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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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: 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., Methods: 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., Results: 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 mothers <20 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., Conclusion: 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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objectives: 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., Methods: 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., Results: 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 age <20 years, maternal smoking during pregnancy and living in a disadvantaged area were independently associated with decreased vaccine uptake., Conclusions: 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., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Control of measles was the focus of a national workshop held in 2015 in Sydney, Australia, bringing together stakeholders in disease control and immunisation to discuss maintaining Australia's measles elimination status in the context of regional and global measles control. The global epidemiology of measles was reviewed, including outbreaks in countries that have achieved elimination, such as the Disneyland outbreak in the United States and large outbreaks in Sydney, Australia. Transmission of measles between Australia and New Zealand occurs, but has not been a focus of control measures. Risk groups, the genetic and seroepidemiology of measles as well as surveillance, modelling and waning vaccine-induced immunity were reviewed. Gaps in policy, research and practice for maintaining measles elimination status in Australia were identified and recommendations were developed. Elimination of measles globally is challenging because of the infectiousness of measles and the need for 2-dose vaccine coverage rates in excess of 95% in all countries to achieve it. Until this occurs, international travel will continue to permit measles importation from endemic countries to countries that have achieved elimination. When measles cases are imported, failure to diagnose and isolate cases places the health system at risk of measles outbreaks. Vaccine funding models can result in gaps in vaccine coverage for adults and migrants. Australia introduced a whole-of-life immunisation register in 2016 and catch-up vaccination for at-risk communities, which will improve measles control. Research on diagnosis, immunology, case management and modelling of vaccination strategies are important to ensure continued control of measles., (Copyright © 2018.)

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., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: The World Health Organization has targeted rubella virus for elimination regionally. Australia was one of the first countries to implement a nationally funded rubella immunisation program, in 1971, and conducts regular national rubella serosurveillance studies. We aimed to estimate the seroprevalence of rubella-specific IgG antibody in the Australian population by age and sex in 2012-2013, to compare the results with three previous serosurveys conducted in 1996-1999, 2002 and 2007 and to estimate the effective reproduction numbers (R n )., Methods: This study used 2729 serum and plasma specimens, randomly selected from a specimen bank collected in 2012-2013 across Australia. Age groups included in the sample ranged from 1 to 49 years. Sera were tested for rubella-specific IgG-antibody using the Enzygnost anti-rubella IgG enzyme immunoassay and classified as positive, negative or equivocal according to rubella-specific IgG concentrations of >7 IU/ml, <3 IU/ml and 3-7 IU/ml, respectively., Results: The overall proportions seropositive, seronegative and equivocal for rubella-specific IgG were 92.1% (95% CI, 91.0-93.2), 6.7% (95% CI, 5.7-7.7) and 1.2% (95% CI, 0.8-1.6), respectively. The proportion of males seropositive was significantly lower than females in the 30-34 (83.1% vs. 96.8%, p = 0.003), 35-39 (86.1% vs. 96.3%, p = 0.02) and 40-44 (86.1% vs. 95.7%, p = 0.03) year age groups. R n for rubella in 2012-2013 was estimated to be 0.33 (95% CI 0.28-0.39)., Discussion: The 2012-2013 national serosurvey showed levels of rubella-specific IgG seropositivity in the Australian population are relatively high with no evidence of decrease compared to previous serosurveys conducted in 1996-1999, 2002 and 2007. The lower proportion of seropositive males aged 30-44 years likely reflects the initial immunisation program targeting females only. To our knowledge this study represents the longest period of serosurveillance following introduction of a nationally funded rubella immunisation program. The lack of evidence of decreasing rubella-specific IgG seropositivity is therefore reassuring for Australia and other countries with longstanding high vaccine coverage., (Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

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 <10 (negative) in the measles microneutralisation assay., 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., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Re-exposure to varicella infection is believed to delay the occurrence of herpes zoster (HZ), which has led to predictions of increased HZ following introduction of varicella vaccination programs. However, there is evidence of rising HZ rates before vaccination was introduced. Here, we explore a potential explanation for this effect through demographic change leading to reductions in varicella exposure and boosting in the context of Australia over the 20th century. To study this hypothesis, we integrated observed changes in Australian birth and age-specific death rates with a varicella transmission model. The model was then calibrated to age-specific pre-vaccination seroprevalence (1997-9) and hospitalization data (1993-2009). Model simulations predicted that declining birth rates led to a 50% reduction in varicella incidence over the 20th century. When combined with the impacts of an aging population, the simulations further suggested that HZ incidence should have increased by 50% over the 20th century. However, we found that after age-standardization, the residual increase in HZ due to reduced boosting was only about 8% over the 20th century. Results were also sensitive to the assumed duration of immunity to HZ and whether multiple HZ episodes were possible. Despite a strong predicted effect of demographic change on varicella incidence, our findings suggest that improved survival is the main contributor to any rise in HZ rates prior to vaccination in Australia. Removing survival effects through age-standardization is recommended when considering epidemiologic or model-based analysis of past trends in HZ., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Febrile seizures (FS) are common in childhood with incidence peaking in the second year of life when measles and varicella-containing vaccines are administered. This study aimed to examine the vaccine-attributable risk of FS following separate administration of MMR and monovalent varicella vaccines (VV) prior to a planned change to MMRV as the second dose of measles-containing vaccine at 18 months of age., Methods: All FS cases in children aged <5 years from 1st January 2012 to 30th April 2013 were identified from emergency department (ED) and inpatient databases at five Australian tertiary paediatric hospitals participating in PAEDS (Paediatric Active Enhanced Disease Surveillance). Immunization records were obtained from the Australian Childhood Immunization Register (ACIR). The relative incidence (RI) of FS following MMR dose 1 (MMR1) and VV in children aged 11-23 months was determined using the self-controlled case series (SCCS) method and used to calculate attributable risk., Results: There were 2013 FS episodes in 1761 children. The peak age at FS was 18 months. The risk of FS was significantly increased 5-12 days post receipt of MMR1 at 12 months (RI=1.9 [95% CI: 1.3-2.9]), but not after VV at 18 months (RI=0.6 [95% CI: 0.3-1.2]. The estimated excess annual number of FS post MMR1 was 24 per 100,000 vaccinated children aged 11-23 months (95% CI=7-49 cases per 100,000) or 1 per 4167 doses., Conclusions: Our study detected the expected increased FS risk post MMR1 vaccine at 12 months, but monovalent varicella vaccine at age 18 months was not associated with increased risk of FS. This provides baseline data to assess the risk of FS post MMRV, introduced in Australia as the second dose of measles-containing vaccine at 18 months of age in July 2013., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

A nationally funded Q fever vaccination program was introduced in Australia in 2002. The evaluation of this unique program included measures of program uptake, safety, and notification and hospitalisation rates for Q fever pre- and post-program implementation. Program uptake ranged from close to 100% amongst abattoir workers to 43% in farmers. The most commonly reported adverse event was injection site reaction. Q fever notification rates declined by over 50% between 2002 and 2006, particularly in young adult males, consistent with the profile of the abattoir workforce. Hospitalisation data showed similar trends. Available evidence suggests a significant impact of Australia's Q fever vaccination program; such a program merits consideration in other countries with a comparable Q fever disease burden.

The second dose of MMR vaccine (MMR2) is scheduled at 4 years in Australia and the USA but earlier in some European countries. We modelled the effect on measles elimination status and population susceptibility of shifting delivery of MMR2 from 4 years to 18 months using relevant Australian data. Susceptibility in young children was reduced but elimination was not sustainable past 2015 if 6% of vaccinated seroconverters became susceptible after 10 years. One-dose MMR coverage of 96% or greater maintained elimination more effectively than modelled changes in scheduling, suggesting that maximising one-dose MMR coverage should be the highest priority.

We compared the results of two national serosurveys in Australia to evaluate the impact of universal infant vaccination and school-based programs for adolescents. Immunity improved significantly overall, especially in 1-year-olds (40.0% versus 86%; p<0.0001); in adolescents it was significantly higher in regions with established school-based programs (56.6% versus 38.8%; p=0.0008). 6.1% of 1-59-year-olds were positive for HBcAb and 0.7% for HBsAg. We have demonstrated successful implementation of universal infant hepatitis B vaccination in Australia and that school-based programs for adolescents are effective. This experience should be applicable to low prevalence countries in northern Europe which have not implemented universal hepatitis B immunisation.

We used the 2002 national serosurvey to evaluate a primary care-based young adult vaccination campaign, measure the reproductive number (R) and, together with vaccination coverage estimates, predict R until 2012. The campaign had no impact on immunity in young adults. R was estimated to be 0.69 and predicted to stay well below the epidemic threshold of 1 until at least 2012, indicating that Australia should remain free of endemic measles in the medium term. To maintain elimination in the longer term, the timeliness and coverage of childhood vaccinations must improve and innovative strategies will be required to improve measles immunity among young adults. This experience is likely to apply to developed countries that have achieved or are approaching measles elimination.

We compared estimates of the age-specific population immunity to measles, mumps, rubella, hepatitis B and varicella zoster viruses in Victorian school children obtained by a national sero-survey, using a convenience sample of residual sera from diagnostic laboratories throughout Australia, with those from a three-stage random cluster survey. When grouped according to school age (primary or secondary school) there was no significant difference in the estimates of immunity to measles, mumps, hepatitis B or varicella. Compared with the convenience sample, the random cluster survey estimated higher immunity to rubella in samples from both primary (98.7% versus 93.6%, P = 0.002) and secondary school students (98.4% versus 93.2%, P = 0.03). Despite some limitations, this study suggests that the collection of a convenience sample of sera from diagnostic laboratories is an appropriate sampling strategy to provide population immunity data that will inform Australia's current and future immunisation policies., (Copyright 2002 Elsevier Science Ltd.)