Cost-effectiveness analysis of COVID-19 booster doses and oral antivirals: Case studies in the Indo-Pacific.

BACKGROUND: Decision-makers in middle-income countries need evidence on the cost-effectiveness of COVID-19 booster doses and oral antivirals to appropriately prioritise these healthcare interventions. METHODS: We used a dynamic transmission model to assess the cost-effectiveness of COVID-19 booster doses and oral antivirals in Fiji, Indonesia, Papua New Guinea, and Timor-Leste. We conducted cost-effectiveness analysis from both healthcare and societal perspectives using data collated from publicly available sources. We developed an interactive R Shiny which allows the user to vary key model assumptions, such as the choice of discounting rate, and view how these assumptions affect model results. FINDINGS: Booster doses were cost saving and therefore cost-effective in all four middle-income settings from both healthcare and societal perspectives using 3% discounting. Providing oral antivirals was cost-effective from a healthcare perspective if procured at a low generic price (US$25) or middle-income reference price (US$250); however, their cost-effectiveness was strongly influenced by rates of wastage or misuse, and the ongoing costs of care for patients hospitalised with COVID-19. The cost or wastage of rapid antigen tests did not appear strongly influential over the cost-effectiveness of oral antivirals in any of the four study settings. CONCLUSIONS: Our results support that COVID-19 booster programs are cost-effective in middle-income settings. Oral antivirals demonstrate the potential to be cost-effective if procured at or below a middle-income reference price of US$250 per schedule. Further research should quantify the rates of wastage or misuse of oral COVID-19 antivirals in middle-income settings.

Burden and Cost of Campylobacter Risk Factors in Australia.

Campylobacter is a globally important pathogen with well-studied risk factors, but the burden of risk factors has not been quantified. We quantified the cost of illness attributable to specific domestic risk factors for C. jejuni and C. coli in Australia. We used data from a 2018-2019 case-control study to estimate odds ratios and attributable fractions for risk factors. We used data on national incidence, hospitalization, and premature mortality to quantify burden. We then applied costs related to healthcare utilization, pain and suffering, premature mortality, and lost productivity to each risk factor. In Australia, C. jejuni caused 83.0% of campylobacteriosis infections and chicken consumption resulted in the highest attributable fraction (30.0%), costing approximately US$110 million annually. The excess burden of campylobacteriosis associated with the use of proton-pump inhibitors (PPIs) was US$45 million, with almost half these costs due to disease in adults over 65 years of age. Contact with young dogs (US$30 million) and chicken feces (US$10 million) also contributed to costs and burden. Campylobacteriosis is a significant cost to Australia, particularly because of lost productivity. Effective cross-sectoral interventions to improve chicken meat safety and reduce inappropriate use of PPIs might have substantial economic and human benefits.

Investigating a Novel Two-Bag N-Acetylcysteine Regimen for Acetaminophen Toxicity.

BACKGROUND: Acetaminophen toxicity remains one of the most common causes of liver failure and is treated with a course of n-acetylcysteine (NAC). This exceptionally effective medication is traditionally administered using a complicated three-bag protocol that is prone to administration errors. OBJECTIVE: We aimed to assess whether switching to a novel two-bag protocol (150 mg/kg over 1 h followed by 150 mg/kg over 20 h) reduced administration errors while not increasing liver injury or anaphylactoid reactions. METHODS: This was a retrospective chart review of hospital encounters for patients with acetaminophen toxicity, comparing outcomes before and after the change from a three-bag protocol to a two-bag protocol at two affiliated institutions. The primary outcome was incidence of medication errors with secondary outcomes including acute liver injury (ALI) and incidence of non-anaphylactoid allergic reactions (NAAR). The study was approved by the health system's Institutional Review Board. RESULTS: 483 encounters were included for analysis (239 in the three-bag and 244 in the two-bag groups). NAAR were identified in 11 patients with no difference seen between groups. Similarly, no differences were seen in ALI. Medication administration errors were observed significantly less often in the two-bag group (OR 0.24) after adjusting for confounders. CONCLUSION: Transitioning to a novel two-bag NAC regimen decreased administration errors. This adds to the literature that two-bag NAC regimens are not only safe but also may have significant benefits over the traditional NAC protocol.

African swine fever in wild boar: investigating model assumptions and structure.

African swine fever (ASF) is a highly virulent viral disease that affects domestic pigs and wild boar. Current ASF transmission in Europe is in part driven by wild boar populations, which act as a disease reservoir. Wild boar are abundant throughout Europe and are highly social animals with complex social organization. Despite the known importance of wild boar in ASF spread and persistence, knowledge gaps remain surrounding wild boar transmission. We developed a wild boar modelling framework to investigate the influence of contact-density functions and wild boar social structure on disease dynamics. The framework included an ordinary differential equation model, a homogeneous stochastic model and various network-based stochastic models that explicitly included wild boar social grouping. We found that power-law functions (transmission ∝ density0.5) and frequency-based contact-density functions were best able to reproduce recent Baltic outbreaks; however, power-law function models predicted considerable carcass transmission, while frequency-based models had negligible carcass transmission. Furthermore, increased model heterogeneity caused a decrease in the relative importance of carcass-based transmission. The transmission pathways predicted by each model type affected the efficacy of idealized interventions, which highlights the importance of evaluating model type and structure when modelling systems with significant uncertainties.

Mathematical modelling of the 100-day target for vaccine availability after the detection of a novel pathogen: A case study in Indonesia.

Globally, there has been a commitment to produce and distribute a vaccine within 100 days of the next pandemic. This 100-day target will place pressure on countries to make swift decisions on how to optimise vaccine delivery. We used data from the COVID-19 pandemic to inform mathematical modelling of future pandemics in Indonesia for a wide range of pandemic characteristics. We explored the benefits of vaccination programs with different start dates, rollout capacity, and age-specific prioritisation within a year of the detection of a novel pathogen. Early vaccine availability, public uptake of vaccines, and capacity for consistent vaccine delivery were the key factors influencing vaccine benefit. Monitoring age-specific severity will be essential for optimising vaccine benefit. Our study complements existing pathogen-specific pandemic preparedness plans and contributes a tool for the rapid assessment of future threats in Indonesia and similar middle-income countries.

Spatio-Temporal Variation in the Exceedance of Enterococci in Lake Burley Griffin: An Analysis of 16 Years' Recreational Water Quality Monitoring Data.

Recreational waterbodies with high levels of faecal indicator bacteria (FIB) pose health risks and are an ongoing challenge for urban-lake managers. Lake Burley Griffin (LBG) in the Australian Capital city of Canberra is a popular site for water-based recreation, but analyses of seasonal and long-term patterns in enterococci that exceed alert levels (>200 CFU per 100 mL, leading to site closures) are lacking. This study analysed enterococci concentrations from seven recreational sites from 2001-2021 to examine spatial and temporal patterns in exceedances during the swimming season (October-April), when exposure is highest. The enterococci concentrations varied significantly across sites and in the summer months. The frequency of the exceedances was higher in the 2009-2015 period than in the 2001-2005 and 2015-2021 periods. The odds of alert-level concentrations were greater in November, December, and February compared to October. The odds of exceedance were higher at the Weston Park East site (swimming beach) and lower at the Ferry Terminal and Weston Park West site compared to the East Basin site. This preliminary examination highlights the need for site-specific assessments of environmental and management-related factors that may impact the public health risks of using the lake, such as inflows, turbidity, and climatic conditions. The insights from this study confirm the need for targeted monitoring efforts during high-risk months and at specific sites. The study also advocates for implementing measures to minimise faecal pollution at its sources.

Modelling respiratory syncytial virus age-specific risk of hospitalisation in term and preterm infants.

BACKGROUND: Respiratory syncytial virus (RSV) is the most common cause of acute lower respiratory infections in children worldwide. The highest incidence of severe disease is in the first 6 months of life, with infants born preterm at greatest risk for severe RSV infections. The licensure of new RSV therapeutics (a long-acting monoclonal antibody and a maternal vaccine) in Europe, USA, UK and most recently in Australia, has driven the need for strategic decision making on the implementation of RSV immunisation programs. Data driven approaches, considering the local RSV epidemiology, are critical to advise on the optimal use of these therapeutics for effective RSV control. METHODS: We developed a dynamic compartmental model of RSV transmission fitted to individually-linked population-based laboratory, perinatal and hospitalisation data for 2000-2012 from metropolitan Western Australia (WA), stratified by age and prior exposure. We account for the differential risk of RSV-hospitalisation in full-term and preterm infants (defined as < 37 weeks gestation). We formulated a function relating age, RSV exposure history, and preterm status to the risk of RSV-hospitalisation given infection. RESULTS: The age-to-risk function shows that risk of hospitalisation, given RSV infection, declines quickly in the first 12 months of life for all infants and is 2.6 times higher in preterm compared with term infants. The hospitalisation risk, given infection, declines to < 10% of the risk at birth by age 7 months for term infants and by 9 months for preterm infants. CONCLUSIONS: The dynamic model, using the age-to-risk function, characterises RSV epidemiology for metropolitan WA and can now be extended to predict the impact of prevention measures. The stratification of the model by preterm status will enable the comparative assessment of potential strategies in the extended model that target this RSV risk group relative to all-population approaches. Furthermore, the age-to-risk function developed in this work has wider relevance to the epidemiological characterisation of RSV.

Modelling African swine fever introduction in diverse Australian feral pig populations.

African swine fever (ASF) is a viral disease that affects domestic and feral pigs. While not currently present in Australia, ASF outbreaks have been reported nearby in Indonesia, Timor-Leste, and Papua New Guinea. Feral pigs are found in all Australian states and territories and are distributed in a variety of habitats. To investigate the impacts of an ASF introduction event in Australia, we used a stochastic network-based metapopulation feral pig model to simulate ASF outbreaks in different regions of Australia. Outbreak intensity and persistence in feral pig populations was governed by local pig recruitment rates, population size, carcass decay period, and, if applicable, metapopulation topology. In Northern Australia, the carcass decay period was too short for prolonged persistence, while endemic transmission could possibly occur in cooler southern areas. Populations in Macquarie Marshes in New South Wales and in Namadgi National Park in the Australian Capital Territory had the highest rates of persistence. The regions had different modes of transmission that led to long-term persistence. Endemic Macquarie Marshes simulations were characterised by rapid transmission caused by high population density that required a fragmented metapopulation to act as a bottleneck to slow transmission. Endemic simulations in Namadgi, with low density and relatively slow transmission, relied on large, well-connected populations coupled with long carcass decay times. Despite the potential for endemic transmission, both settings required potentially unlikely population sizes and dynamics for prolonged disease survival.

A pilot study using hospital surveillance and a birth cohort to investigate enteric pathogens and malnutrition in children, Dili, Timor-Leste.

In low-to-middle-income countries (LMICs), enteric pathogens contribute to child malnutrition, affecting nutrient absorption, inducing inflammation, and causing diarrhoea. This is a substantial problem in LMICs due to high disease burden, poor sanitation and nutritional status, and the cyclical nature of pathogen infection and malnutrition. This relationship remains understudied in Timor-Leste. In our pilot study of enteric pathogens and malnutrition in Dili, Timor-Leste (July 2019-October 2020), we recruited 60 infants in a birth cohort from Hospital Nacional Guido Valadares (HNGV) with up to four home visits. We collected faecal samples and details of demographics, anthropometrics, diet and food practices, and animal husbandry. Additionally, we collected faecal samples, diagnostics, and anthropometrics from 160 children admitted to HNGV with a clinical diagnosis of severe diarrhoea or severe acute malnutrition (SAM). We tested faeces using the BioFire® FilmArray® Gastrointestinal Panel. We detected high prevalence of enteric pathogens in 68.8% (95%CI 60.4-76.2%) of infants at home, 88.6% of SAM cases (95%CI 81.7-93.3%) and 93.8% of severe diarrhoea cases (95%CI 67.7-99.7%). Diarrhoeagenic Escherichia coli and Campylobacter spp. were most frequently detected. Pathogen presence did not significantly differ in birth cohort diarrhoeal stool, but hospital data indicated associations between Salmonella and Shigella and diarrhoea. We observed wasting in 18.4% (95%CI 9.2-32.5%) to 30.8% (95%CI 17.5-47.7%) of infants across home visits, 57.9% (95%CI 34.0-78.9%) of severe diarrhoea cases, and 92.5% (95%CI 86.4-96.2%) of SAM cases. We associated bottle feeding with increased odds of pathogen detection when compared with exclusive breastfeeding at home (OR 8.3, 95%CI 1.1-62.7). We detected high prevalence of enteric pathogens and signs of malnutrition in children in Dili. Our pilot is proof of concept for a study to fully explore the risk factors and associations between enteric pathogens and malnutrition in Timor-Leste.

Genomic and clinical characteristics of campylobacteriosis in Australia.

Campylobacter spp. are a common cause of bacterial gastroenteritis in Australia, primarily acquired from contaminated meat. We investigated the relationship between genomic virulence characteristics and the severity of campylobacteriosis, hospitalisation, and other host factors.We recruited 571 campylobacteriosis cases from three Australian states and territories (2018-2019). We collected demographic, health status, risk factors, and self-reported disease data. We whole genome sequenced 422 C. jejuni and 84 C. coli case isolates along with 616 retail meat isolates. We classified case illness severity using a modified Vesikari scoring system, performed phylogenomic analysis, and explored risk factors for hospitalisation and illness severity.On average, cases experienced a 7.5 day diarrhoeal illness with additional symptoms including stomach cramps (87.1 %), fever (75.6 %), and nausea (72.0 %). Cases aged ≥75 years had milder symptoms, lower Vesikari scores, and higher odds of hospitalisation compared to younger cases. Chronic gastrointestinal illnesses also increased odds of hospitalisation. We observed significant diversity among isolates, with 65 C. jejuni and 21 C. coli sequence types. Antimicrobial resistance genes were detected in 20.4 % of isolates, but multidrug resistance was rare (0.04 %). Key virulence genes such as cdtABC (C. jejuni) and cadF were prevalent (>90 % presence) but did not correlate with disease severity or hospitalisation. However, certain genes (e.g. fliK, Cj1136, and Cj1138) appeared to distinguish human C. jejuni cases from food source isolates.Campylobacteriosis generally presents similarly across cases, though some are more severe. Genotypic virulence factors identified in the literature to-date do not predict disease severity but may differentiate human C. jejuni cases from food source isolates. Host factors like age and comorbidities have a greater influence on health outcomes than virulence factors.

COVID-19 vaccination strategies in settings with limited rollout capacity: a mathematical modelling case study in Sierra Leone.

BACKGROUND: COVID-19 vaccine coverage in low- and middle-income countries continues to be challenging. As supplies increase, coverage is increasingly becoming determined by rollout capacity. METHODS: We developed a deterministic compartmental model of COVID-19 transmission to explore how age-, risk-, and dose-specific vaccine prioritisation strategies can minimise severe outcomes of COVID-19 in Sierra Leone. RESULTS: Prioritising booster doses to older adults and adults with comorbidities could reduce the incidence of severe disease by 23% and deaths by 34% compared to the use of these doses as primary doses for all adults. Providing a booster dose to pregnant women who present to antenatal care could prevent 38% of neonatal deaths associated with COVID-19 infection during pregnancy. The vaccination of children is not justified unless there is sufficient supply to not affect doses delivered to adults. CONCLUSIONS: Our paper supports current WHO SAGE vaccine prioritisation guidelines (released January 2022). Individuals who are at the highest risk of developing severe outcomes should be prioritised, and opportunistic vaccination strategies considered in settings with limited rollout capacity.

Prediction of Ross River Virus Incidence Using Mosquito Data in Three Cities of Queensland, Australia.

Ross River virus (RRV) is the most common mosquito-borne disease in Australia, with Queensland recording high incidence rates (with an annual average incidence rate of 0.05% over the last 20 years). Accurate prediction of RRV incidence is critical for disease management and control. Many factors, including mosquito abundance, climate, weather, geographical factors, and socio-economic indices, can influence the RRV transmission cycle and thus have potential utility as predictors of RRV incidence. We collected mosquito data from the city councils of Brisbane, Redlands, and Mackay in Queensland, together with other meteorological and geographical data. Predictors were selected to build negative binomial generalised linear models for prediction. The models demonstrated excellent performance in Brisbane and Redlands but were less satisfactory in Mackay. Mosquito abundance was selected in the Brisbane model and can improve the predictive performance. Sufficient sample sizes of continuous mosquito data and RRV cases were essential for accurate and effective prediction, highlighting the importance of routine vector surveillance for disease management and control. Our results are consistent with variation in transmission cycles across different cities, and our study demonstrates the usefulness of mosquito surveillance data for predicting RRV incidence within small geographical areas.

Factors Predicting Secondary Respiratory Morbidity Following Early-Life Respiratory Syncytial Virus Infections: Population-Based Cohort Study.

Background: The association between early-life respiratory syncytial virus (RSV) infections and later respiratory morbidity is well established. However, there is limited evidence on factors that influence this risk. We examined sociodemographic and perinatal factors associated with later childhood respiratory morbidity requiring secondary care following exposure to a laboratory-confirmed RSV episode in the first 2 years. Methods: We used a probabilistically linked whole-of-population-based birth cohort including 252 287 children born in Western Australia between 2000 and 2009 with follow-up to the end of 2012. Cox proportional hazards models estimated adjusted hazard ratios (aHRs) of the association of various risk factors with the first respiratory episode for asthma, wheezing, and unspecified acute lower respiratory infection beyond the age of 2 years. Results: The analytic cohort included 4151 children with a confirmed RSV test before age 2 years. The incidence of subsequent respiratory morbidity following early-life RSV infection decreased with child age at outcome (highest incidence in 2-<4-year-olds: 41.8 per 1000 child-years; 95% CI, 37.5-46.6), increased with age at RSV infection (6-<12-month-olds: 23.6/1000 child-years; 95% CI, 19.9-27.8; 12-<24-month-olds: 22.4/1000 child-years; 95% CI, 18.2-22.7) and decreasing gestational age (50.8/1000 child-years; 95% CI, 33.5-77.2 for children born extremely preterm, <28 weeks gestation). Risk factors included age at first RSV episode (6-<12 months: aHR, 1.42; 95% CI, 1.06-1.90), extreme prematurity (<28 weeks: aHR, 2.22; 95% CI, 1.40-3.53), maternal history of asthma (aHR, 1.33; 95% CI, 1.04-1.70), and low socioeconomic index (aHR, 1.76; 95% CI, 1.03-3.00). Conclusions: Our results suggest that in addition to preterm and young infants, children aged 12-<24 months could also be potential target groups for RSV prevention to reduce the burden of later respiratory morbidities associated with RSV.

Assessing the potential impact of COVID-19 booster doses and oral antivirals: A mathematical modelling study of selected middle-income countries in the Indo-Pacific.

Continued efforts to reduce the burden of COVID-19 require the consideration of additional booster doses and emerging oral antivirals. This study explored the individual- and population-level impacts of booster dose and oral antivirals in Indonesia, Fiji, Papua New Guinea, and Timor-Leste. Our mathematical model included age structure, vaccine coverage, prevalence of comorbidities, and immunity from prior infection fit to incidence data from our study settings. We explored a range of eligibility criteria and found that boosters had the largest impact per dose when prioritised to high-risk adults and adults who had not previously received a booster. Antivirals were most effective in settings with low vaccine-derived immunity. In general, fewer antivirals than booster doses were required to prevent a hospitalisation or death. Only in settings with very high vaccine uptake was the impact per dose of providing booster doses to high-risk adults comparable to providing oral antivirals to high-risk adults. Together, booster doses and oral antivirals could prevent 80%, 64%, 49%, and 65% of deaths, and 38%, 37%, 16%, and 34% of hospitalisations in Fiji, Indonesia, Papua New Guinea, and Timor-Leste respectively. Therefore, our findings support the continued provision of COVID-19 booster doses to high-risk adults in 2023, and advocate for increased access to oral antivirals, especially in settings with low vaccine coverage such as Papua New Guinea. Future work should consider the threshold at which self-financing of COVID-19 oral antivirals would be viable for middle-income countries in South-East Asia and the Pacific.

Economic evaluations of whole-genome sequencing for pathogen identification in public health surveillance and health-care-associated infections: a systematic review.

Whole-genome sequencing (WGS) has resulted in improvements to pathogen characterisation for the rapid investigation and management of disease outbreaks and surveillance. We conducted a systematic review to synthesise the economic evidence of WGS implementation for pathogen identification and surveillance. Of the 2285 unique publications identified through online database searches, 19 studies met the inclusion criteria. The economic evidence to support the broader application of WGS as a front-line pathogen characterisation and surveillance tool is insufficient and of low quality. WGS has been evaluated in various clinical settings, but these evaluations are predominantly investigations of a single pathogen. There are also considerable variations in the evaluation approach. Economic evaluations of costs, effectiveness, and cost-effectiveness are needed to support the implementation of WGS in public health settings.

The Cost of Foodborne Illness and Its Sequelae in Australia Circa 2019.

Foodborne illnesses cause a significant health burden, with Campylobacter and norovirus the most common causes of illness and Salmonella a common cause of hospitalization and occasional cause of death. Estimating the cost of illness can assist in quantifying this health burden, with pathogen-specific costs informing prioritization of interventions. We used a simulation-based approach to cost foodborne disease in Australia, capturing the cost of premature mortality, direct costs of nonfatal illness (including health care costs, medications, and tests), indirect costs of illness due to lost productivity, and costs associated with pain and suffering. In Australia circa 2019, the cost in Australian Dollars (AUD) of foodborne illness and its sequelae was 2.44 billion (90% uncertainty interval 1.65-3.68) each year, with the highest pathogen-specific costs for Campylobacter, non-typhoidal Salmonella, non-Shiga toxin-producing pathogenic Escherichia coli, and norovirus. The highest cost per case was for Listeria monocytogenes (AUD 776,000). Lost productivity was the largest component cost for foodborne illness due to all causes and for most individual pathogens; the exceptions were pathogens causing more severe illness such as Salmonella and L. monocytogenes, where premature mortality was the largest component cost. Foodborne illness results in a substantial cost to Australia; interventions to improve food safety across industry, retail, and consumers are needed to maintain public health safety.

Cost-effectiveness analysis of a maternal pneumococcal vaccine in low-income, high-burden settings such as Sierra Leone.

Maternal pneumococcal vaccines have been proposed as a method of protecting infants in the first few months of life. In this paper, we use results from a dynamic transmission model to assess the cost-effectiveness of a maternal pneumococcal polysaccharide vaccine from both healthcare and societal perspectives. We estimate the costs of delivering a maternal pneumococcal polysaccharide vaccine, the healthcare costs averted, and productivity losses avoided through the prevention of severe pneumococcal outcomes such as pneumonia and meningitis. Our model estimates that a maternal pneumococcal program would cost $606 (2020 USD, 95% prediction interval 437 to 779) from a healthcare perspective and $132 (95% prediction interval -1 to 265) from a societal perspective per DALY averted for one year of vaccine delivery. Hence, a maternal pneumococcal vaccine would be cost-effective from a societal perspective but not cost-effective from a healthcare perspective using Sierra Leone's GDP per capita of $527 as a cost-effectiveness threshold. Sensitivity analysis demonstrates how the choice to discount ongoing health benefits determines whether the maternal pneumococcal vaccine was deemed cost-effective from a healthcare perspective. Without discounting, the cost per DALY averted would be $292 (55% of Sierra Leone's GDP per capita) from a healthcare perspective. Further, the cost per DALY averted would be $142 (27% GDP per capita) from a healthcare perspective if PPV could be procured at the same cost relative to PCV in Sierra Leone as on the PAHO reference price list. Overall, our paper demonstrates that maternal pneumococcal vaccines have the potential to be cost-effective in low-income settings; however, the likelihood of low-income countries self-financing this intervention will depend on negotiations with vaccine providers on vaccine price. Vaccine price is the largest program cost driving the cost-effectiveness of a future maternal pneumococcal vaccine.

Determining the true incidence of seasonal respiratory syncytial virus-confirmed hospitalizations in preterm and term infants in Western Australia.

Respiratory syncytial virus contributes to significant global infant morbidity and mortality. We applied a previously developed statistical prediction model incorporating pre-pandemic RSV testing data and hospital admission data to estimate infant RSV-hospitalizations by birth month and prematurity, focused on infants aged <1 year. The overall predicted RSV-hospitalization incidence rates in infants <6 months were 32.7/1,000 child-years (95 % CI: 31.8, 33.5) and 3.1/1,000 child-years (95 % CI: 3.0, 3.1) in infants aged 6-<12 months. Predicted RSV-hospitalization rates for infants aged <6 months were highest for infants born in April/May. Predicted rates for preterm infants born 29-32 weeks gestation were highest in March-May, whereas infants born >33 weeks had peak RSV-hospitalization rates from May-June, similar to late preterm or term births. RSV-hospitalization rates in the pre-pandemic era were highly seasonal, and seasonality varied with degree of prematurity. Accurate estimates of RSV-hospitalization in high-risk sub-groups are essential to understand preventable burden of RSV especially given the current prevention landscape.

Lymphatic filariasis endgame strategies: Using GEOFIL to model mass drug administration and targeted surveillance and treatment strategies in American Samoa.

American Samoa underwent seven rounds of mass drug administration (MDA) for lymphatic filariasis (LF) from 2000-2006, but subsequent surveys found evidence of ongoing transmission. American Samoa has since undergone further rounds of MDA in 2018, 2019, and 2021; however, recent surveys indicate that transmission is still ongoing. GEOFIL, a spatially-explicit agent-based LF model, was used to compare the effectiveness of territory-wide triple-drug MDA (3D-MDA) with targeted surveillance and treatment strategies. Both approaches relied on treatment with ivermectin, diethylcarbamazine, and albendazole. We simulated three levels of whole population coverage for 3D-MDA: 65%, 73%, and 85%, while the targeted strategies relied on surveillance in schools, workplaces, and households, followed by targeted treatment. In the household-based strategies, we simulated 1-5 teams travelling village-to-village and offering antigen (Ag) testing to randomly selected households in each village. If an Ag-positive person was identified, treatment was offered to members of all households within 100m-1km of the positive case. All simulated interventions were finished by 2027 and their effectiveness was judged by their 'control probability'-the proportion of simulations in which microfilariae prevalence decreased between 2030 and 2035. Without future intervention, we predict Ag prevalence will rebound. With 3D-MDA, a 90% control probability required an estimated ≥ 4 further rounds with 65% coverage, ≥ 3 rounds with 73% coverage, or ≥ 2 rounds with 85% coverage. While household-based strategies were substantially more testing-intensive than 3D-MDA, they could offer comparable control probabilities with substantially fewer treatments; e.g. three teams aiming to test 50% of households and offering treatment to a 500m radius had approximately the same control probability as three rounds of 73% 3D-MDA, but used < 40% the number of treatments. School- and workplace-based interventions proved ineffective. Regardless of strategy, reducing Ag prevalence below the 1% target threshold recommended by the World Health Organization was a poor indicator of the interruption of LF transmission, highlighting the need to review blanket elimination targets.