Integrating immunology, epidemiology, and evolution to understand and control per

整合免疫学、流行病学和进化论来理解和控制

• 批准号: 8342885
• 负责人: Aaron A. King
• 金额: $ 33.95万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-05-01 至 2017-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8342885
• 关键词: Accounting; Address; Affect; Age; Biology; Birth; Cells; Cessation of life; Child; Childhood; Clinical; Communicable Diseases; Comparative Study; Complex; Computer software; Country; Data; Data Set; Databases; Demography; Development; Disease Outbreaks; Economics; Encapsulated; Environmental Impact; Epidemiology; Evolution; Finland; Fruit; Future; Geographic state; Geography; Immigration; Immune; Immunity; Immunization; Immunization Programs; Immunization Schedule; Immunology; Incidence; Infant; Infection; Knowledge; Methods; Mission; Modeling; Natural Immunity; Nature; Notification; Pattern; Perception; Pertussis; Phase; Play; Policies; Population; Relative (related person); Reporting; Research; Role; Schedule; Scheme; Seasons; Secondary Immunization; Senegal; Serotyping; Statistical Methods; Stratification; Sweden; System; Testing; Thailand; Time; Uncertainty; Vaccinated; Vaccination; Vaccines; Variant; Virulent; Work; comparative; cost effective; experience; improved; mathematical model; mortality; novel; open source; optimism; pathogen; programs; public health priorities; success; theories; tool; transmission process; trend; uptake

DESCRIPTION (provided by applicant): Pertussis remains a major epidemiological burden, accounting for roughly 300,000 deaths worldwide each year, most of them children. The early success of infant immunization programs in the 1950s and 1960s led to a substantial reduction in incidence and a sense of optimism that elimination of pertussis might be a achievable. Over the past two decades, however, documented outbreaks in a number of well vaccinated populations has pointed out major gaps in our understanding of pertussis epidemiology, immunology, evolution, and control. The availability and use of various vaccines with poorly understood efficacy and immunity profiles contributes to the uncertainty. We propose to improve our understanding of these important determinants of pertussis transmission by splitting the problem into manageable units. By conducting a comprehensive, comparative testing of multiple alternative hypotheses on long-term, spatially replicated, and age-specific data from different countries in the pre-vaccine era, we will aim to pin down the duration of infection-derived immunity, the epidemiological impact of repeat infections, the role played by sub-clinical immune boosting, and the respective contributions of population demography, age-specific contacts, and seasonality. The next phase of research will aim to address the vaccine-specific aspects of the problem by focusing on countries with known vaccine usage (whole cell vs. a cellular) and immunization schedules. The ultimate test of whether our understanding of pertussis has significantly advanced will be to explain an enigmatic body of data, namely the changing patterns of pertussis incidence in the US over the past thirty years. This work will rely heavily on the use of mathematical models of pertussis transmission and statistical methods for extracting information from data. A major ingredient in this project, therefore, is the development, use, and dissemination of novel methodological tools that will be implemented in open-source public software. Finally, we will bring together the intellectual fruits of this effortin order to develop optimal, cost-effective immunization policy. PUBLIC HEALTH RELEVANCE: The control of infectious diseases by means of immunization remains a critical public health priority. In some nations, including the US, recent decades have coincided with a notable increase in pertussis notifications, despite high vaccine uptake estimates pinpointing significant knowledge gaps in pertussis biology. Therefore, understanding the complex interaction of factors that affect pertussis epidemiology, immunology, evolution, and control is an urgent priority. This is what we propose to do using an extensive database of pertussis reports from a number of countries, including information on age, geography and serotype. We will test alternative competing hypotheses using these data and cutting edge statistical methods. Finally, we will distill the intellectual fruits of this effort into optimal, ost-effective immunization policy.

描述（由申请人提供）：百日咳仍然是一个主要的流行病学负担，每年在全世界造成大约30万人死亡，其中大多数是儿童。20世纪50年代和60年代婴儿免疫接种计划的早期成功导致发病率大幅下降，并乐观地认为消除百日咳可能是可以实现的。 然而，在过去的二十年里，一些疫苗接种良好的人群中爆发的记录表明，我们对百日咳流行病学，免疫学，进化和控制的理解存在重大差距。对各种疫苗的有效性和免疫特性知之甚少的疫苗的可获得性和使用情况助长了这种不确定性。 我们建议通过将问题分解为可管理的单元来提高我们对百日咳传播的这些重要决定因素的理解。通过对来自不同国家的前疫苗时代的长期、空间复制和年龄特异性数据进行多个替代假设的全面比较检验，我们的目标是确定感染源性免疫的持续时间、重复感染的流行病学影响、亚临床免疫增强所发挥的作用，以及人口统计学、年龄特异性接触者、和季节性。下一阶段的研究将致力于解决该问题的疫苗特定方面，重点关注已知疫苗使用（全细胞与细胞）和免疫接种计划的国家。我们对百日咳的理解是否有了显著进步，最终的检验将是解释一组神秘的数据，即过去30年来美国百日咳发病率的变化模式。 这项工作将依靠 主要是使用百日咳传播的数学模型和从数据中提取信息的统计方法。因此，该项目的一个主要组成部分是开发、使用和传播将在开源公共软件中实现的新方法工具。最后，我们将汇集这一努力的智力成果，以制定最佳的、具有成本效益的免疫政策。 公共卫生相关性：通过免疫接种控制传染病仍然是一个关键的公共卫生优先事项。在包括美国在内的一些国家，近几十年来百日咳病例报告显著增加，尽管疫苗接种率高的估计数表明百日咳生物学存在重大知识缺口。因此，了解影响百日咳流行病学、免疫学、进化和控制的因素的复杂相互作用是当务之急。这就是我们建议利用来自一些国家的百日咳报告的广泛数据库，包括年龄、地理和血清型信息来做的事情。我们将使用这些数据和最先进的统计方法来测试替代竞争假设。最后，我们将把这一努力的智力成果提炼成最佳的、最有效的免疫政策。