Risk factors for COVID-19 transmission in England: a multilevel modelling study using routine contact tracing data.

Contact tracing for COVID-19 in England operated from May 2020 to February 2022. The clinical, demographic and exposure information collected on cases and their contacts offered a unique opportunity to study secondary transmission. We aimed to quantify the relative impact of host factors and exposure settings on secondary COVID-19 transmission risk using 550,000 sampled transmission links between cases and their contacts. Links, or 'contact episodes', were established where a contact subsequently became a case, using an algorithm accounting for incubation period, setting, and contact date. A mixed-effects logistic regression model was used to estimate adjusted odds of transmission. Of sampled episodes, 8.7% resulted in secondary cases. Living with a case (71% episodes) was the most significant risk factor (aOR = 2.6, CI = 1.9-3.6). Other risk factors included unvaccinated status (aOR = 1.2, CI = 1.2-1.3), symptoms, and older age (66-79 years; aOR = 1.4, CI = 1.4-1.5). Whilst global COVID-19 strategies emphasized protection outside the home, including education, travel, and gathering restrictions, this study evidences the relative importance of household transmission. There is a need to reconsider the contribution of household transmission to future control strategies and the requirement for effective infection control within households.

Developmental trends in young children's device-measured physical activity and sedentary behaviour.

BACKGROUND: Knowledge of developmental trends in meeting age-specific 24-hour movement behaviour guidelines is lacking. This study describes developmental trends in device-measured physical activity and sedentary time over a three-year period among Western Australian children aged two to seven years, including differences between boys and girls. The proportion of children meeting age-specific physical activity guidelines before and after they transition to full-time school was also examined. METHODS: Data from waves 1 and 2 of the Play Spaces and Environments for Children's Physical Activity (PLAYCE) cohort study were used (analysis n = 1217). Physical activity and sedentary time were measured by accelerometry at ages two to five (preschool, wave 1) and ages five to seven (commenced full-time school, wave 2). Accelerometer data were processed using a validated machine-learning physical activity classification model. Daily time spent in sedentary behaviour, energetic play (moderate-to-vigorous physical activity (MVPA)), total physical activity, and meeting physical activity guidelines were analysed using linear and generalised linear mixed-effects models with age by sex interaction terms. RESULTS: All movement behaviours changed significantly with increasing age, and trends were similar in boys and girls. Total daily physical activity increased from age two to five then declined to age seven. Mean daily total physical activity exceeded 180 min/day from ages two to five. Daily energetic play increased significantly from age two to seven, however, was below 60 min/day at all ages except for seven-year-old boys. Daily sedentary time decreased to age five then increased to age seven but remained lower than at age two. All two-year-olds met their age-specific physical activity guideline, decreasing to 5% of girls and 6% of boys at age four. At age seven, 46% of boys and 35% of girls met their age-specific physical activity guideline. CONCLUSIONS: Young children's energetic play and total physical activity increased with age, but few children aged three to seven met the energetic play (MVPA) guideline. Interventions should focus on increasing children's energetic play in early childhood. Clearer guidance and strategies are needed to support young children as they change developmentally and as they transition from one age-specific movement guideline to the next.

Respiratory Viral Testing Rate Patterns in Young Children Attending Tertiary Care Across Western Australia: A Population-Based Birth Cohort Study.

BACKGROUND: An understanding of viral testing rates is crucial to accurately estimate the pathogen-specific hospitalisation burden. We aimed to estimate the patterns of testing for respiratory syncytial virus (RSV), influenza virus, parainfluenza virus (PIV) and human metapneumovirus (hMPV) by geographical location, age and time in children <5 years old in Western Australia. METHODS: We conducted a population-based cohort study of children born between 1 January 2010 and 31 December 2021, utilising linked administrative data incorporating birth and death records, hospitalisations and respiratory viral surveillance testing records from state-wide public pathology data. We examined within-hospital testing rates using survival analysis techniques and identified independent predictors of testing using binary logistic regression. RESULTS: Our dataset included 46,553 laboratory tests for RSV, influenza, PIV, or hMPV from 355,021 children (52.5% male). Testing rates declined in the metropolitan region over the study period (RSV testing in infants: from 242.11/1000 child-years in 2012 to 155.47/1000 child-years in 2018) and increased thereafter. Conversely, rates increased in non-metropolitan areas (e.g., RSV in Goldfields: from 364.92 in 2012 to 504.37/1000 child-years in 2021). The strongest predictors of testing were age <12 months (adjusted odds ratio [aOR] = 2.25, 95% CI 2.20-2.31), preterm birth (<32 weeks: aOR = 2.90, 95% CI 2.76-3.05) and remote residence (aOR = 0.77, 95% CI 0.73-0.81). CONCLUSION: These current testing rates highlight the potential underestimation of respiratory virus hospitalisations by routine surveillance and the need for estimation of the true burden of respiratory virus admissions.

Impact of early childhood infection on child development and school performance: a population-based study.

BACKGROUND: Childhood infection might be associated with adverse child development and neurocognitive outcomes, but the results have been inconsistent. METHODS: Two population-based record-linkage cohorts of all singleton children born at term in New South Wales, Australia, from 2001 to 2014, were set up and followed up to 2019 for developmental outcome (N=276 454) and school performance (N=644 291). The primary outcome was developmentally high risk (DHR) at age 4-6 years and numeracy and reading below the national minimum standard at age 7-9 years. Cox regression was used to assess the association of childhood infection ascertained from hospital records with each outcome adjusting for maternal, birth and child characteristics, and sensitivity analyses were conducted assessing E-values and sibling analysis for discordant exposure. RESULTS: A higher proportion of children with an infection-related hospitalisation were DHR (10.9% vs 8.7%) and had numeracy (3.7% vs 2.7%) and reading results (4.3% vs 3.1%) below the national minimum standard, compared with those without infection-related hospitalisation. In the multivariable analysis, children with infection-related hospitalisation were more likely to be DHR (adjusted HR 1.12, 95% CI 1.08 to 1.15) and have numeracy (adjusted HR 1.22, 95% CI 1.18 to 1.26) and reading results (adjusted HR 1.16, 95% CI 1.12 to 1.20) below the national minimum standard. However, these results may be impacted by unmeasured confounding, based on E-values of 1.48-1.74, and minimal association with education outcome was found in the sibling analysis. CONCLUSIONS: Infection-related hospitalisation was modestly associated with adverse child development and school performance, but the association may be explained by shared familial factors, particularly in those with most socioeconomic disadvantages.

Pilot postal birth cohort HCV Screening in UK primary care.

BACKGROUND: Birth cohort screening has been implemented in some countries to identify the potentially 'missed population' of undiagnosed chronic Hepatitis C Virus (HCV) in people who may not be found through targeted approaches. AIM: To determine uptake of HCV antibody testing using an oral swab screening method, overall yield, whether those testing positive had risk markers in their primary care record, and cost per case detected. DESIGN AND SETTING: Pilot screening study set in general practices in the Southwest, South London and Yorkshire and Humber. METHOD: Participants consenting were sent an oral swab kit in the post and saliva samples were tested for antibody to HCV. RESULTS: 16,436/98,396 (16.7%) patients consented and were sent an oral swab kit. 12,216 (12.4%) returned a kit, with 31 participants (yield 0.03%) testing positive for HCV antibody. 45% of those positive had a risk marker for HCV on their primary care record. Two (yield 0.002%) were confirmed RNA positive and referred for treatment, both had HCV risk markers. Cost per case detected was £16,000 per HCV antibody and £247,997 per chronic HCV. CONCLUSIONS: Wide-scale screening could be delivered and identified people infected with HCV, however most of these individuals could have been detected through lower-cost targeted screening. Yield and cost per case found were substantially worse than model estimates and targeted screening studies. Birth cohort screening should not be rolled out in primary care in England.

Prevalence of and Risks for Bacterial Infections in Hospitalized Children With Bronchiolitis.

BACKGROUND AND OBJECTIVES: Viral bronchiolitis is a common pediatric illness. Treatment is supportive; however, some children have concurrent serious bacterial infections (cSBIs) requiring antibiotics. Identifying children with cSBI is challenging and may lead to unnecessary treatment. Improved understanding of the prevalence of and risk factors for cSBI are needed to guide treatment. We sought to determine the prevalence of cSBI and identify factors associated with cSBI in children hospitalized with bronchiolitis. METHODS: We performed a retrospective cohort study of children <2 years old hospitalized with bronchiolitis at a free-standing children's hospital from 2012 to 2019 identified by International Classification of Diseases codes. cSBI was defined as bacteremia, urinary tract infection, meningitis, or pneumonia. Risk factors for cSBI were identified using logistic regression. RESULTS: We identified 7871 admissions for bronchiolitis. At least 1 cSBI occurred in 4.2% of these admissions; with 3.5% meeting our bacterial pneumonia definition, 0.4% bacteremia, 0.3% urinary tract infection, and 0.02% meningitis. cSBI were more likely to occur in children with invasive mechanical ventilation (odds ratio [OR] 2.53, 95% confidence interval [CI] 1.78-3.63), a C-reactive protein ≥4 mg/dL (OR 2.20, 95% CI 1.47-3.32), a concurrent complex chronic condition (OR 1.67, 95% CI 1.22-2.25) or admission to the PICU (OR 1.46, 95% CI 1.02-2.07). CONCLUSIONS: cSBI is uncommon among children hospitalized with bronchiolitis, with pneumonia being the most common cSBI. Invasive mechanical ventilation, elevated C-reactive protein, presence of complex chronic conditions, and PICU admission were associated with an increased risk of cSBI.

The Changing Detection Rate of Respiratory Syncytial Virus in Adults in Western Australia between 2017 and 2023.

The incidence of respiratory syncytial virus (RSV) in adults is inadequately defined and the impact of SARS-CoV-2-related non-pharmaceutical interventions (NPIs) is underexplored. Using laboratory data, we described the detection rate of RSV in adults ≥16 years in Western Australia (WA) between 2017 and 2023. With the exception of 2020, RSV detections rose annually between 2017 and 2023, reaching 50.7 per 100,000 in 2023 (95% confidence interval [CI], 47.9-53.8). RSV testing expanded considerably across the study period, with the testing in 2023 more than five times the 2017 total. The detection rate was highest in adults ≥60 years between 2017 and 2019, particularly those ≥75 years. Following 2020, the detections in all age groups increased, with the highest detection rate in 2023 in those ≥75-years (199.5 per 100,000; 95% CI, 180.5-220). NPIs significantly impacted RSV seasonality; the preceding winter pattern was disrupted, resulting in an absent 2020 winter season and two major summer seasons in 2020/21 and 2021/22. The RSV season began to realign in 2022, reverting to a winter seasonal pattern in 2023 and the largest season in the study period. Ongoing surveillance will be required to understand the stability of these increases and to delineate the impact of new immunisation strategies.

Clinical predictors of hypoxic pneumonia in children from the Eastern Highlands Province, Papua New Guinea: secondary analysis of two prospective observational studies.

Background: Pneumonia is the leading cause of death in young children globally and is prevalent in the Papua New Guinea highlands. We investigated clinical predictors of hypoxic pneumonia to inform local treatment guidelines in this resource-limited setting. Methods: Between 2013 and 2020, two consecutive prospective observational studies were undertaken enrolling children 0-4 years presenting with pneumonia to health-care facilities in Goroka Town, Eastern Highlands Province. Logistic regression models were developed to identify clinical predictors of hypoxic pneumonia (oxygen saturation <90% on presentation). Model performance was compared against established criteria to identify severe pneumonia. Findings: There were 2067 cases of pneumonia; hypoxaemia was detected in 36.1%. The strongest independent predictors of hypoxic pneumonia were central cyanosis on examination (adjusted odds ratio [aOR] 5.14; 95% CI 3.47-7.60), reduced breath sounds (aOR 2.92; 95% CI 2.30-3.71), and nasal flaring or grunting (aOR 2.34; 95% CI 1.62-3.38). While the model developed to predict hypoxic pneumonia outperformed established pneumonia severity criteria, it was not sensitive enough to be clinically useful at this time. Interpretation: Given signs and symptoms are unable to accurately detect hypoxia, all health care facilities should be equipped with pulse oximeters. However, for the health care worker without access to pulse oximetry, consideration of central cyanosis, reduced breath sounds, nasal flaring or grunting, age-specific tachycardia, wheezing, parent-reported drowsiness, or bronchial breathing as suggestive of hypoxaemic pneumonia, and thus severe disease, may prove useful in guiding management, hospital referral and use of oxygen therapy. Funding: Funded by Pfizer Global and the Bill & Melinda Gates Foundation.

Modelling respiratory syncytial virus age-specific risk of hospitalisation in term and preterm infants.

BACKGROUND: Respiratory syncytial virus (RSV) is the most common cause of acute lower respiratory infections in children worldwide. The highest incidence of severe disease is in the first 6 months of life, with infants born preterm at greatest risk for severe RSV infections. The licensure of new RSV therapeutics (a long-acting monoclonal antibody and a maternal vaccine) in Europe, USA, UK and most recently in Australia, has driven the need for strategic decision making on the implementation of RSV immunisation programs. Data driven approaches, considering the local RSV epidemiology, are critical to advise on the optimal use of these therapeutics for effective RSV control. METHODS: We developed a dynamic compartmental model of RSV transmission fitted to individually-linked population-based laboratory, perinatal and hospitalisation data for 2000-2012 from metropolitan Western Australia (WA), stratified by age and prior exposure. We account for the differential risk of RSV-hospitalisation in full-term and preterm infants (defined as < 37 weeks gestation). We formulated a function relating age, RSV exposure history, and preterm status to the risk of RSV-hospitalisation given infection. RESULTS: The age-to-risk function shows that risk of hospitalisation, given RSV infection, declines quickly in the first 12 months of life for all infants and is 2.6 times higher in preterm compared with term infants. The hospitalisation risk, given infection, declines to < 10% of the risk at birth by age 7 months for term infants and by 9 months for preterm infants. CONCLUSIONS: The dynamic model, using the age-to-risk function, characterises RSV epidemiology for metropolitan WA and can now be extended to predict the impact of prevention measures. The stratification of the model by preterm status will enable the comparative assessment of potential strategies in the extended model that target this RSV risk group relative to all-population approaches. Furthermore, the age-to-risk function developed in this work has wider relevance to the epidemiological characterisation of RSV.