Ecology and Evolution of Disease Interference

拟议的工作将制定一个生态和进化动力学的一般框架， “疾病社区”。虽然流行病学领域有着辉煌的历史， 尽管这些研究取得了成功，但不相关感染之间相互作用的可能性并未受到太多关注。一 提出了抗原性不同感染之间相互作用的机制：急性感染后， 个人暂时无法感染其他疾病（主要是因为在 恢复期）。因此，可用于每种病原体的潜在“宿主”的数量受到病原体的数量的影响。 其他感染的爆发动态。如果感染与死亡率相关，那么潜在的 宿主被永久地移除，相互作用以疾病之间的竞争形式出现。 这种机制导致所谓的“疾病干扰”。该提案旨在发展这一 概念框架，回答了一些基本的生态和进化问题。做所有 感染与所有其他感染相互作用？答案显然是否定的。直觉上， 感染之间的这种负面相互作用的强度取决于 宿主感染对于人类感染，这将由两种病毒之间的重叠量决定。 感染时宿主年龄的分布。疾病干扰影响进化动力学吗？中央 这项工作的假设是，干扰可能选择增加疾病的毒力。我们能用 在抗原多态性已确立的系统中的干扰效应（如登革热）？的 干扰机制为研究多菌株感染提供了一个无效模型。这是工作吗 可能会对公共卫生产生重大影响吗初步研究表明，干扰效应可能 使用比常规估计更少的疫苗单位，可有益地用于根除感染。这 该提案还旨在构建统计工具，从而可以自信地识别干扰信号。 从数据中检测出来。由于他们优秀的时空数据集，这项工作的大部分将集中在 儿童感染（如麻疹、百日咳、水痘和风疹），尽管提出的机制是 很一般。开发的分析工具将应用于许多长期疾病记录， 探索干扰现象的普遍性。

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 (eg 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 (eg 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.