Cost-effectiveness of SARS-CoV-2 self-testing at routine gatherings to minimize community-level infections in lower-middle income countries: A mathematical modeling study.

Places of worship serve as a venue for both mass and routine gathering around the world, and therefore are associated with risk of large-scale SARS-CoV-2 transmission. However, such routine gatherings also offer an opportunity to distribute self-tests to members of the community to potentially help mitigate transmission and reduce broader community spread of SARS-CoV-2. Over the past four years, self-testing strategies have been an impactful tool for countries' response to the COVID-19 pandemic, especially early on to mitigate the spread when vaccination and treatment options were limited. We used an agent-based mathematical model to estimate the impact of various strategies of symptomatic and asymptomatic self-testing for a fixed percentage of weekly routine gatherings at places of worship on community transmission of SARS-CoV-2 in Brazil, Georgia, and Zambia. Testing strategies assessed included weekly and bi-weekly self-testing across varying levels of vaccine effectiveness, vaccine coverage, and reproductive numbers to simulate developing stages of the COVID-19 pandemic. Self-testing symptomatic people attending routine gatherings can cost-effectively reduce the spread of SARS-CoV-2 within places of worship and the community, resulting in incremental cost-effectiveness ratios of $69-$303 USD. This trend is especially true in contexts where population level attendance at such gatherings is high, demonstrating that a distribution approach is more impactful when a greater proportion of the population is reached. Asymptomatic self-testing of attendees at 100% of places of worship in a country results in the greatest percent of infections averted and is consistently cost-effective but remains costly. Budgetary needs for asymptomatic testing are expensive and likely unaffordable for lower-middle income countries (520-1550x greater than that of symptomatic testing alone), promoting that strategies to strengthen symptomatic testing should remain a higher priority.

Cost of SARS-CoV-2 self-test distribution programmes by different modalities: a micro-costing study in five countries (Brazil, Georgia, Malaysia, Ethiopia and the Philippines).

OBJECTIVE: Diagnostic testing is an important tool to combat the COVID-19 pandemic, yet access to and uptake of testing vary widely 3 years into the pandemic. The WHO recommends the use of COVID-19 self-testing as an option to help expand testing access. We aimed to calculate the cost of providing COVID-19 self-testing across countries and distribution modalities. DESIGN: We estimated economic costs from the provider perspective to calculate the total cost and the cost per self-test kit distributed for three scenarios that differed by costing period (pilot, annual), the number of tests distributed (actual, planned, scaled assuming an epidemic peak) and self-test kit costs (pilot purchase price, 50% reduction). SETTING: We used data collected between August and December 2022 in Brazil, Georgia, Malaysia, Ethiopia and the Philippines from pilot implementation studies designed to provide COVID-19 self-tests in a variety of settings-namely, workplace and healthcare facilities. RESULTS: Across all five countries, 173 000 kits were distributed during pilot implementation with the cost/test distributed ranging from $2.44 to $12.78. The cost/self-test kit distributed was lowest in the scenario that assumed implementation over a longer period (year), with higher test demand (peak) and a test kit price reduction of 50% ($1.04-3.07). Across all countries and scenarios, test procurement occupied the greatest proportion of costs: 58-87% for countries with off-site self-testing (outside the workplace, for example, home) and 15-50% for countries with on-site self-testing (at the workplace). Staffing was the next key cost driver, particularly for distribution modalities that had on-site self-testing (29-35%) versus off-site self-testing (7-27%). CONCLUSIONS: Our results indicate that it is likely to cost between $2.44 and $12.78 per test to distribute COVID-19 self-tests across common settings in five heterogeneous countries. Cost-effectiveness analyses using these results will allow policymakers to make informed decisions on optimally scaling up COVID-19 self-test distribution programmes across diverse settings and evolving needs.

Cost-effectiveness of intervention combinations towards the elimination of vertical transmission of HIV in limited-resource settings: a mathematical modelling study.

BACKGROUND: Since 2000, there has been a substantial global reduction in the vertical transmission of HIV. Despite effective interventions, gaps still remain in progress towards elimination in many low-income and middle-income countries. We developed a mathematical model to determine the most cost-effective combinations of interventions to prevent vertical transmission. METHODS: We developed a 12-month Markov model to follow a cohort of women of childbearing age (aged 15-49 years) in Zambia (n=1 107 255) who were either pregnant, in delivery, or breastfeeding; the population included in the model reflects the estimated number of pregnant women in Zambia from the 2018 Zambia Demographic and Health Survey. The model incorporated nine interventions: infant prophylaxis; three different HIV retesting schedule options; oral pre-exposure prophylaxis; maternal peer-support groups; regimen shift; tracing of loss to follow-up; and point-of-care viral load testing. We analysed incident HIV infections among mothers and infants, intervention costs, and evaluated 190 scenarios of different combinations of inventions to calculate the incremental cost-effectiveness ratios (ICERs) over 1 year. FINDINGS: Three interventions with the greatest reduction in vertical transmission, individually, were support groups for 80% of those in need (35% reduction in infant infections), HIV retesting schedules (6·5% reduction), and infant prophylaxis (4·5% reduction). Of all 190 scenarios evaluated, eight were on the cost-effectiveness frontier (ie, were considered to be cost-effective); all eight included increasing infant prophylaxis, regimen shift, and use of support groups. Excluding the highest-cost scenarios, for a 1-22% increase in total budget, 23-43% of infant infections could be prevented, producing ICERs between US$244 and $16 242. INTERPRETATION: Using the interventions modelled, it is possible to reduce vertical transmission and to cost-effectively prevent up to 1734 infant HIV infections (43% reduction) in Zambia over a period of 1 year. To optimise their effect, these interventions must be scaled with fidelity. Future work is needed to incorporate evidence on additional innovative interventions and HIV risk factors, and to apply the model to other country contexts to support targeted implementation and resource use. FUNDING: The ELMA Foundation.

Impact and cost-effectiveness of SARS-CoV-2 self-testing strategies in schools: a multicountry modelling analysis.

OBJECTIVES: To determine the most epidemiologically effective and cost-effective school-based SARS-CoV-2 antigen-detection rapid diagnostic test (Ag-RDT) self-testing strategies among teachers and students. DESIGN: Mathematical modelling and economic evaluation. SETTING AND PARTICIPANTS: Simulated school and community populations were parameterised to Brazil, Georgia and Zambia, with SARS-CoV-2 self-testing strategies targeted to teachers and students in primary and secondary schools under varying epidemic conditions. INTERVENTIONS: SARS-CoV-2 Ag-RDT self-testing strategies for only teachers or teachers and students-only symptomatically or symptomatically and asymptomatically at 5%, 10%, 40% or 100% of schools at varying frequencies. OUTCOME MEASURES: Outcomes were assessed in terms of total infections and symptomatic days among teachers and students, as well as total infections and deaths within the community under the intervention compared with baseline. The incremental cost-effectiveness ratios (ICERs) were calculated for infections prevented among teachers and students. RESULTS: With respect to both the reduction in infections and total cost, symptomatic testing of all teachers and students appears to be the most cost-effective strategy. Symptomatic testing can prevent up to 69·3%, 64·5% and 75·5% of school infections in Brazil, Georgia and Zambia, respectively, depending on the epidemic conditions, with additional reductions in community infections. ICERs for symptomatic testing range from US$2 to US$19 per additional school infection averted as compared with symptomatic testing of teachers alone. CONCLUSIONS: Symptomatic testing of teachers and students has the potential to cost-effectively reduce a substantial number of school and community infections.

The Purinome and the preBötzinger Complex - A Ménage of Unexplored Mechanisms That May Modulate/Shape the Hypoxic Ventilatory Response.

Exploration of purinergic signaling in brainstem homeostatic control processes is challenging the traditional view that the biphasic hypoxic ventilatory response, which comprises a rapid initial increase in breathing followed by a slower secondary depression, reflects the interaction between peripheral chemoreceptor-mediated excitation and central inhibition. While controversial, accumulating evidence supports that in addition to peripheral excitation, interactions between central excitatory and inhibitory purinergic mechanisms shape this key homeostatic reflex. The objective of this review is to present our working model of how purinergic signaling modulates the glutamatergic inspiratory synapse in the preBötzinger Complex (key site of inspiratory rhythm generation) to shape the hypoxic ventilatory response. It is based on the perspective that has emerged from decades of analysis of glutamatergic synapses in the hippocampus, where the actions of extracellular ATP are determined by a complex signaling system, the purinome. The purinome involves not only the actions of ATP and adenosine at P2 and P1 receptors, respectively, but diverse families of enzymes and transporters that collectively determine the rate of ATP degradation, adenosine accumulation and adenosine clearance. We summarize current knowledge of the roles played by these different purinergic elements in the hypoxic ventilatory response, often drawing on examples from other brain regions, and look ahead to many unanswered questions and remaining challenges.