Update on rotavirus vaccine underperformance in low- to middle-income countries and next-generation vaccines.
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SUBMITTER: Lee B
PROVIDER: S-EPMC8115752 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundLive oral rotavirus vaccines (LORVs) have significantly reduced rotavirus hospitalizations and deaths worldwide. However, LORVs are less effective in low- and middle-income countries (LMICs). Next-generation rotavirus vaccines (NGRVs) may be more effective but require administration by injection or a neonatal oral dose, adding operational complexity. Healthcare providers (HPs) were interviewed to assess rotavirus vaccine preferences and identify delivery issues as part of an NGRV value proposition.ObjectiveDetermine HP vaccine preferences about delivering LORVs compared to injectable (iNGRV) and neonatal oral (oNGRV) NGRVs.Methods64 HPs from Ghana, Kenya, Malawi, Peru, and Senegal were interviewed following a mixed-method guide centered on three vaccine comparisons: LORV vs. iNGRV; LORV vs. oNGRV; oNGRV vs. iNGRV. HPs reviewed attributes for each vaccine in the comparisons, then indicated and explained their preference. Additional questions elicited views about co-administering iNGRV+LORV for greater public health impact, a possible iNGRV-DTP-containing combination vaccine, and delivering neonatal doses.ResultsAlmost all HPs preferred oral vaccine options over iNGRV, with many emphasizing an aversion to additional injections. Despite this strong preference, HPs described challenges delivering oral doses. Preferences for LORV vs. oNGRV were split, marked by disparate views on rotavirus disease epidemiology and the safety, need, and feasibility of delivering neonatal vaccines. Although overwhelmingly enthusiastic about an iNGRV-DTP-containing combination option, several HPs had concerns. HP views were divided on the feasibility of co-administering iNGRV+LORV, citing challenges around logistics and caregiver sensitization.ConclusionOur findings provide valuable insights on delivering NGRVs in routine immunization. Despite opposition to injectables, openness to co-administering LORV+iNGRV to improve efficacy suggests future HP support of iNGRV if adequately informed of its advantages. Rationales for LORV vs. oNGRV underscore needs for training on rotavirus epidemiology and stronger service integration. Expressed challenges delivering existing LORVs merit further examination and indicate need for improved delivery.
| S-EPMC9223340 | biostudies-literature
Project description:A recent report by the World Health Organization calls for implementation of community genetics programs in low- and middle-income countries (LMICs). Their focus is prevention of congenital disorders and genetic diseases at the population level, in addition to providing genetics services, including diagnosis and counseling. The proposed strategies include both newborn screening and population screening for carrier detection, in addition to lowering the incidence of congenital disorders and genetic diseases through the removal of environmental factors. In this article, we consider the potential impact of such testing on global health and highlight the near-term relevance of next-generation sequencing (NGS) and bioinformatic approaches to their implementation. Key attributes of NGS for community genetics programs are homogeneous approach, high multiplexing of diseases and samples, as well as rapidly falling costs of new technologies. In the near future, we estimate that appropriate use of population-specific test panels could cost as little as $10 for 10 Mendelian disorders and could have a major impact on diseases that currently affect 2% of children worldwide. However, the successful deployment of this technological innovation in LMICs will require high value for human life, thoughtful implementation, and autonomy of individual decisions, supported by appropriate genetic counseling and community education.
| S-EPMC3446275 | biostudies-literature
Project description:BACKGROUND:Altering rotavirus vaccine schedules may improve vaccine performance in low- and middle-income countries. We analyzed data from clinical trials of the monovalent (RV1) and pentavalent (RV5) rotavirus vaccines in low- and middle-income countries to understand the association between vaccine dose timing and severe rotavirus gastroenteritis incidence. METHODS:We assessed the association between variations in rotavirus vaccine administration schedules and severe rotavirus gastroenteritis risk. We used the complement of the Kaplan-Meier survival estimator to estimate risk differences for different schedules. To adjust risk differences (RDs) for confounding, we calibrated estimates in the vaccinated arm using estimates from the placebo arm. RESULTS:There were 3,114 and 7,341 children included from the RV1 and RV5 trials, respectively. The 18-month adjusted severe rotavirus gastroenteritis risk was 4.0% (95% confidence interval [CI] = 1.1, 7.1) higher for those receiving their first RV5 dose at <6 versus ?6 weeks. For RV1, there was a 4.0% (95% CI = 0.0, 8.2) increase in 12-month adjusted risk for a 4- versus 6-week interval between doses. Further analysis revealed those receiving their first RV5 dose at 3-4 and 5-7 weeks had 2.9% (95% CI = 0.8, 5.3) and 1.3% (95% CI = -0.3, 3.0), respectively, higher risk compared with those at 9-12 weeks. Those receiving their first dose at 8 weeks had the lowest risk (RD: -2.6% [95% CI = -5.4, -0.1]) compared with those at 9-12 weeks. CONCLUSIONS:A modest delay in rotavirus vaccination start and increase in interval between doses may be associated with lower severe rotavirus gastroenteritis risk in low- and middle-income countries.
| S-EPMC6167161 | biostudies-literature
Project description:BACKGROUND:Rotavirus vaccine schedules may impact vaccine response among children in low- and middle-income countries (LMICs). Our objective was to review the literature evaluating the effects of monovalent (RV1) or pentavalent rotavirus vaccines schedules on vaccine response. METHODS:We searched PubMed, Web of Science, Embase, and ClinicalTrials.gov for eligible trials conducted in LMICs comparing ?2 vaccine schedules and reporting immunologic response or efficacy. We calculated seroconversion proportion differences and geometric mean concentration (GMC) ratios with 95% confidence intervals. RESULTS:We abstracted data from 8 eligible trials of RV1. The point estimates for seroconversion proportions difference ranged from -0.25 to -0.09 for the 6/10-week schedule compared with 10/14. The range for the 6/10/14- compared with 10/14-week schedule was -0.02 to 0.10. Patterns were similar for GMC ratios and efficacy estimates. CONCLUSIONS:The commonly used 6/10-week RV1 schedule in LMICs may not be optimal. Further research on the effect of rotavirus schedules using clinical endpoints is essential.
| S-EPMC5445722 | biostudies-literature
Project description:BackgroundRotavirus causes morbidity and mortality in children particularly in low-income countries (LICs) and lower-middle-income countries (LMICs). This systematic review and meta-analysis aimed to assess cost-effectiveness of rotavirus vaccine in LICs and LMICs.MethodsRelevant studies were identified from PubMed and Scopus from their inception to January 2019. Studies were eligible if they assessed the cost-effectiveness of rotavirus vaccine in children in LICs and LMICs and reported incremental cost-effectiveness ratios. Risk of bias and quality assessment was assessed based on the Consolidated Health Economic Evaluation Reporting Standard checklist. Incremental net benefits (INBs) were estimated, and meta-analysis based on the DerSimonian and Laird method was applied to pool INBs across studies.ResultsWe identified 1614 studies, of which 28 studies (29 countries) were eligible and conducted using cost-utility analysis in LICs (n = 8) and LMICs (n = 21). The pooled INB was estimated at $62.17 (95% confidence interval, $7.12-$117.21) in LICs, with a highly significant heterogeneity (?2 = 33.96; df = 6; P < .001; I 2 = 82.3%), whereas the pooled INB in LMICs was $82.46 (95% confidence interval, $54.52-$110.41) with no heterogeneity (?2 = 8.46; df = 11; P = .67; I 2 = 0%).ConclusionsRotavirus vaccine would be cost-effective to introduce in LICs and LMICs. These findings could aid decision makers and provide evidence for introduction of rotavirus vaccination.
| S-EPMC6488528 | biostudies-literature
Project description:Although a proven and effective preventive health measure, childhood immunization programs remain vulnerable to budgetary pressures. Sustainable financing of immunization programs is an important issue that presents a challenge for middle-income countries (MIC) in particular, in part due to technological advances meaning more vaccines are available. This study aimed to analyse trends in immunization program investment across 15 MIC selected based on availability of data, income level classification, and regional representativeness. We assessed investment trends in relation to vaccine coverage, vaccine access, and broader health indicators. Immunization and expenditure data were obtained from the World Health Organisation (WHO) database and the WHO UNICEF Joint Reporting Form and WHO Vaccine Product, Price and Procurement from 2006-2016. We calculated a weighted average index of vaccine commitment (WAIVC) based on vaccine coverage, vaccine scope, and weighted by vaccine innovation measured by approximating vaccine expenditure. Correlation analyses were conducted between immunization expenditure per-capita and each WAIVC, infant mortality and life expectancy. Correlation analyses at a global and individual country level indicate an improvement in immunization access, vaccination commitment measured by WAIVC, and scope of available vaccines in countries with sustained increases in vaccination funding. Increases in national immunization expenditure were correlated with reduced infant mortality and increased life expectancy. Vaccine expenditure comprises a small proportion (less than 2%) of total healthcare spending and has not uniformly increased in accordance with the scope of available vaccines. The present analysis supports the premise that countries with consistent increases in vaccine expenditure have increased vaccine coverage and commitment measured by WAIVC and improved broader health outcomes, indicating the value of sustained investment in vaccination for improved population health. The benefits of vaccine expenditure in this holistic fashion are critical to inform policy decisions on national budget allocation for vaccine funding.
| S-EPMC6816376 | biostudies-literature
Project description:BackgroundScientific and professional development opportunities for early career scientists in low- and middle- income countries (LMICs) are limited and not consistent. There is a disproportionately low number of biomedical and clinical researchers in LMIC's relative to their high burden of disease, a disparity that is aggravated by emigration of up to 70% of scientists from their countries of birth for education and employment elsewhere. To help address this need, a novel University-accredited, immersive fellowship program was established by a large public-academic-private network. We sought to describe the program and summarize progress and lessons learned over its first 7-years.MethodsHallmarks of the program are a structured learning curriculum and bespoke research activities tailored to the needs of each fellow. Research projects expose the scientists to state-of-the-art methodologies and leading experts in their fields while also ensuring that learnings are implementable within their home infrastructure. Fellows run seminars on drug discovery and development that reinforce themes of scientific leadership and teamwork together with practical modules on addressing healthcare challenges within their local systems. Industry mentors achieve mutual learning to better understand healthcare needs in traditionally underserved settings. We evaluated the impact of the program through an online survey of participants and by assessing research output.ResultsMore than 140 scientists and clinicians from 25 countries participated over the 7-year period. Evaluation revealed strong evidence of knowledge and skills transfer, and beneficial self-reported impact on fellow's research output and career trajectories. Examples of program impact included completion of post-graduate qualifications; establishment and implementation of good laboratory- and clinical- practice mechanisms; and becoming lead investigators in local programs. There was a high retention of fellows in their home countries (>?75%) and an enduring professional network among the fellows and their mentors.ConclusionsOur experience demonstrates an example for how multi-sectoral partners can contribute to scientific and professional development of researchers in LMICs and supports the idea that capacity-building efforts should be tailored to the specific needs of beneficiaries to be maximally effective. Lessons learned may be applied to the design and conduct of other programs to strengthen science ecosystems in LMICs.
| S-EPMC6180641 | biostudies-literature
Project description:There are two internationally available WHO-prequalified oral rotavirus vaccines (Rotarix and RotaTeq), two rotavirus vaccines licensed in India (Rotavac and Rotasiil), one in China (Lanzhou lamb rotavirus vaccine) and one in Vietnam (Rotavin-M1), and several candidates in development. Rotavirus vaccination has been rolled out in Latin American countries and is beginning to be deployed in sub-Saharan African countries but middle- and low-income Asian countries have lagged behind in rotavirus vaccine introduction. We provide a mini-review of the leading newer-generation rotavirus vaccines and compare them with Rotarix and RotaTeq. We discuss how the development and future availability of newer-generation rotavirus vaccines that address the programmatic needs of poorer countries may help scale-up rotavirus vaccination where it is needed.
| S-EPMC5806648 | biostudies-other
Project description:Vaccines may reduce the burden of antimicrobial resistance, in part by preventing infections for which treatment often includes the use of antibiotics1-4. However, the effects of vaccination on antibiotic consumption remain poorly understood-especially in low- and middle-income countries (LMICs), where the burden of antimicrobial resistance is greatest5. Here we show that vaccines that have recently been implemented in the World Health Organization's Expanded Programme on Immunization reduce antibiotic consumption substantially among children under five years of age in LMICs. By analysing data from large-scale studies of households, we estimate that pneumococcal conjugate vaccines and live attenuated rotavirus vaccines confer 19.7% (95% confidence interval, 3.4-43.4%) and 11.4% (4.0-18.6%) protection against antibiotic-treated episodes of acute respiratory infection and diarrhoea, respectively, in age groups that experience the greatest disease burden attributable to the vaccine-targeted pathogens6,7. Under current coverage levels, pneumococcal and rotavirus vaccines prevent 23.8 million and 13.6 million episodes of antibiotic-treated illness, respectively, among children under five years of age in LMICs each year. Direct protection resulting from the achievement of universal coverage targets for these vaccines could prevent an additional 40.0 million episodes of antibiotic-treated illness. This evidence supports the prioritization of vaccines within the global strategy to combat antimicrobial resistance8.
| S-EPMC7332418 | biostudies-literature
Project description:Background:Cost-effectiveness analysis (CEA) is frequently used as an input for guiding priority setting in health. However, CEA seldom incorporates information about trade-offs between total health gains and equity impacts of interventions. This study investigates to what extent equity considerations have been taken into account in CEA in low- and middle-income countries (LMICs), using rotavirus vaccination as a case study. Methods:Specific equity-related indicators for vaccination were first mapped to the Guidance on Priority Setting in Health Care (GPS-Health) checklist criteria. Economic evaluations of rotavirus vaccine in LMICs identified via a systematic review of the literature were assessed to explore the extent to which equity was considered in the research objectives and analysis, and whether it was reflected in the evaluation results. Results:The mapping process resulted in 18 unique indicators. Under the 'disease and intervention' criteria, severity of illness was incorporated in 75% of the articles, age distribution of the disease in 70%, and presence of comorbidities in 5%. For the 'social groups' criteria, relative coverage reflecting wealth-based coverage inequality was taken into account in 30% of the articles, geographic location in 27%, household income level in 8%, and sex at birth in 5%. For the criteria of 'protection against the financial and social effects of ill health', age weighting was incorporated in 43% of the articles, societal perspective in 58%, caregiver's loss of productivity in 45%, and financial risk protection in 5%. Overall, some articles incorporated the indicators in their model inputs (20%) while the majority (80%) presented results (costs, health outcomes, or incremental cost-effectiveness ratios) differentiated according to the indicators. Critically, less than a fifth (17%) of articles incorporating indicators did so due to an explicit study objective related to capturing equity considerations. Most indicators were increasingly incorporated over time, with a notable exception of age-weighting of DALYs. Conclusion:Integrating equity criteria in CEA can help policy-makers better understand the distributional impact of health interventions. This study illustrates how equity considerations are currently being incorporated within CEA of rotavirus vaccination and highlights the components of equity that have been used in studies in LMICs. Areas for further improvement are identified.
| S-EPMC5960127 | biostudies-literature