Economic evaluation of second measles containing vaccine (MCV) dose: a systematic review of available evidence.

INTRODUCTION: The global measles incidence has decreased from 145 to 49 cases per 1 million population from 2000 to 2018, but evaluating the economic benefits of a second measles-containing vaccine (MCV2) is crucial. This study reviewed the evidence and quality of economic evaluation studies to guide MCV2 introduction. METHODS: The systematic review of model-based economic evaluation studies was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The search yielded 2231 articles, with 876 duplicates removed and 1355 articles screened, with nine studies included for final analysis. RESULTS: Six studies reported a positive benefit-cost ratio with one resulting in net savings of $11.6 billion, and two studies estimated a 2-dose MMR vaccination program would save $119.24 to prevent one measles case, and a second dose could prevent 9,200 cases at 18 months, saving $548.19 per case. The most sensitive variables were the discount rate and vaccination administration cost. CONCLUSIONS: Two MCV doses or a second opportunity with an additional dose of MCV were highly cost-beneficial and resulted in substantial cost savings compared to a single routine vaccine. But further research using high-quality model-based health economic evaluation studies of MCV2 should be made available to decision-makers. PROSPERO REGISTRATION: CRD42020200669.

Modeling the Cost of Vaccinating a Measles Zero-Dose Child in Zambia Using Three Vaccination Strategies.

Countries with moderate to high measles-containing vaccine coverage face challenges in reaching the remaining measles zero-dose children. There is growing interest in targeted vaccination activities to reach these children. We developed a framework for prioritizing districts for targeted measles and rubella supplementary immunization activities (SIAs) for Zambia in 2020, incorporating the use of the WHO's Measles Risk Assessment Tool (MRAT) and serosurveys. This framework was used to build a model comparing the cost of vaccinating one zero-dose child under three vaccination scenarios: standard nationwide SIA, targeted subnational SIA informed by MRAT, and targeted subnational SIA informed by both MRAT and measles seroprevalence data. In the last scenario, measles seroprevalence data are acquired via either a community-based serosurvey, residual blood samples from health facilities, or community-based IgG point-of-contact rapid diagnostic testing. The deterministic model found that the standard nationwide SIA is the least cost-efficient strategy at 13.75 USD per zero-dose child vaccinated. Targeted SIA informed by MRAT was the most cost-efficient at 7.63 USD per zero-dose child, assuming that routine immunization is just as effective as subnational SIA in reaching zero-dose children. Under similar conditions, a targeted subnational SIA informed by both MRAT and seroprevalence data resulted in 8.17-8.35 USD per zero-dose child vaccinated, suggesting that use of seroprevalence to inform SIA planning may not be as cost prohibitive as previously thought. Further refinement to the decision framework incorporating additional data may yield strategies to better target the zero-dose population in a financially feasible manner.

Assessment of using Google Trends for real-time monitoring of infectious disease outbreaks: a measles case study.

Measles remains a significant threat to children worldwide despite the availability of effective vaccines. The COVID-19 pandemic exacerbated the situation by leading to the postponement of supplementary measles immunization activities. Along with this postponement, measles surveillance also deteriorated, with the lowest number of submitted specimens in over a decade. In this study, we focus on measles as a challenging case study due to its high vaccination coverage, which leads to smaller outbreaks and potentially weaker signals on Google Trends. Our research aimed to explore the feasibility of using Google Trends for real-time monitoring of infectious disease outbreaks. We evaluated the correlation between Google Trends searches and clinical case data using the Pearson correlation coefficient and Spearman's rank correlation coefficient across 30 European countries and Japan. The results revealed that Google Trends was most suitable for monitoring acute disease outbreaks at the regional level in high-income countries, even when there are only a few weekly cases. For example, from 2017 to 2019, the Pearson correlation coefficient was 0.86 (p-value< 0.05) at the prefecture level for Okinawa, Japan, versus 0.33 (p-value< 0.05) at the national level for Japan. Furthermore, we found that the Pearson correlation coefficient may be more suitable than Spearman's rank correlation coefficient for evaluating the correlations between Google Trends search data and clinical case data. This study highlighted the potential of utilizing Google Trends as a valuable tool for timely public health interventions to respond to infectious disease outbreaks, even in the context of diseases with high vaccine coverage.

Measles, mumps, and rubella vaccination coverage: an ecological study of primary health care and socio-economic factors in Catalonia, Spain.

This study examined the association of socio-economic factors and the structure of primary care centres (PCCs) with measles, mumps, and rubella (MMR) vaccination coverage among the 8-year-old population in Catalonia, Spain. We conducted an ecological study to retrospectively assess the MMR vaccination-recorded status of children born in 2012, using public health data extracted in December 2020. For each of 300 PCCs serving 70,498 children, we calculated vaccination coverage rates from electronic health records and linked these rates to a composite deprivation index corresponding to the territory served by each PCC. We identified a relationship between unfavourable socio-economic factors and higher recorded vaccination coverage. On average, directly managed PCCs had higher vaccination coverage rates than indirectly managed PCCs. Greater utilisation of primary care services by the population was also associated with higher vaccination coverage rates. Further research is needed to generate knowledge valuable for informing more equitable child-vaccination service delivery models.

Group-based trajectory models of integrated vaccine delivery and equity in low- and middle-income countries.

BACKGROUND: Integrated vaccine delivery - the linkage of routine vaccination with provision of other essential health services - is a hallmark of robust primary care systems that has been linked to equitable improvements in population health outcomes. METHODS: We gathered longitudinal data relating to routine immunization coverage and vaccination equity in 78 low- and middle-income countries that have ever received support from Gavi, the Vaccine Alliance, using multiple imputation to handle missing values. We then estimated several group-based trajectory models to describe the relationship between integrated vaccine delivery and vaccination equity in these countries. Finally, we used multinomial logistic regression to identify predictors of group membership. RESULTS: We identified five distinct trajectories of geographic vaccination equity across both the imputed and non-imputed datasets, along with two and four trajectories of socioeconomic vaccination equity in the imputed and non-imputed datasets, respectively. Integration was associated with reductions in the slope index of inequality of measles vaccination in the countries analyzed. Integration was also associated with an increase in the percentage of districts reporting high measles vaccination coverage. CONCLUSIONS: Integrated vaccine delivery is most strongly associated with improvements in vaccination equity in settings with high baseline levels of inequity. Continued scholarship is needed to further characterize the relationship between integration and health equity, as well as to improve measurement of vaccination coverage and integration.

Boletín OPS Adelante, n. 2, Ene. - Abr. 2024

Este boletín es elaborado por la Representación de la Organización Panamericana de la Salud, Organización Mundial de la Salud (OPS/OMS) en México. Su objetivo primordial es difundir las actividades de cooperación técnica que la OPS realiza en el país, con la Secretaría de Salud Federal, así como con todas las instituciones que forman parte del sistema de salud.

Impact and cost-effectiveness of measles vaccination through microarray patches in 70 low-income and middle-income countries: mathematical modelling and early-stage economic evaluation.

BACKGROUND: Microarray patches (MAPs) are a promising technology being developed to reduce barriers to vaccine delivery based on needles and syringes (N&S). To address the evidence gap on the public health value of applying this potential technology to immunisation programmes, we evaluated the health impact on measles burden and cost-effectiveness of introducing measles-rubella MAPs (MR-MAPs) in 70 low-income and middle-income countries (LMICs). METHODS: We used an age-structured dynamic model of measles transmission and vaccination to project measles cases, deaths and disability-adjusted life-years during 2030-2040. Compared with the baseline scenarios with continuing current N&S-based practice, we evaluated the introduction of MR-MAPs under different measles vaccine coverage projections and MR-MAP introduction strategies. Costs were calculated based on the ingredients approach, including direct cost of measles treatment, vaccine procurement and vaccine delivery. Model-based burden and cost estimates were derived for individual countries and country income groups. We compared the incremental cost-effectiveness ratios of introducing MR-MAPs to health opportunity costs. RESULTS: MR-MAP introduction could prevent 27%-37% of measles burden between 2030 and 2040 in 70 LMICs, compared with the N&S-only immunisation strategy. The largest health impact could be achieved under lower coverage projection and accelerated introduction strategy, with 39 million measles cases averted. Measles treatment cost is a key driver of the net cost of introduction. In countries with a relatively higher income, introducing MR-MAPs could be a cost-saving intervention due to reduced treatment costs. Compared with country-specific health opportunity costs, introducing MR-MAPs would be cost-effective in 16%-81% of LMICs, depending on the MR-MAPs procurement prices and vaccine coverage projections. CONCLUSIONS: Introducing MR-MAPs in LMICs can be a cost-effective strategy to revitalise measles immunisation programmes with stagnant uptake and reach undervaccinated children. Sustainable introduction and uptake of MR-MAPs has the potential to improve vaccine equity within and between countries and accelerate progress towards measles elimination.

Cost-effectiveness of measles and rubella elimination in low-income and middle-income countries.

BACKGROUND: Since 2000, the incidence of measles and rubella has declined as measles-rubella (MR) vaccine coverage increased due to intensified routine immunisation (RI) and supplementary immunisation activities (SIAs). The World Health Assembly commissioned a feasibility assessment of eliminating measles and rubella. The objective of this paper is to present the findings of cost-effectiveness analysis (CEA) of ramping up MR vaccination with a goal of eliminating transmission in every country. METHODS: We used projections of impact of routine and SIAs during 2018-2047 for four scenarios of ramping up MR vaccination. These were combined with economic parameters to estimate costs and disability-adjusted life years averted under each scenario. Data from the literature were used for estimating the cost of increasing routine coverage, timing of SIAs and introduction of rubella vaccine in countries. RESULTS: The CEA showed that all three scenarios with ramping up coverage above the current trend were more cost-effective in most countries than the 2018 trend for both measles and rubella. When the measles and rubella scenarios were compared with each other, the most cost-effective scenario was likely to be the most accelerated one. Even though this scenario is costlier, it averts more cases and deaths and substantially reduces the cost of treatment. CONCLUSIONS: The Intensified Investment scenario is likely the most cost-effective of the vaccination scenarios evaluated for reaching both measles and rubella disease elimination. Some data gaps on costs of increasing coverage were identified and future efforts should focus on filling these gaps.

The societal cost of vaccine refusal: A modelling study using measles vaccination as a case study.

BACKGROUND: Increasing vaccine hesitancy and refusal poses a challenge to public health as even small reductions in vaccine uptake can result in large outbreaks of infectious diseases. Here we estimate the societal costs of vaccine refusal using measles as a case study. METHODS: We developed a compartmental metapopulation model of measles transmission to explore how the changes in the size and level of social mixing between populations that are "pro-vaccination", and "anti-vaccination" impacts the burden of measles. Using the projected cases and deaths, we calculated the health, healthcare, direct medical costs, and productivity loss associated with vaccine refusal. Using measles in England as a case study, we quantified the societal costs that each vaccine refusal imposes on society. FINDINGS: When there is a high level of mixing between the pro- and anti-vaccination populations, those that refuse to be vaccinated benefit from the herd immunity afforded by the pro-vaccination population. At the same time, their refusal to be vaccinated increases the burden in those that are vaccinated due to imperfect vaccines, and in those that are not able to be vaccinated due to other underlying health conditions. Using England as a case study, we estimate that this translates to a societal loss of GBP 292 million and disease burden of 17 630 quality-adjusted-life-years (sensitivity range 10 594-50 379) over a 20-year time horizon. Of these costs, 26 % are attributable to healthcare costs and 74 % to productivity losses for patients and their carers. This translates to a societal loss per vaccine refusal of GBP 162.21 and 0.01 (0.006-0.03) quality-adjusted-life-years. INTERPRETATION: Our findings demonstrate that even low levels of vaccine refusal can have a substantial and measurable societal burden on the population. These estimates can support the value of investment in interventions that address vaccine hesitancy and vaccine refusal, providing not only improved public health but also potential economic benefits to society.

Analysis of the different interventions scenario for programmatic measles control in Bangladesh: A modelling study.

In recent years measles has been one of the most critical public health problem in Bangladesh. Although the Ministry of Health in Bangladesh employs a broad extension of measles control policies, logistical challenges exist, and there is significant doubt regarding the disease burden. Mathematical modelling of measles is considered one of the most effective ways to understand infection transmission and estimate parameters in different countries, such as Bangladesh. In this study, a mathematical modelling framework is presented to explore the dynamics of measles in Bangladesh. We calibrated the model using cumulative measles incidence data from 2000 to 2019. Also, we performed a sensitivity analysis of the model parameters and found that the contact rate had the most significant influence on the basic reproduction number R0. Four hypothetical intervention scenarios were developed and simulated for the period from 2020 to 2035. The results show that the scenario which combines enhanced treatment for exposed and infected population, first and second doses of vaccine is the most effective at rapidly reducing the total number of measles incidence and mortality in Bangladesh. Our findings also suggest that strategies that focus on a single interventions do not dramatically affect the decline in measles incidence cases; instead, those that combine two or more interventions simultaneously are the most effective in decreasing the burden of measles incidence and mortality. In addition, we also evaluated the cost-effectiveness of varying combinations of three basic control strategies including distancing, vaccination and treatment, all within the optimal control framework. Our finding suggested that combines distancing, vaccination and treatment control strategy is the most cost-effective for reducing the burden of measles in Bangladesh. Other strategies can be comprised to measles depending on the availability of funds and policymakers' choices.

[Analysis of the direct economic burden of measles cases and its influencing factors in Shanghai from 2017 to 2019].

Objective: To analyze the direct economic burden caused by measles cases in Shanghai from 2017 to 2019 and its influencing factors. Methods: A total of 161 laboratory-confirmed measles cases reported from January 1, 2017, to December 31, 2019, in Shanghai were included in the study through the "Measles Surveillance Information Reporting and Management System" of the "China Disease Surveillance Information Reporting and Management System". Through telephone follow-up and consulting hospital data, the basic information of population, medical treatment situation, medical treatment costs and other information were collected, and the direct economic burden of cases was calculated, including registration fees, examination fees, hospitalization fees, medical fees and other disease treatment expenses, as well as transportation and other expenses of cases. The multiple linear regression model was used to analyze the main influencing factors of the direct economic burden. Results: The age of 161 measles cases M (Q1, Q3) was 28.21 (13.33, 37.00) years. Male cases (56.52%) were more than female cases (43.48%). The largest number of cases was≥18 years old (70.81%). The total direct economic burden of 161 measles cases was 540 851.14 yuan, and the per capita direct economic burden was 3 359.32 yuan. The direct economic burden M (Q1, Q3) was 873.00 (245.01, 4 014.79) yuan per person. The results of multiple linear regression model analysis showed that compared with other and unknown occupations, central areas and non-hospitalized cases, the direct economic burden of measles cases was higher in scattered children, childcare children, students, and cadre staff in the occupational distribution, suburban areas and hospitalized, with the coefficient of ß (95%CI) values of 0.388 (0.150-0.627), 0.297 (0.025-0.569), 0.327 (0.148-0.506) and 1.031 (0.853-1.209), respectively (all P values<0.05). Conclusion: The direct economic burden of some measles cases in Shanghai is relatively high. Occupation, area of residence and hospitalization are the main factors influencing the direct economic burden of measles cases.

State Policy Removing the Personal Belief Exemption for Measles, Mumps, and Rubella (MMR) School Immunization Requirement, Washington State, 2014-2022.

Objectives. To assess the impact of Washington State's 2019 Engrossed House Bill (EHB) 1638-which removed measles, mumps, and rubella (MMR) personal belief exemptions-on MMR vaccine series completion and exemption rates in K-12 students. Methods. We used interrupted time-series analyses to examine changes in MMR vaccine series completion rates before and after EHB 1638 was passed and the χ2 test for differences in exemption rates. Results. EHB 1638 implementation was associated with a 5.4% relative increase in kindergarten MMR vaccine series completion rates (95% confidence interval = 3.8%, 7.1%; P ≤ .001), and results were similar with Oregon as a control state (no change observed in Oregon; P = .68). MMR exemptions overall decreased 41% (from 3.1% in 2018-2019 to 1.8% in 2019-2020; P ≤ .001), and religious exemptions increased 367% (from 0.3% to 1.4%; P ≤ .001). Conclusions. EHB 1638 was associated with an increase in MMR vaccine series completion rates and a decrease in any MMR exemption. However, effects were partially offset by an increase in religious exemption rates. Public Health Implications. Removal of personal belief exemptions for the MMR immunization requirement only may be an effective approach to increase MMR vaccine coverage rates statewide and among underimmunized communities. (Am J Public Health. 2023;113(7):795-804. https://doi.org/10.2105/AJPH.2023.307285).

A model for estimating costs and benefits of new vaccine technologies from the perspective of both buyers and sellers.

Although vaccination is widely considered one of the most cost-effective health interventions available, global coverage rates for many vaccines remain lower than necessary for disease elimination and eradication. New vaccine technologies can play an important role in addressing barriers to vaccination and increasing coverage rates. To identify and prioritize vaccine technology investments, decision makers must be able to compare the overall costs and benefits of each investment option. While these data points may exist, they are often confined to silos. Decision makers would benefit from a model that synthesizes this broad range of data and provides clear and actionable information. To facilitate vaccine investment, purchasing and deployment decisions, we developed a systematic and transparent cost-benefit model that estimates the value and risk of a given investment scenario from the perspective of both "buyers" (e.g., global donors, country governments) and "sellers" (e.g., developers, manufacturers) of vaccines. This model, which can be used to evaluate scenarios related to a single vaccine presentation or a portfolio of vaccine presentations, leverages our published approach for estimating the impact of improved vaccine technologies on vaccination coverage rates. This article presents a description of the model and provides an illustrative example application to a portfolio of measles-rubella vaccine technologies currently under development. Although the model is generally applicable to organizations involved in vaccine investment, manufacturing or purchasing, we believe it may be particularly useful to those engaged in vaccine markets that rely strongly on funding from institutional donors.

Impact of a free care policy on routine health service volumes during a protracted Ebola virus disease outbreak in the Democratic Republic of Congo.

BACKGROUND: In response to the DRC's 10th Ebola Virus Disease (EVD) outbreak, the government subsidized routine health services in select health zones with the goal of maintaining routine service volumes. We assess the impact of the initial and revised Free Care Policies (FCP) on total clinic visits, uncomplicated malaria, simple pneumonia, fourth antenatal care clinic visits, and measles vaccinations, testing the hypothesis that routine services would not significantly decrease during the FCP. METHODS AND FINDINGS: We used data from the DRC's national health information system spanning January 2017 to November 2020. Intervention facilities were those that were initially and secondarily enrolled in the FCP, which occurred in August 2018 and November 2018, respectively. Comparison facilities were limited to the North Kivu Province and were from health zones that recorded at least one case of Ebola. A controlled interrupted time series analysis was conducted. The FCP appeared to have a positive effect in increasing overall clinic attendance rates, uncomplicated malaria case rates, and simple pneumonia case rates in those health zones where the policy was enacted relative to comparison sites. The longer-term effects of the FCP were mostly non-significant or, if significant, relatively modest in nature. Rates for measles vaccinations and fourth ANC clinic visits appeared to be unaffected or minimally affected, respectively, by the implementation of the FCP and relative to comparison sites. We did not observe the decrease in measles vaccinations that has been observed elsewhere. The study is limited in that we were unable to account for health facility bypassing and service volumes at private health facilities. CONCLUSIONS: Our findings provide evidence that FCPs can be used to maintain routine service provision during outbreaks. Additionally, the study design demonstrates that routinely reported health information from the DRC are sensitive enough to detect changes in health policy.

Accounting for Adverse Events Following Immunization in Economic Evaluation: Systematic Review of Economic Evaluations of Pediatric Vaccines Against Pneumococcus, Rotavirus, Human Papillomavirus, Meningococcus and Measles-Mumps-Rubella-Varicella.

OBJECTIVES: Economic evaluations of vaccines should accurately represent all relevant economic and health consequences of vaccination, including losses due to adverse events following immunization (AEFI). We investigated to what extent economic evaluations of pediatric vaccines account for AEFI, which methods are used to do so and whether inclusion of AEFI is associated with study characteristics and the vaccine's safety profile. METHODS: A systematic literature search (MEDLINE, EMBASE, Cochrane Systematic Reviews and Trials, Database of the Centre for Reviews and Dissemination of the University of York, EconPapers, Paediatric Economic Database Evaluation, Tufts New England Cost-Effectiveness Analysis Registry, Tufts New England Global Health CEA, International Network of Agencies for Health Technology Assessment Database) was performed for economic evaluations published between 2014 and 29 April 2021 (date of search) pertaining to the five groups of pediatric vaccines licensed in Europe and the United States since 1998: the human papillomavirus (HPV) vaccines, the meningococcal vaccines (MCV), the measles-mumps-rubella-varicella (MMRV) combination vaccines, the pneumococcal conjugate vaccines (PCV) and the rotavirus vaccines (RV). Rates of accounting for AEFI were calculated, stratified by study characteristics (e.g., region, publication year, journal impact factor, level of industry involvement) and triangulated with the vaccine's safety profile (Advisory Committee on Immunization Practices [ACIP] recommendations and information on safety-related product label changes). The studies accounting for AEFI were analyzed in terms of the methods used to account for both cost and effect implications of AEFI. RESULTS: We identified 112 economic evaluations, of which 28 (25%) accounted for AEFI. This proportion was significantly higher for MMRV (80%, four out of five evaluations), MCV (61%, 11 out of 18 evaluations) and RV (60%, nine out of 15 evaluations) compared to HPV (6%, three out of 53 evaluations) and PCV (5%, one out of 21 evaluations). No other study characteristics were associated with a study's likelihood of accounting for AEFI. Vaccines for which AEFI were more frequently accounted for also had a higher frequency of label changes and a higher level of attention to AEFI in ACIP recommendations. Nine studies accounted for both the cost and health implications of AEFI, 18 studies considered only costs and one only health outcomes. While the cost impact was usually estimated based on routine billing data, the adverse health impact of AEFI was usually estimated based on assumptions. DISCUSSION: Although (mild) AEFI were demonstrated for all five studied vaccines, only a quarter of reviewed studies accounted for these, mostly in an incomplete and inaccurate manner. We provide guidance on which methods to use to better quantify the impact of AEFI on both costs and health outcomes. Policymakers should be aware that the impact of AEFI on cost-effectiveness is likely to be underestimated in the majority of economic evaluations.

The methodological quality of economic evaluations of measles outbreaks: A systematic review of cost-of-illness studies.

OBJECTIVES: To identify the main cost components included in the economic evaluations of measles outbreaks, their items and cost drivers, and evaluate the quality of costing methodology, analyzing the key features that may affect the validity of these studies in countries with different income levels. METHODS: We systematically searched multiple databases EMBASE, MEDLINE (via PubMed), Biblioteca Virtual em Saúde do Ministério da Saúde (BVS MS), NHS Economic Evaluation Database (NHS EED) and NHS Health Technology Assessment (NHS HTA) (via The Centre for Reviews and Dissemination Library - CRD), and EconLit, SCOPUS, and Web of Science, selecting cost analysis and cost of illness studies (COI) of measles outbreaks. Two independent reviewers screened articles for relevance and extracted the data. The quality of costing methods was assessed using a guide to critical evaluation of COI studies. We performed a qualitative narrative synthesis. RESULTS: Twenty-two studies were reviewed. Most studies evaluated outbreaks that occurred from 2011 to 2013 and 2017 to 2019. Total costs varied from $40,147 to $39.3 million. Per case cost varied from $168 to $49,439. The main drivers of measles outbreak costs were outbreak response, personnel, and productivity losses. Most studies (20/22) did not report the costing methodology adopted, the degree of disaggregation used in the identification and measurement of resource and costs components and the method for the valuation of resource and cost components. CONCLUSIONS: The quality of the costing methodology, its transparency and accuracy are essential to the validity of these studies results and their potential use to allocate public health resources in the most efficient manner and to inform measles outbreak control strategies, with rapid and effective response.

Implementation of a quality improvement programme using the Active Patient Link call and recall system to improve timeliness and equity of childhood vaccinations: protocol for a mixed-methods evaluation.

INTRODUCTION: Call and recall systems provide actionable intelligence to improve equity and timeliness of childhood vaccinations, which have been disrupted during the COVID-19 pandemic. We will evaluate the effectiveness, fidelity and sustainability of a data-enabled quality improvement programme delivered in primary care using an Active Patient Link Immunisation (APL-Imms) call and recall system to improve timeliness and equity of uptake in a multiethnic disadvantaged urban population. We will use qualitative methods to evaluate programme delivery, focusing on uptake and use, implementation barriers and service improvements for clinical and non-clinical primary care staff, its fidelity and sustainability. METHODS AND ANALYSIS: This is a mixed-methods observational study in 284 general practices in north east London (NEL). The target population will be preschool-aged children eligible to receive diphtheria, tetanus and pertussis (DTaP) or measles, mumps and rubella (MMR) vaccinations and registered with an NEL general practice. The intervention comprises an in-practice call and recall tool, facilitation and training, and financial incentives. The quantitative evaluation will include interrupted time Series analyses and Slope Index of Inequality. The primary outcomes will be the proportion of children receiving at least one dose of a DTaP-containing or MMR vaccination defined, respectively, as administered between age 6 weeks and 6 months or between 12 and 18 months of age. The qualitative evaluation will involve a 'Think Aloud' method and semistructured interviews of stakeholders to assess impact, fidelity and sustainability of the APL-Imms tool, and fidelity of the implementation by facilitators. ETHICS AND DISSEMINATION: The research team has been granted permission from data controllers in participating practices to use deidentified data for audit purposes. As findings will be specific to the local context, research ethics approval is not required. Results will be disseminated in a peer-reviewed journal and to stakeholders, including parents, health providers and commissioners.

Economic impact of vaccine safety incident in Ukraine: The economic case for safety system investment.

BACKGROUND: Vaccine confidence and coverage decreased following a death temporally but not causally related to measles vaccination in Ukraine in 2008. Large measles outbreaks including international exportations followed. Herein we characterize this experience including associated costs. METHODS: Mixed-methods were used to characterize this vaccine safety incident and quantify health and economic costs. Qualitative interviews illuminate the incident, social climate, and corruption that influenced vaccine confidence in Ukraine. A literature review explored attitudes toward vaccines in the USSR and post-independence Ukraine. Infectious disease incidence was examined before and after the vaccine safety incident. An economic analysis estimated associated healthcare costs, including prevention and outbreak control measures, additional vaccination activities due to failure of the 2008 campaign, treatment costs for new cases domestically and foreign exportation, and productivity loss from treatment time and mortality for new cases. FINDINGS: Vaccine hesitancy and distrust in government and public health programs due to corruption existed in Ukraine before the vaccine safety incident. The mishandling of the 2008 incident catalyzed the decline of vaccine confidence and prompted poor procurement decisions, leading to a drop in infant vaccination coverage, increased domestic measles cases, and exportation of measles. The estimated cost of this incident was approximately $140 million from 2008 to 2018. INTERPRETATION: Absent a rapid and credible vaccine safety response, a coincidental death following immunization resulted in major outbreaks of measles with substantial economic costs. Adequate investments in a post-licensure safety system may help avoid similar future incidents.

The measles epidemic model assessment under real statistics: an application of stochastic optimal control theory.

A stochastic epidemic model with random noise transmission is taken into account, describing the dynamics of the measles viral infection. The basic reproductive number is calculated corresponding to the stochastic model. It is determined that, given initial positive data, the model has bounded, unique, and positive solution. Additionally, utilizing stochastic Lyapunov functional theory, we study the extinction of the disease. Stationary distribution and extinction of the infection are examined by providing sufficient conditions. We employed optimal control principles and examined stochastic control systems to regulate the transmission of the virus using environmental factors. Graphical representations have been offered for simplicity of comprehending in order to further verify the acquired analytical findings.