New Serological Measures of Infectious Disease Transmission Intensity

传染病传播强度的新血清学测量方法

• 批准号: 8947064
• 负责人: Benjamin F Arnold
• 金额: $ 14.21万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-06-18 至 2020-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8947064
• 关键词: Age; Antibodies; Antibody Response; Antigens; Applied Research; Area; Biological Assay; Biometry; Blood; California; Campylobacter; Caregivers; Centers for Disease Control and Prevention (U.S.); Child; Cluster randomized trial; Collaborations; Communicable Diseases; Computer software; Country; Cross-Sectional Studies; Cryptosporidium; Cryptosporidium parvum; Data; Development; Diagnostic tests; Diarrhea; Disease; Doctor of Philosophy; Effectiveness of Interventions; Entamoeba histolytica; Enteral; Environment; Epidemiologic Methods; Epidemiologist; Epidemiology; Faculty; Family; Filarial Elephantiases; Future; Giardia; Goals; Haiti; Handwashing; Health; Immune response; Immunologist; Immunology; Individual; Infection; Infectious Disease Epidemiology; Infectious Disease Immunology; Infectious Diseases Research; International; Intervention; Intervention Studies; Kenya; Literature; Low income; Machine Learning; Measles; Measurement; Measures; Mentors; Methodology; Methods; Modeling; Monitor; Mumps; Outcome; Pharmaceutical Preparations; Play; Population; Public Health; Qualifying; Recording of previous events; Reporting; Research; Research Personnel; Research Training; Role; Rubella; Running; Salmonella; Sanitation; Serological; Seroprevalences; Source; Spottings; Staging; Statistical Methods; Statistical Models; Survival Analysis; Tanzania; Testing; Time; Training; Translating; Translations; Universities; Vibrio cholerae; Viral; Water; Work; base; career; cohort; comparison group; cost; disease transmission; drinking water; effectiveness measure; enteric pathogen; enterotoxigenic Escherichia coli; experience; flexibility; high risk; improved; intervention effect; intervention program; member; multidisciplinary; neglected tropical diseases; novel; novel strategies; open source; pathogen; professor; programs; public health intervention; public health relevance; research study; response; seroconversion; seropositive; skills; statistics; theories; therapy design; tool; transmission process; user-friendly

 DESCRIPTION (provided by applicant): Candidate: Benjamin Arnold I am an epidemiologist at the University of California, Berkeley. I completed my MA in Biostatistics and a PhD in Epidemiology from UC Berkeley in 2009. Since then, I have worked as an epidemiologist in Professor Jack Colford's group. The opportunity to work as the coordinating epidemiologist for a touchstone, multi-country cluster randomized trial - combined with the addition of two children to my family - led me to delay my academic career. I am now ready to restart my career progress toward independent investigator status. My long-term career goal is to become a leader in the application of novel statistical methods to target and evaluate interventions that reduce the burden of enteric infections and neglected tropical diseases (NTDs) in low-income countries. This research focus and career objective build from my experience and from a growing collaboration with Dr. Patrick Lammie at the US Centers for Disease Control (CDC) that started in 2013 and has introduced me to seroepidemiologic research. My background in epidemiologic methods, biostatistics, and international field research makes me uniquely qualified to make significant contributions to infectious disease epidemiology at the interface between recent advances in statistical methodology and serological assays. Environment: University of California, Berkeley To achieve my career goal, I have developed a training and mentoring plan that focuses on recent advances in statistics (semi-parametric estimation theory and machine learning) and on infectious disease immunology. These are two areas where additional training will open up significant and unique opportunities for me to make meaningful contributions to seroepidemiologic research, and will enable me to launch an independent career as a productive faculty member at UC Berkeley. I have assembled a multidisciplinary mentoring team of senior investigators in biostatistics and immunology to support my training, research, and career objectives. Mark van der Laan (primary mentor, biostatistics) will guide my training in semi-parametric methods and machine learning. Alan Hubbard (co-mentor, biostatistics) will guide my translation of the methodology to applications for enteric pathogens and NTDs. Patrick Lammie (co-mentor at CDC, immunology) will guide my immunology training and research with his expertise in the immunology of enteric pathogens and NTDs Research: New Serological Measures of Infectious Disease Transmission Background: Recent advances in multiplex antigen assays have led to the development of low-cost and sensitive methods to measure enteric pathogens and neglected tropical diseases (NTDs). There have not been commensurate advances in the statistical methods used to derive measures of transmission intensity from antibody response. Translating antibody response into metrics of transmission intensity is a key step from a public health perspective because it enables us to target intervention programs to the populations most in need and then measure the effectiveness of those programs. Aims and Methods: The overarching goal of this research is to develop a methodologic framework to translate antibody response measured in cross-sectional surveys into measures of transmission intensity for enteric pathogens (7 included in the study, e.g., Cryptosporidium parvum, enterotoxigenic E. coli) and neglected tropical diseases (principal focus: lymphatic filariasis). We approach this goal from two novel perspectives. In Aim 1, we draw on the "peak shift" phenomenon for infectious diseases, and hypothesize that changes in transmission will be detectable in the age-specific antibody response curve. At lower transmission, antibody levels should decline across all ages due to fewer and less frequent active infections, leading to an overall shift in the age-specific response curve. We will evaluate the approach by comparing antibody response curves for young children with different exposures (improved vs. unimproved drinking water for enteric pathogens; pre- versus post- mass drug administration for lymphatic filariasis) in large, well characterized cohorts in Kenya, Tanzania, and Haiti. In Aim 2, we will develop semi-parametric methods to estimate the force of infection (seroconversion rate) from seroprevalence data for pathogens where seroreversion is possible, using lymphatic filariasis as an example. Our new approach marks a significant advance over previous work in this area by making few modeling assumptions and by allowing for the flexible control of confounding between comparison groups. We will evaluate the approach in Haiti by measuring the effect of mass drug administration on the force of infection for lymphatic filariasis For all of the methods, we will create user-friendly, open source software to accelerate translation to applied research. The Future: This mentored training and research plan represents a natural next step for me on a productive and collaborative path to independence at UC Berkeley. It will set the stage for a broader R01-level research portfolio that applies the newly developed methods to primary research studies that evaluate the impact of interventions on enteric infections, and help target and monitor global elimination efforts for NTDs.

 描述（由申请人提供）： 候选人：本杰明·阿诺德 我是加州大学伯克利分校的流行病学家。 2009年，我在加州大学伯克利分校获得了生物统计学硕士学位和流行病学博士学位。此后，我在Jack Colford教授的团队中担任流行病学家。作为一项试金石、多国整群随机试验的协调流行病学家的机会，再加上我家里多了两个孩子，导致我推迟了我的学术生涯。我现在已准备好重新开始我的职业生涯，争取独立调查员身份。 我的长期职业目标是成为应用新型统计方法的领导者，以制定和评估旨在减轻低收入国家肠道感染和被忽视的热带病 (NTD) 负担的干预措施。这一研究重点和职业目标源于我的经验以及与美国疾病控制中心 (CDC) 的 Patrick Lammie 博士的不断深入的合作，该合作始于 2013 年，让我开始了血清流行病学研究。我在流行病学方法、生物统计学和国际实地研究方面的背景使我有资格在统计方法和血清学检测的最新进展之间为传染病流行病学做出重大贡献。 环境：加州大学伯克利分校 为了实现我的职业目标，我制定了一项培训和指导计划，重点关注统计学（半参数估计理论和机器学习）和传染病免疫学的最新进展。在这两个领域，额外的培训将为我提供重要而独特的机会，为血清流行病学研究做出有意义的贡献，并使我能够在加州大学伯克利分校作为一名富有成效的教员开启独立的职业生涯。 我组建了一支由生物统计学和免疫学高级研究人员组成的多学科指导团队，以支持我的培训、研究和职业目标。 Mark van der Laan（生物统计学主要导师）将指导我进行半参数方法和机器学习方面的培训。 Alan Hubbard（联合导师，生物统计学）将指导我将该方法转化为肠道病原体和 NTD 的应用。 Patrick Lammie（疾病预防控制中心免疫学联合导师）将以其在肠道病原体和 NTD 免疫学方面的专业知识指导我的免疫学培训和研究 研究：传染病传播的新血清学方法 背景：多重抗原检测的最新进展促进了低成本、灵敏方法的开发，用于测量肠道病原体和被忽视的热带病 (NTD)。用于从抗体反应推导出传输强度的统计方法尚未取得相应的进展。从公共卫生的角度来看，将抗体反应转化为传播强度的指标是关键一步，因为它使我们能够针对最需要的人群制定干预计划，然后衡量这些计划的有效性。 目的和方法：本研究的总体目标是开发一个方法框架，将横断面调查中测量的抗体反应转化为肠道病原体（研究中包括的 7 种，例如隐孢子虫、产肠毒素大肠杆菌）和被忽视的热带疾病（主要焦点：淋巴丝虫病）传播强度的测量。我们从两个新颖的角度来实现这一目标。在目标 1 中，我们利用传染病的“峰移”现象，并假设在年龄特异性抗体反应曲线中可以检测到传播的变化。在传播率较低的情况下，由于活动性感染越来越少，所有年龄段的抗体水平都会下降，从而导致特定年龄反应曲线的整体变化。我们将通过在肯尼亚、坦桑尼亚和海地的大型、特征明确的队列中比较具有不同暴露（肠道病原体的改良饮用水与未改良饮用水；淋巴丝虫病大规模给药前与大规模给药后）的幼儿的抗体反应曲线来评估该方法。 在目标 2 中，我们将开发半参数方法，根据可能发生血清逆转的病原体的血清阳性率数据来估计感染力（血清转化率），以淋巴丝虫病为例。我们的新方法通过很少的建模假设并允许灵活控制比较组之间的混杂因素，标志着该领域先前工作的重大进步。我们将通过测量大规模给药对淋巴丝虫病感染力的影响来评估海地的方法。对于所有方法，我们将创建用户友好的开源软件，以加速转化为应用研究。 未来：这个指导性的培训和研究计划代表了我在加州大学伯克利分校走向独立的富有成效和协作的道路上自然而然的下一步。它将为更广泛的 R01 级研究组合奠定基础，将新开发的方法应用于初级研究，评估干预措施对肠道感染的影响，并帮助确定和监测全球消除被忽视热带病的努力。