Cost-Effectiveness Analysis of Vaccination With Recombinant Zoster Vaccine Among Hematopoietic Cell Transplant Recipients and Persons With Other Immunocompromising Conditions Aged 19 to 49 Years

ObjectivesThis study aimed to estimate the cost-effectiveness of the use of recombinant zoster vaccine (RZV) (Shingrix), which protects against herpes zoster (HZ), among immunocompromised adults aged 19 to 49 years, as a contribution to deliberations of the Advisory Committee on Immunization Practices.MethodsHematopoietic cell transplant (HCT) recipients experience a high incidence of HZ, and the efficacy of RZV in preventing HZ has been studied in clinical trials. The cost-effectiveness model calculated incremental cost-effectiveness ratios that compared vaccination with RZV with a no vaccination strategy among adults aged 19 to 49 years. Costs and outcomes were calculated until age 50 years using the healthcare sector perspective and summarized as cost per quality-adjusted life-year (QALY) gained. The base case represents HCT recipients, with scenario analyses representing persons with other immunocompromising conditions, including hematologic malignancies, human immunodeficiency virus, and autoimmune and inflammatory conditions. Uncertainty was investigated using univariate, multivariate, and probabilistic sensitivity analyses.ResultsBase-case results indicated vaccination with RZV would avert approximately 35% of HZ episodes and complications, while saving approximately 11% of net costs. Compared with no vaccination, vaccination of HCT recipients with RZV generated cost-savings (ie, lower costs and improved health) in the base case and in 81% of simulations in the probabilistic analysis. In scenario analyses, vaccination cost US dollar ($) 9500/QALY among patients with hematologic malignancies, $79 000/QALY among persons living with human immunodeficiency virus, and $208 000/QALY among persons with selected autoimmune and inflammatory conditions.ConclusionsGenerally favorable economic estimates supported recommendations for vaccination of immunocompromised adults with RZV to prevent episodes of HZ and related complications.     

中国成年双生子高脂血症的分布特征

目的描述中国双生子登记系统(CNTR)成年双生子高脂血症的分布特征, 初步探索遗传和环境因素对高脂血症的影响。方法研究对象来自CNTR在全国11个项目地区募集的双生子, 纳入成年且具有高脂血症信息的69 130名(34 565对)双生子进行分析。采用随机效应模型描述高脂血症的人群、地区分布特征。分别计算不同卵型双生子的高脂血症同病率, 估算遗传度。结果研究对象年龄为(34.2±12.4)岁。双生子人群高脂血症患病率为1.3%(895/69 130)。男性、年长、城镇、已婚、大专及以上文化程度、超重、肥胖、体力活动不足、当前吸烟和曾经吸烟、当前饮酒和曾经饮酒人群中高脂血症患病率较高。双生子对内分析发现, 同卵双生子高脂血症同病率为29.1%(118/405), 高于异卵双生子的18.1%(57/315), 差异有统计学意义(P<0.05)。在不同年龄、地区及性别分层中, 同卵双生子同病率仍呈现高于异卵双生子的趋势。进一步同性别双生子对内分析发现, 在北方组和女性组中, 高脂血症遗传度分别为13.04%(95%CI:2.61%～23.47%)、18.59%(95%CI:4.43%～3...     

Burden of invasive pneumococcal disease (IPD) in Sri-Lanka: Deriving a reasonable measure for vaccine introduction decision making

PurposeThe lack of evidence on the disease burden has been an obstacle for decision-making on introducing pneumococcal vaccines in Sri-Lanka. Hence, the purpose of this study is to determine the incidence of invasive pneumococcal disease among children under five-years of age in Sri-Lanka's Colombo district.MethodsIn a community-based study, using a sample of 2310 children, we identified syndromes associated with pneumococcal disease (pneumonia, meningitis, sepsis). The estimates of annual cumulative incidence of invasive pneumococcal disease were derived by having applied proportions of laboratory confirmed invasive pneumococcal disease among all-cause syndromes associated with pneumococcal infection obtained from the hospital-based invasive bacterial disease sentinel surveillance and findings of the community-based study to population parameters of the district. The estimates of invasive pneumococcal pneumonia and sepsis based on low-sensitive, culture confirmation were adjusted by a correction factor.ResultsThe annual cumulative incidence of all-cause clinical syndromes associated with pneumococcal disease (pneumonia, meningitis, sepsis) were 1.3, 0.52, 0.39 per 100 children, respectively. The estimate of adjusted, invasive pneumococcal disease cumulative incidence was 206.3 per 100,000 while estimates of pneumococcal pneumonia, meningitis and sepsis cumulative incidence were 147.9, 13.2 and 45.2 per 100,000 under-five children.ConclusionReasonable estimates of invasive pneumococcal disease could be derived by using incidence of clinical syndromes associated with pneumococcal disease obtained from population-based studies and proportion of pneumococcal infection among all-cause clinical syndromes associated with pneumococcal disease generated from hospital-based sentinel surveillance. These estimates may help informed decision-making on introduction of pneumococcal conjugated vaccine.     

The frequency of early-activated hapten-specific B cell subsets predicts the efficacy of vaccines for nicotine dependence

Therapeutic vaccines for nicotine addiction show pre-clinical efficacy. Yet, clinical evaluation of the first-generation nicotine vaccines did not meet expectations because only a subset of immunized subjects achieved effective serum antibody levels. Recent studies suggest that vaccine design affects B cell activation, and that the frequency of the hapten-specific B cell subsets contributes to vaccine efficacy against drugs of abuse. To extend this hypothesis to nicotine immunogens, we synthesized a novel hapten containing a carboxymethylureido group at the 2-position of the nicotine structure (2CMUNic) and compared its efficacy to the previously characterized 6CMUNic hapten. Haptens were conjugated to the keyhole limpet hemocyanin (KLH) carrier protein, and evaluated for efficacy against nicotine in mice using the clinically approved alum adjuvant. Using a novel fluorescent antigen-based magnetic enrichment strategy paired with multicolor flow cytometry analysis, polyclonal hapten-specific B cell subsets were measured in mice immunized with either 6CMUNic-KLH or 2CMUNic-KLH. The 6CMUNic-KLH showed significantly greater efficacy than 2CMUNic-KLH on nicotine distribution to serum and to the brain. The 6CMUNic-KLH elicited higher anti-nicotine serum antibody titers, and greater expansion of hapten-specific B cells than 2CMUNic-KLH. Within the splenic polyclonal B cell population, a higher number of hapten-specific IgM^high and germinal centre B cells predicted greater vaccine efficacy against nicotine distribution. These early pre-clinical findings suggest that hapten structure affects activation of B cells, and that variations in the frequency of early-activated hapten-specific B cell subsets underlie individual differences in vaccine efficacy.     

A systematic review of the social and economic burden of influenza in low- and middle-income countries

ObjectivesThe economic burden of seasonal influenza outbreaks as well as influenza pandemics in lower- and middle-income countries (LMIC) has yet to be specifically systematically reviewed. The aim of this systematic review is to assess the evidence of influenza economic burden assessment methods in LMIC and to quantify the economic consequences of influenza disease in these countries, including broader opportunity costs in terms of impaired social progress and economic development.MethodsWe conducted an all language literature search across 5 key databases using an extensive list of key words for the time period 1950–2013. We included studies which explored direct costs (medical and non-medical), indirect costs (productivity losses), and broader economic impact in LMIC associated with different influenza outcomes such as confirmed seasonal influenza infection, influenza-like illnesses, and pandemic influenza.ResultsWe included 62 full-text studies in English, Spanish, Russian, Chinese languages, mostly from the countries of Latin American and the Caribbean and East Asia and Pacific with pertinent cost data found in 39 papers. Estimates for direct and indirect costs were the highest in Latin American and the Caribbean. Compared to high-income economies, direct costs in LMIC were lower and productivity losses higher. Evidence on broader impact of influenza included impact on the wider national economy, security dimension, medical insurance policy, legal frameworks, distributional impact, and investment flows.ConclusionThe economic burden of influenza in LMIC encompasses multiple dimensions such as direct costs to the health service and households, indirect costs due to productivity losses as well as broader detriments to the wider economy. Evidence from sub-Saharan Africa and in pregnant women remains very limited. Heterogeneity of methods used to estimate cost components makes data synthesis challenging. There is a strong need for standardizing research, data collection and evaluation methods for both direct and indirect cost components.     

Research priorities for accelerating progress toward measles and rubella elimination identified by a cross-sectional web-based survey

BackgroundIn 2012, the World Health Assembly endorsed the Global Vaccine Action Plan (GVAP) that set a target to eliminate measles and rubella in five of the six World Health Organization (WHO) regions by 2020. Significant progress has been made toward achieving this goal through intensive efforts by countries and Measles & Rubella Initiative (M&RI) partners. Accelerating progress will require evidence-based approaches to improve implementation of the core strategies in the Global Measles and Rubella Strategic Plan. The M&RI Research and Innovation Working Group (R&IWG) conducted a web-based survey as part of a process to identify measles and rubella research priorities. Survey findings were used to inform discussions during a meeting of experts convened by the M&RI at the Pan American Health Organization in November 2016.MethodsThe cross-sectional web-based survey of scientific and programmatic experts included questions in four main topic areas: (1) epidemiology and economics (epidemiology); (2) new tools for surveillance, vaccine delivery, and laboratory testing (new tools); (3) immunization strategies and outbreak response (strategies); and (4) vaccine demand and communications (demand). Analyses were stratified by the six WHO regions and by global, regional, or national/sub-national level of respondents.ResultsThe six highest priority research questions selected by survey respondents from the four topic areas were the following: (1) What are the causes of outbreaks in settings with high reported vaccination coverage? (epidemiology); (2) Can affordable diagnostic tests be developed to confirm measles and rubella cases rapidly and accurately at the point of care? (new tools); (3) What are effective strategies for increasing coverage of the routine first dose of measles vaccine administered at 9 or 12 months? (strategies); (4) What are effective strategies for increasing coverage of the second dose given after the first year of life? (strategies); (5) How can communities best be engaged in planning, implementing and monitoring health services including vaccinations? (demand); (6) What capacity building is needed for health workers to be able to identify and work more effectively with community leaders? (demand). Research priorities varied by region and by global/regional/national levels for all topic areas.ConclusionsResearch and innovation will be critical to make further progress toward achieving the GVAP measles and rubella elimination goals. The results of this survey can be used to inform decision-making for investments in research activities at the global, regional, and national levels.     

Supporting national immunization technical advisory groups (NITAGs) in resource-constrained settings. New strategies and lessons learned from the Task Force for Global Health’s Partnership for influenza vaccine introduction

National Immunization Technical Advisory Groups (NITAGs) are multidisciplinary national experts who provide independent, evidence-informed vaccine policy recommendations to national health authorities. An essential NITAG function is to ensure that these decisions are grounded in the best available evidence generated through a systematic, transparent process. However, in many low- and middle-income countries (LMICs), experience with this decision making method is limited. The Task Force for Global Health manages the Partnership for Influenza Vaccine Introduction (PIVI) program in collaboration with the Centers for Disease Control and Prevention, Ministries of Health, corporate partners and others. During 2017, PIVI worked with its country partners and the World Health Organization regional and local offices to assess NITAG strengthening needs and to provide technical assistance in 7 LMIC countries (Laos Peoples Democratic Republic, Mongolia, Vietnam, Armenia, Côte d’Ivoire; Moldova and the Republic of Georgia). Our workshops supported general NITAG capacity building and the evidence-based review process using vaccines of interest to the country. For NITAGs reviewing evidence on seasonal influenza, we developed an influenza resource package to support their review and provide country-relevant information in an easy to use format. Of the seven NITAGs trained, six have applied some of the concepts learnt: revision or development of formal transparent, systematic procedures for their operations; preparation of recommendations on seasonal influenza vaccination using quality-assessed data from systematic searches and local data; and have applied the principles learned for making other new vaccine recommendations. Our experience confirms that LMIC NITAGs are considerably under-resourced without adequate technical support or access to global peer-reviewed literature. Ongoing support from NITAG partners must be secured and creative approaches might be needed to help countries achieve the GVAP 2020 target and support development of sustainable vaccine policies and programs.     

Differences between coverage of yellow fever vaccine and the first dose of measles-containing vaccine: A desk review of global data sources

IntroductionThe strategy to Eliminate Yellow Fever Epidemics (EYE) is a global initiative that includes all countries with risk of yellow fever (YF) virus transmission. Of these, 40 countries (27 in Africa and 13 in the Americas) are considered high-risk and targeted for interventions to increase coverage of YF vaccine. Even though the World Health Organization (WHO) recommends that YF vaccine be given concurrently with the first dose of measles-containing vaccine (MCV1) in YF-endemic settings, estimated coverage for MCV1 and YF vaccine have varied widely. The objective of this study was to review global data sources to assess discrepancies in YF vaccine and MCV1 coverage and identify plausible reasons for these discrepancies.MethodsWe conducted a desk review of data from 34 countries (22 in Africa, 12 in Latin America), from 2006 to 2016, with national introduction of YF vaccine and listed as high-risk by the EYE strategy. Data reviewed included procured and administered doses, immunization schedules, routine coverage estimates and reported vaccine stock-outs. In the 30 countries included in the comparitive analysis, differences greater than 3 percentage points between YF vaccine and MCV1 coverage were considered meaningful.ResultsIn America, there were meaningful differences (7–45%) in coverage of the two vaccines in 6 (67%) of the 9 countries. In Africa, there were meaningful differences (4–27%) in coverage of the two vaccines in 9 (43%) of the 21 countries. Nine countries (26%) reported MVC1 stock-outs while sixteen countries (47%) reported YF vaccine stock-outs for three or more years during 2006–2016.ConclusionIn countries reporting significant differences in coverage of the two vaccines, differences may be driven by different target populations and vaccine availability. However, these were not sufficient to completely explain observed differences. Further follow-up is needed to identify possible reasons for differences in coverage rates in several countries where these could not fully be explained.     

The Global Vaccine Action Plan – insights into its utility,application, and ways to strengthen future plans

BackgroundThe pace of global progress must increase if the Global Vaccine Action Plan (GVAP) goals are to be achieved by 2020. We administered a two-phase survey to key immunization stakeholders to assess the utility and application of GVAP, including how it has impacted country immunization programs, and to find ways to strengthen the next 10-year plan.MethodsFor the Phase I survey, an online questionnaire was sent to global immunization stakeholders in summer 2017. The Phase II survey was sent to regional and national immunization stakeholders in summer 2018, including WHO Regional Advisors on Immunization, Expanded Programme on Immunization managers, and WHO and UNICEF country representatives from 20 countries. Countries were selected based on improvements (10) versus decreases (10) in DTP3 coverage from 2010 to 2016.ResultsGlobal immunization stakeholders (n = 38) cite global progress in improving vaccine delivery (88%) and engaging civil society organizations as advocates for vaccines (83%). Among regional and national immunization stakeholders (n = 58), 70% indicated reaching mobile and underserved populations with vaccination activities as a major challenge. The top ranked activities for helping country programs achieve progress toward GVAP goals include improved monitoring of vaccination coverage and upgrading disease surveillance systems. Most respondents (96%) indicated GVAP as useful for determining immunization priorities and 95% were supportive of a post-2020 GVAP strategy.ConclusionsImmunization stakeholders see GVAP as a useful tool, and there is cause for excitement as the global immunization community looks toward the next decade of vaccines. The next 10-year plan should attempt to increase political will, align immunization activities with other health system agendas, and address important issues like reaching mobile/migrant populations and improving data reporting systems.