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.

The impact of pre-pregnancy body mass index and gestational weight gain on placental abruption risk: a systematic review and meta-analysis.

PURPOSE: The aim of this systematic review was to evaluate the associations between pre-pregnancy body mass index and gestational weight gain and placental abruption. METHODS: Relevant studies were identified from PubMed, EMBASE, Scopus and CINAHL. Unpublished findings from analyses of linked population-based data sets from Western Australia (2012-2015, n = 114,792) were also included. Studies evaluating pre-pregnancy body mass index and/or gestational weight gain and placental abruption were included. Two independent reviewers evaluated studies for inclusion and quality. Data including odds ratios (ORs) and 95% confidence intervals (CIs) were extracted and analysed by random effects meta-analysis. RESULTS: 21 studies were included, of which 15 were eligible for meta-analyses. The summary ORs for the association of being underweight, overweight and obese, and placental abruption, compared to normal weight women, were 1.4 (95% CI 1.1, 1.7), 0.8 (95% CI 0.8, 0.9) and 0.8 (95% CI 0.7, 0.9), respectively. These findings remained unchanged when each study was eliminated from the analysis and in subgroup analyses. Although data were scarce, women with gestational weight gain below the Institute of Medicine recommendations appeared to be at greater risk of abruption compared with women who had optimal weight gain. CONCLUSIONS: Mothers that are underweight prior to or in early pregnancy are at a moderately increased risk of placental abruption.

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.

Geographical disparities in emergency department presentations for acute respiratory infections and risk factors for presenting: a population-based cohort study of Western Australian children.

INTRODUCTION: Studies examining acute respiratory infections (ARIs) in emergency department (EDs), particularly in rural and remote areas, are rare. This study aimed to examine the burden of ARIs among Aboriginal and non-Aboriginal children presenting to Western Australian (WA) EDs from 2002 to 2012. METHOD: Using a retrospective population-based cohort study linking ED records to birth and perinatal records, we examined presentation rates for metropolitan, rural and remote Aboriginal and non-Aboriginal children from 469 589 births. We used ED diagnosis information to categorise presentations into ARI groups and calculated age-specific rates. Negative binomial regression was used to investigate association between risk factors and frequency of ARI presentation. RESULTS: Overall, 26% of presentations were for ARIs. For Aboriginal children, the highest rates were for those aged <12 months in the Great Southern (1233 per 1000 child-years) and Pilbara regions (1088 per 1000 child-years). Rates for non-Aboriginal children were highest in children <12 months in the Southwest and Kimberley (400 and 375 per 1000 child-years, respectively). Presentation rates for ARI in children from rural and remote WA significantly increased over time in all age groups <5 years. Risk factors for children presenting to ED with ARI were: male, prematurity, caesarean delivery and residence in the Kimberley region and lower socio-economic areas. CONCLUSION: One in four ED presentations in WA children are for ARIs, representing a significant out-of-hospital burden with some evidence of geographical disparity. Planned linkages with hospital discharge and laboratory detection data will aid in assessing the sensitivity and specificity of ARI diagnoses in ED.

Record linkage study of the pathogen-specific burden of respiratory viruses in children.

BACKGROUND: Reliance on hospital discharge diagnosis codes alone will likely underestimate the burden of respiratory viruses. OBJECTIVES: To describe the epidemiology of respiratory viruses more accurately, we used record linkage to examine data relating to all children hospitalized in Western Australia between 2000 and 2012. PATIENTS/METHODS: We extracted hospital, infectious disease notification and laboratory data of a cohort of children born in Western Australia between 1996 and 2012. Laboratory records of respiratory specimens collected within 48 hours of admission were linked to hospitalization records. We calculated the frequency and rates of virus detection. To identify groups where under-ascertainment for respiratory viruses was greatest, we used logistic regression to determine factors associated with failure to test. RESULTS AND CONCLUSIONS: Nine percentage of 484 992 admissions linked to a laboratory record for respiratory virus testing. While 62% (n = 26 893) of laboratory-confirmed admissions received respiratory infection diagnosis codes, 38% (n = 16 734) had other diagnoses, notably viral infection of unspecified sites. Of those tested, incidence rates were highest for respiratory syncytial virus (247 per 100 000 child-years) followed by parainfluenza (63 per 100 000 child-years). Admissions among older children and those without a respiratory diagnosis were associated with failure to test for respiratory viruses. Linked data can significantly enhance diagnostic codes when estimating the true burden of disease. In contrast to current emphasis on influenza, respiratory syncytial virus and parainfluenza were the most common viral pathogens among hospitalized children. By characterizing those failing to be tested, we can begin to quantify the under-ascertainment of respiratory viruses.

Potential impact of a maternal vaccine for RSV: A mathematical modelling study.

Respiratory syncytial virus (RSV) is a major cause of respiratory morbidity and one of the main causes of hospitalisation in young children. While there is currently no licensed vaccine for RSV, a vaccine candidate for pregnant women is undergoing phase 3 trials. We developed a compartmental age-structured model for RSV transmission, validated using linked laboratory-confirmed RSV hospitalisation records for metropolitan Western Australia. We adapted the model to incorporate a maternal RSV vaccine, and estimated the expected reduction in RSV hospitalisations arising from such a program. The introduction of a vaccine was estimated to reduce RSV hospitalisations in Western Australia by 6-37% for 0-2month old children, and 30-46% for 3-5month old children, for a range of vaccine effectiveness levels. Our model shows that, provided a vaccine is demonstrated to extend protection against RSV disease beyond the first three months of life, a policy using a maternal RSV vaccine could be effective in reducing RSV hospitalisations in children up to six months of age, meeting the objective of a maternal vaccine in delaying an infant's first RSV infection to an age at which severe disease is less likely.

Viral Etiology and the Impact of Codetection in Young Children Presenting With Influenza-Like Illness.

BACKGROUND: Children with acute respiratory tract infection (ARTI) frequently exhibit virus-virus codetection, yet the clinical significance of ARTI remains contentious. Using data from a prospective cohort of children with influenza-like illness, we examined the virology of ARTI and determined the clinical impact of virus-virus codetection. METHODS: Children aged 6 to 59 months who presented to a tertiary pediatric hospital between influenza seasons 2008 and 2012 with fever and acute respiratory symptoms were enrolled, and nasal samples were collected. Respiratory viruses were identified by culture and polymerase chain reaction. We compared demographics, presenting symptoms, and clinical outcomes of children with a single-virus infection and those in whom 2 or more viruses were detected (virus-virus codetection). We used logistic regression models and estimated marginal means to calculate the adjusted odds ratios and probabilities of symptom presentation, prescription of antibiotics, and hospitalization. RESULTS: Of 2356 children, a virus was detected in 1630 (69.2%) of them; rhinovirus (40.8%), influenza (29.5%), and respiratory syncytial virus (26.4%) were detected most commonly. Two or more viruses were detected in 25% of these children. After we adjusted for demographic factors, children with virus-virus codetection had greater odds of presenting with cough (adjusted odds ratio [aOR], 1.9; 95% confidence interval [CI], 1.2-3.1) and rhinorrhea (aOR, 1.8; 95% CI, 1.1-2.9) than those with a single-virus infection, although both symptoms were common. Children with influenza and respiratory syncytial virus combined had the highest probability of hospitalization (55%; 95% CI, 35%-73%), which was significantly greater than for those with influenza infection alone (22%; 95% CI, 16%-29%). CONCLUSIONS: Overall, virus-virus codetection has limited impact on clinical severity among children with influenza-like illness. However, infection with specific pathogen pairs might be associated with more severe outcomes. Routine diagnostics to identify specific viruses should be restricted to common pathogens.

Time series analysis of RSV and bronchiolitis seasonality in temperate and tropical Western Australia.

Respiratory syncytial virus (RSV) causes respiratory illness in young children and is most commonly associated with bronchiolitis. RSV typically occurs as annual or biennial winter epidemics in temperate regions, with less pronounced seasonality in the tropics. We sought to characterise and compare the seasonality of RSV and bronchiolitis in temperate and tropical Western Australia. We examined over 13 years of RSV laboratory identifications and bronchiolitis hospitalisations in children, using an extensive linked dataset from Western Australia. We applied mathematical time series analyses to identify the dominant seasonal cycle, and changes in epidemic size and timing over this period. Both the RSV and bronchiolitis data showed clear winter epidemic peaks in July or August in the southern Western Australia regions, but less identifiable seasonality in the northern regions. Use of complex demodulation proved very effective at comparing disease epidemics. The timing of RSV and bronchiolitis epidemics coincided well, but the size of the epidemics differed, with more consistent peak sizes for bronchiolitis than for RSV. Our results show that bronchiolitis hospitalisations are a reasonable proxy for the timing of RSV detections, but may not fully capture the magnitude of RSV epidemics.

Optimization is required when using linked hospital and laboratory data to investigate respiratory infections.

OBJECTIVE: Despite a recommendation for microbiological testing, only 45% of children hospitalized for respiratory infections in our previous data linkage study linked to a microbiological record. We conducted a chart review to validate linked microbiological data. STUDY DESIGN AND SETTING: The chart review consisted of children aged <5 years admitted to seven selected hospitals for respiratory infections in Western Australia, 2000-2011. We calculated the proportion of admissions where testing was performed and any pathogens detected. We compared these proportions between the chart review and our previous data linkage study. Poisson regression was used to identify factors predicting the likelihood of microbiological tests in the chart review cohort. RESULTS: From the chart review, 77% of 746 records had a microbiological test performed compared with 46% of 18,687 records from our previous data linkage study. Of those undergoing testing, 66% of the chart review and 64% of data linkage records had ≥1 respiratory pathogen(s) detected. In the chart review cohort, frequency of testing was highest in children admitted to metropolitan hospitals. CONCLUSION: Validation studies are essential to ensure the quality of linked data. Our previous data linkage study failed to capture all relevant microbiological records. Findings will be used to optimize extraction protocols for future linkage studies.

Risk factors and comorbidities for invasive pneumococcal disease in Western Australian Aboriginal and non-Aboriginal people.

Australian Aboriginal people have among the highest rates of invasive pneumococcal disease (IPD) worldwide. We investigated clinical diagnosis, risk factors, comorbidities and vaccine coverage in Aboriginal and non-Aboriginal IPD cases. Using enhanced surveillance, we identified IPD cases in Western Australia, Australia, between 1997 and 2007. We calculated the proportion with risk factors and comorbidities in children (<5 years) and adults (=15 years), as well as adults living in metropolitan and non-metropolitan regions. We then calculated the proportion of cases eligible for vaccination who were vaccinated before contracting IPD. Of the 1,792 IPD cases that were reported, 355 (20%) were Aboriginal and 1,155 (65%) were adults. Pneumonia was the most common diagnosis (61% of non-Aboriginal and 49% of Aboriginal adult IPD cases in 2001-2007). Congenital abnormality was the most frequent comorbidity in non-Aboriginal children (11%). In Aboriginal children, preterm delivery was most common (14%). Ninety-one percent of non-Aboriginal and 96% of Aboriginal adults had one or more risk factors or comorbidities. In non-Aboriginal adults, cardiovascular disease (34%) was the predominant comorbidity whilst excessive alcohol use (66%) was the most commonly reported risk factor in Aboriginal adults. In adults, comorbidities were more frequently reported among those in metropolitan regions than those in non-metropolitan regions. Vaccination status was unknown for 637 of 1,082 cases post-July 2001. Forty-one percent of non-Aboriginal and 60% of Aboriginal children were eligible for vaccination but were not vaccinated. Among adults with risk factors who were eligible for vaccination and with known vaccination status, 75% Aboriginal and 94% non-Aboriginal were not vaccinated. An all-of-life immunisation register is needed to evaluate vaccine coverage and effectiveness in preventing IPD in adults.