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

百日咳仍然是一个主要的流行病负担，约占30万人， 全世界每年都有死亡，其中大多数是儿童。婴儿早期的成功 20世纪50年代和60年代的免疫计划导致了 发病率和乐观情绪，消灭百日咳可能是可以实现的。 然而，在过去的20年里，在一些接种良好的国家， 已经指出了我们对百日咳的认识上的主要差距 流行病学、免疫学、进化论和控制。提供和使用各种 疫苗的效力和免疫特性知之甚少， 不确定性 我们建议提高我们对百日咳这些重要决定因素的认识 通过将问题分解为可管理的单元来解决传输问题。通过进行 对多个备选假设进行全面的比较性检验， 来自不同国家的前疫苗时代的空间复制和年龄特定数据， 我们的目标是确定感染源性免疫力的持续时间，流行病学特征， 重复感染的影响，亚临床免疫增强所起的作用，以及 人口统计学、特定年龄接触者和 季节性下一阶段的研究将致力于解决疫苗的具体问题 通过关注已知疫苗使用情况的国家（全细胞疫苗与 无细胞的）和免疫时间表。最终的考验是我们的理解 对百日咳的研究取得了重大进展，将是解释一个神秘的数据体， 即过去30年来美国百日咳发病率的变化模式。 这项工作将在很大程度上依赖于百日咳传播的数学模型的使用 以及从数据中提取信息的统计方法。其中一个主要成分是 项目，因此，是开发，使用和传播新的方法 这些工具将在开源公共软件中实现。最后，我们将带来 结合这一努力的智力成果，以开发最佳的，具有成本效益的 免疫政策。

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 wellvaccinated 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. acellular) 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 effort in order to develop optimal, cost-effective immunization policy.