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.

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.

Parental awareness and attitudes towards prevention of respiratory syncytial virus in infants and young children in Australia.

AIM: To assess parental awareness of respiratory syncytial virus (RSV) and the level of acceptance of future RSV prevention strategies. METHODS: A cross-sectional online survey was implemented targeting "future" and "current" parents of children aged ≤5 years in Australia. RESULTS: From 1992 eligible participants, two non-mutually exclusive subgroups were formed: "current" parents (N = 1931) and "pregnant/planning" parents (N = 464: 403 also "current" parents and 61 "future" parents). Participants were predominantly (86.6%) aged 25-39 years and 68.5% with university education. The majority (89.6% current; 78.7% future) had heard of RSV. Of those, 64.2% (current) and 50.0% (future) were aware that pneumonia is associated with RSV; 71.8% (current) and 52.1% (future) were aware that bronchiolitis is associated with RSV. In multivariable logistic regression analyses, Australian-born parents (aOR = 2.47 [95% CI: 1.48-4.12]), living in the eastern states (e.g., New South Wales: aOR = 6.15 [95% CI:2.10-18.04]), with a university-level education (aOR = 2.61 [95% CI:1.38-4.94]) and being a current parent (aOR = 12.26 [95% CI:2.82-53.28]) were associated with higher RSV awareness. There was a high level of acceptance for maternal vaccines (future: 79.3%) and infant immunisation (all: 81.7%). CONCLUSION: While RSV awareness and immunisation acceptance were high, there was limited knowledge of severity of RSV, especially in future parents. Education campaigns need to be developed to increase RSV knowledge.

The effectiveness of maternal pertussis vaccination for protecting Aboriginal and Torres Strait Islander infants against infection, 2012-2017: a retrospective cohort study.

OBJECTIVES: To evaluate the effectiveness of maternal pertussis vaccination for preventing pertussis infections in Aboriginal and Torres Strait Islander infants under seven months of age. STUDY DESIGN: Retrospective cohort study; analysis of linked administrative health data. SETTING, PARTICIPANTS: Mother-infant cohort (Links2HealthierBubs) including all pregnant women who gave birth to live infants (gestational age ≥ 20 weeks, birthweight ≥ 400 g) in the Northern Territory, Queensland, and Western Australia during 1 January 2012 - 31 December 2017. MAIN OUTCOME MEASURES: Proportions of women vaccinated against pertussis during pregnancy, rates of pertussis infections among infants under seven months of age, and estimated effectiveness of maternal vaccination for protecting infants against pertussis infection, each by Indigenous status. RESULTS: Of the 19 892 Aboriginal and Torres Strait Islander women who gave birth to live infants during 2012-2017, 7398 (37.2%) received pertussis vaccine doses during their pregnancy, as had 137 034 of 259 526 non-Indigenous women (52.8%; Indigenous v non-Indigenous: adjusted odds ratio, 0.66; 95% confidence interval [CI], 0.62-0.70). The annual incidence of notified pertussis infections in non-Indigenous infants declined from 16.8 (95% CI, 9.9-29) in 2012 to 1.4 (95% CI, 0.3-8.0) cases per 10 000 births in 2017; among Aboriginal and Torres Strait Islander infants, it declined from 47.6 (95% CI, 16.2-139) to 38.6 (95% CI, 10.6-140) cases per 10 000 births. The effectiveness of maternal vaccination for protecting non-Indigenous infants under seven months of age against pertussis infection during 2014-17 was 68.2% (95% CI, 51.8-79.0%); protection of Aboriginal and Torres Strait Islander infants was not statistically significant (36.1%; 95% CI, -41.3% to 71.1%). CONCLUSIONS: During 2015-17, maternal pertussis vaccination did not protect Aboriginal and Torres Strait Islander infants in the NT, Queensland, and WA against infection. Increasing the pertussis vaccination rate among pregnant Aboriginal and Torres Strait Islander women requires culturally appropriate, innovative strategies co-designed in partnership with Indigenous organisations and communities.

Infant Whole-Cell Versus Acellular Pertussis Vaccination in 1997 to 1999 and Risk of Childhood Hospitalization for Food-Induced Anaphylaxis: Linked Administrative Databases Cohort Study.

BACKGROUND: Evidence suggests that children who had received an initial priming dose of whole-cell pertussis (wP) vaccine, rather than acellular pertussis (aP) vaccine, had a lower risk of developing IgE-mediated food allergy, the most common cause of anaphylaxis-related hospital presentations of childhood. OBJECTIVE: To assess the association between wP versus aP vaccination in infancy and subsequent hospital presentations for anaphylaxis. METHODS: This study was preregistered under PMID 34874968. Perinatal records for a cohort of New South Wales-born children (1997-1999) receiving their first dose of pertussis-containing vaccine before age 4 months were probabilistically linked to hospital and immunization records. We used adjusted Cox models to estimate hazard ratios (aHRs) and 95% CIs for anaphylaxis-coded hospitalizations. RESULTS: There were 218,093 New South Wales-born children who received a first dose of wP or aP before age 4 months. Among these children, 86 experienced at least one hospitalization for food-induced anaphylaxis at age 5-15 years (range of events per patient, one to three). The person-time of follow-up was 1,476,969 years, and 665,519 years for children vaccinated with wP as a first dose (wP-1 children) and aP as a first dose (aP-1 children), respectively. The incidence rates for first hospitalization for food anaphylaxis were 3.5 (95% CI, 2.6-4.6) and 5.1 (95% CI, 3.5-7.1) per 100,000 child-years among wP-1 children and aP-1 children, respectively (aHR for wP vs aP = 0.47; 95% CI, 0.26-0.83). For first admission for venom anaphylaxis, the incidence rate was 4.9 (95% CI, 3.9-6.2) per 100,000 child-years among wP-1 children and 5.1 (95% CI, 3.5-7.1) per 100,000 child-years among aP-1 children (aHR for wP vs aP = 0.92; 95% CI, 0.53-1.60), and for all-cause anaphylaxis, the incidence rate was 10.6 (95% CI, 9.0-12.4) per 100,000 child-years among wP-1 children and 12.8 (95% CI, 10.2-15.8) per 100,000 child-years among aP-1 children (aHR for wP vs aP = 0.92; 95% CI, 0.53-1.60). CONCLUSION: Vaccination with wP in infancy was associated with a lower risk of hospitalizations for food-induced anaphylaxis (and therefore severe IgE-mediated food allergy) occurring in childhood.

Respiratory Syncytial Virus Reinfections in Children in Western Australia.

Respiratory syncytial virus (RSV) reinfection in children is poorly understood. We examined the incidence, characteristics, and outcomes of hospital-attended RSV reinfections in children <16 years in Western Australia between 2012 and 2022. Individuals with repeat RSV detections ≥56 days apart were identified using laboratory data. The incidence of reinfection in the first five years of life was estimated using the total birth population from 2012 to 2017. Clinical data on a subset of reinfection episodes were obtained from two metropolitan pediatric centers. A total of 466 children with hospital-attended reinfections were identified. The median interval between RSV detections was 460 days (interquartile range: 324, 812), with a reinfection rate of 95 per 100,000 individuals (95% confidence interval: 82, 109). Reinfection was most common in children who experienced their first RSV detection <6 months of age. Predisposing factors were identified in 56% of children; children with predisposing factors were older at first and second detections, were more likely to be admitted, and had a longer length of stay. This study highlights the significant burden of hospital-attended RSV reinfections in children with and without predisposing factors. Expanded surveillance with in-depth clinical data is required to further characterize the impact of RSV reinfection.

Influenza vaccination in Western Australian children: Exploring the health benefits and cost savings of increased vaccine coverage in children.

Introduction: To assess potential benefits and direct healthcare cost savings with expansion of an existing childhood influenza immunisation program, we developed a dynamic transmission model for the state of Western Australia, evaluating increasing coverage in children < 5 years and routinely immunising school-aged children. Methods: A deterministic compartmental Susceptible-Exposed-Infectious-Recovered age-stratified transmission model was developed and calibrated using laboratory-notification and hospitalisation data. Base case vaccine coverage estimates were derived from 2019 data and tested under moderate, low and high vaccine effectiveness settings. The impact of increased coverage on the burden of influenza, influenza-associated presentations and net costs were assessed using the transmission model and estimated health utilisation costs. Results: Under base case vaccine coverage and moderate vaccine effectiveness settings, 225,460 influenza cases are expected annually across all ages. Direct healthcare costs of influenza were estimated to be A$27,608,286 per annum, dominated by hospital costs. Net cost savings of >$A1.5 million dollars were observed for every 10 % increase in vaccine coverage in children < 5 years. Additional benefits were observed by including primary school age children (5-11 years) in the funded influenza vaccination program - a reduction in cases, presentations, hospitalisations and approximately $A4 million net costs savings were observed for every 10 % increase in coverage. The further addition of older children (12-17 years) resulted in only moderate additional net cost savings figures, compared with a 5-11year-old program alone. Net costs savings were predominantly derived by a reduction in influenza-associated hospitalisation in adults. Conclusions: Any increase in influenza vaccine coverage in children < 5 years, above a base case of 50 % coverage resulted in a substantive reduction in influenza cases, presentations, hospitalisations and net costs when applied to the West Australian population. However, the most impactful pediatric program, from both a disease prevention and costs perspective, would be one that increased vaccination coverage among primary-school aged children.

Factors Predicting Secondary Respiratory Morbidity Following Early-Life Respiratory Syncytial Virus Infections: Population-Based Cohort Study.

Background: The association between early-life respiratory syncytial virus (RSV) infections and later respiratory morbidity is well established. However, there is limited evidence on factors that influence this risk. We examined sociodemographic and perinatal factors associated with later childhood respiratory morbidity requiring secondary care following exposure to a laboratory-confirmed RSV episode in the first 2 years. Methods: We used a probabilistically linked whole-of-population-based birth cohort including 252 287 children born in Western Australia between 2000 and 2009 with follow-up to the end of 2012. Cox proportional hazards models estimated adjusted hazard ratios (aHRs) of the association of various risk factors with the first respiratory episode for asthma, wheezing, and unspecified acute lower respiratory infection beyond the age of 2 years. Results: The analytic cohort included 4151 children with a confirmed RSV test before age 2 years. The incidence of subsequent respiratory morbidity following early-life RSV infection decreased with child age at outcome (highest incidence in 2-<4-year-olds: 41.8 per 1000 child-years; 95% CI, 37.5-46.6), increased with age at RSV infection (6-<12-month-olds: 23.6/1000 child-years; 95% CI, 19.9-27.8; 12-<24-month-olds: 22.4/1000 child-years; 95% CI, 18.2-22.7) and decreasing gestational age (50.8/1000 child-years; 95% CI, 33.5-77.2 for children born extremely preterm, <28 weeks gestation). Risk factors included age at first RSV episode (6-<12 months: aHR, 1.42; 95% CI, 1.06-1.90), extreme prematurity (<28 weeks: aHR, 2.22; 95% CI, 1.40-3.53), maternal history of asthma (aHR, 1.33; 95% CI, 1.04-1.70), and low socioeconomic index (aHR, 1.76; 95% CI, 1.03-3.00). Conclusions: Our results suggest that in addition to preterm and young infants, children aged 12-<24 months could also be potential target groups for RSV prevention to reduce the burden of later respiratory morbidities associated with RSV.

Maternal Pertussis Vaccination, Infant Immunization, and Risk of Pertussis.

OBJECTIVES: Following the introduction of jurisdictional maternal pertussis vaccination programs in Australia, we estimated maternal vaccine effectiveness (VE) and whether maternal pertussis vaccination modified the effectiveness of the first 3 primary doses of pertussis-containing vaccines. METHODS: We conducted a population-based cohort study of 279 418 mother-infant pairs using probabilistic linkage of administrative health records in 3 Australian jurisdictions. Infants were maternally vaccinated if their mother had a documented pertussis vaccination ≥14 days before birth. Jurisdictional immunization records were used to identify receipt of the first 3 infant doses of pertussis-containing vaccines. Infant pertussis infections were identified using notifiable disease records. VE was estimated using Cox proportional hazard models. RESULTS: Pertussis was administered during 51.7% (n = 144 429/279 418) of pregnancies, predominantly at 28-31 weeks' gestation. VE of maternal pertussis vaccination declined from 70.4% (95% confidence interval [CI], 50.5-82.3) among infants <2 months old to 43.3% (95% CI, 6.8-65.6) among infants 7-8 months old and was not significant after 8 months of age. Although we observed slightly lower VE point estimates for the third dose of infant pertussis vaccine among maternally vaccinated compared with unvaccinated infants (76.5% vs 92.9%, P = .002), we did not observe higher rates of pertussis infection (hazard ratio, 0.70; 95% CI, 0.61-3.39). CONCLUSIONS: Pertussis vaccination near 28 weeks' gestation was associated with lower risk of infection among infants through 8 months of age. Although there was some evidence of lower effectiveness of infant vaccination among maternally vaccinated infants, this did not appear to translate to greater risk of disease.

Respiratory syncytial virus in children: epidemiology and clinical impact post-COVID-19.

PURPOSE OF REVIEW: Respiratory syncytial virus (RSV) remains a leading cause of mortality and morbidity worldwide. RSV seasonality was disrupted by COVID-19-associated nonpharmaceutical interventions (NPIs). We review RSV seasonality, molecular epidemiology, clinical manifestations, and community awareness to inform future prevention strategies. RECENT FINDINGS: An initial reduction of RSV disease observed with NPIs, and subsequent global resurgence was associated with a collapse in genetic diversity. A lack of immunity is suggested to have contributed to the resurgence of RSV cases experienced post COVID-19. The median age of children admitted with RSV increased during the resurgence, likely secondary to the expanded cohort of RSV-immune naive children. The pandemic also played a role in increased community awareness, which can be utilized as part of a coordinated public health effort to introduce prevention strategies. Further education on signs and symptoms of RSV is still required. SUMMARY: mAbs and maternal vaccines targeting RSV have the potential to reduce paediatric morbidity, however this new era of RSV prevention will require ongoing research to facilitate community awareness and engagement, and better respiratory surveillance. Tackling the global burden of RSV will require a coordinated effort and measures to ensure access and affordability of new prevention strategies.

Association between pertussis vaccination in infancy and childhood asthma: A population-based record linkage cohort study.

BACKGROUND: Asthma is among the commonest noncommunicable diseases of childhood and often occurs with other atopic comorbidities. A previous case-control study found evidence that compared to children who received acellular pertussis (aP) vaccines in early infancy, children who received one or more doses of whole-cell pertussis (wP) vaccine had lower risk of developing IgE-mediated food allergy. We hypothesized that wP vaccination in early infancy might protect against atopic asthma in childhood. METHODS: Retrospective record-linkage cohort study of children between 5 and < 15 years old and born between January 1997, and December 1999, in the Australian states of Western Australia (WA) and New South Wales (NSW), receiving wP versus aP vaccine as the first pertussis vaccine dose. The main outcome and measures were first and recurrent hospitalizations for asthma; hazard ratios (HRs) and 95% confidence intervals (CIs) were computed by means of Cox and Andersen and Gill models. RESULTS: 274,405 children aged between 5 and < 15 years old (78.4% NSW-born) received a first dose of either wP (67.8%) or aP vaccine before 4 months old. During the follow-up period, there were 5,905 hospitalizations for asthma among 3,955 children. The incidence rate for first hospitalization was 1.5 (95% CI 1.4-1.5) per 1,000 child-years among children receiving wP vaccine as a first dose, and 1.5 (95% CI 1.4-1.6) among those vaccinated with aP vaccine as a first dose. The adjusted HRs for those who received wP vaccine versus aP vaccine as the first dose were 1.02 (95% CI 0.94-1.12) for first hospitalizations and 1.07 (95% CI 0.95-1.2) for recurrent hospitalizations for asthma. CONCLUSIONS: We found no convincing evidence of a clinically relevant association between receipt of wP versus aP vaccines in early infancy and hospital presentations for asthma in childhood.

Health service utilisation for acute respiratory infections in infants graduating from the neonatal intensive care unit: a population-based cohort study.

BACKGROUND: Despite advances in neonatal intensive care, babies admitted to Neonatal Intensive Care Units (NICU) suffer from adverse outcomes. We aim to describe the longer-term respiratory infectious morbidity of infants discharged from NICU using state-wide population-based linked data in Western Australia. STUDY DESIGN: We used probabilistically linked population-based administrative data to analyse respiratory infection morbidity in a cohort of 23,784 infants admitted to the sole tertiary NICU, born 2002-2013 with follow up to 2015. We analysed incidence rates of secondary care episodes (emergency department presentations and hospitalisations) by acute respiratory infection (ARI) diagnosis, age, gestational age and presence of chronic lung disease (CLD). Poisson regression was used to investigate the differences in rates of ARI hospital admission between gestational age groups and those with CLD, after adjusting for age at hospital admission. RESULTS: From 177,367 child-years at risk (i.e., time that a child could experience an ARI outcome), the overall ARI hospitalisation rate for infants and children aged 0-8 years was 71.4/1000 (95% confidence interval, CI: 70.1, 72.6), with the highest rates in infants aged 0-5 months (242.9/1000). For ARI presentations to emergency departments, equivalent rates were 114/1000 (95% CI: 112.4, 115.5) and 337.6/1000, respectively. Bronchiolitis was the most common diagnosis among both types of secondary care, followed by upper respiratory tract infections. Extremely preterm infants (< 28 weeks gestation at birth) were 6.5 (95% CI: 6.0, 7.0) times more likely and those with CLD were 5.0 (95% CI: 4.7, 5.4) times more likely to be subsequently admitted for ARI than those in NICU who were not preterm or had CLD after adjusting for age at hospital admission. CONCLUSIONS: There is an ongoing burden of ARI in children who graduate from the NICU, especially those born extremely preterm, that persists into early childhood. Early life interventions to prevent respiratory infections in these children and understanding the lifelong impact of early ARI on later lung health are urgent priorities.

Non-specific benefit of seasonal influenza vaccine on respiratory syncytial virus-hospitalisations in children: An instrumental variable approach using population-based data.

BACKGROUND: Seasonal influenza vaccine is effective against influenza hospitalisations, but little is known about non-specific effects of the vaccine on other respiratory pathogens with similar seasonal patterns. We aimed to assess the causal impact of seasonal influenza vaccine on laboratory-confirmed hospitalisations for respiratory syncytial virus (RSV) in children using an instrumental variable (IV) strategy. METHODS: We used probabilistically linked population-based data on childhood immunisations, births, deaths, hospitalisations, perinatal factors, and microbiology test results (2000-2013) of all Western Australian (WA) children born 2000-2012, observed longitudinally until the earliest of 7 years of age or 31 December 2013. We exploited a unique natural experiment created from the WA's state-funded preschool influenza vaccination policy commencing in 2008 and used this as an instrument for children's seasonal influenza vaccination status. We estimated a system of two simultaneous probit equations: determinants of influenza vaccine uptake, and determinants of RSV-confirmed hospitalisation. RESULTS: Influenza vaccine coverage was low prior to 2008 but increased to 36 % in children aged 6-23 months in 2009. The majority (90 %) of RSV-hospitalisations occurred in children <2 years. Receipt of influenza vaccine reduced RSV-hospitalisations, especially in those <2 years with a rate reduction of 2.27 per 1000 (95 % CI: -3.26; -1.28), and a smaller rate reduction of 0.53 per 1000 (95 % CI: -1.04; -0.02) in those 2-7 years. Over the 5-year period (2008-2013), the state-funded preschool-influenza vaccine program resulted in 1,193 fewer RSV-hospitalisations. Of these, 793 (67 %) were in young children <2 years. CONCLUSIONS: To our knowledge, this is the first analysis utilising an IV estimation strategy on a population level to assess the causal impact of seasonal influenza vaccine on risk of RSV-hospitalisations. We estimated a small protective effect that warrants further investigation.

Incremental effectiveness of 23-valent pneumococcal polysaccharide vaccine against pneumonia hospitalisation among Australian Indigenous children: A record linkage study.

BACKGROUND: The impact of pneumococcal conjugate vaccines (PCVs) on pneumonia in children is well-documented but data on 23-valent pneumococcal polysaccharide vaccine (PPV23) are lacking. Between 2001 and 2011, Indigenous children in Western Australia (WA) were recommended to receive PPV23 at 18-24 months of age following 3 doses of 7-valent PCV. We evaluated the incremental effectiveness of PPV23 against pneumonia hospitalisation. METHODS: Indigenous children born in WA between 2001 and 2012 who received PCV dose 3 by 12 months of age were followed from 18 to 60 months of age for the first episode of pneumonia hospitalisation (all-cause and 3 subgroups: presumptive pneumococcal, other specified causes, and unspecified). We used Cox regression modelling to estimate hazard ratios (HRs) for pneumonia hospitalisation among children who had, versus had not, received PPV23 between 18 and 30 months of age after adjustment for confounders. RESULTS: 11,120 children had 327 first episodes of all-cause pneumonia hospitalisation, with 15 (4.6%) coded as presumptive pneumococcal, 46 (14.1%) as other specified causes and 266 (81.3%) unspecified. No statistically significant reduction in all-cause pneumonia was seen with PPV23 (HR 1.11; 95% CI: 0.87-1.43), but the direction of the association differed for presumptive pneumococcal (HR 0.47; 95% CI: 0.16-1.35) and specified (HR 0.89; 95% CI: 0.49-1.62) from unspecified causes (HR 1.13; 95% CI: 0.86-1.49). During the baseline period before PPV23 vaccination (12-18 months), all-cause pneumonia risk was higher among PPV23-vaccinated than unvaccinated children (RR: 1.73; 95% CI: 1.30-2.28). CONCLUSION: In this high-risk population, no statistically significant incremental effect of a PPV23 booster at 18-30 months was observed against hospitalised all-cause pneumonia or the more specific outcome of presumptive pneumococcal pneumonia. Confounding by indication may explain the slight trend towards an increased risk against all-cause pneumonia. Larger studies with better control of confounding are needed to further inform PPV23 vaccination.

Determining the true incidence of seasonal respiratory syncytial virus-confirmed hospitalizations in preterm and term infants in Western Australia.

Respiratory syncytial virus contributes to significant global infant morbidity and mortality. We applied a previously developed statistical prediction model incorporating pre-pandemic RSV testing data and hospital admission data to estimate infant RSV-hospitalizations by birth month and prematurity, focused on infants aged <1 year. The overall predicted RSV-hospitalization incidence rates in infants <6 months were 32.7/1,000 child-years (95 % CI: 31.8, 33.5) and 3.1/1,000 child-years (95 % CI: 3.0, 3.1) in infants aged 6-<12 months. Predicted RSV-hospitalization rates for infants aged <6 months were highest for infants born in April/May. Predicted rates for preterm infants born 29-32 weeks gestation were highest in March-May, whereas infants born >33 weeks had peak RSV-hospitalization rates from May-June, similar to late preterm or term births. RSV-hospitalization rates in the pre-pandemic era were highly seasonal, and seasonality varied with degree of prematurity. Accurate estimates of RSV-hospitalization in high-risk sub-groups are essential to understand preventable burden of RSV especially given the current prevention landscape.

Modeling the potential health impact of prospective Strep A vaccines.

The World Health Organization published the preferred product characteristics for a Group A Streptococcus (Strep A) vaccine in 2018. Based on these parameters for the age of vaccination, vaccine efficacy, duration of protection from vaccine-derived immunity, and vaccination coverage, we developed a static cohort model to estimate the projected health impact of Strep A vaccination at the global, regional, and national levels and by country-income category. We used the model to analyse six strategic scenarios. Based on Strep A vaccine introduction between 2022 and 2034 for the primary scenario, we estimated vaccination at birth for 30 vaccinated cohorts could avert 2.5 billion episodes of pharyngitis, 354 million episodes of impetigo, 1.4 million episodes of invasive disease, 24 million episodes of cellulitis, and 6 million cases of rheumatic heart disease globally. Vaccination impact in terms of burden averted per fully vaccinated individual is highest in North America for cellulitis and in Sub-Saharan Africa for rheumatic heart disease.

Inequity of antenatal influenza and pertussis vaccine coverage in Australia: the Links2HealthierBubs record linkage cohort study, 2012-2017.

BACKGROUND: Pregnancy and early infancy are increased risk periods for severe adverse effects of respiratory infections. Aboriginal and/or Torres Strait Islander (respectfully referred to as First Nations) women and children in Australia bear a disproportionately higher burden of respiratory diseases compared to non-Indigenous women and infants. Influenza vaccines and whooping cough (pertussis) vaccines are recommended and free in every Australian pregnancy to combat these infections. We aimed to assess the equity of influenza and/or pertussis vaccination in pregnancy for three priority groups in Australia: First Nations women; women from culturally and linguistically diverse (CALD) backgrounds; and women living in remote areas or socio-economic disadvantage. METHODS: We conducted individual record linkage of Perinatal Data Collections with immunisation registers/databases between 2012 and 2017. Analysis included generalised linear mixed model, log-binomial regression with a random intercept for the unique maternal identifier to account for clustering, presented as prevalence ratios (PR) and 95% compatibility intervals (95%CI). RESULTS: There were 445,590 individual women in the final cohort. Compared with other Australian women (n = 322,848), First Nations women (n = 29,181) were less likely to have received both recommended antenatal vaccines (PR 0.69, 95% CI 0.67-0.71) whereas women from CALD backgrounds (n = 93,561) were more likely to have (PR 1.16, 95% CI 1.10-1.13). Women living in remote areas were less likely to have received both vaccines (PR 0.75, 95% CI 0.72-0.78), and women living in the highest areas of advantage were more likely to have received both vaccines (PR 1.44, 95% CI 1.40-1.48). CONCLUSIONS: Compared to other groups, First Nations Australian families, those living in remote areas and/or families from lower socio-economic backgrounds did not receive recommended vaccinations during pregnancy that are the benchmark of equitable healthcare. Addressing these barriers must remain a core priority for Australian health care systems and vaccine providers. An extension of this cohort is necessary to reassess these study findings.

Pneumococcal Conjugate Vaccines Are Protective Against Respiratory Syncytial Virus Hospitalizations in Infants: A Population-Based Observational Study.

Background: Pneumococcal conjugate vaccines (PCV) reduced the risk of respiratory syncytial virus (RSV) in a randomized clinical trial. We aimed to assess the real-world effectiveness of PCV on RSV-hospitalizations among Western Australian infants. Methods: We conducted a population-based cohort study of births during 2000-2012, using probabilistically linked individual-level immunization, hospitalization, respiratory microbiology testing, and perinatal data. We performed Cox proportional hazard models with time-varying exposure (receipt of infant PCV doses) against the first RSV-confirmed hospitalization 0-12 months adjusted for perinatal and sociodemographic factors. Results: From 360 994 children, 3-dose PCV coverage in Aboriginal infants ranged from 29% to 51% in 2001-2004 when PCV was funded for Aboriginal children only. Following universal funding in 2005, coverage increased to 85% for Aboriginal and 73% for non-Aboriginal infants. RSV-hospitalization rates were highest in young infants aged 0-5 months (22.5/1000 child-years) and >2 times higher in Aboriginal infants than in non-Aboriginal infants. Receipt of ≥3 PCV doses in the universal funded period was associated with a 30% reduction in RSV-hospitalization in Aboriginal infants (adjusted hazard ratio, aHR 0.70 [95% confidence interval, CI 0.46-1.06]) and 21% reduction in non-Aboriginal infants (aHR 0.79 [95% CI 0.63-0.99]) compared with unvaccinated infants. Conclusions: Prior to the introduction of RSV vaccines, our study suggests that universal childhood PCV vaccination may result in a reduction in severe RSV infections in children and may be important for countries that are yet to consider PCV programs.