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Abstract Background Studies have shown that the coronavirus (COVID-19) pandemic negatively impacted the mental health of young Australians. However, there is limited longitudinal research exploring how individual factors and COVID-19 related public-health restrictions influenced mental health in young people over the acute phase of the COVID-19 pandemic. This study aimed to identify risk and protective factors associated with changes in individual symptoms of anxiety and depression among young Australians during the COVID-19 pandemic. Methods This prospective cohort study collected data on anxiety and depression symptoms of young Australians aged 15–29 years old using the Depression, Anxiety and Stress Scale short form (DASS-21). We delivered four online questionnaires from April 2020 to August 2021 at intervals of 3, 6, and 12 months after the initial survey. We implemented linear mixed-effects regression models to determine the association among demographic, socioeconomic, lifestyle and COVID–19 public health restrictions related factors and the severity of anxiety and depression symptoms over time. Results Analyses included 1936 young Australians eligible at baseline. There was a slight increase in DASS-21 anxiety mean scores from timepoint 3 to timepoint 4. DASS-21 depression scores showed slight fluctuations across timepoints with the highest mean score observed in timepoint 2. Factors associated with increases in anxiety and depression severity symptoms included LGBTQIA + identity, financial insecurity both before and during the pandemic, higher levels of loneliness, withdrawal or deferral of studies, spending more time on social media, and difficulties to sleep. Risk factors for only depression symptoms include unemployment during COVID-19 pandemic and being in lockdown. Living with someone was a protective factor for both anxiety and depression symptoms, pre-COVID-19 unemployment for depression symptoms, and older age and unemployment during the pandemic for anxiety symptoms. Conclusion These findings indicate that during the first year of the pandemic in Australia, there were significant changes in young people’s mental health which were associated with multiple demographic, socioeconomic, lifestyle, and lockdown factors. Hence, in future public health crises, we suggest more inclusive guidelines that involve young people in their development and implementation ensuring that their unique perspectives and needs are adequately considered.

Summary: Background: As Greater Mekong Subregion countries approach malaria elimination, the motivation and social role of community health workers (CHWs), and malaria blood examination rates, have declined in parallel with decreasing malaria burden. To address this issue, a health system model which expanded the role for CHWs was co-designed with communities and health stakeholders in the Mekong Subregion and field-tested in Myanmar. Methods: An open stepped-wedge cluster-randomised (at the village-level) controlled trial (ClinicalTrials.gov NCT04695886) was conducted in 72 villages in Myanmar from Nov 1, 2021 to April 17, 2022 to evaluate the effectiveness and cost-effectiveness of the expanded CHW model. One-off and continuous implementation costs of the models were calculated. Findings: A total of 2886 malaria rapid diagnostic tests (RDTs) (control period: 1365; intervention period: 1521) were undertaken across 72 villages during the 24-week study period. Compared to the existing CHW model, the introduction of an expanded role for CHWs resulted in a 23% relative increase in village weekly malaria blood examination rates by RDT, the primary outcome, (adjusted incidence rate ratio (AIRR) = 1.23, 95% CI = 1.01, 1.50, p = 0.036), adjusting for time and season. A 3.3-fold relative increase in village weekly referral rate of dengue, tuberculosis, diarrhoea, or RDT-negative fever cases after the introduction of the expanded CHW model (AIRR = 3.17, 95% CI = 1.23, 8.18, p = 0.017), was also observed. The total cost per CHW per five-year period was US$14,794 for the expanded CHW model and $5816 for the existing CHW model. Interpretation: An expanded CHW model, co-designed with communities and health stakeholders, can increase malaria blood examination rates in malaria elimination settings and referral rates for other infectious diseases. Expanded CHW models will facilitate maintaining annual blood examination rates required for malaria elimination accreditation by the WHO. Funding: An International Multilateral Donor (QSE-M-UNOPS-BI-20864-007-40).

Introduction Despite universal access to government-funded direct-acting antivirals (DAAs) in 2016, the rate of hepatitis C treatment uptake in Australia has declined substantially. Most hepatitis C is related to injecting drug use; reducing the hepatitis C burden among people who inject drugs (PWID) is, therefore, paramount to reach hepatitis C elimination targets. Increasing DAA uptake by PWID is important for interrupting transmission and reducing incidence, as well as reducing morbidity and mortality and improving quality of life of PWID and meeting Australia’s hepatitis C elimination targets.Methods and analysis A cluster randomised cross-over trial will be conducted with three intervention arms and a control arm. Arm A will receive rapid hepatitis C virus (HCV) antibody testing; arm B will receive rapid HCV antibody and rapid RNA testing; arm C will receive rapid HCV antibody testing and same-day treatment initiation for HCV antibody-positive participants; the control arm will receive standard of care. The primary outcomes will be (a) the proportion of participants with HCV commencing treatment and (b) the proportion of participants with HCV achieving cure. Analyses will be conducted on an intention-to-treat basis with mixed-effects logistic regression models.Ethics and dissemination The study has been approved by the Alfred Ethics Committee (number HREC/64731/Alfred-2020-217547). Each participant will provide written informed consent. Reportable adverse events will be reported to the reviewing ethics committee. The findings will be presented at scientific conferences and published in peer-reviewed journals.Trial registration number NCT05016609.Trial progression The study commenced recruitment on 9 March 2022 and is expected to complete recruitment in December 2024.

[This corrects the article DOI: 10.1371/journal.pmed.1003818.].

IntroductionA disproportionate number of COVID-19 deaths occur in Residential Aged Care Facilities (RACFs), where better evidence is needed to target COVID-19 interventions to prevent mortality. This study used an agent-based model to assess the role of community prevalence, vaccination strategies, and non-pharmaceutical interventions (NPIs) on COVID-19 outcomes in RACFs in Victoria, Australia.MethodsThe model simulated outbreaks in RACFs over time, and was calibrated to distributions for outbreak size, outbreak duration, and case fatality rate in Victorian RACFs over 2022. The number of incursions to RACFs per day were estimated to fit total deaths and diagnoses over time and community prevalence.Total infections, diagnoses, and deaths in RACFs were estimated over July 2023–June 2024 under scenarios of different: community epidemic wave assumptions (magnitude and frequency); RACF vaccination strategies (6-monthly, 12-monthly, no further vaccines); additional non-pharmaceutical interventions (10, 25, 50% efficacy); and reduction in incursions (30% or 60%).ResultsTotal RACF outcomes were proportional to cumulative community infections and incursion rates, suggesting potential for strategic visitation/staff policies or community-based interventions to reduce deaths. Recency of vaccination when epidemic waves occurred was critical; compared with 6-monthly boosters, 12-monthly boosters had approximately 1.2 times more deaths and no further boosters had approximately 1.6 times more deaths over July 2023–June 2024. Additional NPIs, even with only 10–25% efficacy, could lead to a 13–31% reduction in deaths in RACFs.ConclusionFuture community epidemic wave patterns are unknown but will be major drivers of outcomes in RACFs. Maintaining high coverage of recent vaccination, minimizing incursions, and increasing NPIs can have a major impact on cumulative infections and deaths.

Background Menstrual health is essential for gender equity and the well-being of women and girls. Qualitative research has described the burden of poor menstrual health on health and education; however, these impacts have not been quantified, curtailing investment. The Adolescent Menstrual Experiences and Health Cohort (AMEHC) Study aims to describe menstrual health and its trajectories across adolescence, and quantify the relationships between menstrual health and girls’ health and education in Khulna, Bangladesh.Methods and analysis AMEHC is a prospective longitudinal cohort of 2016 adolescent girls recruited at the commencement of class 6 (secondary school, mean age=12) across 101 schools selected through a proportional random sampling approach. Each year, the cohort will be asked to complete a survey capturing (1) girls’ menstrual health and experiences, (2) support for menstrual health, and (3) health and education outcomes. Survey questions were refined through qualitative research, cognitive interviews and pilot survey in the year preceding the cohort. Girls’ guardians will be surveyed at baseline and wave 2 to capture their perspectives and household demographics. Annual assessments will capture schools’ water, sanitation and hygiene, and support for menstruation and collect data on participants’ education, including school attendance and performance (in maths, literacy). Cohort enrolment and baseline survey commenced in February 2023. Follow-up waves are scheduled for 2024, 2025 and 2026, with plans for extension. A nested subcohort will follow 406 post-menarche girls at 2-month intervals throughout 2023 (May, August, October) to describe changes across menstrual periods. This protocol outlines a priori hypotheses regarding the impacts of menstrual health to be tested through the cohort.Ethics and dissemination AMEHC has ethical approval from the Alfred Hospital Ethics Committee (369/22) and BRAC James P Grant School of Public Health Institutional Review Board (IRB-06 July 22-024). Study materials and outputs will be available open access through peer-reviewed publication and study web pages.

Abstract Background and Aim The availability of direct‐acting antiviral (DAA) treatment and point‐of‐care diagnostic testing has made hepatitis C (HCV) elimination possible even in low‐ and middle‐income countries (LMICs); however, testing and treatment costs remain a barrier. We estimated the cost and cost‐effectiveness of a decentralized community‐based HCV testing and treatment program (CT2) in Myanmar. Methods Primary cost data included the costs of DAAs, investigations, medical supplies and other consumables, staff salaries, equipment, and overheads. A deterministic cohort‐based Markov model was used to estimate the average cost of care, the overall quality‐adjusted life years (QALYs) gained, and the incremental cost‐effectiveness ratio (ICER) of providing testing and DAA treatment compared with a modeled counterfactual scenario of no testing and no treatment. Results From 30 January to 30 September 2019, 633 patients were enrolled, of whom 535 were HCV RNA‐positive, 489 were treatment eligible, and 488 were treated. Lifetime discounted costs and QALYs of the cohort in the counterfactual no testing and no treatment scenario were estimated to be USD61790 (57 898–66 898) and 6309 (5682–6363) respectively, compared with USD123 248 (122 432–124 101) and 6518 (5894–6671) with the CT2 model of care, giving an ICER of USD294 (192–340) per QALY gained. This “one‐stop‐shop” model of care has a 90% likelihood of being cost‐effective if benchmarked against a willingness to pay of US$300, which is 20% of Myanmar's GDP per capita (2020). Conclusions The CT2 model of HCV care is cost‐effective in Myanmar and should be expanded to meet the National Hepatitis Control Program's 2030 target, alongside increasing the affordability and accessibility of services.

Introduction Globally, resources for health spending, including HIV and tuberculosis (TB), are constrained, and a substantial gap exists between spending and estimated needs. Optima is an allocative efficiency modelling tool that has been used since 2010 in over 50 settings to generate evidence for country-level HIV and TB resource allocation decisions. This evaluation assessed the utilisation of modelling to inform financing priorities from the perspective of country stakeholders and their international partners.Methods In October to December 2021, the World Bank and Burnet Institute led 16 semi-structured small-group virtual interviews with 54 representatives from national governments and international health and funding organisations. Interviews probed participants’ roles and satisfaction with Optima analyses and how model findings have had been used and impacted resource allocation. Interviewed stakeholders represented nine countries and 11 different disease programme-country contexts with prior Optima modelling analyses. Interview notes were thematically analysed to assess factors influencing the utilisation of modelling evidence in health policy and outcomes.Results Common influences on utilisation of Optima findings encompassed the perceived validity of findings, health system financing mechanisms, the extent of stakeholder participation in the modelling process–including engagement of funding organisations, sociopolitical context and timeliness of the analysis. Using workshops can facilitate effective stakeholder engagement and collaboration. Model findings were often used conceptually to localise global evidence and facilitate discussion. Secondary outputs included informing strategic and financial planning, funding advocacy, grant proposals and influencing investment shifts.Conclusion Allocative efficiency modelling has supported evidence-informed decision-making in numerous contexts and enhanced the conceptual and practical understanding of allocative efficiency. Most immediately, greater involvement of country stakeholders in modelling studies and timing studies to key strategic and financial planning decisions may increase the impact on decision-making. Better consideration for integrated disease modelling, equity goals and financing constraints may improve relevance and utilisation of modelling findings.

Introduction Longitudinal studies can provide timely and accurate information to evaluate and inform COVID-19 control and mitigation strategies and future pandemic preparedness. The Optimise Study is a multidisciplinary research platform established in the Australian state of Victoria in September 2020 to collect epidemiological, social, psychological and behavioural data from priority populations. It aims to understand changing public attitudes, behaviours and experiences of COVID-19 and inform epidemic modelling and support responsive government policy.Methods and analysis This protocol paper describes the data collection procedures for the Optimise Study, an ongoing longitudinal cohort of ~1000 Victorian adults and their social networks. Participants are recruited using snowball sampling with a set of seeds and two waves of snowball recruitment. Seeds are purposively selected from priority groups, including recent COVID-19 cases and close contacts and people at heightened risk of infection and/or adverse outcomes of COVID-19 infection and/or public health measures. Participants complete a schedule of monthly quantitative surveys and daily diaries for up to 24 months, plus additional surveys annually for up to 48 months. Cohort participants are recruited for qualitative interviews at key time points to enable in-depth exploration of people’s lived experiences. Separately, community representatives are invited to participate in community engagement groups, which review and interpret research findings to inform policy and practice recommendations.Ethics and dissemination The Optimise longitudinal cohort and qualitative interviews are approved by the Alfred Hospital Human Research Ethics Committee (# 333/20). The Optimise Study CEG is approved by the La Trobe University Human Ethics Committee (# HEC20532). All participants provide informed verbal consent to enter the cohort, with additional consent provided prior to any of the sub studies. Study findings will be disseminated through public website (https://optimisecovid.com.au/study-findings/) and through peer-reviewed publications.Trial registration number NCT05323799.

Abstract Background Policy responses to COVID-19 in Victoria, Australia over 2020–2021 have been supported by evidence generated through mathematical modelling. This study describes the design, key findings, and process for policy translation of a series of modelling studies conducted for the Victorian Department of Health COVID-19 response team during this period. Methods An agent-based model, Covasim, was used to simulate the impact of policy interventions on COVID-19 outbreaks and epidemic waves. The model was continually adapted to enable scenario analysis of settings or policies being considered at the time (e.g. elimination of community transmission versus disease control). Model scenarios were co-designed with government, to fill evidence gaps prior to key decisions. Results Understanding outbreak risk following incursions was critical to eliminating community COVID-19 transmission. Analyses showed risk depended on whether the first detected case was the index case, a primary contact of the index case, or a ‘mystery case’. There were benefits of early lockdown on first case detection and gradual easing of restrictions to minimise resurgence risk from undetected cases. As vaccination coverage increased and the focus shifted to controlling rather than eliminating community transmission, understanding health system demand was critical. Analyses showed that vaccines alone could not protect health systems and need to be complemented with other public health measures. Conclusions Model evidence offered the greatest value when decisions needed to be made pre-emptively, or for questions that could not be answered with empiric data and data analysis alone. Co-designing scenarios with policy-makers ensured relevance and increased policy translation.

The impact of outbreak response immunization (ORI) can be estimated by comparing observed outcomes to modelled counterfactual scenarios without ORI, but the most appropriate metrics depend on stakeholder needs and data availability. This study developed a framework for using mathematical models to assess the impact of ORI for vaccine-preventable diseases. Framework development involved (1) the assessment of impact metrics based on stakeholder interviews and literature reviews determining data availability and capacity to capture as model outcomes; (2) mapping investment in ORI elements to model parameters to define scenarios; (3) developing a system for engaging stakeholders and formulating model questions, performing analyses, and interpreting results; and (4) example applications for different settings and pathogens. The metrics identified as most useful were health impacts, economic impacts, and the risk of severe outbreaks. Scenario categories included investment in the response scale, response speed, and vaccine targeting. The framework defines four phases: (1) problem framing and data sourcing (identification of stakeholder needs, metrics, and scenarios); (2) model choice; (3) model implementation; and (4) interpretation and communication. The use of the framework is demonstrated by application to two outbreaks, measles in Papua New Guinea and Ebola in the Democratic Republic of the Congo. The framework is a systematic way to engage with stakeholders and ensure that an analysis is fit for purpose, makes the best use of available data, and uses suitable modelling methodology.

Abstract Between June and August 2020, an agent-based model was used to project rates of COVID-19 infection incidence and cases diagnosed as positive from 15 September to 31 October 2020 for 72 geographic settings. Five scenarios were modelled: a baseline scenario where no future changes were made to existing restrictions, and four scenarios representing small or moderate changes in restrictions at two intervals. Post hoc, upper and lower bounds for number of diagnosed Covid-19 cases were compared with actual data collected during the prediction window. A regression analysis with 17 covariates was performed to determine correlates of accurate projections. It was found that the actual data fell within the lower and upper bounds in 27 settings and out of bounds in 45 settings. The only statistically significant predictor of actual data within the predicted bounds was correct assumptions about future policy changes (OR 15.04; 95% CI 2.20–208.70; p = 0.016). Frequent changes in restrictions implemented by governments, which the modelling team was not always able to predict, in part explains why the majority of model projections were inaccurate compared with actual outcomes and supports revision of projections when policies are changed as well as the importance of modelling teams collaborating with policy experts.

Plain language summary The new WHO Labour Care Guide (LCG) is an innovative partograph that emphasises women-centred, evidence-based care during labour and childbirth. Together with clinicians working at four hospitals in India, we will develop and test a strategy to implement the LCG into routine care in labour wards of these hospitals. We will use a randomised trial design where this LCG strategy is introduced sequentially in each of the four hospitals, in a random order. We will collect data on all women giving birth and their newborns during this period and analyse whether the LCG strategy has any effects on the use of Caesarean section, women’s and newborn’s health outcomes, and women’s experiences during labour and childbirth. While the trial is being conducted, we will also collect qualitative and quantitative data from doctors, nurses and midwives working in these hospitals, to understand their perspectives and experiences of using the LCG in their day-to-day work. In addition, we will collect economic data to understand how much the LCG strategy costs, and how much money it might save if it is effective. Through this study, our international collaboration will generate critical evidence and innovative tools to support implementation of the LCG in other countries.

Abstract The COVID-19 pandemic has brought the combined disciplines of public health, infectious disease and policy modelling squarely into the spotlight. Never before have decisions regarding public health measures and their impacts been such a topic of international deliberation, from the level of individuals and communities through to global leaders. Nor have models—developed at rapid pace and often in the absence of complete information—ever been so central to the decision-making process. However, after nearly 3 years of experience with modelling, policy-makers need to be more confident about which models will be most helpful to support them when taking public health decisions, and modellers need to better understand the factors that will lead to successful model adoption and utilization. We present a three-stage framework for achieving these ends.

Abstract Background Countries of the Greater Mekong Sub-region aim to achieve malaria elimination by 2030. In the region, malaria is concentrated in high-risk areas and populations such as forest-going mobile and migrant populations (MMPs). However, routine protective measures such as long-lasting insecticidal nets do not prevent all infectious bites in these high-risk populations. Evidence for the effectiveness of a personal protection package tailored to forest-going MMPs which is acceptable, feasible, and cost-effective for reducing malaria transmission is required to inform the malaria elimination toolkit in the region. Methods A personal protection package consisting of long-lasting insecticidal hammock net, insect repellent and health communication pamphlet was developed in consultation with relevant implementing partners from Cambodia and Lao PDR. An open stepped-wedge cluster-randomised controlled trial will be conducted over a period of 12 months in a minimum of 488 villages (~ 428 in Lao PDR and ~ 60 in Cambodia) to evaluate the effectiveness of the personal protection package. Villages will be randomised into 11 blocks, with blocks transitioned in random order from control to intervention states at monthly intervals, following a 1-month baseline period. The primary outcome of the trial is the prevalence of Plasmodium spp. infection diagnosed by rapid diagnostic test. Difference in prevalence of malaria infection will be estimated across intervention and control periods using generalized linear mixed modelling. Nested within the stepped-wedge cluster-randomised controlled trial is a mixed-methods study to explore the acceptability of the personal protection package, feasibility of implementing a personal protection package as a vector control intervention, and knowledge, attitude and practice of MMPs regarding malaria prevention; and cost-analysis to determine the cost-effectiveness of implementing a personal protection package. Discussion This study, using a rigorous design and mixed-methods methodology, will evaluate whether a personal protection package can reduce residual malaria transmission among forest-going MMPs in Cambodia and Lao PDR. It will also measure implementation research outcomes such as effectiveness of the intervention package, cost-effectiveness, acceptability, and feasibility, in order to inform potential national and regional policy. Trial registration This trial was prospectively registered on ClinicalTrials.gov (NCT05117567) on 11th November 2021

BackgroundIn 2021, the Australian Government Department of Health commissioned a consortium of modelling groups to generate evidence assisting the transition from a goal of no community COVID-19 transmission to ‘living with COVID-19’, with adverse health and social consequences limited by vaccination and other measures. Due to the extended school closures over 2020–21, maximizing face-to-face teaching was a major objective during this transition. The consortium was tasked with informing school surveillance and contact management strategies to minimize infections and support this goal.MethodsOutcomes considered were infections and days of face-to-face teaching lost in the 45 days following an outbreak within an otherwise COVID-naïve school setting. A stochastic agent-based model of COVID-19 transmission was used to evaluate a ‘test-to-stay’ strategy using daily rapid antigen tests (RATs) for close contacts of a case for 7 days compared with home quarantine; and an asymptomatic surveillance strategy involving twice-weekly screening of all students and/or teachers using RATs.FindingsTest-to-stay had similar effectiveness for reducing school infections as extended home quarantine, without the associated days of face-to-face teaching lost. Asymptomatic screening was beneficial in reducing both infections and days of face-to-face teaching lost and was most beneficial when community prevalence was high.InterpretationUse of RATs in school settings for surveillance and contact management can help to maximize face-to-face teaching and minimize outbreaks. This evidence supported the implementation of surveillance testing in schools in several Australian jurisdictions from January 2022.

Abstract Background The city of Melbourne, Australia experienced two waves of the COVID-19 epidemic peaking, the first in March and a more substantial wave in July 2020. During the second wave, a series of control measure were progressively introduced that initially slowed the growth of the epidemic then resulted in decreasing cases until there was no detectable local transmission. Methods To determine the relative efficacy of the progressively introduced intervention measures, we modelled the second wave as a series of exponential growth and decay curves. We used a linear regression of the log of daily cases vs time, using a four-segment linear spline model corresponding to implementation of the three successive major public health measures. The primary model used all reported cases between 14 June and 15 September 2020 then compared the projection of the model with observed cases predicting future case trajectory up until the 31 October 2020 to assess the use of exponential models in projecting the future course and planning future interventions. The main outcome measures were the exponential daily growth constants, analysis of residuals and estimates of the 95% confidence intervals for the expected case distributions, comparison of predicted daily cases. Results The exponential growth/decay constants in the primary analysis were: 0.122 (s.e. 0.004), 0.035 (s.e. 0.005), − 0.037 (s.e. 0.011), and − 0.069 (s.e. 0.003) for the initial growth rate, Stage 3, Stage 3 + compulsory masks and Stage 4, respectively. Extrapolation of the regression model from the 14 September to the 31 October matched the decline in observed cases over this period. Conclusions The four-segment exponential model provided an excellent fit of the observed reported case data and predicted the day-to-day range of expected cases. The extrapolated regression accurately predicted the decline leading to epidemic control in Melbourne.

Background Evidence on the affordability and cost-effectiveness of interventions is critical to decision-making for clinical practice guidelines and development of national health policies. This study aimed to develop a repository of primary economic evaluations to support global maternal health guideline development and provide insights into the body of research conducted in this field. Methods A scoping review was conducted to identify and map available economic evaluations of maternal health interventions. We searched six databases (NHS Economic Evaluation Database, EconLit, PubMed, Embase, CINAHL and PsycInfo) on 20 November 2020 with no date, setting or language restrictions. Two authors assessed eligibility and extracted data independently. Included studies were categorised by subpopulation of women, level of care, intervention type, mechanism, and period, economic evaluation type and perspective, and whether the intervention is currently recommended by the World Health Organization. Frequency analysis was used to determine prevalence of parameters. Results In total 923 studies conducted in 72 countries were included. Most studies were conducted in high-income country settings (71.8%). Over half pertained to a general population of pregnant women, with the remainder focused on specific subgroups, such as women with preterm birth (6.2%) or those undergoing caesarean section (5.5%). The most common interventions of interest related to non-obstetric infections (23.9%), labour and childbirth care (17.0%), and obstetric complications (15.7%). Few studies addressed the major causes of maternal deaths globally. Over a third (36.5%) of studies were cost-utility analyses, 1.4% were cost-benefit analyses and the remainder were cost-effectiveness analyses. Conclusions This review provides a navigable, consolidated resource of economic evaluations in maternal health. We identified a clear evidence gap regarding economic evaluations of maternal health interventions in low- and middle-income countries. Future economic research should focus on interventions to address major drivers of maternal morbidity and mortality in these settings.

Abstract Background In settings with zero community transmission, any new SARS-CoV-2 outbreaks are likely to be the result of random incursions. The level of restrictions in place at the time of the incursion is likely to considerably affect possible outbreak trajectories, but the probability that a large outbreak eventuates is not known. Methods We used an agent-based model to investigate the relationship between ongoing restrictions and behavioural factors, and the probability of an incursion causing an outbreak and the resulting growth rate. We applied our model to the state of Victoria, Australia, which has reached zero community transmission as of November 2020. Results We found that a future incursion has a 45% probability of causing an outbreak (defined as a 7-day average of > 5 new cases per day within 60 days) if no restrictions were in place, decreasing to 23% with a mandatory masks policy, density restrictions on venues such as restaurants, and if employees worked from home where possible. A drop in community symptomatic testing rates was associated with up to a 10-percentage point increase in outbreak probability, highlighting the importance of maintaining high testing rates as part of a suppression strategy. Conclusions Because the chance of an incursion occurring is closely related to border controls, outbreak risk management strategies require an integrated approaching spanning border controls, ongoing restrictions, and plans for response. Each individual restriction or control strategy reduces the risk of an outbreak. They can be traded off against each other, but if too many are removed there is a danger of accumulating an unsafe level of risk. The outbreak probabilities estimated in this study are of particular relevance in assessing the downstream risks associated with increased international travel.

Objectives: The exact characteristics of a coronavirus disease 2019 (COVID-19) outbreak that trigger public health interventions are poorly defined. The aim of this study was to assess the critical timing and extent of public health interventions to contain COVID-19 outbreaks in Australia. Methods: A practical model was developed using existing epidemic data in Australia. The effective combinations of public health interventions and the critical number of daily cases for intervention commencement under various scenarios of changes in transmissibility of new variants and vaccination coverage were quantified. Results: In the past COVID-19 outbreaks in four Australian states, the number of reported cases on the day that interventions commenced strongly predicted the size and duration of the outbreaks. In the early phase of an outbreak, containing a wildtype-dominant epidemic to a low level (≤10 cases/day) would require effective combinations of social distancing and face mask use interventions to be commenced before the number of daily reported cases reaches six. Containing an Alpha-dominant epidemic would require more stringent interventions that commence earlier. For the Delta variant, public health interventions alone would not contain the epidemic unless the vaccination coverage was ≥70%. Conclusions: This study highlights the importance of early and decisive action in the initial phase of an outbreak. Vaccination is essential for containing variants.

Introduction Reducing unmet need for modern contraception and expanding access to quality maternal health (MH) services are priorities for improving women’s health and economic empowerment. To support investment decisions, we estimated the additional cost and expected health and economic benefits of achieving the United Nations targets of zero unmet need for modern contraceptive choices and 95% coverage of MH services by 2030 in select Small Island Developing States.Methods Five Pacific (Kiribati, Samoa, Solomon Islands, Tonga and Vanuatu) and four Caribbean (Barbados, Guyana, Jamaica and Saint Lucia) countries were considered based on population survey data availability. For each country, the Lives Saved Tool was used to model costs, health outcomes and economic benefits for two scenarios: business-as-usual (BAU) (coverage maintained) and coverage-targets-achieved, which scaled linearly from 2022 (following COVID-19 disruptions) coverage of evidence-based family planning and MH interventions to reach United Nations targets, including modern contraceptive methods and access to complete antenatal, delivery and emergency care. Unintended pregnancies, maternal deaths, stillbirths and newborn deaths averted by the coverage-targets-achieved scenario were converted to workforce, education and social economic benefits; and benefit–cost ratios were calculated.Results The coverage-targets-achieved scenario required an additional US$12.6M (US$10.8M−US$15.9M) over 2020–2030 for the five Pacific countries (15% more than US$82.4M to maintain BAU). This additional investment was estimated to avert 126 000 (40%) unintended pregnancies, 2200 (28%) stillbirths and 121 (29%) maternal deaths and lead to a 15-fold economic benefit of US$190.6M (US$67.0M−US$304.5M) by 2050. For the four Caribbean countries, an additional US$17.8M (US$15.3M−US$22.4M) was needed to reach the targets (4% more than US$405.4M to maintain BAU). This was estimated to avert 127 000 (23%) unintended pregnancies, 3600 (23%) stillbirths and 221 (25%) maternal deaths and lead to a 24-fold economic benefit of US$426.2M (US$138.6M−US$745.7M) by 2050.Conclusion Achieving full coverage of contraceptive and MH services in the Pacific and Caribbean is likely to have a high return on investment.

Introduction With limited resources, attaining maximal average health service coverage can be at odds with maximising equity which attempts to promote greater reach among underserved populations. In this study, we examined the trade-offs in immunisation coverage levels and equity for children under 5 years of age in Pakistan across various subpopulations who can be targeted with different combinations of immunisation service modalities.Methods We conducted a detailed costing exercise across 16 geographically and demographically diverse districts in Pakistan. These data were the basis for (a) technical efficiency benchmarking via Data Envelopment Analysis to identify potential efficiency gains by location, delivery model and cost ingredient; (b) allocative efficiency optimisation modelling to understand how resource allocations could be optimised and to devise recommended budget allocations and operational metrics. Finally, the hypothetical overall efficiency gains attainable were estimated if available resources were allocated with the optimal emphases, and if service delivery models operated at productivity levels at the benchmarked frontier of efficiency.Results Benchmarking suggests that ~44% of delivery models are running efficiently and 37% are highly inefficient. While coverage and equity are usually at odds, surprisingly, the optimisation modelling revealed that substantial improvements in equity between subpopulations does not necessarily cost very much in overall immunisation coverage: theoretically, equity can be achieved while still attaining close to maximal immunisation coverage. Overall, analyses suggest greater emphases should be placed on outreach delivery models which particularly target rural areas and slum populations.Conclusion The unit cost differentials within districts are not sufficiently large for there to be a large reduction in potential Fully Immunised Children coverage if one focuses on maximising equity. However, reallocations of programme budgets can have a significant impact on equity outcomes, particularly at current low spending amounts. Therefore, it is recommended to address equity as the key objective in national immunisation programming.

Summary: Background: After considerable debate, there is now unequivocal evidence that use of antenatal corticosteroids improves outcomes in preterm neonates when used in women at risk of early preterm birth in reasonably equipped hospitals in low-resource countries. We aimed to evaluate the cost-effectiveness of dexamethasone administration in the management of preterm birth in a cohort of pregnant women from five low-resource countries. Methods: We performed a cost-effectiveness analysis using data from 2828 women (and 3051 babies) who participated in the WHO ACTION-I trial, a multicentre, randomised, placebo-controlled trial that assessed the safety and efficacy of dexamethasone in pregnant women at risk of early preterm birth in 29 hospitals across Bangladesh, India, Kenya, Nigeria, and Pakistan. We used a decision tree model to assess the cost-effectiveness of dexamethasone treatment compared with no intervention from a health-care sector perspective. Outcome data were taken from the primary results of the trial and primary data on cost were collected in 28 hospitals. The primary cost-effectiveness outcome was cost per neonatal death or the cost per disability-adjusted life-years (DALYs) averted, or costs saved per 1000 woman–baby units if the intervention was found to be cost-saving. Findings: Administration of dexamethasone averted 38 neonatal deaths per 1000 woman–baby units and 1132 DALYs per 1000 woman–baby units. Compared with no intervention, use of antenatal corticosteroids was cost-saving in all five countries, ranging from a saving of US$1778 per 1000 woman–baby units (95% uncertainty interval [UI] –13 878 to 9483) in Nigeria, to $20 531 per 1000 woman–baby units (–46 387 to 4897) in Pakistan, to $36 870 per 1000 woman–baby units (–61 569 to –15 672) in Bangladesh, to $38 303 per 1000 woman–baby units (–64 183 to –10 753) in India, and to $53 681 per 1000 woman–baby units (–113 822 to 2394) in Kenya. Findings remained consistent following sensitivity analyses. In all five countries, dexamethasone was more effective and cost less compared with no treatment. Interpretation: Antenatal dexamethasone for early preterm birth was cost-saving when used in hospitals in low-resource countries. Decision makers in low-resource settings can be confident that use of antenatal dexamethasone for early preterm birth is cost-effective, and often cost-saving when used in reasonably equipped hospitals in low-resource countries. Funding: Bill & Melinda Gates Foundation and WHO.

The Pacific Island country of Vanuatu is considering strategies to remove border restrictions implemented during 2020 to prevent imported coronavirus disease. We performed mathematical modeling to estimate the number of infectious travelers who had different entry scenarios and testing strategies. Travel bubbles and testing on entry have the greatest importation risk reduction.

Summary: Background: Preterm birth is a leading cause of neonatal mortality and morbidity, and imposes high health and societal costs. Antenatal corticosteroids (ACS) to accelerate fetal lung maturation are commonly used in conjunction with tocolytics for arresting preterm labour in women at risk of imminent preterm birth. Methods: We conducted a systematic review on the cost-effectiveness of ACS and/or tocolytics as part of preterm birth management. We systematically searched MEDLINE and Embase (December 2021), as well as a maternal health economic evidence repository collated from NHS Economic Evaluation Database, EconLit, PubMed, Embase, CINAHL and PsycInfo, with no date cutoff. Eligible studies were economic evaluations of ACS and/or tocolytics for preterm birth. Two reviewers independently screened citations, extracted data on cost-effectiveness and assessed study quality using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement. Findings: 35 studies were included: 11 studies on ACS, eight on tocolytics to facilitate ACS administration, 12 on acute and maintenance tocolysis, and four studies on a combination of ACS and tocolytics. ACS was cost-effective prior to 34 weeks’ gestation, but economic evidence on ACS use at 34-

Abstract Background To achieve malaria elimination in the Greater Mekong Subregion, including Myanmar, it is necessary to ensure all malaria cases are detected, treated, and reported in a timely manner. Mobile phone-based applications for malaria reporting, case management, and surveillance implemented at a community-level may overcome reporting limitations associated with current paper-based reporting (PBR), but their effectiveness in this context is unknown. Methods A mixed methods evaluation study was undertaken to determine the effectiveness of a national Malaria Case-Based Reporting (MCBR) mobile phone application in improving malaria case reporting compared to the existing PBR reporting system in Myanmar. Methods included secondary analysis of malaria case report data, questionnaires, focus group discussions and field observations of community volunteers, interviews and direct observations of malaria programme stakeholders, and cost analysis. Using a combination of these approaches the following areas were investigated: data quality and completeness, data access and usage, capacity for timely reporting, the acceptability, functionality, and ease of use of the application and facilitators and barriers to its use, and the relative cost of MCBR compared to the PBR system. Results Compared to PBR, MCBR enabled more accurate and complete data to be reported in a much timelier manner, with 63% of MCBR users reporting they transmit rapid diagnostic test outcomes within 24 h, compared to 0% of PBR users. MCBR was favoured by integrated community malaria volunteers and their supervisors because of its efficiency. However, several technical and operational challenges associated with internet coverage, data transmission, and e-literacy were identified and stakeholders reported not being confident to rely solely on MCBR data for programmatic decision-making. Conclusions Implementation of MCBR provided timely and accurate data for malaria surveillance. Findings from this evaluation study will enable the optimization of an application-based reporting system for malaria monitoring and surveillance in the Greater Mekong Subregion and advance systems to track progress towards, and certify, the achievement of malaria elimination targets.

Abstract Background Sustainable Development Goal (SDG) 2.2 calls for an end to all forms of malnutrition, with 2025 targets of a 40% reduction in stunting (relative to 2012), for wasting to occur in less than 5% of children, and for a 50% reduction in anaemia in women (15–49 years). We assessed the likelihood of countries reaching these targets by scaling up proven interventions and identified priority interventions, based on cost-effectiveness. Methods For 129 countries, the Optima Nutrition model was used to compare 2019–2030 nutrition outcomes between a status quo (maintained intervention coverage) scenario and a scenario where outcome-specific interventions were scaled up to 95% coverage over 5 years. The average cost-effectiveness of each intervention was calculated as it was added to an expanding package of interventions. Results Of the 129 countries modelled, 46 (36%), 66 (51%) and 0 (0%) were on track to achieve the stunting, wasting and anaemia targets respectively. Scaling up 18 nutrition interventions increased the number of countries reaching the SDG 2.2 targets to 50 (39%), 83 (64%) and 7 (5%) respectively. Intermittent preventative treatment of malaria during pregnancy (IPTp), infant and young child feeding education, vitamin A supplementation and lipid-based nutrition supplements for children produced 88% of the total impact on stunting, with average costs per case averted of US$103, US$267, US$556 and US$1795 when interventions were consecutively scaled up, respectively. Vitamin A supplementation and cash transfers produced 100% of the total global impact on prevention of wasting, with average costs per case averted of US$1989 and US$19,427, respectively. IPTp, iron and folic acid supplementation for non-pregnant women, and multiple micronutrient supplementation for pregnant women produced 85% of the total impact on anaemia prevalence, with average costs per case averted of US$9, US$35 and US$47, respectively. Conclusions Prioritising nutrition investment to the most cost-effective interventions within the country context can maximise the impact of funding. A greater focus on complementing nutrition-specific interventions with nutrition-sensitive ones that address the social determinants of health is critical to reach the SDG targets.

Abstract Aims We report on motivations for crystal methamphetamine-opioid co-use/co-injection through narratives of people who inject drugs during a period of increased crystal methamphetamine use reporting in Australia. Methods Fourteen in-depth interviews were undertaken with selected participants (12 male, 2 female) from the Melbourne Injecting Drug User Cohort Study, including those in and out of opioid substitution therapy (OST). Results The main motivations for co-use reported by participants were as follows: (1) that heroin could be used to reduce the negative side effects of heavy crystal methamphetamine use, particularly during the ‘comedown’ phase; (2) that small quantities of crystal methamphetamine used with heroin could prolong the intoxication effect of heroin, and hence the time before opioid withdrawal; (3) that co-injection of crystal methamphetamine and heroin produced a more desirable intoxication effect than using either substance on its own and; (4) that crystal methamphetamine provided a substitute ‘high’ for heroin after commencing OST treatment. Conclusions Co-use of methamphetamine and opioids has been used by people who inject drugs to facilitate intoxication, sometimes as the result of ineffective opioid substitution therapy (OST) treatment and perceived lack of pleasure after stabilisation on OST treatment.

Timely birth dose vaccination is key for achieving elimination of hepatitis B, however, programmatic requirements for delivering current vaccine presentations to births outside of health facilities inhibits coverage within many low-and middle-income countries (LMICs). Vaccine technologies in development such as microarray patches (MAPs) could assist in overcoming these barriers, but procurement could incur higher per-dose commodity costs than current ten-dose (US$0.34) and single-dose (US$0.62) vial presentations, necessitating an evaluation of the economic value proposition for MAPs. Within 80 LMICs offering universal hepatitis B birth dose vaccination, the cost-effectiveness of using MAPs to expand coverage was evaluated using a mathematical model. We considered three potential per dose MAP prices (US$1.65, US$3.30, and US$5.00), and two potential MAP use-cases: (1) MAPs are used by lay-health workers to expand birth dose coverage outside of health facility settings, and (2) MAPs are also preferred by qualified health workers, replacing a proportion of existing coverage from vaccine vials. Analysis took the health system perspective, was costed in 2020 US$, and discounted at 3% annually. Across minimal (1% additional coverage) and maximal (10% additional and 10% replacement coverage) MAP usage scenarios, between 2.5 (interquartile range [IQR]: 1.9, 3.1) and 38 (IQR: 28,44) thousand DALYs were averted over the estimated 2020 birth cohort lifetime in 80 LMICs. Efficiency of MAPs was greatest when used to provide additional coverage (scenario 1), on average saving US$88.65 ($15.44, $171.22) per DALY averted at a price of US$5.00 per MAP. Efficiency was reduced when used to replace existing coverage (scenario 2); however, at prices up to US$5.00 per MAP, we estimate this use-case could remain cost-effective in at least 73 (91%) modelled LMICs. Our findings suggest even at higher procurement costs, MAPs are likely to represent a highly cost-effective or cost-saving mechanism to expand reach of birth dose vaccination in LMICs.

BackgroundModelling suggests that achieving the WHO incidence target for hepatitis C virus (HCV) elimination in Pakistan could cost US$3.87 billion over 2018 to 2030. However, the economic benefits from integrating services or improving productivity were not included.Methods and findingsWe adapt a HCV transmission model for Pakistan to estimate the impact, costs, and cost-effectiveness of achieving HCV elimination (reducing annual HCV incidence by 80% by 2030) with stand-alone service delivery, or partially integrating one-third of initial HCV testing into existing healthcare services. We estimate the net economic benefits by comparing the required investment in screening, treatment, and healthcare management to the economic productivity gains from reduced HCV-attributable absenteeism, presenteeism, and premature deaths. We also calculate the incremental cost-effectiveness ratio (ICER) per disability-adjusted life year (DALY) averted for HCV elimination versus maintaining current levels of HCV treatment. This is compared to an opportunity cost-based willingness-to-pay threshold for Pakistan (US$148 to US$198/DALY). Compared to existing levels of treatment, scaling up screening and treatment to achieve HCV elimination in Pakistan averts 5.57 (95% uncertainty interval (UI) 3.80 to 8.22) million DALYs and 333,000 (219,000 to 509,000) HCV-related deaths over 2018 to 2030. If HCV testing is partially integrated, this scale-up requires an investment of US$1.45 (1.32 to 1.60) billion but will result in US$1.30 (0.94 to 1.72) billion in improved economic productivity over 2018 to 2030. This elimination strategy is highly cost-effective (ICER = US$29 per DALY averted) by 2030, with it becoming cost-saving by 2031 and having a net economic benefit of US$9.10 (95% UI 6.54 to 11.99) billion by 2050. Limitations include uncertainty around what level of integration is possible within existing primary healthcare services as well as a lack of Pakistan-specific data on disease-related healthcare management costs or productivity losses due to HCV.ConclusionsInvestment in HCV elimination can bring about substantial societal health and economic benefits for Pakistan.

Introduction In the Greater Mekong Subregion, community health workers, known as malaria volunteers, have played a key role in reducing malaria in the control phase, providing essential malaria services in areas with limited formal healthcare. However, the motivation and social role of malaria volunteers, and testing rates, have declined with decreasing malaria burden and reorientation of malaria programmes from control to elimination. Provision of additional interventions for common health concerns could help sustain the effectiveness of volunteers and maintain malaria testing rates required for malaria elimination accreditation by the WHO.Methods and analysis The Community-delivered Integrated Malaria Elimination (CIME) volunteer model, integrating interventions for malaria, dengue, tuberculosis, childhood diarrhoea and malaria Rapid Diagnostic Test (RDT)-negative fever, was developed based on global evidence and extensive stakeholder consultations. An open stepped-wedge cluster-randomised controlled trial, randomised at the volunteer level, will be conducted over 6 months to evaluate the effectiveness of the CIME model in Myanmar. One hundred and forty Integrated Community Malaria Volunteers (ICMVs, current model of care) providing malaria services in 140 villages will be retrained as CIME volunteers (intervention). These 140 ICMVs/villages will be grouped into 10 blocks of 14 villages, with blocks transitioned from control (ICMV) to intervention states (CIME), fortnightly, in random order, following a 1-week training and transition period. The primary outcome of the trial is blood examination rate determined by the number of malaria RDTs performed weekly. Difference in rates will be estimated across village intervention and control states using a generalised linear mixed modelling analytical approach with maximum likelihood estimation.Ethics and dissemination The study was approved by Institutional Review Board, Myanmar Department of Medical Research (Ethics/DMR/2020/111) and Alfred Hospital Ethics Review Committee, Australia (241/20). Findings will be disseminated in peer-review journals, conferences and regional, national and local stakeholder meetings.Trial registration number NCT04695886

The COVID-19 pandemic has created an urgent need for models that can project epidemic trends, explore intervention scenarios, and estimate resource needs. Here we describe the methodology of Covasim (COVID-19 Agent-based Simulator), an open-source model developed to help address these questions. Covasim includes country-specific demographic information on age structure and population size; realistic transmission networks in different social layers, including households, schools, workplaces, long-term care facilities, and communities; age-specific disease outcomes; and intrahost viral dynamics, including viral-load-based transmissibility. Covasim also supports an extensive set of interventions, including non-pharmaceutical interventions, such as physical distancing and protective equipment; pharmaceutical interventions, including vaccination; and testing interventions, such as symptomatic and asymptomatic testing, isolation, contact tracing, and quarantine. These interventions can incorporate the effects of delays, loss-to-follow-up, micro-targeting, and other factors. Implemented in pure Python, Covasim has been designed with equal emphasis on performance, ease of use, and flexibility: realistic and highly customized scenarios can be run on a standard laptop in under a minute. In collaboration with local health agencies and policymakers, Covasim has already been applied to examine epidemic dynamics and inform policy decisions in more than a dozen countries in Africa, Asia-Pacific, Europe, and North America.

Abstract Background Tuberculosis (TB) control efforts are hampered by an imperfect understanding of TB epidemiology. The true age distribution of disease is unknown because a large proportion of individuals with active TB remain undetected. Understanding of transmission is limited by the asymptomatic nature of latent infection and the pathogen’s capacity for late reactivation. A better understanding of TB epidemiology is critically needed to ensure effective use of existing and future control tools. Methods We use an agent-based model to simulate TB epidemiology in the five highest TB burden countries—India, Indonesia, China, the Philippines and Pakistan—providing unique insights into patterns of transmission and disease. Our model replicates demographically realistic populations, explicitly capturing social contacts between individuals based on local estimates of age-specific contact in household, school and workplace settings. Time-varying programmatic parameters are incorporated to account for the local history of TB control. Results We estimate that the 15–19-year-old age group is involved in more than 20% of transmission events in India, Indonesia, the Philippines and Pakistan, despite representing only 5% of the local TB incidence. According to our model, childhood TB represents around one fifth of the incident TB cases in these four countries. In China, three quarters of incident TB were estimated to occur in the ≥ 45-year-old population. The calibrated per-contact transmission risk was found to be similar in each of the five countries despite their very different TB burdens. Conclusions Adolescents and young adults are a major driver of TB in high-incidence settings. Relying only on the observed distribution of disease to understand the age profile of transmission is potentially misleading.

Abstract Background The introduction of highly effective direct-acting antiviral (DAA) therapy for hepatitis C has led to calls to eliminate it as a public health threat through treatment-as-prevention. Recent studies suggest it is possible to develop a vaccine to prevent hepatitis C. Using a mathematical model, we examined the potential impact of a hepatitis C vaccine on the feasibility and cost of achieving the global WHO elimination target of an 80% reduction in incidence by 2030 in the era of DAA treatment. Methods The model was calibrated to 167 countries and included two population groups (people who inject drugs (PWID) and the general community), features of the care cascade, and the coverage of health systems to deliver services. Projections were made for 2018–2030. Results The optimal incidence reduction strategy was to implement test and treat programmes among PWID, and in settings with high levels of community transmission undertake screening and treatment of the general population. With a vaccine available, the optimal strategy was to include vaccination within test and treat programmes, in addition to vaccinating adolescents in settings with high levels of community transmission. Of the 167 countries modelled, between 0 and 48 could achieve an 80% reduction in incidence without a vaccine. This increased to 15–113 countries if a 75% efficacious vaccine with a 10-year duration of protection were available. If a vaccination course cost US$200, vaccine use reduced the cost of elimination for 66 countries (40%) by an aggregate of US$7.4 (US$6.6–8.2) billion. For a US$50 per course vaccine, this increased to a US$9.8 (US$8.7–10.8) billion cost reduction across 78 countries (47%). Conclusions These findings strongly support the case for hepatitis C vaccine development as an urgent public health need, to ensure hepatitis C elimination is achievable and at substantially reduced costs for a majority of countries.

Background: Myanmar has set national hepatitis C (HCV) targets to achieve 50% of people diagnosed and 50% treated by 2030. The WHO has additional targets of reducing incidence by 80% and mortality by 65% by 2030. We aimed to estimate the impact, cost, cost-effectiveness and net economic benefit of achieving these targets. Methods: Mathematical models of HCV transmission, disease progression and the care cascade were calibrated to 15 administrative regions of Myanmar. Cost data were collected from a community testing and treatment program in Yangon. Three scenarios were projected for 2020–2030: (1) baseline (current levels of testing/treatment); and testing/treatment scaled up sufficiently to reach (2) the national strategy targets; and (3) the WHO targets. Findings: Without treatment scale-up, 333,000 new HCV infections and 97,000 HCV-related deaths were estimated to occur in Myanmar 2020–2030, with HCV costing a total $100 million in direct costs (testing, treatment, disease management) and $10.4 billion in lost productivity. In the model, treating 55,000 people each year was sufficient to reach the national strategy targets and prevented a cumulative 40,000 new infections (12%) and 25,000 HCV-related deaths (25%) 2020–2030. This was estimated to cost a total $189 million in direct costs ($243 per DALY averted compared to no treatment scale-up), but only $9.8 billion in lost productivity, making it cost-saving from a societal perspective by 2024 with an estimated net economic benefit of $553 million by 2030. Reaching the WHO targets required further treatment scale-up and additional direct costs but resulted in greater longer-term benefits. Interpretation: Current levels of HCV testing and treatment in Myanmar are insufficient to reach the national strategy targets. Scaling up HCV testing and treatment in Myanmar to reach the national strategy targets is estimated to generate significant health and economic benefits. Funding: Gilead Sciences.

Objectives The early stages of the COVID-19 pandemic illustrated that SARS-CoV-2, the virus that causes the disease, has the potential to spread exponentially. Therefore, as long as a substantial proportion of the population remains susceptible to infection, the potential for new epidemic waves persists even in settings with low numbers of active COVID-19 infections, unless sufficient countermeasures are in place. We aim to quantify vulnerability to resurgences in COVID-19 transmission under variations in the levels of testing, tracing and mask usage.Setting The Australian state of New South Wales (NSW), a setting with prolonged low transmission, high mobility, non-universal mask usage and a well-functioning test-and-trace system.Participants None (simulation study).Results We find that the relative impact of masks is greatest when testing and tracing rates are lower and vice versa. Scenarios with very high testing rates (90% of people with symptoms, plus 90% of people with a known history of contact with a confirmed case) were estimated to lead to a robustly controlled epidemic. However, across comparable levels of mask uptake and contact tracing, the number of infections over this period was projected to be 2–3 times higher if the testing rate was 80% instead of 90%, 8–12 times higher if the testing rate was 65% or 30–50 times higher with a 50% testing rate. In reality, NSW diagnosed 254 locally acquired cases over this period, an outcome that had a moderate probability in the model (10%–18%) assuming low mask uptake (0%–25%), even in the presence of extremely high testing (90%) and near-perfect community contact tracing (75%–100%), and a considerably higher probability if testing or tracing were at lower levels.Conclusions Our work suggests that testing, tracing and masks can all be effective means of controlling transmission. A multifaceted strategy that combines all three, alongside continued hygiene and distancing protocols, is likely to be the most robust means of controlling transmission of SARS-CoV-2.

BackgroundWhilst evidence of use of face masks in reducing COVID-19 cases is increasing, the impact of mandatory use across a large population has been difficult to assess. Introduction of mandatory mask use on July 22, 2020 during a resurgence of COVID-19 in Melbourne, Australia created a situation that facilitated an assessment of the impact of the policy on the epidemic growth rate as its introduction occurred in the absence of other changes to restrictions.Methods and findingsExponential epidemic growth or decay rates in daily COVID-19 diagnoses were estimated using a non-weighted linear regression of the natural logarithm of the daily cases against time, using a linear spline model with one knot (lspline package in R v 3.6.3). The model's two linear segments pivot around the hinge day, on which the mask policy began to take effect, 8 days following the introduction of the policy. We used two forms of data to assess change in mask usage: images of people wearing masks in public places obtained from a major media outlet and population-based survey data. Potential confounding factors (including daily COVID-19 tests, number of COVID-19 cases among population subsets affected differentially by the mask policy-e.g., healthcare workers) were examined for their impact on the results. Daily cases fitted an exponential growth in the first log-linear segment (k = +0.042, s.e. = 0.007), and fitted an exponential decay in the second (k = -0.023, s.e. = 0.017) log-linear segment. Over a range of reported serial intervals for SARS-CoV-2 infection, these growth rates correspond to a 22-33% reduction in an effective reproduction ratio before and after mandatory mask use. Analysis of images of people in public spaces showed mask usage rose from approximately 43% to 97%. Analysis of survey data found that on the third day before policy introduction, 44% of participants reported "often" or "always" wearing a mask; on the fourth day after, 100% reported "always" doing so. No potentially confounding factors were associated with the observed change in growth rates.ConclusionsThe mandatory mask use policy substantially increased public use of masks and was associated with a significant decline in new COVID-19 cases after introduction of the policy. This study strongly supports the use of masks for controlling epidemics in the broader community.

INTRODUCTION:Botswana offers publicly financed HIV treatment to citizens, but not migrants, who comprised about 7% of the population in 2016. However, HIV incidence is not declining in proportion to Botswana's HIV response. In 2018, Botswana had 86% of citizens living with HIV diagnosed, 95% of people diagnosed on treatment, and 95% viral suppression among those on treatment. We hypothesised that continued exclusion of migrants is hampering reduction of HIV incidence in Botswana. Hence, we modelled the impact of including migrants in Botswana's HIV response on achieving 90-90-90 and 95-95-95 Fast-Track targets by 2020 and 2030, respectively. METHODS:The Optima HIV model, with demographic, epidemiological, and behavioural inputs, was applied to citizens of and migrants to Botswana. Projections of new HIV infections and HIV-related deaths were compared for three scenarios to the end of 2030: (1) continued status quo for HIV testing and treatment coverage, and maintenance of levels of linkage to care, loss to follow-up, and viral suppression among citizens and migrants (baseline); (2) with scaled-up budget, optimised to achieve 90-90-90 and 95-95-95 Fast-Track targets by 2020 and 2030, respectively, for citizens only; and (3) scaled-up optimised budget to achieve these targets for both citizens and migrants. RESULTS:A baseline of 172,000 new HIV infections and 8,400 HIV-related deaths was projected over 2020-2030. Scaling up to achieve targets among citizens only averted an estimated 48,000 infections and 1,700 deaths. Achieving targets for both citizens and migrants averted 16,000 (34%) more infections and 442 (26%) more deaths. Scaling up for both populations reduced numbers of new HIV infections and deaths by 44% and 39% respectively compared with 2010 levels. Treating migrants when scaling up in both populations was estimated to cost USD 74 million over 2020-2030. CONCLUSIONS:Providing HIV services to migrants in Botswana could lead to further reductions in HIV incidence and deaths. However, even with an increased, optimised budget that achieves 95-95-95 targets for both citizens and migrants by 2030, the 90% incidence reduction target for 2020 will be missed. Further efficiencies and innovations will be needed to meet HIV targets in Botswana.

Abstract Background Artemisinin-resistant Plasmodium falciparum has emerged in the Greater Mekong Subregion, an area of relatively low transmission, but has yet to be reported in Africa. A population-based mathematical model was used to investigate the relationship between P. falciparum prevalence, exposure-acquired immunity and time-to-emergence of artemisinin resistance. The possible implication for the emergence of resistance across Africa was assessed. Methods The model included human and mosquito populations, two strains of malaria (“wild-type”, “mutant”), three levels of human exposure-acquired immunity (none, low, high) with two types of immunity for each level (sporozoite/liver stage immunity and blood-stage/gametocyte immunity) and drug pressure based on per-capita treatment numbers. Results The model predicted that artemisinin-resistant strains may circulate up to 10 years longer in high compared to low P. falciparum prevalence areas before resistance is confirmed. Decreased time-to-resistance in low prevalence areas was explained by low genetic diversity and immunity, which resulted in increased probability of selection and spread of artemisinin-resistant strains. Artemisinin resistance was estimated to be established by 2020 in areas of Africa with low ( 25%) prevalence areas, respectively. Conclusions Areas of low transmission and low immunity give rise to a more rapid expansion of artemisinin-resistant parasites, corroborating historical observations of anti-malarial resistance emergence. Populations where control strategies are in place that reduce malaria transmission, and hence immunity, may be prone to a rapid emergence and spread of artemisinin-resistant strains and thus should be carefully monitored.

Background and aim: Direct-acting antiviral (DAA) treatments became available for all people living with hepatitis C virus (HCV) in Australia in March 2016. We assess variations in treatment rates and prescribing patterns across Australia's 338 Statistical Area 3 (SA3) geographical units. Methods: Geocoded DAA treatment initiation data were analysed for the period 1 March 2016 to 30 June 2017. Regression models tested associations between the population demographics and healthcare service coverage of geographical areas and (a) their treatment rates; and (b) the proportion of prescriptions written by specialists compared to non-specialists. Results: Across the 320 areas (95%) recording treatments, a median 76 (interquartile range [IQR] 35–207, range 4–3834) per 100,000 were initiated, corresponding to an estimated median 7.9% (IQR 2.9–23.6%, range 0–100%) treatment uptake. Major cities, areas of socioeconomic advantage and areas with lower proportions of the population born overseas had the highest per capita treatment rates. Non-specialists prescribed 46% (20,323/44,382) of treatment initiations. Prescriptions were written by non-specialists only in 163 areas (51%), while in other areas a median 40.0% (IQR 21.8–62.5%) of prescriptions were written by non-specialists. Non-specialist prescribing was higher in regional areas, as well as areas that had greater proportions of Indigenous Australians. Conclusions: High national-level treatment uptake of 20% in Australia masks underlying health system limitations; more than half of geographical areas may have treated less than 8% of people living with HCV. Areas of socioeconomic disadvantage and areas with a higher proportion of the population born overseas may need targeting with interventions to improve treatment uptake.

Abstract Background Child stunting due to chronic malnutrition is a major problem in low- and middle-income countries due, in part, to inadequate nutrition-related practices and insufficient access to services. Limited budgets for nutritional interventions mean that available resources must be targeted in the most cost-effective manner to have the greatest impact. Quantitative tools can help guide budget allocation decisions. Methods The Optima approach is an established framework to conduct resource allocation optimization analyses. We applied this approach to develop a new tool, ‘Optima Nutrition’, for conducting allocative efficiency analyses that address childhood stunting. At the core of the Optima approach is an epidemiological model for assessing the burden of disease; we use an adapted version of the Lives Saved Tool (LiST). Six nutritional interventions have been included in the first release of the tool: antenatal micronutrient supplementation, balanced energy-protein supplementation, exclusive breastfeeding promotion, promotion of improved infant and young child feeding (IYCF) practices, public provision of complementary foods, and vitamin A supplementation. To demonstrate the use of this tool, we applied it to evaluate the optimal allocation of resources in 7 districts in Bangladesh, using both publicly available data (such as through DHS) and data from a complementary costing study. Results Optima Nutrition can be used to estimate how to target resources to improve nutrition outcomes. Specifically, for the Bangladesh example, despite only limited nutrition-related funding available (an estimated $0.75 per person in need per year), even without any extra resources, better targeting of investments in nutrition programming could increase the cumulative number of children living without stunting by 1.3 million (an extra 5%) by 2030 compared to the current resource allocation. To minimize stunting, priority interventions should include promotion of improved IYCF practices as well as vitamin A supplementation. Once these programs are adequately funded, the public provision of complementary foods should be funded as the next priority. Programmatic efforts should give greatest emphasis to the regions of Dhaka and Chittagong, which have the greatest number of stunted children. Conclusions A resource optimization tool can provide important guidance for targeting nutrition investments to achieve greater impact.

Although different structures are used in modern tuberculosis (TB) models to simulate TB latency, it remains unclear whether they are all capable of reproducing the particular activation dynamics empirically observed. We aimed to determine which of these structures replicate the dynamics of progression accurately. We reviewed 88 TB-modelling articles and classified them according to the latency structure employed. We then fitted these different models to the activation dynamics observed from 1352 infected contacts diagnosed in Victoria (Australia) and Amsterdam (Netherlands) to obtain parameter estimates. Six different model structures were identified, of which only those incorporating two latency compartments were capable of reproducing the activation dynamics empirically observed. We found important differences in parameter estimates by age. We also observed marked differences between our estimates and the parameter values used in many previous models. In particular, when two successive latency phases are considered, the first period should have a duration that is much shorter than that used in previous studies. In conclusion, structures incorporating two latency compartments and age-stratification should be employed to accurately replicate the dynamics of TB latency. We provide a catalogue of parameter values and an approach to parameter estimation from empiric data for calibration of future TB-models.

Abstract Background The high burden of malaria and limited funding means there is a necessity to maximize the allocative efficiency of malaria control programmes. Quantitative tools are urgently needed to guide budget allocation decisions. Methods A geospatial epidemic model was coupled with costing data and an optimization algorithm to estimate the optimal allocation of budgeted and projected funds across all malaria intervention approaches. Interventions included long-lasting insecticide-treated nets (LLINs), indoor residual spraying (IRS), intermittent presumptive treatment during pregnancy (IPTp), seasonal mass chemoprevention in children (SMC), larval source management (LSM), mass drug administration (MDA), and behavioural change communication (BCC). The model was applied to six geopolitical regions of Nigeria in isolation and also the nation as a whole to minimize incidence and malaria-attributable mortality. Results Allocative efficiency gains could avert approximately 84,000 deaths or 15.7 million cases of malaria in Nigeria over 5 years. With an additional US$300 million available, approximately 134,000 deaths or 37.3 million cases of malaria could be prevented over 5 years. Priority funding should go to LLINs, IPTp and BCC programmes, and SMC should be expanded in seasonal areas. To minimize mortality, treatment expansion is critical and prioritized over some LLIN funding, while to minimize incidence, LLIN funding remained a priority. For areas with lower rainfall, LSM is prioritized over IRS but MDA is not recommended unless all other programmes are established. Conclusions Substantial reductions in malaria morbidity and mortality can be made by optimal targeting of investments to the right malaria interventions in the right areas.

Abstract Objective: Many variations of venue lockout and last‐drink policies have been introduced in attempts to reduce drinking‐related harms. We estimate the public health gains and licensee costs of these policies using a computer simulated population of young adults engaging in heavy drinking. Method: Using an agent‐based model we implemented 1 am/2 am/3 am venue lockouts in conjunction with last drinks zero/one/two hours later, or at current closing times. Outcomes included: the number of incidents of verbal aggression in public drinking venues, private venues or on the street; and changed revenue to public venues. Results: The most effective policy in reducing verbal aggression among agents was 1 am lockouts with current closing times. All policies produced substantial reductions in street‐based incidents of verbal aggression among agents (33–81%) due to the smoothing of transport demand. Direct revenue losses were 1–9% for simulated licensees, with later lockout times and longer periods between lockout and last drinks producing smaller revenue losses. Conclusion: Simulation models are useful for exploring consequences of policy change. Our simulation suggests that additional hours between lockout and last drinks could reduce aggression by easing transport demand, while minimising revenue loss to venue owners. Implications for public health: Direct policies to reduce late‐night transport‐related disputes should be considered.

Abstract Objective: To determine what percentage of Victorians with a history of notified hepatitis C exposure received appropriate follow‐up diagnostic services between 2001 and 2012. Methods: Individual notification data and aggregate Medicare and supplementary testing data were entered into a compartmental transition model, which was used to estimate the percentage of people with a hepatitis C notification who were yet to receive either a negative diagnostic test for viral nucleic acid, or a test for viral genotype, at the end of 2012. Results: We estimate that 58.2% (uncertainty interval: 42.2%, 72.4%) of Victorians with a hepatitis C notification between 2001 and 2012 did not receive either a negative test for viral nucleic acid or a viral genotyping test during the study period. At the end of 2012, we estimate there were approximately 20,400 Victorians living with hepatitis C antibodies who were yet to receive testing, of which approximately 9,300 would have been aged 45 years or older. Conclusions: A majority of people living with HCV antibodies in Victoria had not received appropriate secondary diagnostic services as of the end of 2012. Implications: As improved therapeutic options become available for people living with chronic hepatitis C, measures to support appropriate follow‐up of people with suspected or confirmed chronic infections via primary care services will be required.

Summary: Background: The World Health Assembly calls for elimination of viral hepatitis as a public health threat by 2030 (ie, −90% incidence and −65% mortality). However, WHO's 2017 cost projections to achieve health-related Sustainable Development Goals did not include the resources needed for hepatitis testing and treatment. We aimed to estimate the incremental commodity cost of adding scaled up interventions for testing and treatment of hepatitis to WHO's investment scenarios. Methods: We added modelled costs for implementing WHO recommended hepatitis testing and treatment to the 2017 WHO cost projections. We quantified additional requirements for diagnostic tests, medicines, health workers' time, and programme support across 67 low-income and middle-income countries, from 2016–30. A progress scenario scaled up interventions and a more ambitious scenario was modelled to reach elimination by 2030. We used 2018 best available prices of diagnostics and generic medicines. We estimated total costs and the additional investment needed over the projection of the 2016 baseline cost. Findings: The 67 countries considered included 230 million people living with hepatitis B virus (HBV) and 52 million people living with hepatitis C virus (HCV; 90% and 73% of the world's total, respectively). Under the progress scenario, 3250 million people (2400 million for HBV and 850 million for HCV) would be tested and 58·2 million people (24·1 million for HBV and 34·1 million for HCV) would be treated (total additional cost US$ 27·1 billion). Under the ambitious scenario, 11 631 million people (5502 million for HBV and 6129 million for HCV) would be tested and 93·8 million people (32·2 million for HBV and 61·6 million for HCV) would be treated (total additional cost $58·7 billion), averting 4·5 million premature deaths and leading to a gain of 51·5 million healthy life-years by 2030. However, if affordable HCV medicines remained inaccessible in 13 countries where medicine patents are protected, the additional cost of the ambitious scenario would increase to $118 billion. Hepatitis elimination would account for a 1·5% increase to the WHO ambitious health-care strengthening scenario costs, avert an additional 4·6% premature deaths, and add an additional 9·6% healthy life-years from 2016–30. Interpretation: Access to affordable medicines in all countries will be key to reach hepatitis elimination. This study suggests that elimination is feasible in the context of universal health coverage. It points to commodities as key determinants for the overall price tag and to options for cost reduction strategies. Funding: WHO, United States Centers for Disease Control and Prevention, Unitaid.

Summary: Background: The controlled temperature chain (CTC) strategy allows vaccines to be kept outside the cold chain for a short period of time. In remote rural areas, the CTC strategy for the hepatitis B virus (HBV) birth dose vaccination could improve its geographical coverage and timeliness of delivery, but with additional outreach costs. We assessed the cost-effectiveness of the CTC strategy for the HBV birth dose across six world regions and 72 countries according to their HBV prevalence, delivery costs, and birth dose coverage and timing. Methods: By use of a mathematical model of perinatal HBV transmission and disease progression, we calculated per 1000 births the total HBV-related disability-adjusted life-years (DALYs) and costs, including vaccine delivery costs and costs associated with HBV-related disease, with and without the CTC strategy. Findings: A CTC strategy produced health benefits in all regions and was cost-saving in the regions of east Asia and Pacific, Latin America and Caribbean, sub-Saharan Africa, and north Africa and Middle East. The CTC strategy cost US$0·15 (IQR −7·11 to 4·75) per DALY averted in the central and eastern Europe and central Asia region and $79·72 (66·47 to 94·47) in the south Asia region. Within individual countries, more savings were achieved and more DALYs averted in areas with above average HBV prevalence, below average birth dose coverage, or later than average birth dose delivery. Interpretation: A CTC outreach strategy that improves the timing and coverage of the HBV birth dose vaccination is likely to be cost-saving and reduce the burden of HBV infection associated with perinatal transmission. Funding: Burnet Institute.

BACKGROUND:Poor access to health services is a significant barrier to achieving the World Health Organization's hepatitis C virus (HCV) elimination targets. We demonstrate how geospatial analysis can be performed with commonly available data to identify areas with the greatest unmet demand for HCV services. METHODS:We performed an Australia-wide cross-sectional analysis of 2015 HCV notification rates using local government areas (LGAs) as our unit of analysis. A zero-inflated negative binomial regression was used to determine associations between notification rates and socioeconomic/demographic factors, health service and geographic remoteness area (RA) classification variables. Additionally, component scores were extracted from a principal component analysis (PCA) of the healthcare service variables to provide rankings of relative service coverage and unmet demand across Australia. RESULTS:Among LGAs with non-zero notifications, higher rates were associated with areas that had increased socioeconomic disadvantage, more needle and syringe services (incidence rate ratio [IRR] 1.022; 95%CI 1.001, 1.044) and more alcohol and other drug services (IRR 1.019; 1.005, 1.034). The distribution of PCA component scores indicated that per-capita healthcare service coverage was lower in areas outside of major Australian cities. Areas outside of major cities also contained 94% of LGAs in the lowest two socioeconomic quintiles, as well as 35% of HCV notifications despite only representing 29% of the population. CONCLUSIONS:As countries aim for HCV elimination, routinely collected data can be used to identify geographical areas for priority service delivery. In Australia, the unmet demand for HCV treatment services is greatest in socioeconomically disadvantaged and non-metropolitan areas.

To determine whether the self-reported personal wellbeing of a cohort of people who inject drugs (PWID) changes over time, and to identify longitudinal correlates of change.We used Personal Wellbeing Index (PWI) scores reported between April 2008 and February 2015 by 757 PWID (66% male) enrolled in the Melbourne Injecting Drug Use Cohort Study (2,862 interviews; up to seven follow-up waves). A mixed-effects model was used to identify correlations between changes in temporal variables and changes in individual PWI scores while controlling for demographic variables.The cohort's mean PWI score did not significantly differ over time (between 54.4/100 and 56.7/100 across the first four interview waves), and was 25-28% lower than general Australian population scores (76.0/100). However, there were large variations in individuals' PWI scores between interviews. Increased psychological distress, moving into unstable accommodation, reporting intentional overdose in the past 12 months and being the victim of assault in the past six months were associated with declines in PWI scores.Participants experienced substantially lower levels of personal wellbeing than the general Australian population, influenced by experiences of psychological distress, assault, overdose and harms related to low socioeconomic status. The results of this study suggest a need to ensure referral to appropriate housing and health support services for PWID.

BACKGROUND AND AIMS:The advent of highly effective hepatitis C (HCV) treatments has questioned the need for a vaccine to control HCV amongst people who inject drugs (PWID). However, high treatment costs and ongoing reinfection risk suggest it could still play a role. We compared the impact of HCV vaccination amongst PWID against providing HCV treatment. METHODS:Dynamic HCV vaccination and treatment models among PWID were used to determine the vaccination and treatment rates required to reduce chronic HCV prevalence or incidence in the UK over 20 or 40 years. Projections considered a low (50% protection for 5 years), moderate (70% protection for 10 years) or high (90% protection for 20 years) efficacy vaccine. Sensitivities to various parameters were examined. RESULTS:To halve chronic HCV prevalence over 40 years, the low, moderate and high efficacy vaccines required annual vaccination rates (coverage after 20 years) of 162 (72%), 77 (56%) and 44 (38%) per 1000 PWID, respectively. These vaccination rates were 16, 7.6 and 4.4 times greater than corresponding treatment rates. To halve prevalence over 20 years nearly doubled these vaccination rates (moderate and high efficacy vaccines only) and the vaccination-to-treatment ratio increased by 20%. For all scenarios considered, required annual vaccination rates and vaccination-to-treatment ratios were at least a third lower to reduce incidence than prevalence. Baseline HCV prevalence had little effect on the vaccine's impact on prevalence or incidence, but substantially affected the vaccination-to-treatment ratios. Behavioural risk heterogeneity only had an effect if we assumed no transitions between high and low risk states and vaccinations were targeted or if PWID were high risk for their first year. CONCLUSIONS:Achievable coverage levels of a low efficacy prophylactic HCV vaccine could greatly reduce HCV transmission amongst PWID. Current high treatment costs ensure vaccination could still be an important intervention option.