Vaccine Preventable Disease Seroprevalence in a Nationwide Assessment of Timor-Leste (VASINA-TL): study protocol for a population-representative cross-sectional serosurvey.

INTRODUCTION: Historic disruption in health infrastructure combined with data from a recent vaccine coverage survey suggests there are likely significant immunity gaps to vaccine preventable diseases and high risk of outbreaks in Timor-Leste. Community-based serological surveillance is an important tool to augment understanding of population-level immunity achieved through vaccine coverage and/or derived from prior infection. METHODS AND ANALYSIS: This national population-representative serosurvey will take a three-stage cluster sample and aims to include 5600 individuals above 1 year of age. Serum samples will be collected by phlebotomy and analysed for measles IgG, rubella IgG, SARS-CoV-2 antispike protein IgG, hepatitis B surface antibody and hepatitis B core antigen using commercially available chemiluminescent immunoassays or ELISA. In addition to crude prevalence estimates and to account for differences in Timor-Leste's age structure, stratified age-standardised prevalence estimates will be calculated, using Asia in 2013 as the standard population. Additionally, this survey will derive a national asset of serum and dried blood spot samples which can be used for further investigation of infectious disease seroepidemiology and/or validation of existing and novel serological assays for infectious diseases. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Research Ethics and Technical Committee of the Instituto Nacional da Saúde, Timor-Leste and the Human Research Ethics Committee of the Northern Territory Department of Health and Menzies School of Health Research, Australia. Co-designing this study with Timor-Leste's Ministry-of-Health and other relevant partner organisations will allow immediate translation of findings into public health policy, which may include changes to routine immunisation service delivery and/or plans for supplementary immunisation activities.

ATAGI Targeted Review 2022: Vaccination for prevention of herpes zoster in Australia.

Abstract: In November 2016, herpes zoster (HZ) vaccination for older adults, using the live-attenuated zoster vaccine (Zostavax; ZVL) was added to the Australian National Immunisation Program (NIP) with the aim of reducing morbidity from HZ and its complications, particularly for people at increased risk. Prior to the program, there were on average 5.6 cases of HZ per 1,000 persons annually in Australia, with highest risk of disease in older and in immunocompromised people. The burden of complications of HZ, such as post-herpetic neuralgia (PHN), was also highest in older and immunocompromised groups. No formal comprehensive program evaluation has been undertaken since program commencement. This review examined published literature and available vaccine administration data to summarise the evidence and considerations underpinning current use of HZ vaccines and potential future program directions in Australia. There have been modest reductions in the incidence of HZ and its complications since program introduction. However, five years into the program, challenges remain, including suboptimal vaccine coverage and significant safety concerns arising from inadvertent use of ZVL in immunocompromised people, who are contraindicated to receive this vaccine. This reduces opportunities to offset the burden of HZ-related disease. The recombinant subunit zoster vaccine (Shingrix; RZV), first registered in Australia in 2018, became available on the Australian market in June 2021. This vaccine has higher efficacy than ZVL and, as a non-live vaccine, can be used in both immunocompetent and immunocompromised people. RZV has potential to address the unmet needs of at-risk population groups. However, it has not yet demonstrated cost-effectiveness for inclusion as a funded vaccine under the NIP. The Australian HZ vaccination program has had limited effectiveness in meeting its aim in highest risk groups. Future options and challenges anticipated in using vaccination to reduce the burden of HZ and its complications are discussed in this review.

Rotavirus Vaccination Likely to Be Cost Saving to Society in the United States.

BACKGROUND: Following the introduction of rotavirus immunization in 2006 in the United States, there were substantial declines in the domestic rotavirus disease burden. In this study, we assess the value for money achieved by the program in the decade following vaccine introduction. METHODS: We applied an age-specific, static, multicohort compartmental model to examine the impact and cost-effectiveness of the US rotavirus immunization program in children <5 years of age using healthcare utilization data from 2001 to 2015 inclusive. We calculated the incremental cost-effectiveness ratio (ICER) per quality-adjusted life year (QALY) gained from both a healthcare system and societal perspective. RESULTS: Declines in healthcare use associated with the rotavirus and acute gastroenteritis occurred from 2006 and continued to grow before stabilizing from 2010 through 2011. From 2011 to 2015, an estimated annual average of approximately 118 000 hospitalizations, 86 000 emergency department presentations, and 460 000 outpatient and physician office visits were prevented. From a societal perspective during this same period, the program was estimated to be cost saving in the base case model and in >90% of probabilistic sensitivity analysis simulations and from a healthcare system perspective >98% of simulations found an ICER below $100 000 per QALY gained. CONCLUSIONS: After the program stabilized, we found the rotavirus immunization in the United States was likely to have been cost saving to society. The greater than expected healthcare and productivity savings reflect the success of the rotavirus immunization program in the United States.

Immunisation Coverage Annual Report 2019.

Abstract: Australian Immunisation Register data have been analysed for children aged < 5 years, focusing on changes in vaccination coverage at standard age milestones (12, 24 and 60 months) between 2018 and 2019. 'Fully vaccinated' coverage in 2019 increased by 0.1-0.4% at the three age milestones to 94.3% at 12 months, 90.2% at 24 months (in the context of additional antigens required at 24 months) and 94.2% at 60 months. Rotavirus vaccine coverage (2 doses) increased from 90.9% in 2018 to 91.9% in 2019. 'Fully vaccinated' coverage in Aboriginal and Torres Strait Islander (hereafter respectfully referred to as Indigenous) children increased by 0.5-1.1% in 2019, reaching 92.9% at 12 months, 88.9% at 24 months and 96.9% at the 60 months (2.7 percentage points higher than in children overall). Recorded influenza vaccination coverage in children aged 6 months to < 5 years increased by 11.4 percentage points to 42.7% in Indigenous children in 2019, and by 15.6 percentage points to 41.8% in children overall. Longstanding issues with timeliness of vaccination in Indigenous children persisted, although the disparity between Indigenous and non-Indigenous children in on-time coverage (within 30 days of due date), for vaccines due at 4 months of age, decreased from 10.4-10.7 to 9.6-9.8 percentage points between 2018 and 2019. The timeliness of 'fully vaccinated' coverage was also examined at earlier age milestones (3 months after due date of last scheduled vaccine) of 9, 15, 21 and 51 months, by Indigenous status, socioeconomic status and remoteness of area of residence. Coverage in children living in the least-advantaged residential area quintile was 2.6-2.7% lower than that for those living in the most-advantaged quintile at the 9-, 15- and 21-month milestones, although these disparities were 0.5-1.5 percentage points lower than in 2018. Coverage at the earlier milestones in Indigenous children in remote areas was 1.5-6.7% percentage points lower than that for Indigenous children in major cities and regional areas, although there were some improvements since 2018. Importantly, although Indigenous children had lower coverage for the second dose of measles-mumps-rubella vaccine at 24 months (92.7% versus 93.3% overall), coverage increased to 98.8% at 60 months; coverage was also high overall at 96.4%, above the 95% target critical to measles control. In conclusion, this report demonstrates continuing improvements across a range of immunisation indicators in Australia in 2019. However, some issues with timeliness persist, particularly in Indigenous and socioeconomically disadvantaged children. New coverage targets for earlier protection in the first 2 years of life may be indicated, along with a review of current 'fully vaccinated' assessment algorithms, particularly at the 60-month age milestone.

"No jab, no pay": catch-up vaccination activity during its first two years.

OBJECTIVES: To assess catch-up vaccination of older children and adolescents during the first two years of the "No jab, no pay" policy linking eligibility for federal family assistance payments with childhood vaccination status. DESIGN, SETTING, PARTICIPANTS: Cross-sectional analysis of Australian Immunisation Register data on catch-up vaccination of children aged 5 to less than 7 years before (January 2013 - December 2014; baseline) and during the first two years of "No jab, no pay" (December 2015 - December 2017), and of children aged 7 to less than 10 years and young people aged 10 to less than 20 years ("No jab, no pay" period only). MAIN OUTCOMES: Catch-up vaccination rates for measles-mumps-rubella vaccine second dose (MMR2), by age group, Indigenous status, and socio-economic status; catch-up vaccination of children aged 5 to less than 7 years (third dose of diphtheria-tetanus-pertussis vaccine [DTPa3], MMR1), before and after introduction of "No jab, no pay". RESULTS: The proportion of incompletely vaccinated children aged 5 to less than 7 years who received catch-up DTPa3 was higher under "No jab, no pay" than during the baseline period (15.5% v 9.4%). Of 407 332 incompletely vaccinated people aged 10 to less than 20 years, 71 502 (17.6%) received catch-up MMR2 during the first two years of "No jab, no pay", increasing overall coverage for this age group from 86.6% to 89.0%. MMR2 catch-up activity in this age group was greater in the lowest socio-economic status areas than in the highest status areas (29.1% v 7.6%), and also for Indigenous than for non-Indigenous Australians (35.8% v 17.1%). MMR2 catch-up activity in 2016 and 2017 peaked mid-year. CONCLUSIONS: Linking family assistance payments with childhood vaccination status and associated program improvements were followed by substantial catch-up vaccination activity, particularly in young people from families of lower socio-economic status.

Active surveillance of acute paediatric hospitalisations demonstrates the impact of vaccination programmes and informs vaccine policy in Canada and Australia.

Sentinel surveillance of acute hospitalisations in response to infectious disease emergencies such as the 2009 influenza A(H1N1)pdm09 pandemic is well described, but recognition of its potential to supplement routine public health surveillance and provide scalability for emergency responses has been limited. We summarise the achievements of two national paediatric hospital surveillance networks relevant to vaccine programmes and emerging infectious diseases in Canada (Canadian Immunization Monitoring Program Active; IMPACT from 1991) and Australia (Paediatric Active Enhanced Disease Surveillance; PAEDS from 2007) and discuss opportunities and challenges in applying their model to other contexts. Both networks were established to enhance capacity to measure vaccine preventable disease burden, vaccine programme impact, and safety, with their scope occasionally being increased with emerging infectious diseases' surveillance. Their active surveillance has increased data accuracy and utility for syndromic conditions (e.g. encephalitis), pathogen-specific diseases (e.g. pertussis, rotavirus, influenza), and adverse events following immunisation (e.g. febrile seizure), enabled correlation of biological specimens with clinical context and supported responses to emerging infections (e.g. pandemic influenza, parechovirus, COVID-19). The demonstrated long-term value of continuous, rather than incident-related, operation of these networks in strengthening routine surveillance, bridging research gaps, and providing scalable public health response, supports their applicability to other countries.

Epidemic and Inter-epidemic Burden of Pediatric Human Parechovirus Infection in New South Wales, Australia, 2017-2018.

BACKGROUND: Human parechovirus (HPeV) typically infects young children, and although infection is often asymptomatic, some types (eg, HPeV3) are associated with severe clinical manifestations, including central nervous system infection or sepsis-like syndrome, particularly affecting young infants. The third documented national epidemic of HPeV occurred in Australia in 2017-2018. METHODS: Four public laboratories that perform almost all of the HPeV PCR testing in New South Wales provided data regarding HPeV tests performed from July 1, 2017 to June 30, 2018. Limited demographic and clinical data were obtained from electronic medical records for laboratory test-positive cases that presented to each of the 3 pediatric hospitals in New South Wales. RESULTS: Five hundred eighty-one HPeV-positive samples obtained from 395 cases were included in the analysis. The peak of the outbreak occurred in late November 2017 (approximately 35 new cases each week), with the main HPeV epidemic occurring between the spring and summer months of September 2017 to January 2018; although this seasonality was observed primarily in infants less than 12 months of age. Among the 388 pediatric cases, almost half were younger than 2 months (188; 47%) and only 10 were children older than 2 years. The annualized estimated incidence of laboratory confirmed HPeV infection in children was approximately 142.4 cases per 100,000 children younger than 5 years in New South Wales during the epidemic season. CONCLUSIONS: The large burden of HPeV infection and disease identified in young infants in this and previous Australian studies highlight the need for more comprehensive national surveillance of HPeV infections and improved prevention strategies.

Evaluation of bacille Calmette-Guérin immunisation programs in Australia.

BACKGROUND: bacille Calmette-Guérin (BCG) immunisation programs in Australia are funded and operated by the individual states and territories. In recent years BCG vaccine shortages have required use of unregistered products. We aimed to evaluate BCG immunisation programs in Australia, with particular reference to program implementation and national consistency.
 Methods: Between September and November 2015, 12 key stakeholders, representing Australian states and territories, completed surveys. We analysed BCG vaccination coverage data from the Australian Childhood Immunisation Register (ACIR), and data on adverse events following immunisation (AEFI) with BCG vaccine from the Therapeutic Goods Administration's Adverse Drug Reactions System, for 2001 to 2014.
 Results: Access to BCG vaccination varies between jurisdictions, with some states providing this only in major city locations. Analysis of ACIR data suggests significant differences in vaccine delivery between jurisdictions, but varying levels of under-reporting to the ACIR were also acknowledged. The rate of BCG AEFI appeared to increase between 2011 and 2014; however, these data need to be interpreted with caution due to small numbers, likely under-reporting of both numerator (AEFI) and denominator (vaccine doses administered), and the general increase in reporting of AEFI related to other vaccines in children over this period.
 Conclusions: BCG immunisation programs aim to prevent severe forms of tuberculosis in young children who live in or travel to high burden settings. A range of factors, particularly inconsistent vaccine supply are leading to low, variable and inequitable vaccine delivery across Australian jurisdictions. Improved BCG vaccination uptake and AEFI data quality are required for accurate monitoring of program delivery and vaccine safety - this is particularly important given the current need to use unregistered vaccines. Improved and consistent access to BCG vaccine is suggested to optimise equity for at-risk children Australia-wide.

Hepatitis B immunization for indigenous adults, Australia.

OBJECTIVE: To quantify the disparity in incidence of hepatitis B between indigenous and non-indigenous people in Australia, and to estimate the potential impact of a hepatitis B immunization programme targeting non-immune indigenous adults. METHODS: Using national data on persons with newly acquired hepatitis B disease notified between 2005 and 2012, we estimated incident infection rates and rate ratios comparing indigenous and non-indigenous people, with adjustments for underreporting. The potential impact of a hepatitis B immunization programme targeting non-immune indigenous adults was projected using a Markov chain Monte Carlo simulation model. FINDINGS: Of the 54 522 persons with hepatitis B disease notified between 1 January 2005 and 31 December 2012, 1953  infections were newly acquired. Acute hepatitis B infection notification rates were significantly higher for indigenous than non-indigenous Australians. The rates per 100 000 population for all ages were 3.6 (156/4 368 511) and 1.1 (1797/168 449 302) for indigenous and non-indigenous people respectively. The rate ratio of age-standardized notifications was 4.0 (95% confidence interval: 3.7-4.3). If 50% of non-immune indigenous adults (20% of all indigenous adults) were vaccinated over a 10-year programme a projected 527-549 new cases of acute hepatitis B would be prevented. CONCLUSION: There continues to be significant health inequity between indigenous and non-indigenous Australians in relation to vaccine-preventable hepatitis B disease. An immunization programme targeting indigenous Australian adults could have considerable impact in terms of cases of acute hepatitis B prevented, with a relatively low number needed to vaccinate to prevent each case.

Disseminated tuberculosis and tuberculous meningitis in Australian-born children; case reports and review of current epidemiology and management.

We present two cases of tuberculous meningitis in Australian-born children. We review the current literature surrounding management of paediatric tuberculosis and disseminated disease, emphasising the importance of prompt diagnosis and intervention. We discuss the epidemiology of tuberculosis in the Australian paediatric population and highlight the sentinel role of childhood infection in public health surveillance.

Population-wide vaccination against human papillomavirus in adolescent boys: Australia as a case study.

Female-only vaccination programmes for human papillomavirus (HPV) have been introduced in many countries aimed at the prevention of cervical cancer in women. One HPV vaccine is registered for male vaccination, but boys, men, or both, are not yet included in nationally funded HPV vaccination programmes. In this Review we discuss the different considerations relevant to the introduction of population-wide HPV vaccination of boys in Australia, which was the first country to publicly fund HPV vaccination of girls. Several factors need to be taken into account during decision making around the introduction of population-based vaccination programmes, such as local disease burden, vaccine efficacy, vaccine safety, and cost-effectiveness. Social and ethical factors are also important. Although evidence for men is increasing in these areas, uncertainties need to be kept in mind. The features discussed in this Review are likely to be applicable, with caveats, to policy making in other developed countries.

Reduction in rotavirus-associated acute gastroenteritis following introduction of rotavirus vaccine into Australia's National Childhood vaccine schedule.

INTRODUCTION: : Rotavirus vaccines were introduced into the funded Australian National Immunization Program (NIP) in July 2007. Due to purchasing arrangements, individual states and territories chose either a 2-dose RV1 (Rotarix, GSK) regimen or 3-dose RV5 (Rotateq, Merck/CSL) regimen. This allowed comparison of both vaccines in similar populations with high infant vaccination coverage. METHODS: : Admission and rotavirus identification data from the major pediatric hospitals in 3 states (2 using RV5, 1 RV1), together with state-based hospitalization and vaccination data from Queensland (RV5) were analyzed for the years before, and up to 30 months following rotavirus vaccine introduction. Emergency encounters and short-stay unit admissions for gastroenteritis are also described. RESULTS: : Rotavirus vaccine coverage in Australia is high, with 87% of infants receiving at least 1 dose. Hospital admissions for both rotavirus gastroenteritis and nonrotavirus-coded gastroenteritis were reduced following vaccine introduction in all states, not only for the age group eligible for NIP rotavirus vaccination, but also for children born prior. RV5 vaccine efficacy in Queensland has been estimated at 89.3%. Marked reductions in acute gastroenteritis emergency presentations and short-stay unit admissions have also been observed. CONCLUSIONS: : Early evidence from the NIP in Australia has demonstrated high rotavirus coverage with both RV1 and RV5. The introduction of both vaccines has been associated with a marked reduction in gastroenteritis admissions, supportive of both direct vaccine protection, as well as with indirect herd protection.

The cost-effectiveness of rotavirus vaccination in Australia.

Rotavirus is a common cause of acute gastroenteritis in young children. Two rotavirus vaccines with demonstrated safety and efficacy in large scale clinical trials have recently received universal funding in Australia. We modelled specific outcomes of disease (hospitalisations, emergency department visits, general practitioner visits, and deaths) and examined the effectiveness and cost-effectiveness of both vaccines in the Australian context. From the healthcare payer perspective, the base-case showed only slightly different results for the two vaccines (Rotarix would cost $60,073/QALY gained and RotaTeq $67,681/QALY gained). From a societal perspective both vaccines were found to be cost saving under base-case assumptions. Rotavirus vaccination could be considered a cost-effective health intervention in Australia, however, the cost-effectiveness ratio depends heavily on several parameters, most notably the appropriate scope of the quality of life impact (that of the child, and one or both caregivers), as well as the negotiated vaccine price for a routine program.

Burden of severe rotavirus disease in Australia.

AIM: To analyse the epidemiology of coded rotavirus hospitalisations in Australia from 1993 to 2002, with a view to understanding the pre-vaccination burden of severe disease in Australia. This study also seeks to determine the burden of rotavirus-related mortality. METHODS: Hospitalisation data from the Australian Institute of Health and Welfare for the period 1993-2002 were analysed. Rotavirus-related mortality data from the National Mortality Database were also analysed for the period 1990-2002. RESULTS: There were an average of 4260 patients hospitalised for rotavirus each year. The majority of rotavirus hospitalisations occurred in those under the age of 5 years, with the highest rate being in those aged 6-12 months (618.4 per 100,000). The Northern Territory was the most distinct region, with exceptionally high rates of admission (148.9 per 100,000 total population), younger age of admission and longer lengths of stay. Mapping of rotavirus hospitalisation in Australia showed well-defined areas of high hospitalisation rates. Thirteen rotavirus-related deaths occurred during 1990-2002. CONCLUSION: Rotavirus infection causes considerable morbidity and mortality in Australia. A vaccination programme would need to be completed by 6 months of age to have maximal impact.