Protecting Patients with Glomerular Disease from Vaccine-Preventable Infections

保护肾小球疾病患者免受疫苗可预防的感染

基本信息

批准号：
10445593
负责人：
Dorey Glenn
金额：
$ 20.18万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-02-15 至 2027-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10445593
关键词：
Address Adult Advisory Committees Age Antibodies Antibody titer measurement Attenuated Biological Assay Biopsy Caring Cause of Death Cell physiology Characteristics Child Clinical Communicable Diseases Complement Data Data Analyses Databases Development Disease Epidemiology Exposure to Foundations Frequencies Goals Guidelines Healthcare Hospitals IgG Deficiency Immune Immune response Immunity Immunoglobulins Immunosuppression Impairment Incidence Individual Infection Infection prevention Influenza Kidney Diseases Lead Lower Respiratory Tract Infection Measurement Measures Mediating Mentorship Methods Monitor Morbidity - disease rate National Institute of Diabetes and Digestive and Kidney Diseases Nephrotic Syndrome Participant Patients Pharmaceutical Preparations Pneumococcal Infections Pneumococcal vaccine Population Preparation Prevention Measures Prevention strategy Preventive measure Prospective cohort study Proteinuria Rare Diseases Regimen Renal function Renal glomerular disease Research Research Design Research Training Resources Risk Factors Sample Size Scientist Statistical Methods Streptococcus pneumoniae Testing Time Training Use Effectiveness Vaccinated Vaccination Vaccines Work career career development clinical practice cohort cost effective epidemiology study experience health care service utilization high risk high risk population immunogenicity in vivo influenza infection influenza virus vaccine longitudinal analysis longitudinal dataset mortality patient population pragmatic trial prophylactic prospective seroconversion urinary vaccination strategy vaccine effectiveness vaccine immunogenicity vaccine response

项目摘要

ABSTRACT Influenza and pneumococcal infections occurring in individuals with glomerular disease are preventable contributors to excess healthcare utilization, morbidity, and mortality, and occur at a rate approximately 30 times higher among individuals with glomerular diseases compared to the general US population. Vaccination is a powerful and cost-effective method to reduce infectious burden, however, vaccine immunogenicity and effectiveness have not been adequately studied in this high-risk patient population. Vaccination may not yield protective or sustained immune responses in individuals with glomerular disease as a result of exposure to immunosuppressive medications, altered immune cell function, and urinary loss of immunoglobulin and complement factors. As a result, there remain pressing questions regarding whether these antibodies confer in- vivo protection from influenza and pneumococcal infection. Evidence gaps that need to be addressed in preparation for pragmatic trials focused on infection-prevention measures in this population include frequency of administration of recommended vaccines, pervasiveness of infectious complications, and rates of influenza and pneumococcal vaccine seroconversion and seroprotection. Prior studies have been limited by small sample size, insufficiently characterized cohorts, and the use of assays that measure non-opsonic, and thus potentially non- functional, antibodies. The objective of this proposal is to describe the association of influenza and pneumococcal vaccination with influenza and pneumococcal infections and describe functional vaccine immunogenicity in patients with glomerular disease. Three projects have been proposed to achieve this objective: an analysis of influenza and pneumococcal vaccine use and effectiveness in a nationwide healthcare claims database (MarketScan®), a study examining vaccine immunogenicity in the multicenter NIDDK-sponsored Cure Glomerulonephropathy (CureGN) study, and creation of a multicenter cohort to examine 23-valent pneumococcal vaccine immunogenicity in children with nephrotic syndrome. The primary hypothesis is that, independent of kidney function, rates of influenza and pneumococcal infection and suboptimal vaccine response will be higher in individuals with active glomerular disease, greater immunosuppression exposure, greater proteinuria, and younger age. Dr. Glenn’s career development goals include gaining advanced training in statistical methods and epidemiologic study design, with a focus on the analysis of longitudinal datasets, healthcare claims data, and multicenter vaccine immunogenicity studies. Dr. Glenn will receive mentorship from Dr. Amy Mottl and Dr. Ronald Falk, both experts in the field of glomerular kidney disease. Additionally, Dr. Glenn will have a scientific advisory committee comprised of experts in vaccine immunogenicity, infectious disease, healthcare claims data analysis, and epidemiology. This work will inform the development of an R01 application in which Dr. Glenn leads a pragmatic trial investigating pneumococcal vaccination strategies among children with nephrotic syndrome.

抽象的在肾小球疾病中发生的流感和肺炎球菌感染是可预防的过多的医疗保健利用，发病率和死亡率的贡献者，以大约30次的速度发生与美国普通人群相比，肾小球疾病的个体中的人数更高。疫苗接种是但是，有力且具有成本效益的方法可减少感染性伯恩，但是，疫苗免疫原性和在这个高危患者人群中，有效性尚未充分研究。疫苗接种可能无法产生由于暴露于肾小球疾病的个体中的保护性或持续免疫调查免疫抑制药物，免疫细胞功能改变以及免疫球蛋白的尿丧失和补充因素。结果，关于这些抗体是否会议是否涉及 - 免受影响力和肺炎球菌感染的体内保护。需要解决的证据差距为重点在该人群中进行预防措施的务实试验的准备工作包括给予推荐疫苗，传染性并发症的普遍性以及影响力和影响力的发生率肺炎球菌疫苗血清转化和血清保护。先前的研究受到小样本量的限制，人群的表征不足，以及测量非上语的测定法，因此潜在的非 - 功能，抗体。该提案的目的是描述影响力和肺炎球菌疫苗接种与肺炎球菌的关联流感和肺炎球菌感染并描述患者的功能疫苗免疫原性肾小球疾病。已经提出了三个项目来实现这一目标：对影响力和分析全国医疗保健索赔数据库（MarketScan®）中的肺炎球菌疫苗使用和有效性研究在多中心NIDDK赞助的治疗肾小球肾病中检查疫苗免疫原性的研究（治疗）研究，并创建多中心队列以检查23个价值肺炎球菌疫苗肾病综合征儿童的免疫原性。主要假设是，独立于肾脏功能，影响力和肺炎球菌感染的速率以及次优疫苗反应的功能，率在患有活跃肾小球疾病的个体，更大的免疫抑制暴露，蛋白尿较大，并且年轻的年龄。格伦博士的职业发展目标包括获得统计方法的高级培训和流行病学研究设计，重点是分析纵向数据集，医疗保健索赔数据和数据多中心疫苗免疫原性研究。格伦博士将从艾米·莫特（Amy Mottl）和罗纳德（Ronald）博士那里获得心态福尔克（Falk）是肾小球肾脏疾病领域的两位专家。此外，格伦博士将有科学咨询委员会完成了疫苗免疫原性，传染病，医疗保健索赔数据分析的专家，和流行病学。这项工作将为Glenn博士领导的R01应用程序的开发提供信息务实的试验研究了肾病综合征儿童中肺炎球菌疫苗接种策略。