Inferring the source of transmission with phylogenetic data.
Inferring the source of transmission with phylogenetic data.
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DOI：
10.1371/journal.pcbi.1003397
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发表时间：
2013
影响因子：
4.3
通讯作者：
Frost SD
中科院分区：
文献类型：
--
作者：
Volz EM;Frost SD
利用病原体遗传数据确定传播源由于许多生物学、免疫学和行为因素而变得复杂。当案例的采样不完整或稀疏时，会产生很大的误差来源。未取样病例可能是感染的共同来源，也可能是遗传相似病原体感染宿主传播链中的中间媒介。很难量化共同来源或中间传播事件的概率，这使得很难开发统计测试来证实或否认具有遗传数据的假定传播对。我们提出了一种方法，将传染病流行的其他信息，如感染的发病率和流行率随时间的推移，告知估计一个样本宿主在病原体基因谱系中是另一个宿主感染的直接来源的概率。这些方法使法医能够应用于采样不完全的传染病流行病，例如病例来源归属，这通常是艾滋病毒、流感和登革热病毒等高发病率社区获得性病原体的情况。这些方法还有助于流行病学应用，例如确定增加传播风险的因素。我们在密歇根州底特律的HIV流行背景下演示了这些方法，并评估了当前序列数据库用于法医和流行病学调查的适用性。我们发现，目前收集的用于艾滋病毒耐药性测试的可用序列不太可能在大多数法医调查中有用，但对于识别传播风险因素是有用的。来自病原体的分子数据可能有助于确定感染源和确定由一个宿主传染给另一个宿主的成对个体。不完整的抽样和仅给出的遗传数据，混淆了谁从谁那里获得感染的推断，因此不可能推断一对传播对的传播方向。如果有关于传染病流行的额外信息，例如随时间推移的感染发生率和抽样宿主的比例，就有可能纠正因对受感染宿主群体抽样不完整而产生的偏差。如果可以获得感染宿主的其他临床、行为和人口统计学协变量，甚至可以推断传播对内的传播方向。我们考虑的问题，确定感染的来源使用HIV序列数据收集的临床目的。我们发现很少有可能推断出高可信度的传播对，但这些数据可能对流行病学调查和确定传播的危险因素有用。
Identifying the source of transmission using pathogen genetic data is complicated by numerous biological, immunological, and behavioral factors. A large source of error arises when there is incomplete or sparse sampling of cases. Unsampled cases may act as either a common source of infection or as an intermediary in a transmission chain for hosts infected with genetically similar pathogens. It is difficult to quantify the probability of common source or intermediate transmission events, which has made it difficult to develop statistical tests to either confirm or deny putative transmission pairs with genetic data. We present a method to incorporate additional information about an infectious disease epidemic, such as incidence and prevalence of infection over time, to inform estimates of the probability that one sampled host is the direct source of infection of another host in a pathogen gene genealogy. These methods enable forensic applications, such as source-case attribution, for infectious disease epidemics with incomplete sampling, which is usually the case for high-morbidity community-acquired pathogens like HIV, Influenza and Dengue virus. These methods also enable epidemiological applications such as the identification of factors that increase the risk of transmission. We demonstrate these methods in the context of the HIV epidemic in Detroit, Michigan, and we evaluate the suitability of current sequence databases for forensic and epidemiological investigations. We find that currently available sequences collected for drug resistance testing of HIV are unlikely to be useful in most forensic investigations, but are useful for identifying transmission risk factors. Molecular data from pathogens may be useful for identifying the source of infection and identifying pairs of individuals such that one host transmitted to the other. Inference of who acquired infection from whom is confounded by incomplete sampling, and given genetic data only, it is not possible to infer the direction of transmission in a transmission pair. Given additional information about an infectious disease epidemic, such as incidence of infection over time, and the proportion of hosts sampled, it is possible to correct for biases stemming from incomplete sampling of the infected host population. It may even be possible to infer the direction of transmission within a transmission pair if additional clinical, behavioral, and demographic covariates of the infected hosts are available. We consider the problem of identifying the source of infection using HIV sequence data collected for clinical purposes. We find that it is rarely possible to infer transmission pairs with high credibility, but such data may nevertheless be useful for epidemiological investigations and identifying risk factors for transmission.
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