Hannah C. Moore

The Changing Epidemiology of Invasive Pneumococcal Disease in Aboriginal and Non-Aboriginal Western Australians from 1997 through 2007 and Emergence of Nonvaccine Serotypes

BACKGROUND. In 2001, Australia introduced a unique 7-valent pneumococcal conjugate vaccine (7vPCV) 2-, 4-, and 6-month schedule with a 23-valent pneumococcal polysaccharide vaccine (23vPPV) booster for Aboriginal children, and in 2005, 7vPCV alone in a 2-, 4-, and 6-month schedule for non-Aboriginal children. Aboriginal adults are offered 23vPPV but coverage is poor. We investigated trends in invasive pneumococcal disease (IPD) in Western Australia (WA). METHODS. Enhanced IPD surveillance has been ongoing since 1996. We calculated IPD incidence rates for Aboriginal and non-Aboriginal Australians before and after introduction of 7vPCV. RESULTS. A total of 1792 cases occurred during the period 1997-2007; the IPD incidence rate was 47 cases per 100,000 population per year among Aboriginal people and 7 cases per 100,000 population per year in non-Aboriginal people. After introduction of 7vPCV, IPD rates among Aboriginal children decreased by 46% for those <2 years of age and by 40% for those 2-4 years of age; rates decreased by 64% and 51% in equivalent age groups for non-Aboriginal children. IPD rates decreased by >30% in non-Aboriginal people 50 years of age but increased among Aboriginal adults (eg, from 59.1 to 109.6 cases per 100,000 population per year among those 30-49 years of age). Although IPD due to 7vPCV serotypes decreased in all age groups, IPD incidence due to non-7vPCV serotypes increased, and it almost doubled among Aboriginal adults 30-49 years of age (from 48.3 to 97.0 cases per 100,000 population per year). Among non-Aboriginal children, 37% of IPD is now due to serotype 19A. CONCLUSIONS. IPD incidence rates have decreased markedly among children and non-Aboriginal adults with a 3-dose infant 7vPCV schedule. However, IPD due to non-7vPCV serotypes has increased and is of particular concern among young Aboriginal adults, for whom an intensive 23vPPV campaign is needed. An immunization register covering all age groups should be established.

Infection is the major component of the disease burden in aboriginal and non-aboriginal Australian children: a population-based study.

Background: Infection accounts for the majority of pediatric mortality and morbidity in developing countries, but there are limited data on the infectious diseases burden in children from developed countries. We investigated reasons for hospitalization before age 2 years in a birth cohort of Western Australian Aboriginal and non-Aboriginal children. Methods: Data on live births between January 1990 and December 2000, and corresponding deaths and hospitalizations in the first 2 years of life, were obtained through linked population-based data. Results: Almost half the cohort of 270,068 children were hospitalized at least once. Aboriginal children had significantly higher admission rates (2196 vs. 779 per 1000 live births), stayed longer and were more likely to die in hospital than non-Aboriginal children. Infections (mainly respiratory and gastrointestinal) were the most common reason for hospitalization, accounting for 34% of all admissions, with higher rates in Aboriginal (1114 per 1000 live births) than non-Aboriginal children (242 per 1000) (P < 0.001). Over time, admission rates for infections declined in Aboriginal children but increased in non-Aboriginal children. Aboriginal children were admitted 14 times more often for pneumonia than non-Aboriginal children. Conclusions: Infections are the leading cause of hospitalization in children under 2 years of age. The continuing heavy burden of serious infections, borne disproportionately by Aboriginal children, needs to be alleviated. Public health interventions such as the development and universal implementation of vaccines for respiratory syncytial virus, rotavirus and influenza are needed, while adequate funding must be committed to Indigenous health services and training.

Vaccine Effectiveness Against Laboratory-confirmed Influenza in Healthy Young Children: A Case-Control Study.

Background: The Western Australian Influenza Vaccine Effectiveness study commenced in 2008 to evaluate a new program to provide free influenza vaccine to all children aged 6 to 59 months. We aimed to assess the protective effect of inactivated influenza vaccination in these children. Methods: We conducted a prospective case–control study in general practices and a hospital emergency department, testing all eligible patients for influenza and a range of other common respiratory viruses. Influenza vaccine effectiveness (VE) against laboratory-confirmed influenza was estimated with cases defined as children with an influenza-like illness who tested positive and controls as those with an influenza-like illness who tested negative for influenza virus. We calculated VE using the adjusted odds ratio from multivariate logistic regression. As a surrogate marker for adequate specimen collection, we explored the difference in VE point estimates defining controls as children in whom another respiratory virus was detected. Results: A total of 75 children were enrolled from general practices and 214 through the emergency department, with 12 (27%) and 36 (17%), respectively, having laboratory-confirmed influenza. Using all the influenza-negative controls, the adjusted VE was 58% (95% confidence interval, 9–81). When controls were limited to those with another virus present, the adjusted VE was 68% (95% confidence interval, 26–86). Conclusions: VE estimates were higher when controls included only those children with another respiratory virus detected. Testing for other common respiratory viruses enables the control group to be restricted to those for whom an adequate sample is likely.

Diverging trends for lower respiratory infections in non-Aboriginal and Aboriginal children.

Aim:  To investigate temporal trends in admission rates for acute lower respiratory infections (ALRI) in a total population birth cohort of non‐Aboriginal and Aboriginal children.

The interaction between respiratory viruses and pathogenic bacteria in the upper respiratory tract of asymptomatic Aboriginal and non-Aboriginal children

Background: Associations between respiratory viruses and the bacterial pathogens Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis may be important in the pathogenesis of otitis media (OM). However, data on asymptomatic identification rates of respiratory viruses are limited, particularly in Indigenous populations, who suffer a high burden of OM. Methods: We describe the identification of respiratory viruses alone and in combination with pathogenic OM bacteria in 1006 nasopharyngeal aspirates collected from asymptomatic Aboriginal and non-Aboriginal children in a longitudinal community-based cohort study in rural Western Australia. Results: Viruses were identified in 42% of samples from Aboriginal and 32% from non-Aboriginal children. Rhinoviruses were the most frequently identified virus with higher identification rates in Aboriginal (23.6%) than non-Aboriginal children (16.5%; P = 0.003). Rhinoviruses were associated with H. influenzae (odds ratio [OR], 2.24; 95% CI, 1.24–4.07 for Aboriginal children) and M. catarrhalis (OR, 1.94; 95% CI, 1.05–3.57 for Aboriginal children). Adenoviruses were positively associated with H. influenzae in Aboriginal children (OR, 3.30; 95% CI, 1.19–9.09) and M. catarrhalis in non-Aboriginal children (OR, 5.75; 95% CI, 1.74–19.23), but negatively associated with S. pneumoniae in Aboriginal children (OR, 0.39; 95% CI, 0.18–0.84). Conclusions: We found a high identification rate of rhinoviruses and adenoviruses in asymptomatic children. The associations between these viruses and OM bacteria have implications for preventive strategies targeted at specific pathogens.

Use of data linkage to investigate the aetiology of acute lower respiratory infection hospitalisations in children

Aim:  To document the aetiology of acute lower respiratory infection (ALRI) hospitalisations in Western Australian children by linking population‐based laboratory data with hospital morbidity data.

A retrospective population-based cohort study identifying target areas for prevention of acute lower respiratory infections in children

BackgroundAcute lower respiratory infections (ALRI) are a major cause of hospitalisation in young children. Many factors can lead to increased risk of ALRI in children and predispose a child to hospitalisation, but population attributable fractions for different risk factors and how these fractions differ between Indigenous and non-Indigenous children is unknown. This study investigates population attributable fractions of known infant and maternal risk factors for ALRI to inform prevention strategies that target high-risk groups or particular risk factors.MethodsA retrospective population-based data linkage study of 245,249 singleton births in Western Australia. Population attributable fractions of known maternal and infant risk factors for hospitalisation with ALRI between 1996 and 2005 were calculated using multiple logistic regression.ResultsThe overall ALRI hospitalisation rate was 16.1/1,000 person-years for non-Aboriginal children and 93.0/1,000 for Aboriginal children. Male gender, being born in autumn, gestational age <33 weeks, and multiple previous pregnancies were significant risk factors for ALRI in both Aboriginal and non-Aboriginal children. In non-Aboriginal children, maternal smoking during pregnancy accounted for 6.3% (95%CI: 5.0, 7.6) of the population attributable fraction for ALRI, being born in autumn accounted for 12.3% (10.8, 13.8), being born to a mother with three or more previous pregnancies accounted for 15.4% (14.1, 17.0) and delivery by elective caesarean accounted for 4.1% (2.8, 5.3). In Aboriginal children, being born to a mother with three or more previous pregnancies accounted for 16.5% (11.8, 20.9), but remote location at birth accounted for 11.7% (8.5, 14.8), maternal age <20 years accounted for 11.2% (7.8, 14.5), and being in the most disadvantaged socio-economic group accounted for 18.4% (-6.5, 37.4) of the population attributable fraction.ConclusionsThe population attributable fractions estimated in this study should help in guiding public health interventions to prevent ALRI. A key risk factor for all children is maternal smoking during pregnancy, and multiple previous pregnancies and autumnal births are important high-risk groups. Specific key target areas are reducing elective caesareans in non-Aboriginal women and reducing teenage pregnancies and improving access to services and living conditions for the Aboriginal population.

Hospitalisation for bronchiolitis in infants is more common after elective caesarean delivery

Background The authors previously reported an increased risk of hospitalisation for acute lower respiratory infection up to age 2 years in children delivered by elective caesarean section. In view of increasing rates of elective caesarean delivery, this association warranted further investigation. Objective To examine associations between the number of hospital admissions for bronchiolitis and pneumonia and elective caesarean delivery. Design Retrospective population-based data linkage cohort study of 212 068 non-Aboriginal singleton births of 37–42 weeks gestation. Methods Negative binomial regression was used to examine associations between mode of delivery and hospitalisations for both bronchiolitis and pneumonia in children aged <12 months and 12–23 months. Models were adjusted for obstetric and known risk factors. Results 16% of children were delivered by elective caesarean section (n=33 421). In adjusted analysis, compared with spontaneous vaginal delivery, these children had increased risk of admissions for bronchiolitis at age <12 months (incidence rate ratio (IRR) 1.11; 95% CI 1.01 to 1.23) and 12–23 months (IRR 1.20; 95% CI 0.94 to 1.53) independent of other fetal and maternal factors. There was no association between elective caesarean delivery and number of pneumonia admissions aged <12 months (IRR 1.03; 95% CI 0.80 to 1.33) and 12–23 months (IRR 1.09; 95% CI 0.88 to 1.34). Conclusion Delivery by elective caesarean was independently associated with infant admissions for bronchiolitis but not pneumonia. Elective caesareans or delivery without labour may result in impaired immunity in the newborn leading to increased risk of early viral lower respiratory infections.

Association of gestational age and growth measures at birth with infection-related admissions to hospital throughout childhood: a population-based, data-linkage study from Western Australia.

BACKGROUND Reduced gestational age and low birthweight are associated with an increased risk of neonatal infections. However, the long-term risk of infection, especially in late preterm infants or those at near-normal birthweight, is unknown. We estimated whether rates of infection-related admissions to hospital for children in Western Australia were associated with age, gestational age, birthweight, and birth length. METHODS We did a population-based, data-linkage study using total-linked, registry data from the Western Australia Birth Register of all liveborn, non-Indigenous Australian singleton births recorded from Jan 1, 1980, to Dec 31, 2010. We followed up individuals from birth-related hospital discharge to age 18 years, death, or end of 2010, and linked to data about subsequent admissions to hospital or death registrations. Gestational age was assessed from both the last menstrual period and from estimates based on ultrasonography. We categorised birthweight by 500 g bands and birth length by 5 cm bands, and approximated the reference ranges for both to the 50th percentile. Because size at birth and gestational age are strongly associated, we calculated Z scores for gestational-specific and sex-specific birthweight, birth length, and ponderal index. Our primary outcomes were the number and type of infection-related admissions to hospital. We used multilevel negative binomial regression to generate rate ratios (RR) for such admissions, identified by codes from the International Classification of Diseases, versions 9 and 10-AM. We adjusted the RRs for maternal age at delivery, birth year, birth season, parity, sex, 5-min Apgar score, delivery method, socioeconomic status, and bronchopulmonary dysplasia. FINDINGS Of 719 311 liveborn singletons included in the analysis and followed up for 8 824 093 person-years, 365 867 infection-related admissions to hospital occurred for 213 683 (30%) children. Of the 719 311 children included in the analysis, 137 124 (19%) had one infection-related admission to hospital, 43 796 (6%) had two, 16 679 (2%) had three, and 16 084 (2%) had four or more. The 365 867 admissions to hospital included a diagnosis of infection of the upper respiratory tract for 174 653 (48%), the lower respiratory tract for 74 297 (20%), the gastrointestinal tract for 44 755 (12%), and a viral infection for 37 213 (10%). Infection-related rates of admissions to hospital increased by 12% for each week reduction in gestational age less than 39-40 weeks (RR 1·12, 95% CI 1·12-1·13), by 19% for each 500 g reduction in birthweight less than 3000-3500 g (1·19, 1·18-1·21), and by 41% for each 5 cm reduction in birth length less than 45-50 cm (1·41, 1·38-1·45). Gestational age-specific and sex-specific birthweight Z scores lower than the 25th to 50th percentile and birth length Z scores lower than the 10th to 25th percentile were associated with increased rates of infection-related admissions to hospital (eg, 1st-5th percentile RR 1·15, 95% CI 1·12-1·19, and 1·11, 1·07-1·14, respectively). Ponderal index Z scores lower than the 25th to 50th percentile were also associated with increased rates of infection-related admissions (eg, 1st-5th percentile RR 1·08, 95% CI 1·04-1·12). A gestational age of 41 weeks or later, a birthweight or birth length Z score above the 50th percentile, or a ponderal index Z score between the 75th and 95th percentile, were associated with modestly reduced rates of infection-related admissions to hospital. INTERPRETATION Children who were born with reduced gestational age, birthweight, and birth length have persistently increased rates of infection-related admissions to hospital until age 18 years. Pregnancy outcomes should be optimised to prevent infection occurring in this population, especially in resource-limited settings where suboptimum intrauterine growth and moderate prematurity are common. FUNDING Australian National Health and Medical Research Council.

Reduction in disparity for pneumonia hospitalisations between Australian indigenous and non-Indigenous children

Background In the 1990s pneumonia hospitalisation rates in Western Australia (WA) were 13 times higher in Indigenous children than in non-Indigenous children. Rates of invasive pneumococcal disease in Indigenous children declined following the introduction in 2001 of 7-valent pneumococcal conjugate vaccine (7vPCV) in a 2–4–6 month schedule with an 18-month pneumococcal polysaccharide booster (PPV). We investigated population trends for pneumonia hospitalisations between 1996 and 2005. Methods Population-based retrospective data linkage cohort study of singleton live births from 1996–2005. Hospitalisations for acute lower respiratory infections in Indigenous and non-Indigenous children less than 5 years of age were extracted and trends in age-specific incidence rates were examined using log-linear modelling. Results From 245 249 births (7.1% Indigenous), there were 7727 pneumonia episodes. Between 1996 and 2000 and 2001 and 2005 all-cause pneumonia hospitalisations fell by 28–44% in Indigenous children aged 6–35 months with no equivalent decline in non-Indigenous children or for other acute lower respiratory infections. Incidence rate ratios for pneumonia comparing Indigenous with non-Indigenous children aged 6–11 months fell from 14.6 (95% CI 12.3 to 17.2) in 1996–2000 to 9.9 (8.4 to 11.6) in 2001–2005. Log-linear modelling showed a steady decline in Indigenous children of 9%/annum (5–12%) at age 12–23 months for all-cause pneumonia and 37%/annum (20–50%) at age 6–11 months for pneumococcal pneumonia from 1996 to 2005, including the years prior to introduction of pneumococcal vaccines. Conclusions Pneumonia hospitalisations and the disparity between Indigenous and non-Indigenous children has declined by a third. The unique Australian pneumococcal vaccine programme is likely to have had a significant effect but changes in socioeconomic factors have also contributed to the declines.