Impact of Meningococcal ACWY Vaccination Program during 2017-18 Epidemic, Western Australia, Australia.

The rising incidence of invasive meningococcal disease (IMD) caused by Neisseria meningitidis serogroup W in Western Australia, Australia, presents challenges for prevention. We assessed the effects of a quadrivalent meningococcal vaccination program using 2012-2020 IMD notification data. Notification rates peaked at 1.8/100,000 population in 2017; rates among Aboriginal and Torres Strait Islander populations were 7 times higher than for other populations. Serogroup W disease exhibited atypical manifestations and increased severity. Of 216 cases, 20 IMD-related deaths occurred; most (19/20) were in unvaccinated persons. After the 2017-2018 targeted vaccination program, notification rates decreased from 1.6/100,000 population in 2018 to 0.9/100,000 population in 2019 and continued to decline in 2020. Vaccine effectiveness (in the 1-4 years age group) using the screening method was 93.6% (95% CI 50.1%-99.2%) in 2018 and 92.5% (95% CI 28.2%-99.2%) in 2019. Strategic planning and prompt implementation of targeted vaccination programs effectively reduce IMD.

Predicting the causative pathogen among children with pneumonia using a causal Bayesian network.

BACKGROUND: Pneumonia remains a leading cause of hospitalization and death among young children worldwide, and the diagnostic challenge of differentiating bacterial from non-bacterial pneumonia is the main driver of antibiotic use for treating pneumonia in children. Causal Bayesian networks (BNs) serve as powerful tools for this problem as they provide clear maps of probabilistic relationships between variables and produce results in an explainable way by incorporating both domain expert knowledge and numerical data. METHODS: We used domain expert knowledge and data in combination and iteratively, to construct, parameterise and validate a causal BN to predict causative pathogens for childhood pneumonia. Expert knowledge elicitation occurred through a series of group workshops, surveys and one-on-one meetings involving 6-8 experts from diverse domain areas. The model performance was evaluated based on both quantitative metrics and qualitative expert validation. Sensitivity analyses were conducted to investigate how the target output is influenced by varying key assumptions of a particularly high degree of uncertainty around data or domain expert knowledge. RESULTS: Designed to apply to a cohort of children with X-ray confirmed pneumonia who presented to a tertiary paediatric hospital in Australia, the resulting BN offers explainable and quantitative predictions on a range of variables of interest, including the diagnosis of bacterial pneumonia, detection of respiratory pathogens in the nasopharynx, and the clinical phenotype of a pneumonia episode. Satisfactory numeric performance has been achieved including an area under the receiver operating characteristic curve of 0.8 in predicting clinically-confirmed bacterial pneumonia with sensitivity 88% and specificity 66% given certain input scenarios (i.e., information that is available and entered into the model) and trade-off preferences (i.e., relative weightings of the consequences of false positive versus false negative predictions). We specifically highlight that a desirable model output threshold for practical use is very dependent upon different input scenarios and trade-off preferences. Three commonly encountered scenarios were presented to demonstrate the potential usefulness of the BN outputs in various clinical pictures. CONCLUSIONS: To our knowledge, this is the first causal model developed to help determine the causative pathogen for paediatric pneumonia. We have shown how the method works and how it would help decision making on the use of antibiotics, providing insight into how computational model predictions may be translated to actionable decisions in practice. We discussed key next steps including external validation, adaptation and implementation. Our model framework and the methodological approach can be adapted beyond our context to broad respiratory infections and geographical and healthcare settings.

Status epilepticus outcomes among vaccinated and unvaccinated children: A population-based study.

AIM: To determine the proportion of first status epilepticus (SE) cases that are vaccine-proximate (VP-) and compare clinical outcomes to non-vaccine-proximate (NVP-) cases. METHODS: Birth records for 1,440,807 Australian children born in 1998-2012, were probabilistically linked to hospitalizations, deaths, and vaccination history available to 2013. First SE coded hospitalizations were categorized as VP-SE or NVP-SE; clinical severity and post-SE vaccination coverage were compared. SE rates were calculated. RESULTS: Of 867 first SE cases (7.9 per 100,000 person-years), 31 (3.6%) were VP-SE; 16 followed dose-1 measles vaccine (1.2 SE per 100,000 doses). Compared with NVP-SE, VP-SE cases were younger (1.0 vs 2.6 years, P < 0.0001) and had longer hospitalizations (4 vs 3 days, P = 0.005). There was no difference in the proportion of VP-SE cases with a coinfection diagnosis compared to NVP-SE (25.8% vs 19.9%, P = 0.42). Controlling for age and history of hospitalization for a neurological condition, intensive care unit (ICU) admission had a stronger association with coinfection (aOR 2.52 (95%CI 1.78-3.57)) than having VP-SE (aOR 1.41 (0.66-3.01)). Groups had similar SE recurrence rates at 12-months (12.9% VP vs 16.9% NVP, P = 0.56) and reduced vaccine uptake following initial SE (from 93.5% to 56.3%). CONCLUSION: Proportionally few first SE cases were VP-SE, with higher ICU admission rates mostly explained by younger age and higher coinfection rates. Vaccination plans are needed to improve vaccine uptake following SE.

Levels of pneumococcal conjugate vaccine coverage and indirect protection against invasive pneumococcal disease and pneumonia hospitalisations in Australia: An observational study.

BACKGROUND: There is limited empiric evidence on the coverage of pneumococcal conjugate vaccines (PCVs) required to generate substantial indirect protection. We investigate the association between population PCV coverage and indirect protection against invasive pneumococcal disease (IPD) and pneumonia hospitalisations among undervaccinated Australian children. METHODS AND FINDINGS: Birth and vaccination records, IPD notifications, and hospitalisations were individually linked for children aged <5 years, born between 2001 and 2012 in 2 Australian states (New South Wales and Western Australia; 1.37 million children). Using Poisson regression models, we examined the association between PCV coverage, in small geographical units, and the incidence of (1) 7-valent PCV (PCV7)-type IPD; (2) all-cause pneumonia; and (3) pneumococcal and lobar pneumonia hospitalisation in undervaccinated children. Undervaccinated children received <2 doses of PCV at <12 months of age and no doses at ≥12 months of age. Potential confounding variables were selected for adjustment a priori with the assistance of a directed acyclic graph. There were strong inverse associations between PCV coverage and the incidence of PCV7-type IPD (adjusted incidence rate ratio [aIRR] 0.967, 95% confidence interval [CI] 0.958 to 0.975, p-value < 0.001), and pneumonia hospitalisations (all-cause pneumonia: aIRR 0.991 95% CI 0.990 to 0.994, p-value < 0.001) among undervaccinated children. Subgroup analyses for children <4 months old, urban, rural, and Indigenous populations showed similar trends, although effects were smaller for rural and Indigenous populations. Approximately 50% coverage of PCV7 among children <5 years of age was estimated to prevent up to 72.5% (95% CI 51.6 to 84.4) of PCV7-type IPD among undervaccinated children, while 90% coverage was estimated to prevent 95.2% (95% CI 89.4 to 97.8). The main limitations of this study include the potential for differential loss to follow-up, geographical misclassification of children (based on residential address at birth only), and unmeasured confounders. CONCLUSIONS: In this study, we observed substantial indirect protection at lower levels of PCV coverage than previously described-challenging assumptions that high levels of PCV coverage (i.e., greater than 90%) are required. Understanding the association between PCV coverage and indirect protection is a priority since the control of vaccine-type pneumococcal disease is a prerequisite for reducing the number of PCV doses (from 3 to 2). Reduced dose schedules have the potential to substantially reduce program costs while maintaining vaccine impact.

Impact of Rotavirus Vaccines on Gastroenteritis Hospitalizations in Western Australia: A Time-series Analysis.

BACKGROUND: Rotavirus vaccination was introduced into the Australian National Immunisation Program in mid-2007. We aimed to assess the impact of the rotavirus vaccination program on the burden of hospitalizations associated with all-cause acute gastroenteritis (including rotavirus gastroenteritis and non-rotavirus gastroenteritis) in the Aboriginal and non-Aboriginal population in Western Australia. METHODS: We identified all hospital records, between July 2004 and June 2012, with a discharge diagnosis code for all-cause gastroenteritis. Age-specific hospitalization rates for rotavirus and non-rotavirus acute gastroenteritis before and after the introduction of the rotavirus vaccination program were compared. Interrupted time-series models were used to examine differences in the annual trends of all-cause gastroenteritis hospitalization between the two periods. RESULTS: Between July 2004 and June 2012, there were a total of 106,974 all-cause gastroenteritis-coded hospitalizations (1,381 rotavirus-coded [15% among Aboriginal] and 105,593 non-rotavirus gastroenteritis-coded [7% among Aboriginal]). Following rotavirus vaccination introduction, significant reductions in rotavirus-coded hospitalization rates were observed in all children aged <5 years (up to 79% among non-Aboriginal and up to 66% among Aboriginal). Among adults aged ≥65 years, rotavirus-coded hospitalizations were 89% (95% confidence interval, 16-187%) higher in the rotavirus vaccination program period. The time-series analysis suggested reductions in all-cause gastroenteritis hospitalizations in the post-vaccination period among both vaccinated and unvaccinated (age-ineligible) children, with increases observed in adults aged ≥45 years. CONCLUSIONS: Rotavirus vaccination has been associated with a significant decline in gastroenteritis hospitalizations among children. The increase in the elderly requires further evaluation, including assessment of the cost-benefits of rotavirus vaccination in this population.

Assessing the Burden of Laboratory-Confirmed Respiratory Syncytial Virus Infection in a Population Cohort of Australian Children Through Record Linkage.

BACKGROUND: Significant progress has been made towards an effective respiratory syncytial virus (RSV) vaccine. Age-stratified estimates of RSV burden are urgently needed for vaccine implementation. Current estimates are limited to small cohorts or clinical coding data only. We present estimates of laboratory-confirmed RSV across multiple severity levels. METHODS: We linked laboratory, perinatal, and hospital data of 469 589 children born in Western Australia in 1996-2012. Respiratory syncytial virus tests and detections were classified into community, emergency department (ED), and hospital levels to estimate infection rates. Clinical diagnoses given to children with RSV infection presenting to ED or hospitalized were identified. RESULTS: In 2000-2012, 10% (n = 45 699) of children were tested for RSV and 16% (n = 11 461) of these tested positive. Respiratory syncytial virus was detected in community, ED (both 0.3 per 1000 child-years), and hospital (2.4 per 1000 child-years) settings. Respiratory syncytial virus-confirmed rates were highest among children aged <3 months (31 per 1000 child-years). At least one third of children with RSV infection presenting to ED were diagnosed as other infection, other respiratory, or other (eg, agranulocytosis). CONCLUSIONS: Respiratory syncytial virus is pervasive across multiple severity levels and diagnoses. Vaccines targeting children <3 months must be prioritized. Given that most children are never tested, estimating the under-ascertainment of RSV infection is imperative.

Mode of birth and risk of infection-related hospitalisation in childhood: A population cohort study of 7.17 million births from 4 high-income countries.

BACKGROUND: The proportion of births via cesarean section (CS) varies worldwide and in many countries exceeds WHO-recommended rates. Long-term health outcomes for children born by CS are poorly understood, but limited data suggest that CS is associated with increased infection-related hospitalisation. We investigated the relationship between mode of birth and childhood infection-related hospitalisation in high-income countries with varying CS rates. METHODS AND FINDINGS: We conducted a multicountry population-based cohort study of all recorded singleton live births from January 1, 1996 to December 31, 2015 using record-linked birth and hospitalisation data from Denmark, Scotland, England, and Australia (New South Wales and Western Australia). Birth years within the date range varied by site, but data were available from at least 2001 to 2010 for each site. Mode of birth was categorised as vaginal or CS (emergency/elective). Infection-related hospitalisations (overall and by clinical type) occurring after the birth-related discharge date were identified in children until 5 years of age by primary/secondary International Classification of Diseases, 10th Revision (ICD-10) diagnosis codes. Analysis used Cox regression models, adjusting for maternal factors, birth parameters, and socioeconomic status, with results pooled using meta-analysis. In total, 7,174,787 live recorded births were included. Of these, 1,681,966 (23%, range by jurisdiction 17%-29%) were by CS, of which 727,755 (43%, range 38%-57%) were elective. A total of 1,502,537 offspring (21%) had at least 1 infection-related hospitalisation. Compared to vaginally born children, risk of infection was greater among CS-born children (hazard ratio (HR) from random effects model, HR 1.10, 95% confidence interval (CI) 1.09-1.12, p < 0.001). The risk was higher following both elective (HR 1.13, 95% CI 1.12-1.13, p < 0.001) and emergency CS (HR 1.09, 95% CI 1.06-1.12, p < 0.001). Increased risks persisted to 5 years and were highest for respiratory, gastrointestinal, and viral infections. Findings were comparable in prespecified subanalyses of children born to mothers at low obstetric risk and unchanged in sensitivity analyses. Limitations include site-specific and longitudinal variations in clinical practice and in the definition and availability of some data. Data on postnatal factors were not available. CONCLUSIONS: In this study, we observed a consistent association between birth by CS and infection-related hospitalisation in early childhood. Notwithstanding the limitations of observational data, the associations may reflect differences in early microbial exposure by mode of birth, which should be investigated by mechanistic studies. If our findings are confirmed, they could inform efforts to reduce elective CS rates that are not clinically indicated.

Association between rotavirus vaccination and intussusception in Australian children: A record linkage study.

BACKGROUND: Post-licensure surveillance studies have shown a small but increased risk of intussusception among infants in the days following rotavirus vaccination (RV). OBJECTIVES: We assessed the temporal trends of intussusception-coded hospitalisations before and after the commencement of a universal rotavirus vaccination programme in Western Australia (WA) in 2007. We also assessed the perinatal factors and pathogens associated with these hospitalisations. METHODS: Intussusception-coded hospitalisations occurring in a cohort of 367 476 WA-born children (2000-2012) aged <5 years were probabilistically linked to perinatal and pathology records. Age-specific incidence rates for overall and pathogen-specific intussusception-coded hospitalisations were calculated before (2000-2006) and after (2008-2012) RV introduction. Adjusted Cox proportional hazards models were used to assess perinatal risk factors for intussusception. RESULTS: The overall rate of intussusception-coded hospitalisation was 26.4 per 100 000 child-years (95% confidence interval [CI] 24.0, 29.0) among children aged <5 years, with rates being 70% higher (95% CI 39, 107) in the RV period than in the pre-RV period. Compared with the pre-RV period, rates were higher among those aged 12-23 months (by 55%, 95% CI 5, 127) and 2-4 years (by 84%, 95% CI 20, 182) in the RV period. However, the risk of intussusception-coded hospitalisations associated with intussusception management-related procedure code(s) was similar among all age groups in both birth periods. Among infants aged <12 months, male sex, non-Aboriginal status, birth to multiparous mothers, and birth in RV era were independent risk factors associated with intussusception-coded hospitalisations. Adenovirus was strongly associated with intussusception (6.7 per 100 000 child-years, 95% CI 5.3, 9.3). CONCLUSIONS: The risk of intussusception-coded hospitalisations was higher post-RV introduction, but not for intussusception-coded hospitalisations associated with procedure code(s). The increase was no higher in the vaccine-eligible age group than in older age groups, suggesting that the apparent increase is likely to be attributable to causes other than vaccination.

RSV prophylaxis use in high-risk infants in Western Australia, 2002-2013: a record linkage cohort study.

BACKGROUND: The monoclonal antibody, palivizumab is licensed for use in high-risk infants to prevent severe illness caused by respiratory syncytial virus (RSV). The level of its use and compliance with current jurisdictional guidelines which were amended in 2010, is unknown. We determined the level of palivizumab use in a cohort of high-risk infants in Western Australia. METHODS: Using probabilistically linked administrative data, we conducted a birth cohort study within tertiary neonatal intensive care units (NICUs) born between 2002 and 2013. We described palivizumab use by patient characteristics, eligibility criteria according to guidelines over the period of study and identified predictors of its use. RESULTS: Of 24,329 infants admitted to tertiary NICUs, 271 (1.1%) were dispensed 744 palivizumab doses with 62.5% being dispensed to infants born 2010-2013. The median number of doses received was 2. A total of 2679 infants met at least one of three criteria for palivizumab (criteria 1: gestational age at birth < 28 weeks and chronic lung disease; criteria 2: gestational age < 28 weeks and Aboriginal; criteria 3: congenital heart disease not otherwise in criteria 1 or 2). The extent of palivizumab use differed across the 3 groups. Of 803 infants meeting criteria 1, 21.8% received at least 1 dose of palivizumab; 52.8% from 2010 onwards. From 174 infants meeting criteria 2, 14.4% received at least 1 dose; 43.1% from 2010 onwards and from 1804 births meeting criteria 3, only 3.7% received at least 1 dose; 5.4% from year of birth 2010 onwards). In adjusted analyses, being born after 2010, being extreme preterm, chronic lung disease, congenital lung disease and being born in autumn or winter were independent predictors of palivizumab use. CONCLUSION: In this high-risk setting and notwithstanding the limitations of our data sources, the level of compliance of palivizumab use against current guidelines was low. Most doses were dispensed to infants meeting at least one high-risk criterion. Evidence of incomplete dosing is an important finding in light of recent developments of single dose monoclonal antibodies offering longer protection.

Effectiveness of Palivizumab against Respiratory Syncytial Virus: Cohort and Case Series Analysis.

OBJECTIVE: To measure the real-world effectiveness of palivizumab immunoprophylaxis against respiratory syncytial virus (RSV)-confirmed infection before age 2 years in a population-cohort of high-risk infants. STUDY DESIGN: Palivizumab is funded for high-risk infants in Western Australia. We used probabilistically linked administrative data encompassing RSV laboratory-confirmed infections, hospital admissions, and palivizumab dispensing records for a cohort of 24 329 high-risk infants admitted to neonatal intensive care units, born 2002-2013 with follow-up to 2015. We used a traditional cohort method with Cox proportional hazards regression and a self-controlled case series analysis to assess effectiveness of palivizumab in reducing RSV-confirmed infection by number of doses. RESULTS: From the cohort of 24 329 infants, 271 (1.1%) received at least 1 dose of palivizumab and 1506 (6.2%) had at least 1 RSV-confirmed infection before age 2 years. Using the traditional cohort approach, we found no protective association of palivizumab receipt with RSV detection (adjusted hazard ratio = 0.99 [95% CI 0.5, 1.9] for 1 dose). However, using a self-controlled case series to eliminate confounding by indication, a protective association was seen with a 74% lower RSV incidence (relative incidence = 0.26; 95% CI 0.11, 0.67) following any dose of palivizumab compared with control (nonexposed) periods. CONCLUSIONS: After accounting for confounding by indication through a self-controlled analysis, palivizumab appeared effective for reducing virologically confirmed RSV in this high-risk cohort.

Perinatal risk factors associated with skin infection hospitalisation in Western Australian Aboriginal and Non-Aboriginal children.

BACKGROUND: Hospitalisation with skin infection in Western Australian (WA) Aboriginal children is common, with the highest rates in infants and children from remote WA. OBJECTIVE: We aimed to quantify infant, maternal, and sociodemographic risk factors for skin infection hospitalisation in WA children, focussing on Aboriginal children aged <17 years. METHODS: We conducted a retrospective population-based cohort study with linked perinatal and hospitalisation data on WA-born children (1996-2012), of whom 31 348 (6.7%) were Aboriginal. We used Cox regression to calculate adjusted hazard ratios and associated population attributable fractions (PAFs) for perinatal factors attributed to first hospitalisation with skin infection. To identify specific risk factors for early-onset infection, we further restricted the cohort to infants aged <1 year. RESULTS: Overall, 5439 (17.4%) Aboriginal and 6750 (1.5%) non-Aboriginal children were hospitalised at least once with a skin infection. Aboriginal infants aged <1 year had the highest skin infection hospitalisation rate (63.2 per 1000 child-years). The strongest risk factors in Aboriginal children aged <17 years were socio-economic disadvantage, very remote location at birth, and multi-parity (≥3 previous pregnancies) accounting for 24%, 23%, and 15% of skin infection hospitalisations, respectively. Other risk factors included maternal age <20 years, maternal smoking during pregnancy, and low birthweight. CONCLUSIONS: We have quantified the relative influence of perinatal risk factors associated with skin infection hospitalisations in WA children, providing measures indicating which factors have the potential to reduce the most hospitalisations. Our evidence not only supports existing calls for substantial government investment in addressing underlying social and environmental barriers to healthy skin in WA Aboriginal children but also identifies potential areas to target health promotion messaging at individuals/families on maternal smoking during pregnancy and skin hygiene for families.

The Impact of Pneumococcal Vaccination on Bacterial and Viral Pneumonia in Western Australian Children: Record Linkage Cohort Study of 469589 Births, 1996-2012.

Background: Pneumococcal conjugate vaccine (PCV) was included in Australia's National Immunisation Program for all children from 2005. We assessed the impact of PCV on all-cause and pathogen-specific pneumonia hospitalizations in Western Australian (WA) children aged ≤16 years. Methods: All hospitalizations with pneumonia-related International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Australian Modification diagnosis codes occurring in WA-born children (1996-2012) were linked to pathology records. Age-specific incidence rate ratios and temporal trends for all-cause and pathogen-specific pneumonia hospitalizations were calculated before and after PCV introduction. Results: Among 469589 births, there were 15175 pneumonia-related hospitalizations. Hospitalization rates were 6.7 (95% confidence interval, 6.4-6.9) times higher in Aboriginal than in non-Aboriginal children. Following PCV introduction, all-cause pneumonia hospitalizations showed significant declines across all age groups. A pathogen was identified in 2785 of 6693 (41.6%) pneumonia hospitalizations that linked to a pathology record. Respiratory syncytial virus (RSV) was most frequently identified, with RSV-associated pneumonia hospitalization rates of 89.6/100000 child-years in Aboriginal and 26.6/100000 child-years in non-Aboriginal children. The most common bacterial pathogen was Streptococcus pneumoniae in Aboriginal children (32.9/100000 child-years) and Mycoplasma pneumoniae in non-Aboriginal children (8.4/100000 child-years). Viral pneumonia rates declined in all children following PCV introduction, with the greatest declines seen in non-Aboriginal children; declines in bacterial pneumonia were observed in non-Aboriginal children. Conclusions: Based on our ecological analyses, PCV seems to have had an impact on hospitalizations for pneumonia, suggesting that the pneumococcus is likely to play a role in both bacterial and viral pneumonia. Respiratory viruses remain an important pathogen in childhood pneumonia. Vaccines targeting respiratory viruses are needed to combat the residual burden of childhood pneumonia.

Using record linkage to validate notification and laboratory data for a more accurate assessment of notifiable infectious diseases.

BACKGROUND: Infectious disease burden is commonly assessed using notification data. Using retrospective record linkage in Western Australia, we described how well notification data captures laboratory detections of influenza, pertussis and invasive pneumococcal disease (IPD). METHODS: We linked data from the Western Australian Notifiable Infectious Diseases Database (WANIDD) and the PathWest Laboratory Database (PathWest) pertaining to the Triple I birth cohort, born in Western Australia in 1996-2012. These were combined to calculate the number of unique cases captured in each dataset alone or in both datasets. To assess the impact of under-ascertainment, we compared incidence rates calculated using WANIDD data alone and using combined data. RESULTS: Overall, there were 5550 influenza, 513 IPD (2001-2012) and 4434 pertussis cases (2000-2012). Approximately 2% of pertussis and IPD cases and 7% of influenza cases were solely recorded in PathWest. Notification of influenza and pertussis cases to WANIDD improved over time. Overall incidence rates of influenza in children aged <5 years using both datasets was 10% higher than using WANIDD data alone (IRR = 1.1, 95% CI = 1.1-1.2). CONCLUSIONS: This is the first time WANIDD data have been validated against routinely collected laboratory data. We anticipated all cases would be captured in WANIDD but found additional laboratory-confirmed cases that were not notified. Studies investigating pathogen-specific infectious disease would benefit from using multiple data sources.

Systematic review and meta-analysis of respiratory viral coinfections in children.

Respiratory infections are a common cause of paediatric morbidity. Clinical outcomes in children hospitalized with single respiratory virus infection are compared with those with two or more viral-viral coinfection. Studies were restricted to those reporting on children aged less than 5 years (PROSPERO CRD#42014009133). Published data to calculate risk ratios (RR) comparing children with single viral infections to coinfection using a random effects model were used. Similar analyses by pathogen pairs and by excluding children with comorbidities were performed. Of 4443 articles reviewed, 19 were included. Overall, no differences in the risk of fever, admission to an intensive care unit (ICU), oxygen use, mechanical ventilation and abnormal radiographs between children with single infection and those with coinfection were found. When analysing only children without comorbidities, the risk of fever (RR = 1.16 to RR = 1.24, 95% confidence intervals (CI) = 1.00-1.55) and ICU admission (RR = 1.08 to RR = 1.31, 95% CI = 0.93-1.83) increased but remained non-significant. Point estimates suggested an increased risk of ICU admission in those coinfected with either respiratory syncytial virus or human metapneumovirus compared with those with single infection but was non-significant. Our findings suggest that coinfection is not associated with increased clinical severity, but further investigations by pathogen pairs are warranted.

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.

Financial incentives to motivate treatment for hepatitis C with direct acting antivirals among Australian adults (The Methodical evaluation and Optimisation of Targeted IncentiVes for Accessing Treatment of Early-stage hepatitis C: MOTIVATE-C): protocol for a dose-response randomised controlled study.

BACKGROUND: Untreated hepatitis C virus (HCV) infection can result in cirrhosis and hepatocellular cancer. Direct-acting antiviral (DAA) therapies are highly effective and have few side effects compared to older interferon-based therapy. Despite the Australian government providing subsidised and unrestricted access to DAA therapy for chronic HCV infection, uptake has not been sufficient to meet the global target of eliminating HCV as a public health threat by 2030. This study will offer people with HCV financial incentives of varying values in order to evaluate its effect on initiation of DAA therapy in primary care. METHODS: Australian adults (18 years or older) who self-report as having current untreated HCV infection can register to participate via an automated SMS-based system. Following self-screening for eligibility, registrants are offered a financial incentive of randomised value (AUD 0 to 1000) to initiate DAA therapy. Study treatment navigators contact registrants who have consented to be contacted, to complete eligibility assessment, outline the study procedures (including the requirement for participants to consult a primary care provider), obtain consent, and finalise enrolment. Enrolled participants receive their offered incentive on provision of evidence of DAA therapy initiation within 12 weeks of registration (primary endpoint). Balanced randomisation is used across the incentive range until the first analysis, after which response-adaptive randomisation will be used to update the assignment probabilities. For the primary analysis, a Bayesian 4-parameter EMAX model will be used to estimate the dose-response curve and contrast treatment initiation at each incentive value against the control arm (AUD 0). Specified secondary statistical and economic analyses will evaluate the effect of incentives on adherence to DAA therapy, virological response, and cost-effectiveness. DISCUSSION: This project seeks to gain an understanding of the dose-response relationship between incentive value and DAA treatment initiation, while maximising the number of people treated for HCV within fixed budget and time constraints. In doing so, we hope to offer policy-relevant recommendation(s) for the use of financial incentives as a pragmatic, efficient, and cost-effective approach to achieving elimination of HCV from Australia. TRIAL REGISTRATION: ANZCTR (anzctr.org.au), Identifier ACTRN12623000024640, Registered 11 January 2023 ( https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=384923&isReview=true ).

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.

Review of the health impact of the oral rotavirus vaccine program in children under 5 years in Australia: 2006 - 2021.

Oral rotavirus vaccines were incorporated into the National Immunisation Program (NIP) for all Australian infants in July 2007. Initially each of the eight jurisdictions implemented Rotarix or RotaTeq rotavirus vaccine, however from July 2017 all states and territories have administered Rotarix only. This review evaluates the health impact of the oral rotavirus vaccine program for Australian children less than 5 years old over the first 15 years of the rotavirus vaccine program, observing long-term changes in rotavirus-related health care attendances, public health notifications, and vaccine effectiveness and safety data for both Rotarix and RotaTeq rotavirus vaccines. We searched Medline for studies published between January 2006 and May 2022 using the search terms 'rotavirus', 'rotavirus vaccine' and 'Australia'. Of 491 items identified, 76 items - 36 peer-reviewed articles and 40 reports - were included in the review. We found evidence that the introduction of the oral rotavirus vaccine program in Australia was associated with a prompt reduction in rotavirus-coded and all-cause gastroenteritis hospitalisations of vaccine-eligible children. In the context of less complete coverage, reduced vaccine timeliness and lower vaccine effectiveness, a less substantial and inconsistent reduction in severe rotavirus disease was observed among Aboriginal and Torres Strait Islander children, particularly those living in rural and remote northern Australia. Additional studies report no evidence for the emergence of non-vaccine serotypes and/ or replacement serotypes in Australia during the vaccine era. While the health impact for young children and consequent cost-savings of the oral rotavirus vaccine program have been high, it is important to find strategies to improve rotavirus vaccine impact for Aboriginal and Torres Strait Islander populations to ensure health benefits for all Australian children.

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.

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.