Understanding rapid implementation from discovery to scale: Rwanda's implementation of rotavirus vaccines and PMTCT in the quest to reduce under-5 mortality.

BACKGROUND: Over the last eight decades, many evidence-based interventions (EBIs) have been developed to reduce amenable under-5 mortality (U5M). Implementation research can help reduce the lag between discovery and delivery, including as new EBIs emerge, or as existing ones are adapted based on new research. Rwanda was the first low-income African country to implement the rotavirus vaccine (RTV) and also adopted Option B+ for effective prevention of mother-to-child transmission (PMTCT) before the World Health Organization's (WHO) recommendation. We use implementation research to identify contextual factors and strategies associated with Rwanda's rapid uptake of these two EBIs developed or adapted during the study period. METHODS: We conducted a mixed methods case study informed by a hybrid implementation research framework to understand how Rwanda outperformed regional and economic peers in reducing U5M, focusing on the implementation of health system-delivered EBIs. The research included review of existing literature and data, and key informant interviews to identify implementation strategies and contextual factors that influenced implementation outcomes. We extracted relevant results from the broader case study and used convergent methods to understand successes and challenges of implementation of RTV, a newly introduced EBI, and PMTCT, an adapted EBI reflecting new research. RESULTS: We found several cross-cutting strategies that supported the rapid uptake and implementation of PMTCT, RTV, and leveraging facilitating contextual factors and identifying and addressing challenging ones. Key implementation strategies included community and stakeholder involvement and education, leveraging of in-country research capacity to drive adoption and adaptation, coordination of donors and implementing partners, data audit and feedback of coverage, a focus on equity, and integration into pre-existing systems, including community health workers and primary care. The availability of donor funding, culture of evidence-based decision-making, preexisting accountability systems, and rapid adoption of innovation were facilitating contextual factors. CONCLUSION: Implementation strategies which are generalizable to other settings were key to success in rapidly achieving high acceptability and coverage of both a new and an evolving EBI. Choosing strategies which leverage their facilitating factors and address barriers are important for other countries working to accelerate uptake of new EBIs and implement needed adaptations based on emerging evidence.

Cost-of-illness of gastroenteritis caused by rotavirus in Chinese children less than 5 years.

Acute gastroenteritis (AGE) caused by rotavirus (RV) remains a public health issue in China. To accelerate the mass rotavirus vaccination, it is important to inform the policy maker, and the public of the economic burden caused by rotavirus infection. A meta-analysis was conducted applying standardized algorithms. Articles published before January 1, 2023, in English and Chinese were searched through PubMed, CNKI, and WanFang Data. Studies with cost analysis of RV AGE were included. A random-effects model was applied to synthesize the total cost of RV AGE from the societal perspective. A prospective survey aimed to measure the cost of RV AGE was conducted in 2021 and 2022 in Shaoxing city, Zhejiang province, that can represent the developed region. The cost data was applied as deviation indicator, in comparison with the pooled estimate generated from meta-analysis. Totally 286 articles were identified, and eventually 12 studies were included. The pooled total social cost of RV AGE was US$282.1 (95%CI: US$213.4-350.7). The pooled private cost of RV AGE was US$206.4 (95%CI: US$155.2-257.5). RV AGE hospitalized and RV AGE incurred in developed regions caused remarkable higher burden (US$631.2 [95%CI: US$512.6-749.8], and US$333.6 [95%CI: US$234.1-433.2] respectively), compared to RV AGE treated at outpatient, and incurred in less developed regions. Our study demonstrates that RV AGE causes a significant economic burden in China. Given the promising effectiveness and highly cost-effective, introduction of rotavirus vaccines in national immunization programs could substantially reduce the economic burden in China.

Adding new childhood vaccines to China's National Immunization Program: evidence, benefits, and priorities.

China's National Immunization Program has made remarkable achievements but does not include several important childhood vaccines that are readily available in the private market, such as pneumococcal conjugate vaccine (PCV), rotavirus vaccine, Haemophilus influenzae serotype b (Hib) vaccine, and varicella vaccine. We reviewed the literature to assess these four non-National Immunization Program vaccines in terms of their disease burdens, coverage, inequalities, and cost-effectiveness in China and aimed to recommend priorities for introducing them to the National Immunization Program. Based on our calculations using the available evidence, incorporating these vaccines into China's National Immunization Program in 2019 could have averted 11 761 deaths among children younger than 5 years, accounting for 10·29% of the total deaths in children younger than 5 years and reducing the mortality rate from 7·8 per 1000 to 7·0 per 1000. The review showed that 13-valent PCV (PCV13) had the lowest and most inequitable coverage but could prevent the highest number of deaths. In a budgetary analysis for the cohort of newborns in 2023, we estimated that the projected aggregate government costs were US$1954·92 million for PCV13, $1273·13 million for pentavalent rotavirus vaccine, $415·30 million for Hib vaccine, and $221·64 million for varicella vaccine. Our overall multicriteria decision analysis suggested the following priority order for introducing these four non-programme vaccines to the National Immunization Program to benefit the Chinese population: PCV13, rotavirus vaccine, Hib vaccine, and varicella vaccine.

Economic Evaluation of Rotavirus Vaccination in Children Aged Under Five Years in South Africa.

BACKGROUND AND OBJECTIVE: Evidence on the economic value of rotavirus vaccines in middle-income countries is limited. We aimed to model the implementation of three vaccines (human rotavirus, live, attenuated, oral vaccine [HRV, 2 doses]; rotavirus vaccine, live, oral, pentavalent [HBRV, 3 doses] and rotavirus vaccine, live attenuated oral, freeze-dried [BRV-PV, 3 doses] presented in 1-dose and 2-dose vials) into the South African National Immunisation Programme. METHODS: Cost and cost-effectiveness analyses were conducted to compare three rotavirus vaccines using a static, deterministic, population model in children aged <5 years in South Africa from country payer and societal perspectives. Deterministic and probabilistic sensitivity analyses were conducted to assess the impact of uncertainty in model inputs. RESULTS: The human rotavirus, live, attenuated, oral vaccine (HRV) was associated with cost savings versus HBRV from both perspectives, and versus BRV-PV 1-dose vial from the societal perspective. In the cost-effectiveness analysis, HRV was estimated to avoid 1,107 home care rotavirus gastroenteritis (RVGE) events, 247 medical visits, 35 hospitalisations, and 4 RVGE-related deaths versus HBRV and BRV-PV. This translated to 73 quality-adjusted life years gained. HRV was associated with lower costs versus HBRV from both payer (-$3.9M) and societal (-$11.5M) perspectives and versus BRV-PV 1-dose vial from the societal perspective (-$3.8M), dominating those options. HRV was associated with higher costs versus BRV-PV 1-dose vial from the payer perspective and versus BRV-PV 2­dose vial from both payer and societal perspectives (ICERs: $51,834, $121,171, and $16,717, respectively), exceeding the assumed cost-effectiveness threshold of 0.5 GDP per capita. CONCLUSION: Vaccination with a 2-dose schedule of HRV may lead to better health outcomes for children in South Africa compared with the 3-dose schedule rotavirus vaccines.

Systematic review of rotavirus vaccination cost-effectiveness in high income settings utilising dynamic transmission modelling techniques.

PURPOSE: This systematic review presents cost-effectiveness studies of rotavirus vaccination in high-income settings based on dynamic transmission modelling to inform policy decisions about implementing rotavirus vaccination programmes. METHODS: We searched CEA Registry, MEDLINE, Embase, Health Technology Assessment Database, Scopus, and the National Health Service Economic Evaluation Database for studies published since 2002. Full economic evaluation studies based on dynamic transmission models, focusing on high-income countries, live oral rotavirus vaccine and children ≤ 5 years of age were eligible for inclusion. Included studies were appraised for quality and risk of bias using the Consensus on Health Economic Criteria (CHEC) list and the Philips checklist. The review protocol was prospectively registered with PROSPERO (CRD42020208406). RESULTS: A total of four economic evaluations were identified. Study settings included England and Wales, France, Norway, and the United States. All studies compared either pentavalent or monovalent rotavirus vaccines to no intervention. All studies were cost-utility analyses that reported incremental cost per quality-adjusted life year (QALY) gained. Included studies consistently concluded that rotavirus vaccination is cost-effective compared with no vaccination relative to the respective country's willingness to pay threshold when herd protection benefits are incorporated in the modelling framework. CONCLUSIONS: Rotavirus vaccination was found to be cost-effective in all identified studies that used dynamic transmission models in high-income settings where child mortality rates due to rotavirus gastroenteritis are close to zero. Previous systematic reviews of economic evaluations considered mostly static models and had less conclusive findings than the current study. This review suggests that modelling choices influence cost-effectiveness results for rotavirus vaccination. Specifically, the review suggests that dynamic transmission models are more likely to account for the full impact of rotavirus vaccination than static models in cost-effectiveness analyses.

Cost-effectiveness analysis of introducing rotavirus vaccine into immunization program in Zhejiang province, China: A decision tree-Markov model study.

Two RV vaccines have been licensed in Zhejiang province, China, including the pentavalent RotaTeq (RV5) and the monovalent RV vaccine (RV1). This study aimed to evaluate the cost-effectiveness of RV1 and RV5 to inform the prioritization of provincial immunization program. A decision tree-Markov model was applied to assess the cost-effectiveness of RV1 or RV5 vaccination, compared to no RV vaccination in a 5-year period. The incremental health cost per disability-adjusted life year (DALY) is averted when each kind of RV vaccine included in the immunization program was estimated. It was also compared to the willingness-to-pay (WTP) threshold of 1 time of the Gross Domestic Product (GDP) per capita of Zhejiang province in 2021 (16865.70US$). The uncertainties of these results were assessed through the one-way sensitivity analysis and probabilistic sensitivity analysis. In the base-case scenario, RV5 was the least costly RV vaccine with a cost-effectiveness ratio of 510 US$ per DALY averted. The other RV1 vaccines provided equivalent benefits but at higher costs, with a cost-effectiveness ratio of 4600 US$ per DALY averted. Compared to no vaccination, the probabilities of being cost-effective were 72.3% for RV1 and 88.4% for RV5, at a WTP threshold of 1 time of the GDP per capita. An RV vaccination program using any of the two China-licensed RV vaccines compared to no vaccination would avert 30-70% of outpatient visits, hospitalizations, and deaths from RVGE. RV5 was currently estimated to be the most cost-effective.

Assessment of the Impact of the Rotavirus Vaccine Against Severe Rotaviral Diarrhea in Uzbekistan.

BACKGROUND: This article presents the results of a long-term study of the impact of rotavirus vaccination in Uzbekistan. Uzbekistan is the first country in the Central Asian region to introduce rotavirus vaccination into the national compulsory vaccination calendar. The study aimed to evaluate the impact of rotavirus vaccination on hospitalizations due to all-cause AGE and RVGE in children < 5 years of age in Uzbekistan. METHODS: Detection of rotavirus antigen was performed using Rotavirus-Antigen-IFA-BEST "Vector Best" kit (Novosibirsk, Russia). RESULTS: The total of 20,128 children under 5 years of age were hospitalized in sentinel hospitals with a diagnosis of acute gastroenteritis during the study period (2019-2020). Of this number of children, 4481 children (22.2%) were included in the study. Of 4481 children, 367 (8.2%) children tested positive for rotavirus. In our study, decrease in the rotavirus rate was noted in all age groups. The peak of rotavirus positivity occurred in the months of January and February. CONCLUSION: The average rotavirus-positive rate in the period (2019-2020) was 8.2% and the absolute percentage decrease was 18.1% compared to the pre-vaccination period (2005-2009) where the rotavirus-positive rate was 26.3%. The percentage of prevented cases averaged 68.8%.

Cost-effectiveness analysis measuring the total costs against the health benefits of three different rotavirus vaccines for Mexico.

Rotavirus (RV) infection causes acute rotavirus gastroenteritis (RVGE) in infants. Safe and effective RV vaccines are available, of which Mexico has included one in its national immunization program (NIP) since 2007. Health outcome gains, expressed in quality-adjusted life years (QALYs), and cost improvements are important additional factors for the selection of a NIP vaccine. These two factors were analyzed here for Mexico over one year implementing three RV vaccines: 2-dose Rotarix (HRV), versus 3-dose RotaTeq (HBRV), and 3-dose Rotasiil (BRV-PV), presented in a 1-dose or 2-dose vial). HRV would annually result in discounted QALY gains of 263 extra years compared with the other vaccines by averting an extra 24,022 homecare cases, 10,779 medical visits, 392 hospitalizations, and 12 deaths. From a payer's perspective and compared with HRV, BRV-PV 2-dose vial and BRV-PV 1-dose vial would annually result in $13,548,179 and $4,633,957 net savings, respectively, while HBRV would result in $3,403,309 extra costs. The societal perspective may also show savings compared with HRV for BRV-PV 2-dose vial of $4,875,860, while BRV-PV 1-dose vial and HBRV may show extra costs of $4,038,363 and $12,075,629 respectively. HRV and HBRV were both approved in Mexico, with HRV requiring less investment than HBRV with higher QALY gains and cost savings. The HRV vaccine produced those higher health gains due to its earlier protection and greater coverage achieved after its schedule completion with two doses only, providing full protection at four months of age instead of longer periods for the other vaccines.

Rotavirus (RV) infection causes acute diarrhea in infants and can be life-threatening. Several safe and effective vaccines against RV and its complications exist. For many governments choosing vaccines for national immunization programs, total costs or savings and health gains are important factors in the selection process. We compared the costs and health benefits of three RV vaccines for Mexico: HRV, HBRV, and BRV-PV, that have different dosing schedules: two doses for HRV and three doses for HBRV and BRV-PV. HRV is currently part of the national immunization program in Mexico. HRV would result in more health benefits as it incurs fewer RV-related cases, medical visits, hospitalizations, and infant deaths than the other vaccines due to its early protection achieved after only two doses to complete its schedule. However, from a payer's perspective, the least expensive vaccine was BRV-PV, while HRV was less expensive than HBRV. From a societal perspective, also accounting for families' costs and loss in income due to an infant's RV disease, and the families' costs and loss in income when accompanying the infant to the vaccination center, the HRV vaccine was less expensive than HBRV and BRV-PV presented in a 1-dose vial, while more expensive than BRV-PV presented in a 2-dose vial. HRV and HBRV are both approved in Mexico, although HBRV requires a greater investment at lower health benefits than HRV, from both a payer's and a societal perspective. A 2-dose vaccination scheme is an important asset for the economic value of this vaccination program.

Economic assessment of childhood rotavirus vaccination in Bangladesh.

Rotavirus is one of the most highly prevalent communicable diseases in Bangladesh. The objective of this study is to evaluate the benefit-cost ratio of childhood rotavirus vaccination program in Bangladesh. A spreadsheet-based model was used to estimate the benefit and cost of a nationwide universal rotavirus vaccination program against rotavirus infections among under-five children in Bangladesh. A benefit-cost analysis was performed to evaluate a universal vaccination program compared with a status quo. Data from various published vaccination-related studies and public reports were used. The introduction of a childhood rotavirus vaccination program in Bangladesh for 14.78 million under-five children is projected to prevent approximately 1.54 million rotavirus cases during the first 2 years including 0.7 million severe rotavirus infections. This study shows that among the WHO-prequalified rotavirus vaccines, the net societal benefit is the highest if the vaccination program adopts ROTAVAC® rather than Rotarix® or ROTASIIL®. For every dollar invested in the outreach-based ROTAVAC® vaccination program, society would gain $2.03 in return, while in a facility-based vaccination program, society would gain up to about $2.2. The findings of this study demonstrate that a universal childhood rotavirus vaccination program is a cost-beneficial investment of public money. Thus, the government should consider the introduction of rotavirus vaccination in their Expanded Program on Immunization since the rotavirus immunization policy in Bangladesh will be economically justifiable.

Drivers of Decline in Diarrhea Mortality Between GEMS and VIDA Studies.

BACKGROUND: Statistical modeling suggests that decreasing diarrhea-associated mortality rates in recent decades are largely attributed to improved case management, rotavirus vaccine, and economic development. METHODS: We examined data collected in 2 multisite population-based diarrhea case-control studies, both conducted in The Gambia, Kenya, and Mali: the Global Enteric Multicenter Study (GEMS; 2008-2011) and Vaccine Impact on Diarrhea in Africa (VIDA; 2015-2018). Population-level diarrhea mortality and risk factor prevalence, estimated using these study data, were used to calculate the attribution of risk factors and interventions for diarrhea mortality using a counterfactual framework. We performed a decomposition of the effects of the changes in exposure to each risk factor between GEMS and VIDA on diarrhea mortality for each site. RESULTS: Diarrhea mortality among children under 5 in our African sites decreased by 65.3% (95% confidence interval [CI]: -80.0%, -45.0%) from GEMS to VIDA. Kenya and Mali had large relative declines in diarrhea mortality between the 2 periods with 85.9% (95% CI: -95.1%, -71.5%) and 78.0% (95% CI: -96.0%, 36.3%) reductions, respectively. Among the risk factors considered, the largest declines in diarrhea mortality between the 2 study periods were attributed to reduction in childhood wasting (27.2%; 95% CI: -39.3%, -16.8%) and an increased rotavirus vaccine coverage (23.1%; 95% CI: -28.4%, -19.4%), zinc for diarrhea treatment (12.1%; 95% CI: -16.0%, -8.9%), and oral rehydration salts (ORS) for diarrhea treatment (10.2%). CONCLUSIONS: The VIDA study sites demonstrated exceptional reduction in diarrhea mortality over the last decade. Site-specific differences highlight an opportunity for implementation science in collaboration with policymakers to improve the equitable coverage of these interventions globally.

Immunogenicity of inactivated rotavirus in rhesus monkey, and assessment of immunologic mechanisms.

Rotavirus is one of the main pathogens causing severe diarrhea in infants and young children < 5 years of age. The development of the next-generation rotavirus vaccine is of great significance for preventing rotavirus infection and reducing severe mortality. The current study aimed to develop and evaluate the immunogenicity of inactivated rotavirus vaccine (IRV) in rhesus monkeys. Monkeys received two or three IRV injections intramuscularly at a 4-week interval. Neutralizing antibodies, cellular immunity, PBMC gene expression profiling, and immune persistence were evaluated. Three-dose immunization of IRV induced a higher level of neutralizing, IgG and IgA antibodies compared to two-dose immunization. IRV induced IFN-γ secretion to mediate cellular immune responses, including robust pro-inflammatory and antiviral responses. Chemokine-mediated signaling pathways and immune response were broadly activated by IRV injection. The IRV-induced neutralizing antibodies resulting from two doses returned to baseline levels 20 weeks after full immunization, while those resulting from three doses returned to baseline levels 44 weeks after full immunization. Increasing immunization dose and injection number will help to improve IRV immunogenicity and neutralizing antibody persistence.

The economic impact of the introduction of universal rotavirus vaccination on rotavirus gastroenteritis related hospitalisations in children in Ireland.

BACKGROUND: Rotavirus gastroenteritis (RVGE), a vaccine preventable disease, remains a common cause of severe gastroenteritis in children globally. Ireland introduced the universal rotavirus vaccination to the national immunisation programme in 2016. In this paper the economic impact on RVGE related hospitalisations amongst children under 5 years is examined. METHODS: Using national data from all Irish public hospitals, an Interrupted Times Series Analysis (ITSA) compares RVGE hospitalisations amongst children under 5 years, pre- and post-vaccine introduction. Costs are estimated and ITSA results are compared to the counterfactual to estimate the economic impact of the vaccine. A probit model examines patient characteristics pre- and post-vaccine introduction. RESULTS: Vaccine introduction coincided with lowered RVGE related hospitalisations. While this effect was delayed (1 year) there is evidence of a sustained impact. RVGE patients' post-vaccine introduction were likely to be over 2 years (p = 0.001) and length of stay was lower on average (p = 0.095). The counterfactual analysis revealed 492 RVGE hospitalisations were avoided on average annually since the introduction of the vaccine. This has an estimated economic value of €0.92 million per annum. CONCLUSIONS: Following the introduction of the rotavirus vaccine in Ireland, hospitalisations for RVGE decreased significantly and those hospitalised were older and with a reduced length of stay on average. This has the potential for significant cost savings for the Irish healthcare system.

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.

Cost-benefit analysis of rotavirus vaccine included in the national immunization program in China.

BACKGROUND: Globally, rotavirus is a leading cause of severe acute gastroenteritis among children aged under 5 years and has a significant economic cost. Currently, rotavirus vaccines are only included in the private market in China. This study aimed to assess the cost-benefit of including a three-dose rotavirus vaccine in China's National Immunization Program (NIP). METHODS: A decision tree Markov model was constructed to evaluate the cost-benefit of universal immunization with three doses of rotavirus vaccine for a 2019 birth cohort of Chinese children. Costs of the universal vaccination program included vaccine price, vaccine wastage, vaccine administration, and indirect costs. All costs were discounted at 3 % per year and converted from 2019 Chinese Yuan to 2019 USD using the 2019 exchange rate. RESULTS: For the 2019 birth cohort of Chinese infants, inclusion of RotaTeq in NIP was estimated to prevent 5,677,911 cases of rotavirus infection, with net savings of $1.1 billion in total societal costs. A cost of $17.55 per vaccine dose was the threshold at which inclusion of rotavirus vaccine in NIP would be cost-saving. CONCLUSIONS: Introducing rotavirus vaccine into the China NIP would have significant costs from a societal perspective at the current private market price.

Cost, health impacts and cost effectiveness of iceless refrigeration in India's last-mile vaccine cold chain delivery.

BACKGROUND: Compared with ice-based vaccine carriers (IBVCs), iceless vaccine carrier (ILVC) last-mile delivery could optimize vaccine effectiveness by reducing spoilage. We estimated ILVC-associated spoilage costs averted and cost effectiveness. METHODS: IBVC vaccine spoilage costs were estimated for six vaccines. ILVC incremental costs were based on yearly ILVC cost over total doses. Cost effectiveness was estimated via Markov modeling of rotavirus vaccine. RESULTS: The spoilage cost using IBVCs was US$9 603 294. Using ILVCs, the incremental cost per vaccine dose was US$0.026, the cost-benefit ratio was 0.28, the number of averted disability-adjusted life years was 0.03 per child and there was a saving of US$0.80 per child vaccinated. CONCLUSIONS: ILVCs may bring cost savings and health gains compared with IBVCs.

Coverage and Equity of Childhood Vaccines in China.

Importance: Measuring vaccination coverage rates and equity is crucial for informing immunization policies in China. Objectives: To estimate coverage rates and multidimensional equity for childhood vaccination in China. Design, Setting, and Participants: This cross-sectional study was conducted via a survey in 10 Chinese provinces between August 5 and October 16, 2019, among children ages 6 months to 5 years and their primary caregivers. Children's vaccination records and their primary caregivers' demographics and socioeconomic status were collected. Data were analyzed from November 2019 to March 2022. Main Outcomes and Measures: Vaccine coverage rates were measured as a percentage of National Immunization Program (NIP) and non-NIP vaccines administered before the day on which the child was surveyed. A multidimensional equity model applied a standardized approach to ranking individuals from least to most unfairly disadvantaged by estimating differences between observed vaccination status and estimated vaccination status as function of fair and unfair variation. Fair sources of variation in coverage included whether the child was of age to receive the vaccine, and unfair sources of variation included sex of the child and sociodemographic characteristics of caregivers. Absolute equity gaps (AEGs), concentration index values, and decompositions of factors associated with vaccine equity were estimated in the model. Results: Vaccine records and sociodemographic information of 5294 children (2976 [52.8%] boys and 2498 [47.2%] girls; age range, 6-59 months; 1547 children aged 12-23 months) and their primary caregivers were collected from 10 provinces. Fully immunized coverage under the NIP was 83.1% (95% CI, 82.0%-84.1%) at the national level and more than 80% in 7 provinces (province coverage ranged from 77.8% [95% CI, 74.3% to 81.3%] in Jiangxi to 88.4% [95% CI, 85.7%-91.1%] in Beijing). For most non-NIP vaccines, however, coverage rates were less than 50%, ranging from 1.8% (95% CI, 1.3%-2.2%) for the third dose of rotavirus vaccine to 67.1% (65.4% to 68.8%) for the first dose of the varicella vaccine. The first dose of Haemophilus influenzae type b vaccine had the largest AEG, at 0.603 (95% CI, 0.570-0.636), and rotavirus vaccine dose 3 had the largest concentration index value, at 0.769 (95% CI, 0.709-0.829). The largest share of non-NIP vaccine inequity was contributed by monthly family income per capita, followed by education level, place of residence, and province for caregivers. For example, the proportion of explained inequity for pneumococcal conjugate vaccine dose 3 was 40.94% (95% CI, 39.49%-42.39%), 22.67% (95% CI, 21.43%-23.9%), 27.15% (95% CI, 25.84%-28.46%), and 0.68% (95% CI, 0.44%-0.92%) for these factors, respectively. Conclusions and Relevance: This cross-sectional study found that NIP vaccination coverage in China was high but there was inequity for non-NIP vaccines. These findings suggest that improvements in equitable coverage of non-NIP vaccination may be urgently needed to meet national immunization goals.

The Challenges and Opportunities of Next-Generation Rotavirus Vaccines: Summary of an Expert Meeting with Vaccine Developers.

The 2nd Next Generation Rotavirus Vaccine Developers Meeting, sponsored by PATH and the Bill and Melinda Gates Foundation, was held in London, UK (7-8 June 2022), and attended by vaccine developers and researchers to discuss advancements in the development of next-generation rotavirus vaccines and to consider issues surrounding vaccine acceptability, introduction, and uptake. Presentations included updates on rotavirus disease burden, the impact of currently licensed oral vaccines, various platforms and approaches for next generation rotavirus vaccines, strategies for combination pediatric vaccines, and the value proposition for novel parenteral rotavirus vaccines. This report summarizes the information shared at the convening and poses various topics worthy of further exploration.

Predicting the long-term impact of rotavirus vaccination in 112 countries from 2006 to 2034: A transmission modeling analysis.

Rotavirus vaccination has been shown to reduce rotavirus burden in many countries, but the long-term magnitude of vaccine impacts is unclear, particularly in low-income countries. We use a transmission model to estimate the long-term impact of rotavirus vaccination on deaths and disability adjusted life years (DALYs) from 2006 to 2034 for 112 low- and middle-income countries. We also explore the predicted effectiveness of a one- vs two- dose series and the relative contribution of direct vs indirect effects to overall impacts. To validate the model, we compare predicted percent reductions in severe rotavirus cases with the percent reduction in rotavirus positivity among gastroenteritis hospital admissions for 10 countries with pre- and post-vaccine introduction data. We estimate that vaccination would reduce deaths from rotavirus by 49.1 % (95 % UI: 46.6-54.3 %) by 2034 under realistic coverage scenarios, compared to a scenario without vaccination. Most of this benefit is due to direct benefit to vaccinated individuals (explaining 69-97 % of the overall impact), but indirect protection also appears to enhance impacts. We find that a one-dose schedule would only be about 57 % as effective as a two-dose schedule 12 years after vaccine introduction. Our model closely reproduced observed reductions in rotavirus positivity in the first few years after vaccine introduction in select countries. Rotavirus vaccination is likely to have a substantial impact on rotavirus gastroenteritis and its mortality burden. To sustain this benefit, the complete series of doses is needed.

Impact and cost-effectiveness of rotavirus vaccination in Niger: a modelling study evaluating alternative rotavirus vaccines.

OBJECTIVES: To evaluate the cost-effectiveness of alternative rotavirus vaccines in Niger, using UNIVAC, a proportionate outcomes model. SETTING: The study leverages global, regional and local data to inform cost-effectiveness modelling. Local data were collected as part of a clinical trial taking place in the Madarounfa district, Maradi region, Niger. PARTICIPANTS: The study models impact of infants vaccination on rotavirus gastroenteritis in children under 5 years of age. INTERVENTIONS: We compared the use of ROTARIX (GlaxoSmithKline, Belgium), ROTAVAC (Bharat Biotech, India) and ROTASIIL (Serum Institute, India) to no vaccination and to each other over a 10-year period starting in 2021. RESULTS: We estimated that ROTARIX, ROTAVAC and ROTASIIL would each prevent 13 million cases and 20 000 deaths of children under 5 years over a 10-year period in Niger. Compared with no vaccination, the cost to avert a disability-adjusted life-year was US$146 with ROTARIX, US$107 with ROTASIIL and US$76 with ROTAVAC from the government perspective. ROTAVAC dominated ROTARIX and ROTASIIL (eg, provided similar or higher benefits at a lower cost) and had 90% chance to be cost-effective at a US$100 willingness-to-pay threshold. CONCLUSIONS: This study can inform decision-making around rotavirus vaccination policy in Niger, demonstrating that ROTAVAC is likely the most cost-effective option. Alternative products (ROTASIIL and ROTARIX) may also be considered by decision-makers if they are priced more competitively, or if their cold chain requirements could bring additional economic benefits.