Within-country age-based prioritisation, global allocation, and public health impact of a vaccine against SARS-CoV-2: A mathematical modelling analysis.
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ABSTRACT:
SUBMITTER: Hogan AB
PROVIDER: S-EPMC8030738 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundThe development and widespread use of an effective SARS-CoV-2 vaccine could prevent substantial morbidity and mortality associated with COVID-19 and mitigate the secondary effects associated with non-pharmaceutical interventions.MethodsWe used an age-structured, expanded SEIR model with social contact matrices to assess age-specific vaccine allocation strategies in India. We used state-specific age structures and disease transmission coefficients estimated from confirmed incident cases of COVID-19 between 1 July and 31 August 2020. Simulations were used to investigate the relative reduction in mortality and morbidity of vaccine allocation strategies based on prioritizing different age groups, and the interactions of these strategies with concurrent non-pharmaceutical interventions. Given the uncertainty associated with COVID-19 vaccine development, we varied vaccine characteristics in the modelling simulations.ResultsPrioritizing COVID-19 vaccine allocation for older populations (i.e., >60 years) led to the greatest relative reduction in deaths, regardless of vaccine efficacy, control measures, rollout speed, or immunity dynamics. Preferential vaccination of this group often produced relatively higher total symptomatic infections and more pronounced estimates of peak incidence than other assessed strategies. Vaccine efficacy, immunity type, target coverage, and rollout speed significantly influenced overall strategy effectiveness, with the time taken to reach target coverage significantly affecting the relative mortality benefit comparative to no vaccination.ConclusionsOur findings support global recommendations to prioritize COVID-19 vaccine allocation for older age groups. Relative differences between allocation strategies were reduced as the speed of vaccine rollout was increased. Optimal vaccine allocation strategies will depend on vaccine characteristics, strength of concurrent non-pharmaceutical interventions, and region-specific goals.
| S-EPMC7834611 | biostudies-literature
Project description:BackgroundCountries 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.MethodsWe 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.FindingsOf 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.InterpretationThe 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.FundingWorld 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.
| S-EPMC8629724 | biostudies-literature
Project description:As part of the Vaccine Innovation Prioritisation Strategy (VIPS), three immunization-stakeholder consultations were conducted between September 2018 and February 2020 to ensure that countries' needs drove the prioritization of vaccine product innovations. All consultations targeted respondents with immunization program experience. They included: (1) an online survey to identify immunization implementation barriers and desired vaccine attributes in three use settings, (2) an online survey to identify and evaluate the most important immunization challenges for ten exemplar vaccines, and (3) in-depth interviews to better understand the perceived programmatic benefits and challenges that could be addressed by nine innovations and to rank the innovations that could best address current challenges. The first consultation included responses from 442 participants in 61 countries, representing 89% of the 496 respondents who correctly completed at least one section of the online survey. For facility-based settings, missed opportunities for vaccination due to reluctance to open multidose vaccine vials was the barrier most frequently selected by respondents. In community-based (outreach) and campaign settings, limited access to immunization services due to geographic barriers was most frequently selected. Multidose presentations with preservative or single-dose presentations were most frequently selected as desired vaccine attributes for facility-based settings while improved thermostability was most frequently selected for outreach and campaign settings. The second online survey was completed by 220 respondents in 54 countries. For the exemplar vaccines, vaccine ineffectiveness or wastage due to heat or freeze exposure and missed opportunities due to multidose vial presentations were identified as the greatest vaccine-specific challenges. In-depth interviews with 84 respondents in six countries ranked microarray patches, dual-chamber delivery devices, and heat-stable/controlled temperature chain qualified liquid vaccines as the three innovations that could have the greatest impact in helping address current immunization program challenges. These findings informed the VIPS prioritization and provided broader application to designing immunization interventions to better meet country needs.
| S-EPMC8657797 | biostudies-literature
Project description:Background: age structured mathematical models have been used to evaluate the impact of rubella-containing vaccine (RCV) introduction into existing measles vaccination programs in several countries. South Africa has a well-established measles vaccination program and is considering RCV introduction. This study aimed to provide a comparison of different scenarios and their relative costs within the context of congenital rubella syndrome (CRS) reduction or elimination. Methods: we used a previously published age-structured deterministic discrete time rubella transmission model. We obtained estimates of vaccine costs from the South African medicines price registry and the World Health Organization. We simulated RCV introduction and extracted estimates of rubella incidence, CRS incidence and effective reproductive number over 30 years. Results: compared to scenarios without mass campaigns, scenarios including mass campaigns resulted in more rapid elimination of rubella and congenital rubella syndrome (CRS). Routine vaccination at 12 months of age coupled with vaccination of nine-year-old children was associated with the lowest RCV cost per CRS case averted for a similar percentage CRS reduction. Conclusion: At 80% RCV coverage, all vaccine introduction scenarios would achieve rubella and CRS elimination in South Africa. Any RCV introduction strategy should consider a combination of routine vaccination in the primary immunization series and additional vaccination of older children.
| S-EPMC7565203 | biostudies-literature
Project description:Several dengue vaccines are under development, and some are expected to become available imminently. Concomitant with the anticipated release of these vaccines, vaccine allocation strategies for dengue-endemic countries in Southeast Asia and Latin America are currently under development. We developed a model of dengue transmission that incorporates the age-specific distributions of dengue burden corresponding to those in Thailand and Brazil, respectively, to determine vaccine allocations that minimize the incidence of dengue hemorrhagic fever, taking into account limited availability of vaccine doses in the initial phase of production. We showed that optimal vaccine allocation strategies vary significantly with the demographic burden of dengue hemorrhagic fever. Consequently, the strategy that is optimal for one country may be sub-optimal for another country. More specifically, we showed that, during the first years following introduction of a dengue vaccine, it is optimal to target children for dengue mass vaccination in Thailand, whereas young adults should be targeted in Brazil.
| S-EPMC3947060 | biostudies-literature
Project description:Tumour spheroids are widely used as an in vitro assay for characterising the dynamics and response to treatment of different cancer cell lines. Their popularity is largely due to the reproducible manner in which spheroids grow: the diffusion of nutrients and oxygen from the surrounding culture medium, and their consumption by tumour cells, causes proliferation to be localised at the spheroid boundary. As the spheroid grows, cells at the spheroid centre may become hypoxic and die, forming a necrotic core. The pressure created by the localisation of tumour cell proliferation and death generates an cellular flow of tumour cells from the spheroid rim towards its core. Experiments by Dorie et al. showed that this flow causes inert microspheres to infiltrate into tumour spheroids via advection from the spheroid surface, by adding microbeads to the surface of tumour spheroids and observing the distribution over time. We use an off-lattice hybrid agent-based model to re-assess these experiments and establish the extent to which the spatio-temporal data generated by microspheres can be used to infer kinetic parameters associated with the tumour spheroids that they infiltrate. Variation in these parameters, such as the rate of tumour cell proliferation or sensitivity to hypoxia, can produce spheroids with similar bulk growth dynamics but differing internal compositions (the proportion of the tumour which is proliferating, hypoxic/quiescent and necrotic/nutrient-deficient). We use this model to show that the types of experiment conducted by Dorie et al. could be used to infer spheroid composition and parameters associated with tumour cell lines such as their sensitivity to hypoxia or average rate of proliferation, and note that these observations cannot be conducted within previous continuum models of microbead infiltration into tumour spheroids as they rely on resolving the trajectories of individual microbeads.
| S-EPMC7455028 | biostudies-literature
Project description:BACKGROUND:Increasing the number of vaccine doses may potentially improve overall efficacy. Decision-makers need information about choosing the most efficient dose schedule to maximise the total health gain of a population when operating under a constrained budget. The objective of this study is to identify the most efficient vaccine dosing schedule within a fixed vaccination budget from a healthcare payer perspective. METHODS:An optimisation model is developed in which maximizing the disease reduction is the functional objective and the constraint is the vaccination budget. The model allows variation in vaccination dosing numbers, in cost difference per dose, in vaccine coverage rate, and in vaccine efficacy. We apply the model using the monovalent rotavirus vaccine as an example. RESULTS:With a fixed budget, a 2-dose schedule for vaccination against rotavirus infection with the monovalent vaccine results in a larger reduction in disease episodes than a 3-dose scheme with the same vaccine under most circumstances. A 3-dose schedule would only be better under certain conditions: a cost reduction of >26% per dose, combined with vaccine efficacy improvement of ?5% and a target coverage rate of 75%. Substantial interaction is observed between cost reduction per dose, vaccine coverage rate, and increased vaccine efficacy. Sensitivity analysis shows that the conditions required for a 3-dose strategy to be better than a 2-dose strategy may seldom occur when the budget is fixed. The model does not consider vaccine herd effect, precise timing for additional doses, or the effect of natural immunity development. CONCLUSIONS:Under budget constraint, optimisation modelling is a helpful tool for a decision-maker selecting the most efficient vaccination dosing schedule. The low dosing scheme could be the optimal option to consider under the many scenarios tested. The model can be applied under many different circumstances of changing dosing schemes with single or multiple vaccines.
| S-EPMC3904011 | biostudies-literature
Project description:Plants synthesize sucrose in source tissues (mainly mature leafs) and supply it for growth of sink tissues (young leafs). Sucrose is derived from photosynthesis during daytime and from starch at night. Because the diurnal regulation of sucrose fluxes is not completely understood, we built a mathematical model designed to reproduce all key experimental observations. For this, assumptions were made about the molecular mechanisms underlying the regulations, which are all motivated by experimental facts. The key regulators in our model are two kinases (SnRK1 and osmo-sensitive kinase OsmK) under the control of the circadian clock. SnRK1 is activated in the night to prepare for regularly occurring carbon-limiting conditions, whereas OsmK is activated during the day to prepare for water deficit, which often occurs in the afternoon. Decrease of SnRK1 and increase of OsmK result in partitioning of carbon towards sucrose to supply growing sink tissues. Concomitantly, increasing levels of the growth regulator trehalose-6-phosphate stimulates the development of new sink tissues and thus sink demand, which further activates sucrose supply in a positive feedback loop. We propose that OsmK acts as a timer to measure the length of the photoperiod and suggest experiments how this hypothesis can be validated.
| S-EPMC4345503 | biostudies-literature
Project description:The current political discourse in the United States focuses on extreme political polarization as a contributor to ills ranging from government shutdowns to awkward family holidays. And indeed, a large body of research has documented differences between liberals and conservatives-primarily focused on Republicans and Democrats in the United States. We combine large international surveys and more fine-grained surveys of United States citizens to compare differences in opinion between Republicans and Democrats to the full range of world opinion on moral issues (N = 37,653 in 39 countries) and issues of free speech (N = 40,786 in 38 countries). When viewed in the full distribution, polarization between Democrats and Republicans appears relatively small, even on divisive issues such as abortion, sexual preference, and freedom of religious speech. The average Democrat-Republic overlap is greater than 70% of the country pair overlaps across eight moral issues, meaning that 70% of the country pairs are more dissimilar from each other than Democrats and Republicans are dissimilar; similarly, the average Democrat-Republic overlap is greater than 79% of the country pair overlaps across five freedom of speech issues. These results suggest that cross-cultural comparisons are useful for putting differences between political partisans within the same country in context.
| S-EPMC7179846 | biostudies-literature
Project description:Mechanistic mathematical models are often employed to understand the dynamics of infectious diseases within a population or within a host. They provide estimates that may not be otherwise available. We have developed a within-host mathematical model in order to understand how the pathophysiology of Salmonella Typhi contributes to its incubation period. The model describes the process of infection from ingestion to the onset of clinical illness using a set of ordinary differential equations. The model was parametrized using estimated values from human and mouse experimental studies and the incubation period was estimated as 9.6 days. A sensitivity analysis was also conducted to identify the parameters that most affect the derived incubation period. The migration of bacteria to the caecal lymph node was observed as a major bottle neck for infection. The sensitivity analysis indicated the growth rate of bacteria in late phase systemic infection and the net population of bacteria in the colon as parameters that most influence the incubation period. We have shown in this study how mathematical models aid in the understanding of biological processes and can be used in estimating parameters of infectious diseases.
| S-EPMC6774937 | biostudies-literature