Acute Q fever in patients with an influenza-like illness in regional New South Wales, Australia.

INTRODUCTION: Query (Q) fever is a zoonosis caused by the bacterium Coxiella burnetii typically presenting as an influenza-like illness (ILI) with or without hepatitis. The infection may be missed by clinicians in settings of low endemicity, as the presentation is clinically not specific, and there are many more common differential diagnoses for ILI including SARS-CoV-2 infection. METHODS: Residual serum samples were retrospectively tested for Phase 1 and 2 Q fever-specific IgM, IgG, IgA antibodies by indirect immunofluorescence and C. burnetii DNA by polymerase chain reaction. They had not been previously tested for Q fever, originating from undiagnosed patients with probable ILI, aged 10-70 years and living in regional New South Wales, Australia. The results were compared with contemperaneous data on acute Q fever diagnostic tests which had been performed based on clinicians requests from a geographically similar population. RESULTS: Only one (0.2%) instance of missed acute Q fever was identified after testing samples from 542 eligible patients who had probable ILI between 2016-2023. Laboratory data showed that during the same period, 731 samples were tested for acute Q fever for clinician-initiated requests and of those 70 (9.6%) were positive. Probability of being diagnosed with Q fever after a clinician initiated request was similar regardless of the patients sex, age and the calendar year of sampling. CONCLUSION: In this sample, Q fever was most likely to be diagnosed via clinician requested testing rather than by testing of undiagnosed patients with an influenza like illness.

Measles, mumps, rubella and varicella antibodies among international and domestic university students.

BACKGROUND: Vaccine-preventable infections are generally well controlled in Australia. However, gaps in immunity can lead to outbreaks and are important to identify. Young adults are a highly mobile population and a potential source of imported infections. We aimed to evaluate anti- measles, mumps, rubella and varicella (MMR&V) IgG seroprevalence and explore factors relating to antibody seropositivity. METHODS: A cross-sectional online survey was conducted among students from a large Australian university to collect demographic, vaccination, infection and travel characteristics. Blood samples were collected to measure MMR&V seroprevalence. Logistic regression was used to identify factors associated with seropositivity. RESULTS: Among 804 university students, seroprevalence (positive or equivocal) for measles was 82.3% (95% CI 79.6-84.8%), mumps 79.5% (95% CI 76.7-82.3%), rubella 91.5% (95% CI 89.6-93.5%) and varicella 86.2% (95% CI 84.1-88.8%), with 452 (56.2%, 95% CI 52.8-59.6) seropositive to all four viruses. Varicella seropositivity was highest in the older birth cohort (born 1988-1991). Measles seropositivity was higher for international students compared to domestic students. Among international students, mumps seroprevalence was significantly lower than measles and rubella seroprevalence. International travel in the previous 12 months was reported by 63.1% of students, but only 18.2% of travellers reported seeking pre-travel health advice prior to most recent international travel. CONCLUSIONS: Overall, this study suggests immunity to MMR&V is sub-optimal. We found the university student population to be highly mobile and unlikely to seek pre-travel advice; thus, they are a potential source of infection importation. The implementation of university immunization policies could address the gaps identified and our findings can inform the development of targeted vaccination campaigns.

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

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

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

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

Effectiveness of COVID-19 vaccination against COVID-19 specific and all-cause mortality in older Australians: a population based study.

Background: Few studies have examined effectiveness of COVID-19 vaccines against COVID-19 and all-cause mortality across different pandemic periods in 2022. Methods: We used linked whole-of-population data from the 2021 Australian Census, Australian Immunisation Register, death registrations and other national datasets including migration data. Among 3.8 million adults aged 65+ years and >170,000 aged care residents, we used survival analysis to estimate vaccine effectiveness (VE) against COVID-19 specific mortality and all-cause mortality, by vaccine dose and time since receipt, adjusted for age, sex and other factors. We also estimated absolute COVID-19 mortality rates. Findings: From January-May 2022 (Omicron BA.1/2), 3250 COVID-19 deaths occurred; from June-November (Omicron BA.4/5) 3185 COVID-19 deaths occurred. During January-May, VE of a 3rd COVID-19 vaccine dose within 3 months was 93% (95% CI 93-94%) whilst VE of a 2nd dose >6 months since receipt was 34% (26-42%). During June-November, VE of a 4th COVID-19 vaccine dose within 3 months was 84% (82-86%) whilst VE of a 3rd dose >6 months since receipt was 56% (50-62%). VE estimates for aged care residents were similar, but absolute risk reductions were substantially greater. During June-November 2022, for all-cause mortality, VE of a 4th dose within 3 months was 58% (56-59%) whilst VE of a 3rd dose >6 months since receipt was 19% (16-22%). Interpretations: COVID-19 vaccination is highly effective against COVID-19 mortality among older adults although effectiveness wanes with time since the last dose. Our findings emphasise the importance of continuing to administer booster doses, particularly to those at highest risk. Funding: This study was funded by the Health Economics Research Division in the Australian Government Department of Health and Aged Care.

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

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

Comparative effectiveness of four COVID-19 vaccines, BNT162b2 mRNA, mRNA-1273, ChAdOx1 nCov-19 and NVX-CoV2373 against SARS-CoV-2 B.1.1.529 (Omicron) infection.

BACKGROUND: There is limited data directly comparing the effectiveness of different COVID-19 vaccines. METHODS: We compared rates of SARS-CoV-2 Omicron BA.1/2 infection during March to May 2022 in Australian adults who had received one of four COVID-19 vaccines in the last 14-63 days as either a primary course or a booster dose using Cox proportional hazards models adjusting for age and other characteristics. RESULTS: As a primary course, over 2318 person-years and 1033 infections, compared to recipients of BNT162b2 mRNA vaccine, adjusted hazard ratios for SARS-CoV-2 infection were 1.03 (95%CI 0.82-1.30), 1.19 (0.95-1.49), 1.70 (1.46-1.97) for respectively mRNA-1273, ChAdOx-1 nCov-19 and NVX-CoV2373. For the booster dose, over 154,984 person-years and 93,580 infections the respective adjusted hazard ratios compared to BNT162b2 mRNA vaccine were 1.02 (95%CI 1.00-1.04), 1.20 (1.10-1.32), 1.39 (1.20-1.60). CONCLUSIONS: Our findings suggest relatively higher effectiveness of ancestral strain mRNA vaccines against SARS-CoV-2 Omicron infection than viral vector and protein subunit vaccines and provide clinical confirmation of immunological data on differences in COVID-19 vaccine performance.

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

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

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

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

Background incidence rates of selected adverse events of special interest (AESI) to monitor the safety of COVID-19 vaccines.

BACKGROUND: Determining background rates of medical conditions identified as adverse events of special interest (AESI) that may occur following COVID-19 vaccination is important for contextualising and investigating potential vaccine safety signals. METHODS: We conducted a retrospective population-based cohort study using linked emergency department, hospitalisation and death data for 2017 and 2018 from Australia's most populous state, New South Wales. Incident cases of select neurological conditions, arterial or venous thromboembolic conditions, secondary thrombocytopenia, myocarditis/pericarditis, and unique events of anaphylaxis and generalised convulsions were identified using internationally agreed upon diagnostic (ICD-10) codes. State-specific rates per 100,000 person-years were calculated, with further stratification by age group and sex where clinically relevant to the condition, and the number of expected cases nationally in one and 6 weeks was estimated. RESULTS: Background rates of selected neurological conditions were low with the exception of generalised convulsions for which 1,599-1,872 cases were estimated nationally in a 1-week period in the absence of vaccination. Using a narrow case definition, rates of Guillain-Barré Syndrome (3.9 per 100,000 person-years) were higher than international rates reported elsewhere. Thromboembolic and cerebral venous sinus thrombosis event rates increased with age. Myocarditis occurred more commonly in males, and was highest in males aged 18-24 years, with an estimated 1-4 cases expected nationally in a 1-week period. CONCLUSIONS: Using routinely collected linked healthcare data provides localised estimates of background rates of new onset or periodic AESI which enables rapid estimation of observed-versus-expected rates of events reported following COVID-19 vaccination. This Australian-specific analysis contributes AESI background rates which can be compared with those from other countries to enhance understanding of geographic variability in the frequency of specific AESI in the absence of vaccination, and can be utilised for signal detection during program implementation.

COVID-19 Vaccine Uptake by Infection Status in New South Wales, Australia.

Using linked public health data from Australia to measure uptake of COVID-19 vaccination by infection status, we found coverage considerably lower among infected than uninfected persons for all ages. Increasing uptake of scheduled doses, including among previously infected persons after the recommended postinfection delay, is needed to reduce COVID-19 illness rates.

Estimating the excess burden of pertussis disease in Australia within the first year of life, that might have been prevented through timely vaccination.

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.

Trends and determinants of active school travel among Australian secondary school students: national cross-sectional data from 2009 to 2018.

OBJECTIVE: To examine active school travel trends and predictors among Australian secondary school students (aged 12-17) between 2009 and 2018. METHODS: Three cross-sectional surveys (2009-10: N=13,790; 2012-13: N=10,309; and 2018: N=9,102) using a web-based self-report questionnaire. Logistic regression was used to identify differences in active travel (to and/or from school every weekday) between survey years and predictors. RESULTS: From 2009-10 to 2012-13 to 2018, active travel decreased from 33.6% to 32.3% to 29.5% among females, and from 37.4% to 36.6% to 32.6% among males. Distance, female sex and regional location were associated with a lower likelihood of active travel. Students with pocket money, those who spoke a language other than English at home, and Aboriginal and/or Torres Strait Islander students were more likely to actively travel. CONCLUSIONS: Between 2009-10 and 2018, active school travel among secondary students in Australia declined. Several factors were found to be associated with active travel. IMPLICATIONS FOR PUBLIC HEALTH: This is the first national study on active travel trends among secondary students in Australia. The recent decline requires action given the increasing prevalence of overweight and climate change.

Relative effectiveness of COVID-19 vaccination with 3 compared to 2 doses against SARS-CoV-2 B.1.1.529 (Omicron) among an Australian population with low prior rates of SARS-CoV-2 infection.

BACKGROUND: We estimate effectiveness of 3 versus 2 vaccine doses against SARS-CoV-2 B.1.1.529 Omicron in a mostly infection-naiive but highly vaccinated Australian population. METHODS: Cohort study of adults aged 40+ years resident in Sydney followed from 1 January 2022 for SARS-CoV-2 infection and COVID-19 hospitalisation or death using linked immunisation, disease notification and hospitalisation registers. Adjusted hazard ratios (aHR) and corresponding relative vaccine effectiveness (rVE) were estimated comparing 3 to 2 vaccine dose recipients by time since dose receipt, vaccine brand, and prior infection. Absolute risk reductions and numbers needed to boost by age groups were calculated. RESULTS: 2,053,123 infection-naiive individuals (mean age 59 years) were followed for 327,272 person-years for infection and 224,269 person-years for severe outcomes (hospitalisation/death). There were 175,849 infections and 4113 hospitalisations/deaths. Compared to individuals receiving dose 2 within the last 3 months, rVE in dose 3 recipients was 7% (95% CI 5-9%) against infection and 65% (95%CI 61-69%) against hospitalisation/death. Almost all dose 3 recipients had an mRNA vaccine; there was little difference in dose 3 rVE by primary course vaccine brand (ChAdOx1 versus BNT162b2). Over the 6-week follow-up, we estimated one hospitalisation/death was avoided for every 192 adults aged ≥70 years boosted with dose 3 in the infection-naiive cohort. The aHR for hospitalisation/death from Omicron was 0.12 (95 %CI 0.07-0.23) for 2-dose recipients with a prior Delta infection compared with 2-dose recipients with no prior infection. CONCLUSIONS: Receipt of a third COVID-19 vaccine dose in adults aged 40 years and above significantly reduced hospitalisations and deaths from SARS-CoV-2 Omicron infections in a primarily infection-naiive population.

Serological testing of blood donors to characterise the impact of COVID-19 in Melbourne, Australia, 2020.

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 (<3 cases/1,000 population), medium (3-7 cases/1,000 population) and high (>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.

Effectiveness of 7-Valent Pneumococcal Conjugate Vaccine Against Invasive Pneumococcal Disease in Medically At-Risk Children in Australia: A Record Linkage Study.

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 <12 months of age or ≥1 PCV dose at ≥12 months of age. Cox proportional hazard modeling was used to estimate hazard ratios (HRs), adjusted for confounders, and vaccine effectiveness (VE) was estimated as (1-HR) × 100. 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.

Pertussis burden and acellular pertussis vaccine effectiveness in high risk children.

BACKGROUND: Pertussis hospitalisation is more common among infants born prematurely, who have significant comorbidities, or are Indigenous, but acellular pertussis (aP) vaccine effectiveness (VE) estimates in these sub-groups are lacking. We measured aP VE by Indigenous status, and policy-relevant categories of prematurity and comorbidity, in a population-based Australian cohort. METHODS: Perinatal, disease notification, hospitalisation, mortality, and vaccination data were linked to birth records in two Australian states (Western Australia and New South Wales) 2001-2012, with follow-up to the end of 2013. Children followed to 18 months of age were stratified by Aboriginality, prematurity (<32 vs 32-<37 weeks gestation) and comorbidities identified from hospital discharge coding. Rates, rate ratios and VE were calculated for first episode of hospitalised and non-hospitalised pertussis notifications using adjusted Cox proportional hazards models. RESULTS: Among >1,300,000 children, 63,867 (4·9%) were Aboriginal, 47,721 (3·6%) had at least one comorbidity and 3,771 first episodes of notified pertussis occurred <18 months of age; of these, 1,207 (32.0%) had an associated pertussis-coded hospitalisation. For hospitalised pertussis in Aboriginal and non-Aboriginal children, there was significant protection post dose 1 (VE 51% v 25%), 2 (VE 69% v 74%) and 3 (VE 76% v 80%). For children with co-morbidities, VE for hospitalised pertussis was low and non-significant post dose 1 (0%) and 2 (30%). Post dose 3, VE was significant for hospitalised pertussis (70%; 95% CI 29-87) but not for non-hospitalised pertussis (24%; 95% CI -49 to 61). CONCLUSIONS: For most Aboriginal and non-Aboriginal children, improved timeliness of current infant doses and higher antenatal coverage should further improve protection against pertussis of any severity. For children at highest risk of severe pertussis (born <32 weeks gestation or with significant medical comorbidities), our data suggest that additional measures-such as extra doses of pertussis-containing vaccines and/or vaccines with improved immunogenicity-are needed for protection.

Seroprevalence of Severe Acute Respiratory Syndrome Coronavirus 2-Specific Antibodies in Australia After the First Epidemic Wave in 2020: A National Survey.

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 (<0.5%) after the only national COVID-19 wave thus far. These data and the subsequent limited community transmission highlight the population's naivety to SARS-CoV-2 and the urgency of increasing vaccine-derived protection.

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

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