Evaluating the probability of silent circulation of polio in small populations using the silent circulation statistic.

As polio-endemic countries move towards elimination, infrequent first infections and incomplete surveillance make it difficult to determine when the virus has been eliminated from the population. Eichner and Dietz [American Journal of Epidemiology, 143, 8 (1996)] proposed a model to estimate the probability of silent polio circulation depending upon when the last paralytic case was detected. Using the same kind of stochastic model they did, we additionally model waning polio immunity in the context of isolated, small, and unvaccinated populations. We compare using the Eichner and Dietz assumption of an initial case at the start of the simulation to a more accurate determination that observes the first case. The former estimates a higher probability of silent circulation in small populations, but this effect diminishes with increasing model population. We also show that stopping the simulation after a specific time estimates a lower probability of silent circulation than when all replicates are run to extinction, though this has limited impact on small populations. Our extensions to the Eichner and Dietz work improve the basis for decisions concerning the probability of silent circulation. Further model realism will be needed for accurate silent circulation risk assessment

Accumulation of Immunity in Heavy-Tailed Sexual Contact Networks Shapes Mpox Outbreak Sizes

Many countries affected by the global outbreak of mpox in 2022 have observed a decline in cases. Our mathematical model accounting for heavy-tailed sexual partnership distributions suggests that mpox epidemics can hit the infection-derived herd immunity threshold and begin to decline with less than 1% of sexually active MSM population infected regardless of interventions or behavioural changes. Consistently, we found that many countries and US states experienced an epidemic peak with cumulative cases of around 0.1-0.5% of MSM population. The observed decline in cases may not necessarily be attributable to interventions or behavioural changes primarily

Pre-vaccination testing could expand coverage of two-dose COVID vaccines

Recent evidence indicates that a single dose of mRNA-based vaccines produce similar immune responses in people with evidence of past infection compared with two doses in immunologically naive individuals. For COVID-19 vaccines with two dose regimens, point-of-care antibody testing for prior infection when administering the first dose could enable expanded vaccine access in a cost-effective manner. Generally, antibody tests with sensitivity and specificity well below that typically accepted for product licensure would still enable expanded vaccine coverage, though to be cost-beneficial total test cost (i.e. procurement and administration) needs to be less than roughly a third of total vaccine dose cost. For highly sensitive (90%) and specific (99%) tests, coverage could be expanded by more than 33%. Tests with the appropriate performance characteristics are plausible, though likely need setting specific tailoring.</ns3:p

Potential test-negative design study bias in outbreak settings: application to Ebola vaccination in Democratic Republic of Congo.

BACKGROUND: Infectious disease outbreaks present unique challenges to study designs for vaccine evaluation. Test-negative design (TND) studies have previously been used to estimate vaccine effectiveness and have been proposed for Ebola virus disease (EVD) vaccines. However, there are key differences in how cases and controls are recruited during outbreaks and pandemics of novel pathogens, whcih have implications for the reliability of effectiveness estimates using this design. METHODS: We use a modelling approach to quantify TND bias for a prophylactic vaccine under varying study and epidemiological scenarios. Our model accounts for heterogeneity in vaccine distribution and for two potential routes to testing and recruitment into the study: self-reporting and contact-tracing. We derive conventional and hybrid TND estimators for this model and suggest ways to translate public health response data into the parameters of the model. RESULTS: Using a conventional TND study, our model finds biases in vaccine effectiveness estimates. Bias arises due to differential recruitment from self-reporting and contact-tracing, and due to clustering of vaccination. We estimate the degree of bias when recruitment route is not available, and propose a study design to eliminate the bias if recruitment route is recorded. CONCLUSIONS: Hybrid TND studies can resolve the design bias with conventional TND studies applied to outbreak and pandemic response testing data, if those efforts collect individuals' routes to testing. Without route to testing, other epidemiological data will be required to estimate the magnitude of potential bias in a conventional TND study. Since these studies may need to be conducted retrospectively, public health responses should obtain these data, and generic protocols for outbreak and pandemic response studies should emphasize the need to record routes to testing

Serostatus testing and dengue vaccine cost-benefit thresholds.

The World Health Organization (WHO) currently recommends pre-screening for past infection prior to administration of the only licensed dengue vaccine, CYD-TDV. Using a threshold modelling analysis, we identify settings where this guidance prohibits positive net-benefits, and are thus unfavourable. Generally, however, our model shows test-then-vaccinate strategies can improve CYD-TDV economic viability: effective testing reduces unnecessary vaccination costs while increasing health benefits. With sufficiently low testing cost, those trends outweigh additional screening costs, expanding the range of settings with positive net-benefits. This work highlights two aspects for further analysis of test-then-vaccinate strategies. We found that starting routine testing at younger ages could increase benefits; if real tests are shown to sufficiently address safety concerns, the manufacturer, regulators and WHO should revisit guidance restricting use to 9-years-and-older recipients. We also found that repeat testing could improve return-on-investment (ROI), despite increasing intervention costs. Thus, more detailed analyses should address questions on repeat testing and testing periodicity, in addition to real test sensitivity and specificity. Our results follow from a mathematical model relating ROI to epidemiology, intervention strategy, and costs for testing, vaccination and dengue infections. We applied this model to a range of strategies, costs and epidemiological settings pertinent to CYD-TDV. However, general trends may not apply locally, so we provide our model and analyses as an R package available via CRAN, denvax. To apply to their setting, decision-makers need only local estimates of age-specific seroprevalence and costs for secondary infections

Projected early spread of COVID-19 in Africa through 1 June 2020.

For 45 African countries/territories already reporting COVID-19 cases before 23 March 2020, we estimate the dates of reporting 1,000 and 10,000 cases. Assuming early epidemic trends without interventions, all 45 were likely to exceed 1,000 confirmed cases by the end of April 2020, with most exceeding 10,000 a few weeks later

A scoping review & taxonomy of epidemiological-macroeconomic models of COVID-19.

OBJECTIVES: The COVID-19 pandemic placed significant strain on many health systems and economies. Mitigation policies decreased health impacts but had major macroeconomic impact. This paper reviews models combining epidemiological and macroeconomic projections to enable policymakers to consider both macroeconomic and health objectives. METHODS: A scoping review of epidemiological-macroeconomic models of COVID-19 was conducted, covering preprints, working papers and journal publications. We assessed model methodologies, scope, and application to empirical data. RESULTS: We found 80 papers modelling both the epidemiological and macroeconomic outcomes of COVID-19. Model scope is often limited to the impact of lockdown on health and total gross domestic product or aggregate consumption, and to high income countries. Just 14% of models assess disparities or poverty. Most models fall under four categories: compartmental-utility-maximization models, epidemiological models with stylized macroeconomic projections, epidemiological models linked to computable general equilibrium or input-output models, and epi-econ-ABMs. We propose a taxonomy comparing these approaches to guide future model development. CONCLUSIONS: The epidemiological-macroeconomic models of COVID-19 identified have varying complexity and meet different modelling needs. Priorities for future modelling include increasing developing country applications, assessing disparities and poverty, and estimating of long-run impacts. This may require better integration between epidemiologists and economists

Accumulation of immunity in heavy-tailed sexual contact networks shapes mpox outbreak sizes.

Many countries affected by the global outbreak of mpox in 2022 have observed a decline in cases. Our mathematical model accounting for heavy-tailed sexual partnership distributions suggests that mpox epidemics can hit the infection-derived herd immunity threshold and begin to decline with less than 1% of sexually active MSM population infected regardless of interventions or behavioural changes. Consistently, we found that many countries and US states experienced an epidemic peak with cumulative cases of around 0.1-0.5% of MSM population. The observed decline in cases may not necessarily be attributable to interventions or behavioural changes primarily

Optimising health and economic impacts of COVID-19 vaccine prioritisation strategies in the WHO European Region: a mathematical modelling study.

BACKGROUND: Countries in the World Health Organization (WHO) European Region differ in terms of the COVID-19 vaccine supply conditions. We evaluated the health and economic impact of different age-based vaccine prioritisation strategies across this demographically and socio-economically diverse region. METHODS: We fitted age-specific compartmental models to the reported daily COVID-19 mortality in 2020 to inform the immunity level before vaccine roll-out. Models capture country-specific differences in population structures, contact patterns, epidemic history, life expectancy, and GDP per capita.We examined four strategies that prioritise: all adults (V+), younger (20-59 year-olds) followed by older adults (60+) (V20), older followed by younger adults (V60), and the oldest adults (75+) (V75) followed by incrementally younger age groups. We explored four roll-out scenarios (R1-4) - the slowest scenario (R1) reached 30% coverage by December 2022 and the fastest (R4) 80% by December 2021. Five decision-making metrics were summarised over 2021-22: mortality, morbidity, and losses in comorbidity-adjusted life expectancy, comorbidity- and quality-adjusted life years, and human capital. Six vaccine profiles were tested - the highest performing vaccine has 95% efficacy against both infection and disease, and the lowest 50% against diseases and 0% against infection. FINDINGS: Of the 20 decision-making metrics and roll-out scenario combinations, the same optimal strategy applied to all countries in only one combination; V60 was more or similarly desirable than V75 in 19 combinations. Of the 38 countries with fitted models, 11-37 countries had variable optimal strategies by decision-making metrics or roll-out scenarios. There are greater benefits in prioritising older adults when roll-out is slow and when vaccine profiles are less favourable. INTERPRETATION: The optimal age-based vaccine prioritisation strategies were sensitive to country characteristics, decision-making metrics, and roll-out speeds. A prioritisation strategy involving more age-based stages (V75) does not necessarily lead to better health and economic outcomes than targeting broad age groups (V60). Countries expecting a slow vaccine roll-out may particularly benefit from prioritising older adults. FUNDING: World Health Organization, Bill and Melinda Gates Foundation, the Medical Research Council (United Kingdom), the National Institute of Health Research (United Kingdom), the European Commission, the Foreign, Commonwealth and Development Office (United Kingdom), Wellcome Trust

The contribution of asymptomatic SARS-CoV-2 infections to transmission on the Diamond Princess cruise ship.

A key unknown for SARS-CoV-2 is how asymptomatic infections contribute to transmission. We used a transmission model with asymptomatic and presymptomatic states, calibrated to data on disease onset and test frequency from the Diamond Princess cruise ship outbreak, to quantify the contribution of asymptomatic infections to transmission. The model estimated that 74% (70-78%, 95% posterior interval) of infections proceeded asymptomatically. Despite intense testing, 53% (51-56%) of infections remained undetected, most of them asymptomatic. Asymptomatic individuals were the source for 69% (20-85%) of all infections. The data did not allow identification of the infectiousness of asymptomatic infections, however low ranges (0-25%) required a net reproduction number for individuals progressing through presymptomatic and symptomatic stages of at least 15. Asymptomatic SARS-CoV-2 infections may contribute substantially to transmission. Control measures, and models projecting their potential impact, need to look beyond the symptomatic cases if they are to understand and address ongoing transmission