Ecology and Evolution of Disease Interference

描述（由申请人提供）：拟议的工作将为“疾病群落”的生态和进化动力学建立一个总体框架。尽管流行病学领域有着辉煌的历史，取得了显著的成功，但不相关感染之间相互作用的可能性并没有受到太多关注。提出了抗原性不同感染之间相互作用的机制：急性感染后，个体暂时无法感染其他疾病（主要是因为恢复期的隔离）。因此，每种病原体可用的潜在“宿主”数量受到其他感染的爆发动态的影响。如果一种感染与大量死亡率有关，那么潜在的宿主就会被永久移除，这种相互作用以疾病之间竞争的形式出现。这种机制导致了所谓的“疾病干扰”。本提案旨在发展这一概念框架，回答一些基本的生态和进化问题。是否所有感染都与其他感染相互作用？答案显然是否定的。直观地说，可以预期，感染之间这种负相互作用的强度将取决于被感染宿主的相似程度。对于人类感染，这将由感染时宿主年龄分布之间的重叠量决定。疾病干扰是否影响进化动力学？这项工作的一个中心假设是，干扰可能会选择增加疾病毒性。我们能否在抗原多态性已经确立的系统（例如登革热）中使用干扰效应？该干扰机制为研究多菌株感染提供了零模型。这项工作可能对公共卫生产生重要影响吗？初步研究表明，使用比传统估计更少的疫苗单位，干扰效应可能有益地用于根除感染。本建议还旨在构建统计工具，从而可以自信地从数据中检测到干扰的特征。由于其出色的时空数据集，这项工作的大部分将集中在儿童感染（例如麻疹、百日咳、水痘和风疹）上，尽管提出的机制相当普遍。开发的分析工具将应用于许多长期疾病记录，以探索干扰现象的普遍性。

DESCRIPTION (provided by applicant): The proposed work will develop a general framework for the ecological and evolutionary dynamics of "disease communities". Although the field of epidemiology has a distinguished history with notable successes, the potential for interaction between unrelated infections has not received much attention. A mechanism for interaction between antigenically distinct infections is proposed: following an acute infection, individuals are temporarily unavailable to contract other diseases (primarily because quarantining during convalescence). Hence, the number of potential "hosts" available for each pathogen is affected by the outbreak dynamics of other infections. If an infection is associated with substantial mortality, then potential hosts become permanently removed and the interaction takes the form of competition between diseases. This mechanism leads to what is called "disease interference". This proposal aims to develop this conceptual framework, answering a number of fundamental ecological and evolutionary questions. Do all infections interact with all other infections? The answer to this is clearly no. Intuitively, it would be expected that the strength of this negative interaction between infections would depend on the degree similarity in hosts infected. For human infections, this would be determined by the amount of overlap between the distributions of the host age at infection. Does disease interference affect evolutionary dynamics? A central hypothesis of this work is that interference is likely to select for increased disease virulence. Can we use interference effects in systems where antigenic polymorphism is well established (e.g. Dengue)? The interference mechanism provides a null model for the study of infections with multiple strains. Is this work likely to have any important public health implications? Preliminary work suggests interference effects may be beneficially used to eradicate infections using fewer vaccine units than using conventional estimates. This proposal also aims to construct statistical tools whereby the signature of interference may be confidently detected from data. Due to their excellent spatio-temporal data sets, much of this work will focus on childhood infections (e.g. as measles, pertussis, chickenpox and rubella), though the proposed mechanism is quite general. The analytical tools developed will be applied to numerous long-term disease records to explore the ubiquity of the interference phenomenon.