A new phylodynamic model of Mycobacterium bovis transmission in a multi-host system uncovers the role of the unobserved reservoir.
A new phylodynamic model of Mycobacterium bovis transmission in a multi-host system uncovers the role of the unobserved reservoir.
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一个新的牛分枝杆菌在多宿主系统中传播的系统动力学模型揭示了未观察到的宿主的作用。
DOI：
10.1371/journal.pcbi.1009005
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发表时间：
2021-06
影响因子：
4.3
通讯作者：
Kao RR
中科院分区：
文献类型：
--
作者：
O'Hare A;Balaz D;Wright DM;McCormick C;McDowell S;Trewby H;Skuce RA;Kao RR
多宿主病原体特别难以控制，特别是当至少一个宿主作为隐藏的宿主时。对密集采样的病原体进行深度测序有可能改变这种认识，但需要采用共同考虑流行病学和遗传数据的分析方法，以最好地解决这一问题。虽然在单物种系统的分析方面取得了相当大的成功，但隐藏的水库问题却相对研究不足。这一问题的一个著名例子是牛结核病，这是一种在英国和爱尔兰牛中发现的由牛分枝杆菌引起的疾病，长期以来，欧亚獾被认为是一个水库，但除了非常特定的地点外，仍然没有量化的重要性。因此，应该努力控制獾的疾病还不清楚。在这里，我们分析了从牛群中收集的流行病学和遗传数据，但没有明确考虑獾的任何数据。我们使用模拟建模的方法来表明，在我们的系统中，一个模型，利用现有的牛的人口统计和牲畜到牛群的运动数据，但只考虑隐藏的水库产生病原体多样性的能力，可以用来选择不同的流行病学场景。在我们的分析中，水库不产生任何多样性，但有助于在当地农场规模的新感染的模型显着优于在更广泛的空间尺度上产生多样性和/或传播疾病的模型。虽然我们不能直接归因于水库的作用，獾基于这一分析，结果支持的假设，在目前的牛控制制度下，感染的牛不能单独维持M。牛循环鉴于从彼此靠近的牛和獾身上取样的细菌之间观察到的密切的系统发育关系，最简约的假设是，水库是受感染的獾种群。更广泛地说，我们的方法表明，精心构建的定制模型可以利用遗传和流行病学数据的组合来克服极端数据偏差的问题，并揭示多宿主病原体系统中传播的重要一般特征。对于单宿主病原体，病原体遗传数据对于理解许多疾病的传播和控制具有变革性意义，特别是快速进化的RNA病毒。然而，在病原体是多宿主的情况下获得类似的见解更具挑战性，特别是当病原体的进化较慢并且病原体采样通常严重偏差时。牛结核分枝杆菌（Mycobacterium bovis）就是这种情况，它是牛结核病（bTB）的病原体，欧亚獾在传播和传播中所起的作用迄今知之甚少。在这里，我们已经开发了一个计算模型，结合M。牛的遗传数据，只有一个高度抽象的模型，一个未观察到的水库。我们的研究表明，一个模型，其中水库不有助于病原体的多样性，但在每个农场周围的空间局部区域的感染源，更好地描述了在一个单一的M的人口水平的样本中观察到的爆发模式。牛的基因型在北方爱尔兰超过15年的一段时间内，相比的模型，无论是水库没有作用，疾病传播是空间广泛的，或在那里他们自己产生相当大的多样性。虽然这个水库模型不是明确的獾的模型，其特征是一致的，其他数据表明，水库组成的受感染的獾，大大有助于牛感染，但不能保持自己的疾病。
Multi-host pathogens are particularly difficult to control, especially when at least one of the hosts acts as a hidden reservoir. Deep sequencing of densely sampled pathogens has the potential to transform this understanding, but requires analytical approaches that jointly consider epidemiological and genetic data to best address this problem. While there has been considerable success in analyses of single species systems, the hidden reservoir problem is relatively under-studied. A well-known exemplar of this problem is bovine Tuberculosis, a disease found in British and Irish cattle caused by Mycobacterium bovis, where the Eurasian badger has long been believed to act as a reservoir but remains of poorly quantified importance except in very specific locations. As a result, the effort that should be directed at controlling disease in badgers is unclear. Here, we analyse densely collected epidemiological and genetic data from a cattle population but do not explicitly consider any data from badgers. We use a simulation modelling approach to show that, in our system, a model that exploits available cattle demographic and herd-to-herd movement data, but only considers the ability of a hidden reservoir to generate pathogen diversity, can be used to choose between different epidemiological scenarios. In our analysis, a model where the reservoir does not generate any diversity but contributes to new infections at a local farm scale are significantly preferred over models which generate diversity and/or spread disease at broader spatial scales. While we cannot directly attribute the role of the reservoir to badgers based on this analysis alone, the result supports the hypothesis that under current cattle control regimes, infected cattle alone cannot sustain M. bovis circulation. Given the observed close phylogenetic relationship for the bacteria taken from cattle and badgers sampled near to each other, the most parsimonious hypothesis is that the reservoir is the infected badger population. More broadly, our approach demonstrates that carefully constructed bespoke models can exploit the combination of genetic and epidemiological data to overcome issues of extreme data bias, and uncover important general characteristics of transmission in multi-host pathogen systems. For single host pathogens, pathogen genetic data have been transformative for understanding the transmission and control of many diseases, particuarly rapidly evolving RNA viruses. However garnering similar insights where pathogens are multi-host is more challenging, particularly when the evolution of the pathogen is slower and pathogen sampling often heavily biased. This is the case for Mycobacterium bovis, the causative agent of bovine Tuberculosis (bTB) and for which the Eurasian badger plays an as yet poorly understood role in transmission and spread. Here we have developed a computational model that incorporates M. bovis genetic data from cattle only with a highly abstracted model of an unobserved reservoir. Our research shows that a model in which the reservoir does not contribute to pathogen diversity, but is a source of infection in spatially localised areas around each farm, better describes the patterns of outbreaks observed in a population-level sample of a single M. bovis genotype in Northern Ireland over a period of 15 years, compared to models in which either the reservoir has no role, disease spread is spatially extensive, or where they generate considerable diversity on their own. While this reservoir model is not explicitly a model of badgers, its characteristics are consistent with other data that would suggest a reservoir consisting of infected badgers that contribute substantially to cattle infection, but could not maintain disease on their own.
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影响因子：
6.7
作者：
Biek, Roman;O'Hare, Anthony;Kao, Rowland R.
通讯作者：
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影响因子：
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