertussis resurgence has been reported from several developed countries with long-standing immunisation programs. Among these, Australia in 2003 discontinued an 18 months (fourth) booster dose in favour of an adolescent (fifth) dose. We developed a model to evaluate determinants of resurgence in Australia and alternative vaccine strategies for mitigation. Novel characteristics of our model included the use of seroepidemiologic data for calibration, and broad investigation of variables relevant to transmission of, and protection against, pertussis. We simulated multiple parameter combinations, retaining those consistent with observed data for subsequent use in predictive models comparing alternative vaccination schedules. Reproducing the early control of pertussis followed by late resurgence observed in Australia required natural immunity to last decades longer than vaccine-acquired immunity, with mean duration exceeding 50 years in almost 90% of simulations. Replacement of the dose at 18 months with an adolescent dose in 2003 resulted in a 40% increase in infections in the age group 18-47 months by 2013. A six dose strategy (2, 4, 6, 18 months, 4 and 15 years) yielded a reduction in infection incidence (pre-school 43%, infants 8%) greater than any alternative strategies considered for timing of five administered doses. Our finding that natural immunity drives long-term trends in pertussis cycles is relevant to a range of pertussis strategies and provides the necessary context in which to consider maternal vaccination. Comparatively short-lived vaccine-acquired immunity requires multiple boosters over the first two decades of life to maximise reduction in infections.