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BackgroundSchools are the primary setting for the delivery of adolescent HPV vaccination in Australia. Although this strategy has achieved generally high vaccination coverage, gaps persist for reasons that are mostly unknown. This study sought to identify school-level correlates of low vaccination course initiation and completion in New South Wales, Tasmania, and Western Australia to inform initiatives to increase uptake.MethodsInitiation was defined as the number of first doses given in a school in 2016 divided by vaccine-eligible student enrolments. Completion was the number of third doses given in a school in 2015-2016 divided by the number of first doses. Low initiation and completion were defined as coverage ≤ 25thpercentile of all reporting schools. We investigated correlations between covariates using Spearman's rank correlation coefficients. Due to multicollinearity, we used univariable logistic regression to investigate associations between school characteristics and low coverage.ResultsMedian initiation was 84.7% (IQR: 75.0%-90.4%) across 1,286 schools and median completion was 93.8% (IQR: 86.0%-97.3%) across 1,295 schools. There were strong correlations between a number of school characteristics, particularly higher Indigenous student enrolments and lower attendance, increasing remoteness, higher postcode socioeconomic disadvantage, and smaller school size. Characteristics most strongly associated with low initiation in univariate analyses were small school size, location in Tasmania, and schools catering for special educational needs. Low completion was most strongly associated with schools in Tasmania and Western Australia, remote location, small size, high proportion of Indigenous student enrolments, and low attendance rates.ConclusionThis study provides indicative evidence that characteristics of schools and school populations are associated with the likelihood of low initiation and completion of the HPV vaccination course. The findings will guide further research and help target initiatives to improve vaccination uptake in schools with profiles associated with lower coverage.

Objectives To estimate SARS‐CoV‐2‐specific antibody seroprevalence after the first epidemic wave of coronavirus disease 2019 (COVID‐19) in Sydney. Setting, participants People of any age who had provided blood for testing at selected diagnostic pathology services (general pathology); pregnant women aged 20–39 years who had received routine antenatal screening; and Australian Red Cross Lifeblood plasmapheresis donors aged 20–69 years. Design Cross‐sectional study; testing of de‐identified residual blood specimens collected during 20 April – 2 June 2020. Main outcome measure Estimated proportions of people seropositive for anti‐SARS‐CoV‐2‐specific IgG, adjusted for test sensitivity and specificity. Results Thirty‐eight of 5339 specimens were IgG‐positive (general pathology, 19 of 3231; antenatal screening, 7 of 560; plasmapheresis donors, 12 of 1548); there were no clear patterns by age group, sex, or location of residence. Adjusted estimated seroprevalence among people who had had general pathology blood tests (all ages) was 0.15% (95% credible interval [CrI], 0.04–0.41%), and 0.29% (95% CrI, 0.04–0.75%) for plasmapheresis donors (20–69 years). Among 20–39‐year‐old people, the age group common to all three collection groups, adjusted estimated seroprevalence was 0.24% (95% CrI, 0.04–0.80%) for the general pathology group, 0.79% (95% CrI, 0.04–1.88%) for the antenatal screening group, and 0.69% (95% CrI, 0.04–1.59%) for plasmapheresis donors. Conclusions Estimated SARS‐CoV‐2 seroprevalence was below 1%, indicating that community transmission was low during the first COVID‐19 epidemic wave in Sydney. These findings suggest that early control of the spread of COVID‐19 was successful, but efforts to reduce further transmission remain important.

Rapidly identifying and isolating people with acute SARS-CoV-2 infection has been a core strategy to contain COVID-19 in Australia, but a proportion of infections go undetected. We estimated SARS-CoV-2 specific antibody prevalence (seroprevalence) among blood donors in metropolitan Melbourne following a COVID-19 outbreak in the city between June and September 2020. The aim was to determine the extent of infection spread and whether seroprevalence varied demographically in proportion to reported cases of infection. The design involved stratified sampling of residual specimens from blood donors (aged 20–69 years) in three postcode groups defined by low (7 cases/1,000 population) COVID-19 incidence based on case notification data. All specimens were tested using the Wantai SARS-CoV-2 total antibody assay. Seroprevalence was estimated with adjustment for test sensitivity and specificity for the Melbourne metropolitan blood donor and residential populations, using multilevel regression and poststratification. Overall, 4,799 specimens were collected between 23 November and 17 December 2020. Seroprevalence for blood donors was 0.87% (90% credible interval: 0.25–1.49%). The highest estimates, of 1.13% (0.25–2.15%) and 1.11% (0.28–1.95%), respectively, were observed among donors living in the lowest socioeconomic areas (Quintiles 1 and 2) and lowest at 0.69% (0.14–1.39%) among donors living in the highest socioeconomic areas (Quintile 5). When extrapolated to the Melbourne residential population, overall seroprevalence was 0.90% (0.26–1.51%), with estimates by demography groups similar to those for the blood donors. The results suggest a lack of extensive community transmission and good COVID-19 case ascertainment based on routine testing during Victoria’s second epidemic wave. Residual blood donor samples provide a practical epidemiological tool for estimating seroprevalence and information on population patterns of infection, against which the effectiveness of ongoing responses to the pandemic can be assessed.

Background Previous Australian studies have shown that delayed vaccination with each of the three primary doses of diphtheria-tetanus-pertussis-containing vaccines (DTP) is up to 50 % in certain subpopulations. We estimated the excess burden of pertussis that might have been prevented if (i) all primary doses and (ii) each dose was given on time. Methods Perinatal, immunization, pertussis notification and death data were probabilistically linked for 1 412 984 infants born in two Australian states in 2000–12. A DTP dose administered >15 days after the recommended age was considered delayed. We used Poisson regression models to compare pertussis notification rates to 1-year of age in infants with ≥1 dose delayed (Aim 1) or any individual dose delayed (Aim 2) versus a propensity weighted counterfactual on-time cohort. Results Of all infants, 42% had ≥1 delayed DTP dose. We estimated that between 39 to 365 days of age, 85 (95% CI: 61–109) cases per 100 000 infants, could have been prevented if all infants with ≥1 delayed dose had received their three doses within the on-time window. Risk of pertussis was higher in the delayed versus the on-time cohort, so crude rates overestimated the excess burden (110 cases per 100 000 infants (95% CI: 95–125)). The estimated dose-specific excess burden per 100 000 infants was 132 for DTP1, 50 for DTP2 and 19 for DTP3. Conclusions We provide robust evidence that improved DTP vaccine timeliness, especially for the first dose, substantially reduces the burden of infant pertussis. Our methodology, using a potential outcomes framework, is applicable to other settings.

Background As of mid-2021, Australia’s only nationwide coronavirus disease 2019 (COVID-19) epidemic occurred in the first 6 months of the pandemic. Subsequently, there has been limited transmission in most states and territories. Understanding community spread during the first wave was hampered by initial limitations on testing and surveillance. To characterize the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibody seroprevalence generated during this time, we undertook Australia’s largest national SARS-CoV-2 serosurvey. Methods Between June 19 and August 6, 2020, residual specimens were sampled from people undergoing general pathology testing (all ages), women attending antenatal screening (20–39 years), and blood donors (20–69 years) based on the Australian population’s age and geographic distributions. Specimens were tested by Wantai total SARS-CoV-2-antibody assay. Seroprevalence estimates adjusted for test performance were produced. The SARS-CoV-2 antibody-positive specimens were characterized with microneutralization assays. Results Of 11 317 specimens (5132 general pathology; 2972 antenatal; 3213 blood-donors), 71 were positive for SARS-CoV-2-specific antibodies. Seroprevalence estimates were 0.47% (95% credible interval [CrI], 0.04%–0.89%), 0.25% (CrI, 0.03%–0.54%), and 0.23% (CrI, 0.04%–0.54%), respectively. No seropositive specimens had neutralizing antibodies. Conclusions Australia’s seroprevalence was extremely low (

Background: Australian adolescents are routinely offered HPV and dTpa (diphtheria, tetanus, pertussis) vaccines simultaneously in the secondary school vaccination program. We identified schools where HPV initiation was lower than dTpa coverage and associated school-level factors across three states. Methods: HPV vaccination initiation rates and dTpa vaccination coverage in 2016 were calculated using vaccine databases and school enrolment data. A multivariate analysis assessed sociodemographic and school-level factors associated with HPV initiation being &gt, 5% absolute lower than dTpa coverage. Results: Of 1280 schools included, the median school-level HPV initiation rate was 85% (interquartile range (IQR):75–90%) and the median dTpa coverage was 86% (IQR:75–92%). Nearly a quarter (24%) of all schools had HPV vaccination initiation &gt, 5% lower than dTpa coverage and 11 % had &gt, 10% difference. School-level factors independently associated with &gt, 5% difference were remote schools (aOR:3.5, 95% CI = 1.7–7.2) and schools in major cities (aOR:1.8, 95% CI = 1.0–3.0), small schools (aOR:3.3, 95% CI = 2.3–5.7), higher socioeconomic advantage (aOR:1.7, 95% CI = 1.1–2.6), and lower proportions of Language-background-other-than-English (aOR:1.9, 95% CI = 1.2–3.0). Conclusion: The results identified a quarter of schools had lower HPV than dTpa initiation coverage, which may indicate HPV vaccine hesitancy, and the difference was more likely in socioeconomically advantaged schools. As hesitancy is context specific, it is important to understand the potential drivers of hesitancy and future research needs to understand the reasons driving differential uptake.

Objectives: To describe and compare vaccination coverage for Aboriginal and Torres Strait Islander (hereafter referred to as Indigenous) adults in 2004–05 and 2012–13, including the impact of national vaccination funding initiatives. Methods: National Aboriginal and Torres Strait Islander Health cross‐sectional surveys – 2004–05 (n=5,757) and 2012–13 (n=5,482) – were compared. Self‐reported influenza and pneumococcal vaccination coverage among Indigenous adults was analysed by age, remoteness, gender and risk factor status. Results: Influenza vaccination coverage among Indigenous adults in 2004–05 and 2012–13 remained low. While coverage increased for those aged 18–49 years from 23% to 29%, it declined for those aged ≥65 years from 84% to 74%. For remote areas, influenza coverage among those aged 50–64 years declined from 76% to 66%. Pneumococcal vaccination coverage remained very low and declined across all age groups in 2004–05 and 2012–13 (50–64 years: 30% to 23%). For remote areas, pneumococcal coverage declined among those aged 50–64 years from 52% to 32%. Conclusions: Indigenous adult vaccination coverage for influenza and pneumococcal disease remains unacceptably low. Between 2004–05 and 2012–13, declines occurred in pneumococcal vaccination coverage across all age groups ≥18 years. Despite national funding of influenza vaccine in 2010, there was no increase in influenza coverage, except for the 18–49‐year age group. Implications for public health: Current approaches to promote, deliver and monitor vaccination of Indigenous adults are inadequate.

Q fever (caused by Coxiella burnetii) is a serious zoonotic disease that occurs almost worldwide. Occupational contact with animals increases the risk of exposure, and Q fever vaccination is recommended for veterinary workers in Australia. This study aimed to investigate C. burnetii seroprevalence among unvaccinated veterinary workers in Australia and determine factors associated with a positive serological result. During 2014 and 2015, convenience sampling at veterinary conferences and workplace vaccination clinics was undertaken. Participants completed a questionnaire and provided a blood sample for C. burnetii serology. Participants were predominantly veterinarians (77%), but veterinary support staff, animal scientists, and administration workers also participated. Blood samples (n = 192) were analysed by an immunofluorescence assay and considered positive where the phase I or phase II IgG titre was ≥1/50. Seroprevalence was 19% (36/192; 95% CI 14%-25%). A positive serological result was significantly associated with (a) working in outer regional/remote areas (odds ratio [OR] 6.2; 95% CI 1.9-20.8; reference = major cities; p = .009) and (b) having spent more than 50% of total career working with ruminants (OR 4.8; 95% CI 1.7-13.5; reference =

Summary Background Reductions in pneumonia hospitalisations following introduction of pneumococcal conjugate vaccines (PCVs) have been reported from high-incidence and low-incidence settings but long-term data comparing vaccinated with unvaccinated children are sparse. Methods We did a retrospective, population-based, record-linkage cohort study in Australian children using administrative health data from the Western Australian Midwives' Notification System and New South Wales Perinatal Data Collection, and the birth and death registries in both states. PCV vaccination details, pneumonia-coded hospital admissions, and invasive pneumococcal disease notification records were individually linked for children born between 2001 and 2012. The primary outcome was defined as the first hospital admission for all-cause pneumonia. Cox models were used to calculate adjusted hazard ratios (HR) to estimate the effect of PCV doses on pneumonia-coded hospital admissions by Aboriginal status, birth period, remoteness, and pneumonia diagnostic category in children younger than 2 years. Person-time of follow-up time for each child started at birth and was censored at the earliest of first hospital admission for all-cause pneumonia, death, invalid PCV dose, when the child reached age 24 months, or the end date of the study period (Dec 31, 2013) Findings The study cohort comprised 1 365 893 children liveborn between Jan 1, 2001, and Dec 31, 2012, of whom 66 484 (4·9%) were identified as Aboriginal. The overall rate for all-cause pneumonia hospital admissions for children younger than 2 years over the entire study period was 17·6/1000 child-years in Aboriginal children and 5·5/1000 child-years in non-Aboriginal children. Compared with children born between 2001 and 2004 (ie, the pre-universal PCV period), the incidence of pneumonia-coded hospital admissions decreased in both vaccinated (6·5 vs 5·7 per 1000 child-years [12% reduction, 95% CI 3–21; p=0·01]) and unvaccinated non-Aboriginal children (6·8 vs 3·7 [45% reduction; 41–49]) born 2005–12 (the universal PCV period); among Aboriginal children, declines were significant only among those vaccinated (27·4 vs 14·1 [49% reduction, 40–55]). Among Aboriginal children born 2005–12, the risk of pneumonia-coded hospital admission after three doses of PCV was lower than those unvaccinated (adjusted HR 0·83, 95% CI 0·65–0·99) but, among non-Aboriginal children, the risk was similar (adjusted HR 1·09, 0·98–1·22). Overall, remote-born Aboriginal children had the highest incidence of hospital admission for pneumonia and among children born 2005–12, the adjusted risk was 37% lower (adjusted HR 0·63, 95% CI 0·42–0·96) among those fully vaccinated than those unvaccinated. Interpretation Reductions in pneumonia-coded hospital admissions in unvaccinated children predominated in non-Aboriginal children with low incidence of pneumonia but were not significant in Aboriginal children with high incidence. These findings have potential implications for measuring PCV effect using a non-specific endpoint such as all-cause pneumonia in high-incidence populations. Funding Commonwealth Government Collaborative Research Infrastructure Strategy and Education Investment Fund Super Science Initiative and the Australian National Health and Medical Research Council.

Little is known about long-term invasive pneumococcal disease (IPD) incidence in children with risk factors (RFs) in populations with high coverage pneumococcal conjugate vaccine (PCV) programs. We measured IPD burden and changes with PCV use in children by RF status.A retrospective cohort of all live births in 2001-2012 in New South Wales, Australia was linked to IPD, hospitalization and death data. RFs were identified from International Classification of Diseases codes in linked hospitalizations. For each RF adjusted hazard ratios (aHRs, using Cox models), population attributable fractions (PAFs) and changes post-PCV relative to baseline for IPD were calculated.One-thousand two-hundred fifty-one IPD cases occurred in ~1.1 million children in 12-year study cohort. The 75,404 children (6.8% of cohort) with RFs accounted for 255 (20.4%) IPD cases [rate (per 100,000 person-years) of 61 compared with 14 in no RFs]. Asthma was most common RF (n = 41,074; 3.6%) but highest IPD risk was in 2452 children (0.2%) with immunosuppression, splenic dysfunction or breach in cerebrospinal fluid barrier (aHR~20; PAF 0.7-1.8%) versus asthma (aHR 5.3; PAF 14.8%). Compared with 2001-2004 birth cohort (baseline), IPD incidence in PCV-eligible 2009-2012 birth cohort was 78% (95% confidence interval: -72% to -82%) less in children without RFs. IPD declined nonsignificantly (13%; 95% confidence interval: -70% to +138%) in highest IPD risk group, but by 67% (-43% to -82%) in children with other RFs.By 8 years of universal PCV, IPD incidence reduced significantly in all children except in the 0.2% at highest risk, for whom antibiotic prophylaxis and additional vaccine doses are recommended but compliance and effectiveness remain uncertain.

Background Finnish studies have shown a significant impact of 10-valent pneumococcal conjugate vaccine (PCV10) on nonnotified clinically suspected invasive pneumococcal disease (IPD). We used a similar vaccine probe design to estimate PCV7 and PCV13 impact in Australian children. Methods Season and age-matched pre-PCV7 cohorts (born in 2002-2004) were compared with PCV7-early and PCV7-late, and PCV13-eligible cohorts. Using linked notification and hospitalization data, we calculated relative rate reductions (RRRs) and absolute rate reductions (ARRs) for notified IPD, and nonnotified clinically suspected IPD or unspecified sepsis (first hospitalization with an International Classification of Diseases 10th Revision-Australian Modification code: A40.3/G00.1/M00.1 or A40.9/A41.9/A49.9/G00/I30.1/M00, respectively). Results Significant reductions in all outcomes were observed comparing PCV7-early and PCV7-late and PCV13-eligible to pre-PCV7 cohorts. RRRs were high for both notified and nonnotified clinically suspected IPD (range 71%-91%), but ARRs were lower for nonnotified (5-6/100,000 person-years) than for notified cases (59-70/100,000 person-years). RRRs for the combined outcome of nonnotified clinically suspected IPD or unspecified sepsis were lower at 21%-24% for PCV7-eligible cohorts and 36% for the PCV13-eligible cohort, but ARRs were considerable due to the high pre-PCV7 rates (ARR 37-31/100,000 person-years for PCV7-early and PCV7-late cohorts and 54/100,000 person-years for PCV13). Conclusions This study provides a quantitative estimate of the total burden of IPD preventable by PCV7 and PCV13 vaccination programs in Australia. ARRs (compared with prevaccination) were significant but smaller than in Finland (122/100,000 for the combined outcome) and longer-term follow-up is required to determine the additional impact of PCV13 above that seen for PCV7. Country-specific studies are needed to accurately estimate the burden of pneumococcal disease preventable by vaccination and cost-effectiveness of PCV vaccination programs.

Background Children with chronic medical conditions are at higher risk of invasive pneumococcal disease (IPD), but little is known about the effectiveness of the primary course of pneumococcal conjugate vaccine (PCV) in these children. Methods A cohort born in 2001–2004 from two Australian states and identified as medically at-risk (MAR) of IPD either using ICD-coded hospitalizations (with conditions of interest identified by 6 months of age) or linked perinatal data (for prematurity) were followed to age 5 years for notified IPD by serotype. We categorized fully vaccinated children as either receiving PCV dose 3 by Results A total of 9220 children with MAR conditions had 53 episodes of IPD (43 vaccine-type); 4457 (48.3%) were unvaccinated and 4246 (46.1%) were fully vaccinated, with 1371 (32.3%) receiving dose 3 by 12 months and 2875 (67.7%) having ≥1 dose at ≥12 months. Estimated VE in fully vaccinated children was 85.9% (95% CI: 33.9–97.0) against vaccine-type IPD and 71.5% (95% CI: 26.6–88.9) against all-cause IPD. Conclusion This is the first population-based study evaluating the effectiveness of PCV in children with MAR conditions using record linkage. Our study provides evidence that the VE for vaccine-type and all-cause IPD in MAR children in Australia is high and not statistically different from previously reported estimates for the general population. This method can be replicated in other countries to evaluate VE in MAR children.

Background Previous Australian studies have shown that on-time Diphtheria-Tetanus-Pertussis (DTP) vaccination coverage is 50-60% in certain subpopulations. We estimated the potentially preventable burden of pertussis if, 1) the full primary course and, 2) each dose was given on-time. Methods Perinatal, immunisation, pertussis notification, and death data were linked for 1,412,984 infants born in two Australian states in 2000-2012. A DTP dose administered >15 days after the recommended age was categorised as delayed. For aim 1, pertussis rates up to 1-year of age were compared in infants with ≥1 dose delayed versus all doses on-time, using Poisson regression methods. For aim 2, the expected number of cases preventable by each dose was calculated as the product of the number of cases observed during the period of delay and (1 – dose-specific vaccine effectiveness). Results 58% of infants had all primary DTP doses on time. We estimated that 85 (95% CI: 61-109) cases per 100,000 infants, aged 39-days to 1-year, could have been prevented if all infants had been vaccinated on time; 77% of these infants had received ≥1 DTP dose within the first year of life. Estimated preventable burden attributable to delayed DTP1 (58/100,000) was higher than for DTP2 (26/100,000) and DTP3 (15/100,000). Conclusions and Key messages Poor vaccine timeliness, especially delayed DTP1, is a key contributor to the residual burden of pertussis. These findings can inform cost-benefit analyses of targeted programs and public health messaging to reduce delays.

Background Australia’s National Immunisation Program recommended a 3-dose primary Diphtheria-Tetanus-Pertussis (DTP) vaccination course at 2, 4 and 6 months and a booster dose at 4 years during 2003-2015. We examined vaccine effectiveness by time since doses 3 and 4, as studies to date have shown conflicting results. Methods Perinatal, immunisation, pertussis notification and death data were linked for 1,086,319 infants born in two Australian states in 2003-2012. Administration of DTP doses 3 and 4 from 5.5-7 months and 47-53 months respectively, was considered age-appropriate. Adjusted Cox proportional hazards models with time-varying vaccination status were used to estimate vaccine effectiveness (VE = 1–hazard ratio) against notified pertussis post age-appropriate doses 3 and 4 compared to unvaccinated children, with additional benefit of dose 4 compared to receipt of primary course alone. Results Dose 3 VE declined from 79% (CI 75%-83%) from 0-6 months to 64% (CI 60%-67%) at 6-36 months and 45% (CI 31%-56%) at 36-42 months post-vaccination. Compared to unvaccinated children, VE after dose 4 declined from 83% (CI 80%-86%) at 0-12 months to 67% (CI 60%-72%) and 55% (CI 46%-63%) in the following two 12-month periods post-vaccination. When compared to dose 3, the relative VE for dose 4 was 58% (CI 51%-64%) in 0-18 months post-vaccination. Conclusion and Key messages Our study adds to previous Australian evidence for substantial waning of vaccine induced immunity against pertussis over a 3-year period following dose 3. VE was significantly higher in the 18 months following dose 4 compared to receipt of primary course alone.

Background Seasonal influenza vaccine is effective against influenza hospitalisations, but little is known about non-specific effects 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 population-based probabilistically linked data on births, childhood immunisations, deaths, hospitalisations, perinatal and statewide microbiology data (2000-2013) in Western Australia (WA). Our analysis cohort included children up to age 7 years. We exploited WA’s unique preschool influenza vaccination policy commencing in 2008 and used this as an instrument for 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 33.7% in children aged 6-23 months in 2009. RSV-hospitalisations ranged from 3.5/1000 children (12-23 months) to 6.4/1000 (6-12 months). Receipt of seasonal influenza vaccine reduced RSV-hospitalisations in the population cohort of children aged Conclusions To our knowledge, this is the first analysis utilising an IV estimation strategy to assess the impact of influenza vaccine on RSV-hospitalisations. We estimated a small, but highly statistically significant impact that warrants further investigation using contemporary data. Key messages RSV is a leading cause of childhood morbidity. The role of influenza vaccine offering cross protection to RSV could be further explored prior to RSV vaccines being commercially available.

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, In an observational study, Jocelyn Chan and colleagues investigate associations between pneumococcal conjugate vaccine coverage and incidence of invasive pneumococcal disease and pneumonia among children under 5 years in Australia., Author summary Why was this study done? Pneumococcal conjugate vaccines (PCVs) reduce the burden of pneumococcal disease in vaccinated and unvaccinated populations through both direct and indirect (herd) effects. The indirect effects of a vaccine comprise a substantial component of overall vaccine impact, contributing to the cost-effectiveness of the vaccine, but little is known about what factors contribute to herd protection, including vaccination coverage. In this study, we examined associations between PCV coverage and indirect effects within diverse populations in Australia. What did the researchers do and find? Using a large dataset of 1.3 million children from 2 states in Australia, we quantified the relationship between PCV coverage within small geographical units and indirect protection against pneumococcal disease. We also performed similar analyses for infants too young to be fully vaccinated, urban, rural, and Indigenous populations. There were strong inverse relationships between PCV coverage and the incidence of severe invasive disease due to vaccine types and pneumonia hospitalisations among undervaccinated children, i.e., higher coverage was associated with greater reductions in disease due to indirect effects. We also found substantial indirect effects at relatively low levels of PCV coverage. We estimated that 50% and 90% coverage of 7-valent PCV (PCV7) among children under 5 years of age prevented almost three-quarters (72.5%, 95% confidence interval [CI] 51.6 to 84.4) and almost all (95.2%, 95% CI 89.4 to 97.8) of PCV7-type severe invasive disease, respectively. For pneumonia, we estimated that 50% and 90% coverage was sufficient to prevent one-third (33.3%, 95% CI 27.3 to 38.8) and about half (51.7%, 95% CI 43.7 to 58.6) of all-cause pneumonia hospitalisations among undervaccinated children. These trends were similar for children less than 4 months old, urban, rural, and Indigenous populations, although these effects were smaller for rural and Indigenous populations. There was also a trend towards decreasing incidence of PCV13-type IPD among undervaccinated children as PCV13 coverage increased. What do these findings mean? Our results challenge existing assumptions that high PCV coverage is required to achieve substantial indirect protection. Understanding the determinants of indirect effects are particularly urgent as countries that have controlled vaccine-type pneumococcal disease consider using reducing the number of PCV doses (from 3 to 2). Reduced dose schedules have the potential to significantly lower program costs while maintaining vaccine impact, providing indirect protection is achieved and preserved.

Chronic hepatitis B prevalence is low in most Australian populations, with universal infant HBV vaccination introduced in 2000. Migrants from high prevalence countries are at risk of acquisition before arrival and non-immune adults are potentially at risk through skin penetrating procedures and sexual contact, particularly during international travel. The risk profile of young adult students, many from high prevalence countries, is inadequately understood. A cross-sectional online survey conducted among university students collected data on demographic, vaccination and travel characteristics and blood samples were tested for hepatitis B surface antibody (HBsAb) and hepatitis B core antibody (HBcAb). Analyses identified factors associated with HBsAb seroprevalence and self-reported vaccination. The serosurvey was completed by 804 students born between 1988 and 1993, with 613/804 (76.2%, 95% CI 73.2-79.1) self-reporting prior HBV vaccination. Overall, 526/804 (65.4%, 95% CI 62.0%-68.6%) students were seropositive to HBsAb, including 438/613 (71.5%, 95% CI 67.8-74.9) students self-reporting a prior HBV vaccine and 88/191 (46.1%, 95% CI 39.2-53.2) students self-reporting no prior HBV vaccine. Overall, 8/804 (1.0%, 95% CI 0.5%-2.0%) students were HBcAb positive, of whom 1/804 (0.1%, 95% CI 0.02%-0.7%) was currently infectious. The prevalence of chronic HBV infection was low. However, more than one in four students were susceptible to HBV and over-estimated their immunity. Future vaccination efforts should focus on domestic students born before the introduction of the infant program and all international students. Screening and vaccination of students, including through campus-based health services, are an opportunity to catch-up young adults prior to undertaking at-risk activities, including international travel.

BackgroundThere is limited empiric evidence on the coverage of pneumococcal conjugate vaccines (PCV) 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 under-vaccinated Australian children.MethodsBirth and vaccination records, IPD notifications and hospitalisations were individually linked for children aged < five years, born between 2001 and 2012 in two 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 under-vaccinated children. Under-vaccinated children received < two 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. The main limitations of this study include the potential for differential loss to follow-up, geographical misclassification of children (based on addressed at birth only) and unmeasured confounders.FindingsThere were strong inverse associations between PCV coverage and the incidence of PCV7-type IPD (adjusted incidence rate ratio [aIRR] 0.967, 95% CI 0.958-0.975, p-value ConclusionsIn this study we observed substantial indirect protection at low PCV coverage, challenging assumptions high vaccine coverage is required.Author summaryWhy was this study done?Pneumococcal conjugate vaccines (PCVs) reduce the burden of pneumococcal disease in vaccinated and unvaccinated populations through both direct and indirect (herd) effects.The indirect effects comprise a substantial component of overall vaccine impact, contributing to the cost-effectiveness of the vaccine but little is known about what factors contribute to herd protection, including vaccination coverage.In this study, we examined association between PCV coverage and indirect effects within in diverse populations within AustraliaWhat did the researchers do and find?Using a large dataset of 1.3 million children from two states in Australia, we quantified the relationship between PCV coverage within small geographical units and indirect protection against pneumococcal disease. We also performed similar analyses for infants too young to be fully vaccinated, urban, rural and Indigenous populations.There were strong inverse relationships between PCV coverage and the incidence of severe invasive disease due to vaccine types and pneumonia hospitalisations among under-vaccinated children i.e. higher coverage were associated with greater reductions in disease due to indirect effects. We also found substantial indirect effects at relatively low levels of PCV coverage. We estimated that 50% and 90% coverage of 7-valent PCV (PCV7) among children under five years of age prevented almost three-quarters (72.5%, 95% CI 51.6-84.4) and almost all (95.2%, 95% CI 89.4-97.8) of PCV7-type severe invasive disease, respectively. For pneumonia, we estimated that 50% and 90% coverage was sufficient to prevent one-third (33.3%, 95% CI 27.3-38.8) and about half (51.7%, 95% CI 43.7-58.6) of all-cause pneumonia hospitalisations among under-vaccinated children.These trends were similar for children less than four months old, urban, rural and Indigenous populations, although these effects were smaller for rural and Indigenous populations. There was also a trend towards decreasing incidence of PCV13-type IPD among under-vaccinated children as PCV13 coverage increased.What do these findings mean?Our results challenge existing assumptions that high PCV coverage is required to achieve substantial indirect protection.Understanding the determinants of indirect effects are particularly urgent as countries that have controlled vaccine-type pneumococcal disease consider using reducing the number of PCV doses (from three to two). Reduced dose schedules have the potential to significantly lower program costs while maintaining vaccine impact, providing indirect protection is achieved and preserved.

Background Overall, infant immunisation coverage is currently >90% in Australia, but there are pockets of under-immunised children including children from migrant backgrounds. This study aimed to examine whether on-time vaccination coverage of diphtheria-tetanus-pertussis dose 3 (DTP3) for children born in Australia differed by mother’s region of birth and if so, what factors were associated with these differences. Methods We conducted a population-based cohort study using linked data on perinatal, immunisation and birth records for 2 million children born in Western Australia and New South Wales between 1996 and 2012. We assessed on-time coverage of DTP3 (vaccination from 2 weeks prior to, and up until 30 days after, the due date) in children with mothers born overseas. Logistic regression models were developed to determine factors associated with on-time coverage for each maternal region of birth and all regions combined, adjusting for a range of demographic factors. Adjusted estimates of coverage were calculated for the different regions of birth. Results On-time DTP3 coverage was 76.2% in children of Australian born mothers, lower in children of mothers from Oceania (66.7%) and North America (68%), and higher in children born to mothers from South-East Asia (79.9%) and Southern Asia (79.3%). While most variables were consistently associated with lower coverage in all regions of birth, higher socioeconomic status and jurisdiction of birth showed varied results. Adjusted estimates of DTP3 coverage increased in children born to mothers from Australia (78.3%), Oceania (70.5%), Northern Africa (81.5%) and the Middle East (79.6%). DTP3 coverage decreased in children born to mothers from Europe and former USSR (74.6%), North-east Asia (75.2%), Southern Asia (76.7%), North America (65.5) and South/Central America and the Caribbean (73.2%). Conclusions On-time vaccination rates differed by mother’s region of birth. More research is needed to determine the main reasons for these remaining differences to improve vaccine uptake and also help guide policy and practice.

Background Risk-based recommendations are common for pneumococcal vaccines but little is known about their uptake. In Australia, pneumococcal conjugate vaccine (PCV) was funded only for Aboriginal or Torres Strait Islander (Indigenous) children and those with underlying medical conditions in 2001, and then there were different booster dose recommendations depending on risk after the introduction of universal PCV vaccination in 2005. Methods We measured coverage of PCV dose 3 and additional PCV and 23-valent pneumococcal polysaccharide vaccine (PPV23) doses by risk group among children born in July 2001–December 2012 in two Australian states using linked immunisation and hospitalisation data (available until December 2013). We ascertained medical risk conditions using hospitalisation diagnosis codes and Indigenous status using an established algorithm, comparing coverage for children born pre (2001–2004) and post (2005–2012) universal PCV funding. Results Among 1.3 million children, 63,897 (4.9%) were Indigenous and 32,934 (2.5%) had at least one medically at-risk condition identified by age 6 months. For births in 2001–2004, coverage for PCV dose 3 by 1 year of age was 37% for Indigenous, 15% for medically at-risk and 11% in other children, increasing to 83%, 91% and 92%, respectively for births in 2005–2012. In children with medically at-risk conditions, PCV dose 4 coverage by 2 years was 1% for 2001–2004 births, increasing to 9% for 2005–2012 births, with PPV23 coverage by 6 years 3% in both cohorts. Among eligible Indigenous children, PPV23 coverage by 3 years was 45% for 2001–2004 births and 51% for 2005–2012 births. Conclusions Coverage with additional recommended booster doses was very low among children with medical conditions, and only modest among Indigenous children. If additional PCV doses are recommended for some risk groups, especially in the context of routine schedules with reduced doses (e.g. 2 + 1 and 1 + 1), measures to improve implementation will be required.

In the absence of a civil registration system, a house-to-house survey is often used to estimate cause-specific mortality in low- and middle-income countries. However, house-to-house surveys are resource and time intensive. We applied a low-cost community knowledge approach to identify maternal deaths from any cause and jaundice-associated deaths among persons aged ≥ 14 years, and stillbirths and neonatal deaths in mothers with jaundice during pregnancy in five rural communities in Bangladesh. We estimated the method’s sensitivity and cost savings compared with a house-to-house survey. In the five communities with a total of 125,570 population, we identified 13 maternal deaths, 60 deaths among persons aged ≥ 14 years associated with jaundice, five neonatal deaths, and four stillbirths born to a mother with jaundice during pregnancy over the 3-year period before the survey using the community knowledge approach. The sensitivity of community knowledge method in identifying target deaths ranged from 80% for neonatal deaths to 100% for stillbirths and maternal deaths. The community knowledge approach required 36% of the staff time to undertake compared with the house-to-house survey. The community knowledge approach was less expensive but highly sensitive in identifying maternal and jaundice-associated mortality, as well as all-cause adult mortality in rural settings in Bangladesh. This method can be applied in rural settings of other low- and middle-income countries and, in conjunction with hospital-based hepatitis diagnoses, used to monitor the impact of programs to reduce the burden of cause-specific hepatitis mortality, a current World Health Organization priority.

Reported infant vaccination coverage at age 12 months in Australia is >90%. On-time coverage of the 2–4–6 month schedule and coverage in specific populations is rarely reported. We conducted a population-based cohort study of 1.9 million Australian births, 1996–2012, combining individual birth and perinatal records with immunisation records through probabilistic linkage. We assessed on-time coverage across 13 demographic and perinatal characteristics of diphtheria-tetanus-pertussis vaccines (DTP) defined as vaccination 14 days prior to the scheduled due date, to 30 days afterwards. On-time DTP vaccination coverage in non-Aboriginal infants was 88.1% for the 2-month dose, 82.0% for 4-month dose, and 76.7% for 6-month dose; 3-dose coverage was 91.3% when assessed at 12 months. On-time DTP coverage for Aboriginal infants was 77.0%, 66.5%, and 61.0% for the 2–4–6 month dose; 3-dose coverage at 12 months was 79.3%. Appreciable differences in on-time coverage were observed across population subgroups. On-time coverage in non-Aboriginal infants born to mothers with ≥3 previous pregnancies was 62.5% for the 6-month dose (47.9% for Aboriginal infants); up to 23.5 percentage points lower than for first-borns. Infants born to mothers who smoked during pregnancy had coverage 8.7–10.3 percentage points lower than infants born to non-smoking mothers for the 4- and 6-month dose. A linear relationship was apparent between increasing socio-economic disadvantage and decreasing on-time coverage. On-time coverage of the 2–4–6 month schedule is only 50–60% across specific population subgroups representing a significant avoidable public health risk. Aboriginal infants, multiparous mothers, and those who are socio-economically disadvantaged are key groups most likely to benefit from targeted programs addressing vaccine timeliness.

Background Australia is one of only a few countries with a long-standing and consistent serosurveillance program. We conducted a national serosurvey in 2012–2013 to estimate population seroprevalence of measles-specific IgG and the effective reproduction number, R, and compare the results with the three previous serosurveys (1996–1999, 2002 and 2007) to examine trends following a decade of sustained measles control. Methods 2729 residual sera from 1 to 49 year olds were tested using the Enzygnost anti-measles IgG enzyme immunoassay (EIA). All sera in the equivocal range by EIA on re-testing and a random sample of low positive and negative sera were later tested by a microneutralisation assay. R was calculated from weighted estimates of the proportion seronegative by age using a previously developed contact matrix. Results In the 2012–13 serosurvey, anti-measles IgG seropositivity for 1–49 year olds was 80.8% (95% CI: 79.4–82.3%) and 8.9% (95% CI: 7.8–10.0%) had equivocal antibody levels. The increasing proportion of seronegative and equivocal individuals in age groups 10–39 years continued a trend seen in previous serosurveys. There was also an increase in equivocal results among 2–4 and 5–9 year old children, >90% of whom were recently vaccinated. R increased from 0.57 in 1999 to above the epidemic threshold of 1 in 2012–13 (R = 1.7). All 20 EIA negative sera, 238/241 (98.8%) equivocal sera, and 89/92 (96.7%) low positive sera had a titre Conclusions A number of countries with sustained measles control have now demonstrated that measles-specific IgG antibodies decline with time since vaccination. As there is good epidemiologic evidence of population-level protection, the implications of declining measles-specific IgG antibody levels for maintaining measles elimination are unclear. Novel studies to determine correlates of protection against measles transmission and disease in the post-elimination era are needed to help answer this question.

Q fever (caused by Coxiella burnetii) is thought to have an almost world-wide distribution, but few countries have conducted national serosurveys. We measured Q fever seroprevalence using residual sera from diagnostic laboratories across Australia. Individuals aged 1–79 years in 2012–2013 were sampled to be proportional to the population distribution by region, distance from metropolitan areas and gender. A 1/50 serum dilution was tested for the Phase II IgG antibody against C. burnetii by indirect immunofluorescence. We calculated crude seroprevalence estimates by age group and gender, as well as age standardised national and metropolitan/non-metropolitan seroprevalence estimates. Of 2785 sera, 99 tested positive. Age standardised seroprevalence was 5.6% (95% confidence interval (CI 4.5%–6.8%), and similar in metropolitan (5.5%; 95% CI 4.1%–6.9%) and non-metropolitan regions (6.0%; 95%CI 4.0%–8.0%). More males were seropositive (6.9%; 95% CI 5.2%–8.6%) than females (4.2%; 95% CI 2.9%–5.5%) with peak seroprevalence at 50–59 years (9.2%; 95% CI 5.2%–13.3%). Q fever seroprevalence for Australia was higher than expected (especially in metropolitan regions) and higher than estimates from the Netherlands (2.4%; pre-outbreak) and US (3.1%), but lower than for Northern Ireland (12.8%). Robust country-specific seroprevalence estimates, with detailed exposure data, are required to better understand who is at risk and the need for preventive measures.

Receiving vaccines at or close to their due date (vaccination timeliness) is a now key measure of program performance. However, studies comprehensively examining predictors of delayed infant vaccination are lacking. We aimed to identify predictors of short and longer-term delays in diphtheria-tetanus-pertussis (DTP) vaccination by dose number and ethnicity.Perinatal, notification, death and immunisation databases were linked for 1.3 million births in 2000-11 from two Australian states (Western Australia and New South Wales), with follow-up data until 2013. Ordinal logistic regression was used to estimate adjusted relative risks (RR) by degree of delay. Separate models were constructed for each vaccine dose and for Aboriginal and non-Aboriginal children.Each dose-specific cohort included at least 49,000 Aboriginal and 1.1 million non-Aboriginal children. Delayed receipt was more common among Aboriginal than non-Aboriginal children (eg for the first dose of DTP [DTP1] 19.4 v 8.1%). Risk factors for delayed vaccination were strongest for DTP1, and delayed receipt of DTP1 was a key driver of subsequent delays; every week DTP1 was delayed was associated with a 1.6 to 2-fold increased risk of delayed DTP2 receipt. For DTP1, ≥3 previous pregnancies (the only factor more strongly associated with longer than shorter delays; RR ≥5 compared to no previous pregnancies), and children born to mothers20 years of age (RR ≥2 compared to ≥35 years) were at highest risk of delay. Other independent predictors were prematurity, maternal smoking during pregnancy, and being born in Western Australia (if Aboriginal) or another country in the Oceania region.The sub-populations at risk for delayed vaccination we have identified are likely generalisable to other high-income settings. Measures to improve their dose 1 timeliness, particularly for children with older siblings, are likely to have significant flow-on benefits for timeliness of later doses.

There is limited information on vaccination coverage and characteristics associated with vaccine uptake in Aboriginal and/or Torres Strait Islander adults. We aimed to provide more current estimates of influenza vaccination coverage in Aboriginal adults.Self-reported vaccination status (n=559 Aboriginal and/or Torres Strait Islander participants, n=80,655 non-Indigenous participants) from the 45 and Up Study, a large cohort of adults aged 45 years or older, was used to compare influenza vaccination coverage in Aboriginal and/or Torres Strait Islander adults with coverage in non-Indigenous adults.Of Aboriginal and non-Indigenous respondents aged 49 to65 years, age-standardised influenza coverage was respectively 45.2% (95% CI 39.5–50.9%) and 38.5%, (37.9–39.0%), p-value for heterogeneity=0.02. Coverage for Aboriginal and non-Indigenous respondents aged ≥65 years was respectively 67.3% (59.9–74.7%) and 72.6% (72.2–73.0%), p-heterogeneity=0.16. Among Aboriginal adults, coverage was higher in obese than in healthy weight participants (adjusted odds ratio (aOR)=2.38, 95%CI 1.44–3.94); in those aged65 years with a medical risk factor than in those without medical risk factors (aOR=2.13, 1.37–3.30); and in those who rated their health as fair/poor compared to those who rated it excellent (aOR=2.57, 1.26–5.20). Similar associations were found among non-Indigenous adults.In this sample of adults ≥65 years, self-reported influenza vaccine coverage was not significantly different between Aboriginal and non-Indigenous adults whereas in those65 years, coverage was higher among Aboriginal adults. Overall, coverage in the whole cohort was suboptimal. If these findings are replicated in other samples and in the Australian Immunisation Register, it suggests that measures to improve uptake, such as communication about the importance of influenza vaccine and more effective reminder systems, are needed among adults.

Background: There is limited information on vaccination coverage and characteristics associated with vaccine uptake in Aboriginal and/or Torres Strait Islander adults. We aimed to provide more current estimates of influenza vaccination coverage in Aboriginal adults. Methods: Self-reported vaccination status (n=559 Aboriginal and/or Torres Strait Islander participants, n=80,655 non-Indigenous participants) from the 45 and Up Study, a large cohort of adults aged 45 years or older, was used to compare influenza vaccination coverage in Aboriginal and/or Torres Strait Islander adults with coverage in non-Indigenous adults. Results: Of Aboriginal and non-Indigenous respondents aged 49 to

In the absence of reliable data on the burden of hepatitis E virus (HEV) in high endemic countries, we established a hospital-based acute jaundice surveillance program in six tertiary hospitals in Bangladesh to estimate the burden of HEV infection among hospitalized acute jaundice patients aged ≥14 years, identify seasonal and geographic patterns in the prevalence of hepatitis E, and examine factors associated with death. We collected blood specimens from enrolled acute jaundice patients, defined as new onset of either yellow eyes or skin during the past three months of hospital admission, and tested for immunoglobulin M (IgM) antibodies against HEV, HBV and HAV. The enrolled patients were followed up three months after hospital discharge to assess their survival status; pregnant women were followed up three months after their delivery to assess pregnancy outcomes. From December’2014 to September’2017, 1925 patients with acute jaundice were enrolled; 661 (34%) had acute hepatitis E, 48 (8%) had hepatitis A, and 293 (15%) had acute hepatitis B infection. Case fatality among hepatitis E patients was 5% (28/589). Most of the hepatitis E cases were males (74%; 486/661), but case fatality was higher among females—12% (8/68) among pregnant and 8% (7/91) among non-pregnant women. Half of the patients who died with acute hepatitis E had co-infection with HAV or HBV. Of the 62 HEV infected mothers who were alive until the delivery, 9 (15%) had miscarriage/stillbirth, and of those children who were born alive, 19% (10/53) died, all within one week of birth. This study confirms that hepatitis E is the leading cause of acute jaundice, leads to hospitalizations in all regions in Bangladesh, occurs throughout the year, and is associated with considerable morbidity and mortality. Effective control measures should be taken to reduce the risk of HEV infections including improvements in water quality, sanitation and hygiene practices and the introduction of HEV vaccine to high-risk groups., Author summary In the absence of reliable surveillance data on the burden of hepatitis E in endemic countries, we conducted a hospital-based acute jaundice surveillance study over a two and a half year period in six tertiary hospitals in Bangladesh. The study confirms that HEV infections occur throughout the year, and is a major (34%) cause of acute jaundice in tertiary hospitals in Bangladesh. Three-quarters of the acute hepatitis E cases were male, and HEV infection was higher among patients residing in urban areas than patients in rural areas (41% vs 32%). The overall case fatality rate of acute HEV infections in hospitals was 5%, but was higher among pregnant women (12%). Hepatitis E patients who died were more likely to have co-infection with HAV or HBV than the HEV infected patients who did not die. Fifteen percent of HEV infected mothers had miscarriage/stillbirth. Of the children who were born alive, 19% died, all within one week of birth. Considering the high burden of hepatitis E among hospitalized acute jaundice patients, Bangladesh could take control measures to reduce this risk including improvements in water quality, sanitation and hygiene practices and the introduction of hepatitis E vaccine in high-risk areas.

Rotavirus vaccines (RV), included in Australia's National Immunisation Program from mid-July 2007, are unique in strict time limits for administration. Here, we report on timeliness of RV uptake, compare cumulative RV coverage to age 12 months with DTPa, and assess factors associated with receipt of RV among Aboriginal and non-Aboriginal children.Birth records for 681,456 children born in two Australian states in 2007-2012 were probabilistically linked to national immunisation records. We assessed on-time coverage (defined as receipt of vaccine dose between 4 days prior to scheduled date and the recommended upper limit) for RV and compared this to diphtheria-tetanus-pertussis (DTPa) vaccine. Logistic regression modelling was used to assess independent determinants of receipt of RV.Compared to non-Aboriginal infants, on-time RV coverage was lower for all doses among Aboriginal infants. Post the upper age limit of RV dose2, DTPa dose2 coverage increased by 9-16% to ≥90%, whereas RV coverage remained around 77% (Aboriginal) and 85% (non-Aboriginal). Compared to first-born children, the adjusted odds of receiving ≥1 RV dose if born to a mother with ≥3 previous births was 0.30 (95%CI: 0.27-0.34) among Aboriginal, and 0.53 (95%CI: 0.51-0.55) among non-Aboriginal children. Prematurity (33 weeks), low birthweight (1500 g), maternal age20 years, maternal smoking during pregnancy and living in a disadvantaged area were independently associated with decreased vaccine uptake.Aboriginal children are at greater risk of rotavirus disease than non-Aboriginal children and delayed vaccine receipt is substantially higher. Although specific programs targeting groups at risk of delayed vaccination might improve RV coverage, relaxation of upper age restrictions is most readily implementable, and its overall risk-benefit should be evaluated.

Routine antenatal screening for chronic hepatitis B (HBV) in countries with high migrant populations provides an opportunity to monitor trends in HBV prevalence and can inform estimates locally and in countries with limited seroprevalence data. We linked perinatal birth register records with HBV notifications in the largest Australian state, over the period 2000-2016. Among women aged 15-44 years, we estimated age-standardized chronic HBV prevalence overall and by country of birth and also estimated trends in age-standardized HBV prevalence over time using regression modelling. Among 903 831 women, 8001 linked to a chronic HBV infection record (overall age-standardized prevalence 0.76%, 95% CI: 0.74-0.78). Prevalence varied by country of birth with the highest estimates among women born in Sierra Leone (11.13%, 95% CI: 8.29-13.96), Taiwan (8.08%, 95% CI: 6.74%-9.43%), Cambodia (7.47%, 95% CI: 6.50%-8.45%) and Vietnam (7.36%, 95% CI: 6.97%-7.75%); more moderate estimates among women from North Korea (2.76%, 95% CI: 1.99-3.53) and Samoa (2.64%, 95% CI: 1.99%-3.29%); prevalence was 0.18% (95% CI: 0.17-0.19) in Australian-born women. Over 17 years, there were significant reductions in HBV prevalence among all women (from 0.88% in 2000 to 0.57% in 2016; P < .0001). Among women from high prevalence countries, the greatest absolute reductions were observed among those from Taiwan (10.1%, P < .001) followed by Tonga (5.4%, P < .001), whereas no reductions were observed for women born in Vietnam (P = .08), South Korea (P = .41) and Sudan (P = .06). In conclusion, routine antenatal HBV testing can be used to inform HBV prevalence estimates and vaccine programme impact in countries with limited surveillance and high migration to Australia.

BACKGROUND: Febrile seizures (FSs) are a common pediatric condition caused by a sudden rise in temperature, affecting 3% to 5% of children aged ≤6 years. Although vaccination can cause FSs, little is known on whether FSs occurring in the time soon after vaccination (vaccine-proximate febrile seizures [VP-FSs] differ clinically from non–vaccine-proximate febrile seizures [NVP-FSs]). We compared the clinical profile and outcomes of VP-FS to NVP-FS. METHODS: Prospective cohort study of children aged ≤6 years presenting with their first FS at 1 of 5 Australian pediatric hospitals between May 2013 and June 2014. Clinical features, management, and outcomes were compared between VP-FS and NVP-FS. RESULTS: Of 1022 first FS cases (median age 19.8 months; interquartile range 13.6–27.6), 67 (6%) were VP-FSs. When comparing VP-FS to NVP-FS, there was no increased risk of prolonged (>1 day) hospitalization (odds ratio [OR] 1.61; 95% confidence interval [95% CI] 0.84–3.10), ICU admission (OR 0.72; 95% CI 0.10–5.48), seizure duration >15 minutes (OR 1.47; 95% CI 0.73–2.98), repeat FS within 24 hours (OR 0.80; 95% CI 0.34–1.89), or requirement for antiepileptic treatment on discharge (OR 1.81; 95% CI 0.41–8.02). VP-FS patients with a laboratory-confirmed infection (12%) were more likely to have a prolonged admission compared with those without. CONCLUSIONS: VP-FS accounted for a small proportion of all FS hospital presentations. There was no difference in outcomes of VP-FS compared with NVP-FS. This is reassuring data for clinicians and parents of children who experience FS after vaccination and can help guide decisions on revaccination.

BACKGROUND Prevalence of anxiety and mood disorders (AMDs) in HIV-infected individuals has varied widely because of the variety of measurements used and differences in risk factor profiles between different populations. We aimed to examine the relationship between HIV status and hospitalization for AMDs in gay and bisexual men (GBM). DESIGN AND METHODS HIV-infected (n = 557) and HIV-uninfected (n = 1325) GBM recruited in Sydney, Australia were probabilistically linked to their hospital admissions and death notifications (2000-2012). Random-effects Poisson models were used to assess HIV risk factors for hospitalization. Cox regression methods were used to assess risk factors for mortality. RESULTS We observed 300 hospitalizations for AMDs in 15.3% of HIV-infected and 181 in 5.4% of HIV-uninfected participants. Being infected with HIV was associated with a 2.5-fold increase in risk of hospitalization for AMDs in GBM. Other risk factors in the HIV-infected cohort included previous hospitalization for HIV-related dementia, a more recent HIV diagnosis, and a CD4 T-cell count above 350 cells per cubic millimeter. Being hospitalized for an AMD was associated with a 5.5-fold increased risk of mortality; this association did not differ by HIV status. An association between substance use and mortality was observed in individuals hospitalized for AMDs. CONCLUSIONS There is a need to provide more effective strategies to identify and treat AMDs in HIV-infected GBM. This research highlights the importance of further examination of the effects of substance use, neurocognitive decline, and AMDs on the health of HIV-infected individuals.

Objectives To examine the validity of deterministic compared to probabilistic record linkage in the ascertainment of hospitalizations in two linked cohorts. Study Design and Setting HIV-negative (HIV-ve) (n = 1,325) and HIV-positive (HIV+ve) gay and bisexual men (n = 557) recruited in Sydney, Australia, were probabilistically and deterministically linked to a statewide hospital registry (July 2000–June 2012). Results Using probabilistic linkage as the reference standard, deterministic linkage had higher specificity but much lower sensitivity [34.67% (95% confidence interval: 33.44, 35.92)]. A disproportionate number of links missed were individuals with poorer socioeconomic and health indicators, including HIV status. Risk of hospitalization compared to the general male population [HIV+ve standardized incidence ratio (SIR) = 1.45 (1.33–1.59); HIV-ve SIR = 0.72 (0.67–0.78)] was significantly underestimated when deterministic linkage was used [HIV+ve SIR = 0.46 (0.37–0.58); HIV-ve SIR = 0.29 (0.24–0.35)]. The impact of linkage strategy on the calculation of incidence rate ratios (IRRs) was less, but a greater discrepancy in IRRs was seen for diagnostic categories where event rates were low or where the sensitivity of the deterministic linkage was differential between the two cohorts. Conclusion Linkage without proven high sensitivity and specificity should be carefully considered. In circumstances of undetermined sensitivity, SIRs should not be calculated as the extent of underestimation is unknown. The comparison of linked events within or between cohorts is more robust to linkage misclassification; however, selection bias does affect estimates and should be considered before linkage.

Objective: To describe the realities of conducting a cross-jurisdictional data linkage project involving state and Australian Government-based data collections to inform future national data linkage programs of work. Methods: We outline the processes involved in conducting a Proof of Concept data linkage project including the implementation of national data integration principles, data custodian and ethical approval requirements, and establishment of data flows. Results: The approval process involved nine approval and regulatory bodies and took more than two years. Data will be linked across 12 datasets involving three data linkage centres. A framework was established to allow data to flow between these centres while maintaining the separation principle that serves to protect the privacy of the individual. Conclusions: This will be the first project to link child immunisation records from an Australian Government dataset to other administrative health datasets for a population cohort covering 2 million births in two Australian states. Implications: Although the project experienced some delays, positive outcomes were realised, primarily the development of strong collaborations across key stakeholder groups including community engagement. We have identified several recommendations and enhancements to this now established framework to further streamline the process for data linkage studies involving Australian Government data.

IntroductionImmunisation coverage is a good measure of immunisation program effectiveness. Coverage of the 3-dose infant schedule in Australia assessed at age 12 months is >90%. Timeliness is an important goal for population immunity, but on-time coverage of the 2-4-6 month schedule and coverage in specific populations is rarely reported. Objectives and ApproachWe conducted a retrospective population-based cohort study of 1.9 million Australian births, 1996-2012 (approximately 42% of Australia’s population). Individual data from state-held birth and perinatal records were combined with Commonwealth-held immunisation and death records, through probabilistic linkage. We assessed on-time coverage across 13 demographic and perinatal characteristics of diphtheria-tetanus-pertussis vaccines (DTP) defined as vaccination 14 days prior to the scheduled due date, to 30 days afterwards. ResultsOn-time DTP vaccination coverage in non-Aboriginal infants was 88.1% for the 2-month dose, 82.0% for 4-month dose, and 76.7% for 6-month dose; 3-dose coverage was 91.3% when assessed at 12 months. On-time DTP coverage for Aboriginal infants was 77.0%, 66.5%, and 61.0%; 3-dose coverage at 12 months was 79.3%. Appreciable differences in on-time coverage were observed across population subgroups. On-time coverage in non-Aboriginal infants born to mothers with ≥3 previous pregnancies was 62.5% for the 6-month dose (47.9% for Aboriginal infants); up to 23.5% lower than for first-borns. Infants born to mothers who smoked during pregnancy had coverage 8.7-10.3% lower than infants born to non-smoking mothers for the 4- and 6-month dose. A linear relationship was apparent with increasing socio-economic disadvantage and decreasing on-time coverage. Conclusion/ImplicationsOn-time vaccination coverage of the 2-4-6 month schedule is only 50-60% across specific population subgroups representing a significant avoidable public health risk. Australian Aboriginal infants, multiparous mothers, and those who are socio-economically disadvantaged are key groups most likely to benefit from targeted programs addressing vaccine timeliness.

Objectives To estimate the prevalence of exposure to the causative agent of Q fever (Coxiella burnetii) and of current infections among blood donors in Australia. Design, setting Cross-sectional study in metropolitan Sydney and Brisbane, and in non-metropolitan regions with high Q fever notification rates (Hunter New England in New South Wales; Toowoomba in Queensland). Participants Blood donors attending Red Cross collection centres during October 2014 - June 2015 who provided sera and completed a questionnaire on Q fever vaccination status, diagnosis and knowledge, and exposure history. Main outcome measures Age- and sex-standardised seroprevalence of phase II IgG antibodies to C. burnetii (indicating past exposure) and independent risk factors for seropositivity; presence of C. burnetii DNA (indicating current infection and risk of transmission by blood transfusion). Results 2740 donors (94.5% response rate) completed the questionnaire and supplied sera for analysis. Crude antibody seroprevalence was 3.6%. Standardised seroprevalence was higher in non-metropolitan than metropolitan regions (NSW, 3.7% v 2.8%; Queensland, 4.9% v 1.6%; statistically significant only in Queensland). Independent predictors of antibody seropositivity were regular contact with sheep, cattle, or goats (adjusted odds ratio [aOR], 5.3; 95% CI, 2.1-14), abattoir work (aOR, 2.2; 95% CI, 1.2-3.9), and assisting at an animal birth (aOR, 2.1; 95% CI, 1.2-3.6). Having lived in a rural area but having only rare or no contact with sheep, cattle or goats was itself a significant risk factor (v never lived rurally: aOR, 2.5; 95% CI, 1.1-5.9). 40% of people in groups recommended for vaccination were aware of the vaccine; 10% of people in these groups had been vaccinated. C. burnetii DNA was not detected in 1681 non-metropolitan samples, suggesting that transmission by blood donation is unlikely. Conclusions Given their exposure to multiple risk factors, vaccination against Q fever should be considered for all rural residents.

Objectives There is evidence that HIV-positive patients are suffering from a greater burden of morbidity as they age due to nonAIDS-related complications. To date it has been difficult to determine what part of this excess risk is due to the health effects of HIV, its treatment or to lifestyle factors common to gay and bisexual men (GBM). We calculated overall and cause-specific hospitalisation rates and risk factors for hospitalisations in HIV-negative and HIV-positive cohorts of GBM and compare these with rates in the general male population. Methods We conducted a record linkage study, linking two cohorts of HIV-negative (n = 1325) and HIV-positive (n = 557) GBM recruited in Sydney, New South Wales (NSW), Australia with the NSW hospital discharge data register. We compared rates of hospitalisation in the two cohorts and risk factors for hospitalisation using random-effects Poisson regression methods. Hospitalisation rates for each cohort were further compared with those in the general male population using indirect standardisation. Results We observed 2032 hospitalisations in the HIV-negative cohort during 13 016 person-years (PYs) [crude rate: 15.6/100PYs (95% CI: 14.9–16.3)] and 2130 hospitalisations in the HIV-positive cohort during 5571 PYs [crude rate: 38.2/100PYs (95% CI: 36.6–39.9)]. HIV-positive individuals had an increased risk of hospitalisation compared with the HIV-negative individuals [adjusted-IRR: 2.34 (95% CI: 1.91–2.86)] and the general population [SHR: 1.45 (95% CI: 1.33–1.59)]. Hospitalisation rates were lower in the HIV-negative cohort compared with the general population [SHR: 0.72 (95% CI: 0.67–0.78)]. The primary causes of hospitalisation differed between groups. Conclusions HIV-positive GBM continue to experience excess morbidity compared with HIV-negative GBM men and the general population. HIV-negative GBM had lower morbidity compared with the general male population suggesting that GBM identity does not confer excess risk.

Most studies use indirect cohort or case-control methods to estimate vaccine effectiveness (VE) of 7- and 13-valent pneumococcal conjugate vaccines (PCV7 and PCV13) against invasive pneumococcal disease (IPD). Neither method can measure the benefit vaccination programs afford the unvaccinated and many studies were unable to estimate dose-specific VE. We linked Australia's national immunisation register with health data from two states to calculate IPD incidence by vaccination status and VE for a 3 + 0 PCV schedule (doses at 2, 4, 6 months, no booster) among a cohort of 1.4 million births.Births records for 2001-2012 were probabilistically linked to IPD notifications, hospitalisations, deaths, and vaccination history (available until December 2013). IPD rates in vaccinated and unvaccinated children2 years old were compared using Cox proportional hazards models (adjusting for potential confounders), with VE = (1 - adjusted hazard ratio) × 100. Separate models were performed for all-cause, PCV7, PCV13 and PCV13-non-PCV7 serotype-specific IPD, and for Aboriginal and non-Aboriginal children.Following introduction of universal PCV7 in 2005, rates of PCV7 serotype and all-cause IPD in unvaccinated children declined 89.5% and 61.4%, respectively, to be similar to rates in vaccinated children. Among non-Aboriginal children, VEs for 3 doses were 94.2% (95%CI: 81.9-98.1) for PCV7 serotype-specific IPD, 85.6% (95%CI: 60.5-94.8) for PCV13-non-PCV7 serotype-specific IPD and 80.1% (95%CI: 59.4-90.3) for all-cause IPD. There were no statistically significant differences between the VEs for 3 doses and for 1 or 2 doses against PCV13 and PCV13-non-PCV7 serotype-specific IPD, or between Aboriginal and non-Aboriginal children.Our population-based cohort study demonstrates that90% coverage in the first year of a universal 3 + 0 PCV program provided high population-level protection, predominantly attributable to strong herd effects. The size of the cohort enabled calculation of robust dose-specific VE estimates for important population sub-groups relevant to vaccination policies internationally.