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.

Dynamics of measles immunity from birth and following vaccination.

Measles remains a major threat to human health despite widespread vaccination. While we know that maternal antibodies can impair vaccine-induced immunity, the relative contributions of pre-existing immunity levels, maternal and infant characteristics on vaccine responses remain unclear, hampering evidence-based vaccination policy development. Here we combine serological data from 1,505 individuals (aged 0-12 years) in a mother-infant cohort and in a child cohort with empirical models to reconstruct antibody trajectories from birth. We show that while highly heterogeneous across a population, measles antibody evolution is strongly predictive from birth at the individual level, including following vaccination. Further, we find that caesarean section births were linked with 2.56 (95% confidence interval: 1.06-6.37) increased odds of primary vaccine failure, highlighting the long-term immunological consequences of birth route. Finally, we use our new understanding of antibody evolution to critically assess the population-level consequences of different vaccination schedules, the results of which will allow country-level evaluations of vaccine policy.

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.

How did the introduction of the measles-containing vaccine second dose (MCV2) affect measles vaccine uptake? - evidence from Nigeria.

Nigeria has the highest burden of measles worldwide, as measles vaccine uptake remains low. Recently, the second dose of the measles-containing vaccine (MCV2) was introduced as part of the routine immunization (RI) program, and this study examined how it changed the uptake of the measles vaccine and the factors associated with vaccination behavior. The Nigeria Multiple Indicator Cluster Survey (MICS) 2021 was used to compare measles vaccination uptake as well as factors associated with vaccination uptake between children before MCV2 introduction (cohort 1) and after the introduction (cohort 2). The overall rate of measles vaccine uptake was higher among cohort 1 (64%-95%) than among cohort 2 (56%-92%) in all zones because of younger age among cohort 2. The dropout from the first to second measles vaccines was similar between the cohorts (around 24%). Higher maternal education levels and higher household wealth levels were both correlated with the vaccine uptake or both cohorts but a positive correlation between the dropout and mother's education level was observed only among cohort 2, especially in the North West and South West zones. The positive correlation between the dropout and mother's education level among cohort 2 indicates that the introduction of MCV2 as part of RI might have helped to narrow the disparity in measles vaccine uptake in North West and South West zones. Further study is required to investigate strategies employed to reduce the disparity in these zones to apply nationwide.

Persistence and heterogeneity of the effects of educating mothers to improve child immunisation uptake: Experimental evidence from Uttar Pradesh in India.

Childhood vaccinations are among the most cost-effective health interventions. Yet, in India, where immunisation services are widely available free of charge, a substantial proportion of children remain unvaccinated. We revisit households 30 months after a randomised experiment of a health information intervention designed to educate mothers on the benefits of child vaccination in Uttar Pradesh, India. We find that the large short-term effects on the uptake of diphtheria-pertussis-tetanus and measles vaccination were sustained at 30 months, suggesting the intervention did not simply bring forward vaccinations. We apply causal forests and find that the intervention increased vaccination uptake, but that there was substantial variation in the magnitude of the estimated effects. We conclude that characterising those who benefited most and conversely those who benefited least provides policy-makers with insights on how the intervention worked, and how the targeting of households could be improved.

Exploring landscape of measles vaccination coverage: A step towards measles elimination goal in India.

INTRODUCTION: Measles remains a critical public health concern causing significant morbidity and mortality globally. Despite the success of measles vaccination programs, challenges persist, particularly in India. This study investigates dose-wise measles vaccination coverage and explores gaps in immunization focusing on zero-dose, one-dose, and two-dose coverage among children aged 24-35 months. DATA SOURCES AND METHODOLOGY: The National Family Health Survey 2019-21 (NFHS-5) served as the data source and the study analyzed information from 43,864 children aged 24-35 months. Sociodemographic variables such as birth order, wealth quintile, gender, social group, religion, residence, mother education, delivery-related factors, and media exposure were considered. Statistical analysis involved weighted estimates, chi-square tests, and multivariate multinomial logistic regression. RESULTS: The study revealed that challenges persist in achieving optimal measles vaccination coverage. Analysis by sociodemographic factors highlighted disparities in coverage, with variations in zero dose prevalence across states and districts. The percentage of zero-dose children was significantly higher, with 11.5% of children in India remaining to receive any measles vaccination. Factors influencing vaccine coverage include birth order, age, wealth quintile, social group, religion, residence, maternal education, place of delivery, media exposure, and mode of delivery. The findings from the spatial analysis show the clustering of zero-dose children is high in the northeastern states of India. DISCUSSION: Measles zero-dose children pose a significant obstacle to achieving elimination goals. Spatial analysis identifies clusters of unvaccinated populations guiding targeted interventions. The study aligns with global initiatives such as the Immunization Agenda 2030 emphasizing equitable vaccine access and discusses how India can tailor its strategies to achieve the goal. Lessons from polio eradication efforts inform strategies for measles elimination, stressing the importance of high-quality data and surveillance. The study underscores the urgency of addressing last-mile measles vaccination gaps in India. Spatially targeted interventions informed by sociodemographic factors can enhance immunization coverage. Achieving measles elimination requires sustained efforts and leveraging lessons from successful vaccination campaigns. The study findings have the potential to contribute to informed decision-making, supporting India's roadmap for the measles and rubella elimination goal.

A measles and rubella vaccine microneedle patch in The Gambia: a phase 1/2, double-blind, double-dummy, randomised, active-controlled, age de-escalation trial.

BACKGROUND: Microneedle patches (MNPs) have been ranked as the highest global priority innovation for overcoming immunisation barriers in low-income and middle-income countries. This trial aimed to provide the first data on the tolerability, safety, and immunogenicity of a measles and rubella vaccine (MRV)-MNP in children. METHODS: This single-centre, phase 1/2, double-blind, double-dummy, randomised, active-controlled, age de-escalation trial was conducted in The Gambia. To be eligible, all participants had to be healthy according to prespecified criteria, aged 18-40 years for the adult cohort, 15-18 months for toddlers, or 9-10 months for infants, and to be available for visits throughout the follow-up period. The three age cohorts were randomly assigned in a 2:1 ratio (adults) or 1:1 ratio (toddlers and infants) to receive either an MRV-MNP (Micron Biomedical, Atlanta, GA, USA) and a placebo (0·9% sodium chloride) subcutaneous injection, or a placebo-MNP and an MRV subcutaneous injection (MRV-SC; Serum Institute of India, Pune, India). Unmasked staff ransomly assigned the participants using an online application, and they prepared visually identical preparations of the MRV-MNP or placebo-MNP and MRV-SC or placebo-SC, but were not involved in collecting endpoint data. Staff administering the study interventions, participants, parents, and study staff assessing trial endpoints were masked to treatment allocation. The safety population consists of all vaccinated participants, and analysis was conducted according to route of MRV administration, irrespective of subsequent protocol deviations. The immunogenicity population consisted of all vaccinated participants who had a baseline and day 42 visit result available, and who had no protocol deviations considered to substantially affect the immunogenicity endpoints. Solicited local and systemic adverse events were collected for 14 days following vaccination. Unsolicited adverse events were collected to day 180. Age de-escalation between cohorts was based on the review of the safety data to day 14 by an independent data monitoring committee. Serum neutralising antibodies to measles and rubella were measured at baseline, day 42, and day 180. Analysis was descriptive and included safety events, seroprotection and seroconversion rates, and geometric mean antibody concentrations. The trial was registered with the Pan African Clinical Trials Registry PACTR202008836432905, and is complete. FINDINGS: Recruitment took place between May 18, 2021, and May 27, 2022. 45 adults, 120 toddlers, and 120 infants were randomly allocated and vaccinated. There were no safety concerns in the first 14 days following vaccination in either adults or toddlers, and age de-escalation proceeded accordingly. In infants, 93% (52/56; 95% CI 83·0-97·2) seroconverted to measles and 100% (58/58; 93·8-100) seroconverted to rubella following MRV-MNP administration, while 90% (52/58; 79·2-95·2) and 100% (59/59; 93·9-100) seroconverted to measles and rubella respectively, following MRV-SC. Induration at the MRV-MNP application site was the most frequent local reaction occurring in 46 (77%) of 60 toddlers and 39 (65%) of 60 infants. Related unsolicited adverse events, most commonly discolouration at the application site, were reported in 35 (58%) of 60 toddlers and 57 (95%) of 60 infants that had received the MRV-MNP. All local reactions were mild. There were no related severe or serious adverse events. INTERPRETATION: The safety and immunogenicity data support the accelerated development of the MRV-MNP. FUNDING: Bill & Melinda Gates Foundation.

Coverage and determinants of second-dose measles vaccination among under-five children in East Africa countries: a systematic review and meta-analysis.

Background: One of the biggest breakthroughs of contemporary medicine is measles vaccination. It is essential for the total elimination of measles. Understanding the magnitude and determinants of effective second-dose measles vaccination coverage is a critical task. Accordingly, we set out to check the best available evidence of the pooled second-dose measles vaccination coverage among under-five children in East Africa. Method: We searched electronic databases such as PubMed, Google Scholar, Cochrane, and others. Two reviewers separately carried out the search of the Joanna Briggs Institute, selection of studies, critical appraisal, and data extraction. A third party was involved in resolving the disagreement among the reviewers. Seven studies included in this study, four from Ethiopia, two from Kenya, and one from Tanzania were cross-sectional and published in English language, with publication dates before 29 November 2023. Articles lacking full-text, the intended outcome, and that are not qualitative studies were excluded from the analysis. The Microsoft Excel checklist was used to extract the data and then exported to STATA 11. In addition, I2, Funnel plots, and Egger's test were employed to measure heterogeneity and detect publication bias, respectively. A random effect model was used. Result: The meta-analysis includes a total sample size of 4,962 children from seven articles. The pooled prevalence of second-dose measles vaccination among under-five children in East Africa was found to be 32.22% [95% CI; (18.82, 45.63)], and the significant factors were as follows: birth order (1.72; OR = 95% CI: 1.32, 2.23), information about measles-containing second-dose vaccine (MCV 2) (7.39; OR = 95% CI: 5.21, 10.50), mother's marital status (1.47; OR = 95% CI: 1.05, 2.07), complete immunization for other vaccines (2.17; OR = 95% CI: 1.49, 3.17), and distance of vaccination site (3.31; OR = 95% CI: 2.42, 4.53). Conclusion: The current study found that pooled prevalence of second-dose measles vaccination coverage among under-five children was still very low. It was also observed that birth order, distance of the vaccination site, complete immunization for other vaccines, mother's marital status, and information about MCV were factors associated with second-dose measles vaccination. These factors imply that there is a need for countries and their partners to act urgently to secure political commitment, expand primary health service and health education, and increase vaccination coverage.

Effect of postpartum family planning intervention and associated factors during child immunization in Addis Ababa, Ethiopia.

Introduction: World Health Organization (WHO) recommends postpartum family planning (PPFP) as a critical component of health care that has the potential to save millions of maternal and infant lives in low- and middle-income countries. Methods: participants in our randomized, controlled trial were mothers coming for vaccination of their child in three selected health centers in Addis Ababa during the first 10 weeks postpartum. Eligible mothers were randomly assigned to intervention (pamphlet-supported counseling about the benefits of family planning) and non-intervention (routine care) arms. Data were collected when mothers came with their infants for a routine measles vaccination at nine months of life. Family planning (FP) use was compared between the groups using logistic regression, and bivariate and multivariate analyses. The study also used Kaplan Meier and Cox regressions to compare the median time of PPFP use and its correlation using SPSS version 26. The research was undertaken from December 2019 to June 2021. Results: a total of 347 women (177 control, 170 intervention) enrolled in the study. Fifty-eight percent were 24-30 years old. Young age, knowledge about FP, previous use of an FP method, and being married were found to be independent predictors for PPFP use. When comparing intervention and non-intervention groups, there was no significant effect on contraceptive use (adjusted OR 0.633 [95% CI 0.385-1.040]). Conclusion: pamphlet-supported counseling of mothers in the first 10 weeks postpartum did not increase PPFP at nine months postpartum. Successful interventions will likely require holistic strategies, especially in resource-limited settings. The trial had been registered with clinicaltrials.gov (NCT04521517) on September 24, 2019.

Measles second dose vaccine uptake and its associated factors among children aged 24-35 months in Northwest Ethiopia, 2022.

Measles is a major public health problem in under-five children, leading to lifelong complications. Therefore, the study aimed to assess the magnitude of measles second-dose vaccine uptake and its determinants among children aged 24-35 months in Northwest Ethiopia. A community-based cross-sectional study was conducted among 418 children aged 24-35 months in Northwest Ethiopia between January 2022 and February 2022. A simple random sampling technique was used to access study subjects. A binary logistic regression model was employed. An adjusted odd ratio with a 95% confidence interval (CI) and a p-value < 0.05 was used to declare significant predictors of measles second dose vaccine uptake. The magnitude of the measles second dose vaccine uptake among children aged 24-35 months was 41.39%. Postnatal care visits (AOR: 4.78, CI 1.49, 15.34), child vaccination status of other scheduled vaccines (AOR: 3.88, CI 2.23, 6.73), awareness of the measles second dose vaccine and its schedule (AOR: 8.924, CI 5.27, 15.09), and distance from the vaccination center (AOR: 0.21, CI 0.06, 0.77) were significantly associated with measles second dose vaccine uptake. The uptake of measles second dose vaccine in the study area was low. Therefore, health workers and other partners should initiate awareness creation programs for mothers/caretaker to improve the uptake of measles second dose vaccine.

Measles outbreak investigation in Berhet District, North Shewa, Ethiopia.

Introduction: Measles, though usually self-limiting, can have severe consequences influenced by factors such as vaccination and nutrition, notably vitamin A deficiency and malnutrition. Despite progress, contextual changes and implementation issues have hampered efforts, resulting in increased outbreaks and cases of measles. This study seeks to pinpoint outbreak features, risk factors, and strategies for preventing and controlling measles. Methods: A descriptive cross-sectional study and a 1:2 unmatched case-control study design were employed. All 101 suspected measles cases listed on the line-list were included in the descriptive research, with 60 measles patients and 120 controls included in the case-control investigation. Line-list data were cleaned and analyzed using a pivot table in Microsoft Excel 2016. Subsequently, the data were cleaned, entered into Epi Info 7.2, and exported to SPSS 26 for analysis. Results: Twenty cases occurred per 10,000 individuals. Men accounted for 67.3% of cases, with ages ranging from 5 months to 45 years and mean and standard deviations of 9.6 and 7.6, respectively. Age group of 5-14 years comprised 57.4% of cases, followed by 1-4 years with 24.8%. Being unvaccinated against measles showed an adjusted odds ratio (AOR) of 12.06 (95% CI: 3.12-46.52). Travel history to regions with active cases had an AOR of 5.73 (95% CI: 1.78-18.38). Contact with a measles patient showed an AOR of 10.3 (95% CI: 3.48-30.5). Understanding the measles transmission mechanism had an AOR of 0.164 (95% CI: 0.049-0.55), and awareness of the disease's preventability had an AOR of 0.233 (95% CI: 0.67-0.811). All factors were independently associated with the illness. Conclusion: This outbreak affected a broader age range with a high attack rate, mainly in the age group of 5-14-years. Over 35% of cases lacked measles vaccination, indicating low administrative vaccine coverage. Factors contributing to the outbreak include lack of measles vaccination, travel to areas with active disease, contact with cases, and insufficient knowledge of measles transmission and prevention strategies among mothers and caregivers.