Natalie Carvalho

Background: High sugar consumption causes dental caries and type 2 diabetes mellitus (T2D), a risk factor of periodontal disease. People experiencing socioeconomic disadvantage experience oral diseases more than their less disadvantaged counterparts. We simulated impacts of an overall sugar tax and a sugar-sweetened beverage (SSB) tax on population health and oral health inequalities.Methods: Data sources include 2019 US Census, 2017-18 US National Health and Nutrition Examination survey, 2019 Global Burden of Disease Study and relative risks from rapid literature reviews. Three state Healthy-Sick-Dead simulation model in R software was tailored using principles of proportional multistate lifetable model for adults aged 20-84 years in 2019 to simulate dental caries, T2D, periodontal disease and tooth loss. Population health changes were quantified as additional Disability-Adjusted-Life-Years (DALYs) averted in 10 years, 25 years and lifetime under a sugar tax and SSB tax, taking 2019 as the base year. Stratified models based on baseline prevalence of outcomes and sugar consumption by household wealth were simulated to generate impacts of interventions on socioeconomic inequalities in oral health outcomes.Findings: Without any intervention, 378 (95% Uncertainty Interval (UI): 359, 397) undiscounted DALYs per 1000 persons over the lifetime of the 2019 adult population were estimated. Under the sugar tax this would be reduced to undiscounted 194 (UI: 124, 267) DALYs per 1000 persons, while under SSB tax, to undiscounted 316 (UI: 284, 348) DALYs per 1000 persons. For dental caries and tooth loss, both SSB tax and sugar tax were equitable. Only SSB tax was equitable overall for all conditions.Interpretation: Policy interventions including sugar tax and SSB tax would significantly reduce oral diseases at the population level and reduce socioeconomic inequalities in oral health.

Background: Evidence of the effectiveness and cost-effectiveness of new vaccines that reduce the burden of respiratory syncytial virus (RSV) in older populations is emerging. The reported cost-effectiveness of these vaccination strategies varies substantially across different settings. This study assessed the cost-effectiveness of older adult-targeted RSV vaccination strategies in the Australian context and compared findings with published evaluations. Methods: We developed an individual-based dynamic transmission model of RSV infection, linked to a clinical pathways and cost-effectiveness model. We modelled different adult vaccination strategies for the general population and the Indigenous population, and present incremental cost-effectiveness ratios (ICERs) as cost per quality-adjusted life year gained, from a healthcare system perspective. Deterministic and probabilistic sensitivity analyses explored drivers of cost-effectiveness and sensitivity of findings to uncertainty in parameter estimates. Results: Vaccinating the general population of older adults in Australia was not found to be cost-effective at a dose price of 100 AUD, but was found to be cost-saving for Indigenous adults, given the higher disease burden in this population. Individual drivers of ICERs in our setting were dose price, hospitalisation incidence and mortality, however conclusions about cost-effectiveness were robust to joint parameter uncertainty. Conclusions: The cost-effectiveness of vaccinating adults against RSV depends on many uncertain and context-specific quantities. Strategies that target high risk populations were found to be cost-effective in Australia due to the larger avertable burden. Key Summary Points: Why Carry Out This Study?: Respiratory syncytial virus (RSV) is a significant cause of respiratory illness and death, particularly in older adults, individuals with medical conditions, and Indigenous populations. The reported cost-effectiveness of RSV vaccination strategies varies substantially across different settings. With the Australian Government beginning to fund RSV vaccines from May 2026, this study aimed to provide timely, Australia-specific evidence on which vaccination strategies offer the greatest benefit relative to their cost. What Was Learned from the Study?: A structured literature review confirmed substantial variability in how costs and benefits of RSV vaccination are evaluated across settings, underscoring the importance of context-specific evidence and transparent reporting when informing national vaccination policy decisions. In our analysis, vaccinating Indigenous Australians aged 60 years and over was found to save money for the health system while also preventing hospitalisations and deaths, primarily because of the high burden of RSV in this population. Vaccinating the broader older adult population was not found to be good value for money at the vaccine prices and willingness-to-pay thresholds assumed in this study. The most influential drivers of cost-effectiveness were vaccine price and in-hospital case fatality rate - two factors that remain uncertain in the Australian context and warrant ongoing monitoring.

Two immunising products are emerging to prevent the burden of respiratory syncytial virus (RSV) in infants: long-lasting monoclonal antibodies (mAbs) and maternal vaccines given during pregnancy (MV). This study assesses the potential cost-effectiveness of programs involving each product to help inform policy decisions related to their implementation in the Australian context. We developed an individual-based dynamic transmission model of RSV infection, linked to a clinical pathways model and cost-effectiveness model. We modelled key scenarios exploring varying eligibility and coverage of immunisation products for at-risk and not-at-risk populations, in addition to sensitivity analyses of immunisation characteristics, program costs and the impact of potential under-ascertainment of RSV burden. We estimated the cost-effectiveness of each program from a health system perspective, with results presented as incremental cost-effectiveness ratios in terms of cost per quality-adjusted life year gained (QALY). We found a combined program in which administration of MV during pregnancy is supplemented with a birth-dose of mAbs for newborns born without protection from MV is likely to be cost-saving, compared with the status quo of no MV or mAbs delivered. This program averted on average 41% of infant hospitalisations per year and reduced QALY losses by 33%. Programs combining infant immunisation products are likely to significantly reduce the burden of RSV disease in Australia, and be cost-saving. However, their estimated impact and cost-effectiveness is strongly dependent on key assumptions (i) the consistency and completeness of ascertainment of disease burden over time; (ii) the cost of a hospitalisation and immunising dose; (iii) the efficacy and durability of protection of the modelled products; and (iv) the timing and coverage of the immunisation delivery.

Lao People’s Democratic Republic (PDR) introduced a National Health Insurance (NHI) scheme in 2016 to all provinces except Vientiane Capital City. We describe the financial impact on households related to treatment of severe childhood illness at a hospital covered by NHI, and one without NHI. We conducted a prospective cohort study (2022–2024) in Lao PDR of children aged one month to 10% annual household expenditure) rates and analysed relative risk (RR) of CHE by socioeconomic status. 200 participants were recruited from each hospital with demographic differences observed between hospitals in urban residence (NCH 87.0%, SPH 14.5%), maternal education (primary level: NCH 95.9%, SPH 76.3%) and wealth status (wealthiest quintile: NCH 79.0%, SPH 20.5%). Median household OOP costs were higher at NCH (USD290.6 [IQR 206.9–422.9]) compared to SPH (USD92.4 [IQR 56.3–52.9]). Impoverishment at two months post-discharge was 0.5% (95%CI 0.0-3.0) at NCH and 10.2% (95%CI 6.2-15.4) at SPH. CHE rates were 34.5% (95%CI 27.9-41.1) at NCH and 26.0% (95%CI 19.9-32.1) at SPH, with higher RR in the poorest versus wealthiest households (NCH: RR 6.6, 95%CI 4.5-9.5; SPH: RR 4.9, 95%CI 1.7-13.7) and households with no formal maternal education versus secondary education (NCH: RR 2.6, 95%CI 1.2-5.5; SPH: RR 4.6, 95%CI 1.92-11.1). Direct medical costs were lower at the provincial hospital where NHI is available, but total OOP costs and CHE rates were high at both hospitals, particularly among disadvantaged households. Additional interventions are required to prevent severe illness and provide financial protection for socioeconomically disadvantaged groups to reduce health-related economic burden on households in Lao PDR.

Background: The introduction of rotavirus vaccine (RVV), pneumococcal conjugate vaccine (PCV) and human papillomavirus vaccine (HPVV) has been slow in Pacific Island Countries, particularly among middle-income countries. To assist decision-making on the simultaneous introduction of these three vaccines, cost-effectiveness and budget impact evaluations were undertaken in Samoa, Tonga, Tuvalu and Vanuatu, using locally relevant data. Methods and findings: A proportionate outcomes model was used to evaluate vaccine introduction in each country from a health systems perspective, using country-specific data supplemented with regional and global estimates. A 10-year vaccination program was modelled from 2021, with costs and outcomes (disability-adjusted life years [DALYs]) summed over a life-time horizon and discounted at 3%. Vaccine dose costs were based on Pan American Health Organization (PAHO) Revolving Fund prices, with lower-priced products also explored. Introduction of all three vaccines in all countries could prevent over 1,000 deaths over the lifetimes of the vaccinated cohorts. The cost per DALY averted at PAHO Revolving Fund prices ranged from 42% to 73% of the per capita gross domestic product (GDP) in each country, and 15% to 58% for lower-priced vaccines. The budget impact ranged from 359% (Samoa) to 1,368% (Vanuatu) of the 2019 vaccine budgets, and 149% (Samoa) to 775% (Vanuatu) for lower-priced vaccines. Cost-effectiveness results were most sensitive to disease burden, discount rate, vaccine efficacy, and program costs. A limitation of our study is the reliance on data from Fiji to inform disease burden, as availability of country-specific data was limited. Conclusions: With development partner support, introduction of HPVV, PCV and RVV may represent good value for money in Samoa, Tonga, Tuvalu and Vanuatu, depending on willingness to pay thresholds. However, inclusion of these three vaccines will place considerable burden on immunisation budgets. Financial sustainability requires increases in immunisation budgets and negotiation of affordable vaccine prices. This analysis provides evidence of the benefit of introducing new vaccines, but shows the importance of affordable pricing to ensure sustainability for small Pacific Island countries.

Background Pneumococcal conjugate vaccines (PCVs) cover only a proportion of disease-causing serotypes. In some settings, population-level introduction of PCVs has resulted in an increase in “non-vaccine” serotype incidence. Higher-valency PCVs were developed to address shifting disease-causing serotypes. We aim to systematically define the trends in vaccine immunogenicity and likely protection over time. Methods We conducted a systematic review and meta-analysis of studies published to Jan 7, 2025, reporting immunoglobulin G (IgG) responses after PCV vaccination in healthy children 95% for all serotypes except serotype 3 (84–92%). A general “downward trend” in IgG GMCs was observed with the increasing vaccine valency. IgG responses increased with the number of primary doses, and were further enhanced by a booster, although magnitude varied by serotype and vaccine. IgG responses post 1-primary dose were low, whereas GMCs post 2- or 3-primary doses exceeded protective thresholds for most serotypes. Booster-containing schedules (3+1, 2+1, 1+1) generally elicited higher post-childhood-schedule IgG response than primary-only schedule (3+0). We observed substantial regional variation of post-childhood-schedule serotype-specific IgG GMCs, with highest GMCs in the Western Pacific Region. Interpretation Vaccine immunogenicity varied by serotype, vaccine product, schedule and WHO region, and should be carefully considered when evaluating potential vaccination programs. Funding PhD Scholarship; Australian Department of Foreign Affairs and Trade. Research in context Evidence before this study We implemented a targeted literature review strategy to identify prior evidence in PubMed on August 14, 2023, without time and language restrictions, using the following search strategies: ((streptococcus pneumoniae[Title]) OR (pneumococc*[Title]) AND (immun*[Title] OR antibod*[Title]) AND (review[Filter])). We identified six systematic reviews quantitatively evaluating the serotype-specific immune responses following pneumococcal conjugate vaccine (PCV) in infants. All reviews focused on PCV7, PCV10-GSK, and PCV13; none included the newer higher-valency PCVs (PCV15, PCV20) or the novel PCV10-SII. Two early reviews (2011) compared 2-dose versus 3-dose primary series in randomized clinical trials (RCTs), reporting differences in seroresponse rates — greatest for serotypes 6B and 23F — without accounting for specific vaccine products. Two reviews in 2014 further explored the impact of dosing schedules, vaccine product, and region on immune responses, but only a subset of vaccine-included serotypes was analysed. A 2020 review investigated regional variation in post-primary responses but was restricted to RCTs and did not assess post-booster immune responses. A 2023 review of head-to-head RCTs in infants comparing PCV7, PCV10-GSK and PCV13 found that 1-month post-primary serotype-specific IgG geometric mean ratios favoured PCV7 over either PCV13 or PCV10 for serotypes 4, 6B, 9V, 14, and 23F. Added value of this study PCV15 and PCV20 were developed in response to changes in patterns of disease-causing serotypes, whereas PCV10-SII was designed for developing countries with distinct serotype distribution. To date, however, no systematic review has synthesised all available PCV data and compared the immunogenicity of newer vaccines relative to earlier ones. As immunogenicity remains the cornerstone of vaccination recommendations in the absence of representative effectiveness studies, our study quantifies and compares immune responses to five widely used PCVs across alternative dosing regimens, populations, and epidemiological contexts. Implications of all the available evidence Vaccine immunogenicity varied by serotype, vaccine product, schedule and World Health Organization (WHO) region. Downward trend of serotype-specific IgG response was generally observed with increasing vaccine valency for most serotypes, indicating the importance of balancing vaccine serotype coverage and the magnitude of immune response for sustained population protection. This evidence should be considered when evaluating potential vaccination programs.

Introduction: Following widespread exposure to Omicron variants, SARS-CoV-2 has transitioned to endemic circulation. Populations now have diverse infection and vaccination histories, resulting in heterogeneous immune landscapes. Careful consideration of the value of ongoing vaccination is required through the post-Omicron phase of COVID-19 management to minimise disease burden. We demonstrate the utility of a modelling approach to address this question, supporting recommendations for targeted vaccine use across different country settings. Methods: We integrated immunological, transmission, clinical and cost-effectiveness models and simulated populations with different characteristics and immune landscapes over the early post-Omicron period. We calculated the expected number of infections, hospitalisations and deaths for different vaccine scenarios. Costs (from a healthcare perspective) were estimated for exemplar country income-level groupings in the Western Pacific Region using pandemic-era vaccine prices and healthcare-seeking behaviour assumptions. We assessed the impact and cost-effectiveness of targeted vaccination strategies. Results are reported as incremental costs and disability-adjusted life years averted compared with no additional vaccination. Parameter and stochastic uncertainty were captured through scenario and sensitivity analysis. Results: Across different population demographics and income levels, we consistently found that annual elder-targeted boosting strategies are most likely to be cost-effective or cost-saving (>75% probability of being cost-effective among older, high-income settings; >50% probability of being cost-effective in younger, middle-income settings), while paediatric programmes are unlikely to be cost-effective. Results remained broadly consistent while accounting for uncertainties in the epidemiological and economic models, although they were sensitive to the cost of home-based care and vaccination. Use of pandemic-era vaccine prices may underestimate current vaccine prices available in upper-middle-income and high-income settings, potentially overestimating the cost-effectiveness of boosting in these settings. Half-yearly boosting may only be cost-effective in higher income settings with older population demographics and higher cost-effectiveness thresholds. Conclusion: Competing health priorities and resource constraints mean COVID-19 vaccine allocation needs to be carefully considered in context. These results, reflecting modelling conducted on the early post-Omicron period, demonstrate the value of continued booster vaccinations to protect against severe COVID-19 disease outcomes across high-income and middle-income settings and show that the biggest health gains relative to vaccine costs are achieved by targeting older age groups.

Background Two immunising products are emerging to prevent the burden of respiratory syncytial virus (RSV) in infants: long-lasting monoclonal antibodies (mAbs) and maternal vaccines given during pregnancy (MV). This study assesses the potential cost-effectiveness of programs involving each product, to help inform policy decisions related to their implementation in the Australian context. Methods We developed an individual-based dynamic transmission model of RSV infection, linked to a clinical pathways model and cost-effectiveness model. We modelled key scenarios exploring varying eligibility and coverage of immunisation products for at-risk and not-at-risk populations, in addition to sensitivity analyses of immunisation characteristics, program costs, and the impact of potential under-ascertainment of RSV burden. We estimated the cost-effectiveness of each program from a health system perspective, with results presented as incremental cost-effectiveness ratios in terms of cost per quality-adjusted life year gained (QALY). Findings We found a combined program in which administration of MV during pregnancy is supplemented with a birth-dose of mAbs for newborns born without protection from MV is likely to be cost-saving, compared to the status quo of no MV or mAbs delivered. This program averted on average 41% of infant hospitalisations per year and reduced QALY losses by 33%. Interpretation Programs combining infant immunisation products are likely to significantly reduce the burden of RSV disease in Australia, and be cost-saving. However, their estimated impact and cost-effectiveness is strongly dependent on key assumptions i) the consistency and completeness of ascertainment of disease burden over time; ii) the cost of a hospitalisation and immunising dose; iii) the efficacy and durability of protection of the modelled products, and; iv) the timing and coverage of the immunisation delivery. Funding This modelling was commissioned by the National Immunisation Division of the Australian Government Department of Health, Disability and Ageing.

Antenatal anaemia affects 48% of pregnant women in South Asia. In Bangladesh, the standard of care is oral iron and folic acid supplementation, but access and adherence are poor. Intravenous iron is an alternative treatment that deliver high dose of iron in a single short infusion and is commonly used in high-income countries. A demonstration project will be conducted to test the real-world feasibility and acceptability of implementing an intravenous iron intervention to treat pregnant women with moderate and severe anaemia in the primary healthcare setting of Bangladesh. This protocol paper outlines the development, implementation, and evaluation of an intravenous iron intervention. The demonstration project consists of three phases, supported by implementation science frameworks: (1) a formative phase involving a review, qualitative research, and readiness assessment; (2) the development and implementation of care pathways and strategies using a participatory research approach; and (3) a process evaluation of care pathways and strategies involving qualitative and quantitative assessment of the costs, processes and contextual factors affecting its implementation. Intravenous iron presents a novel opportunity to reduce antenatal anaemia in low-and-middle income countries. The demonstration project will ascertain whether an intravenous iron intervention can be effectively introduced into routine antenatal care and the extent to which it is considered an acceptable treatment by pregnant women, healthcare providers, and policymakers. If successful, insights into the care pathways and costs will provide guidance for integrating intravenous iron in the primary healthcare system of Bangladesh and other low-and-middle income countries.