McNaughton Anna L, Cameron Iain Dugald, Wignall-Fleming Elizabeth B, Biek Roman, McLauchlan John, Gunson Rory N, Templeton Kate, Tan Harriet Mei-Lin, Leitch E Carol McWilliam
MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom.
MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom IBAHCM, University of Glasgow, Glasgow, United Kingdom.
J Virol. 2015 Nov;89(22):11223-32. doi: 10.1128/JVI.02106-15. Epub 2015 Aug 26.
A more comprehensive understanding of hepatitis C virus (HCV) transmission dynamics could facilitate public health initiatives to reduce the prevalence of HCV in people who inject drugs. We aimed to determine how HCV sequences entered and spread throughout Scotland and to identify transmission hot spots. A Scottish data set with embedded demographic data was created by sequencing the NS5B of 125 genotype 1a (Gt1a) samples and 166 Gt3a samples and analyzed alongside sequences from public databases. Applying Bayesian inference methods, we reconstructed the global origin and local spatiotemporal dissemination of HCV in Scotland. Scottish sequences mainly formed discrete clusters interspersed between sequences from the rest of the world; the most recent common ancestors of these clusters dated to 1942 to 1952 (Gt1a) and 1926 to 1942 (Gt3a), coincident with global diversification and distribution. Extant Scottish sequences originated in Edinburgh (Gt1a) and Glasgow (Gt3a) in the 1970s, but both genotypes spread from Glasgow to other regions. The dominant Gt1a strain differed between Edinburgh (cluster 2 [C2]), Glasgow (C3), and Aberdeen (C4), whereas significant Gt3a strain specificity occurred only in Aberdeen. Specific clusters initially formed separate transmission zones in Glasgow that subsequently overlapped, occasioning city-wide cocirculation. Transmission hot spots were detected with 45% of samples from patients residing in just 9 of Glasgow's 57 postcode districts. HCV was introduced into Scotland in the 1940s, concomitant with its worldwide dispersal likely arising from global-scale historical events. Cluster-specific transmission hubs were identified in Glasgow, the key Scottish city implicated in HCV dissemination. This fine-scale spatiotemporal reconstruction improves understanding of HCV transmission dynamics in Scotland.
HCV is a major health burden and the leading cause of hepatocellular carcinoma. Public health needle exchange and "treatment as prevention" strategies targeting HCV are designed to reduce prevalence of the virus in people who inject drugs (PWID), potentially mitigating the future burden of HCV-associated liver disease. Understanding HCV transmission dynamics could increase the effectiveness of such public health initiatives by identifying and targeting regions playing a central role in virus dispersal. In this study, we examined HCV transmission in Scotland by analyzing the genetic relatedness of strains from PWID alongside data inferring the year individuals became infected and residential information at a geographically finer-scale resolution than in previous studies. Clusters of Scotland-specific strains were identified with regional specificity, and mapping the spread of HCV allowed the identification of key areas central to HCV transmission in Scotland. This research provides a basis for identifying HCV transmission hot spots.
对丙型肝炎病毒（HCV）传播动态有更全面的了解，有助于推动公共卫生举措，以降低注射吸毒者中HCV的流行率。我们旨在确定HCV序列如何进入并在苏格兰传播，并识别传播热点。通过对125个1a基因型（Gt1a）样本和166个Gt3a样本的NS5B进行测序，并与公共数据库中的序列一起分析，创建了一个嵌入人口统计数据的苏格兰数据集。应用贝叶斯推理方法，我们重建了HCV在苏格兰的全球起源和本地时空传播情况。苏格兰的序列主要形成离散的簇，散布在来自世界其他地区的序列之间；这些簇的最近共同祖先可追溯到1942年至1952年（Gt1a）和1926年至1942年（Gt3a），与全球多样化相吻合。现存的苏格兰序列起源于20世纪70年代的爱丁堡（Gt1a）和格拉斯哥（Gt3a），但两种基因型都从格拉斯哥传播到了其他地区。爱丁堡（簇2 [C2]）、格拉斯哥（C3）和阿伯丁（C4）的优势Gt1a毒株有所不同，而显著的Gt3a毒株特异性仅在阿伯丁出现。特定的簇最初在格拉斯哥形成了单独的传播区域，随后重叠，导致全市范围内的共同传播。在格拉斯哥57个邮政编码区中仅9个区居住的患者的45%样本检测到了传播热点。HCV于20世纪40年代传入苏格兰，与此同时，其在全球的传播可能源于全球范围的历史事件。在格拉斯哥确定了特定簇的传播中心，格拉斯哥是苏格兰涉及HCV传播的关键城市。这种精细尺度的时空重建有助于更好地理解HCV在苏格兰的传播动态。
HCV是一项重大的健康负担，也是肝细胞癌的主要病因。针对HCV的公共卫生针头交换和“治疗即预防”策略旨在降低注射吸毒者（PWID）中该病毒的流行率，有可能减轻未来HCV相关肝病的负担。了解HCV传播动态可以通过识别和针对在病毒传播中起核心作用的区域，提高此类公共卫生举措的有效性。在本研究中，我们通过分析来自PWID的毒株的遗传相关性，以及推断个体感染年份和居住信息的数据，以比以往研究更高的地理精细尺度分辨率，研究了苏格兰的HCV传播情况。识别出了具有区域特异性的苏格兰特有序列簇，绘制HCV的传播图有助于确定苏格兰HCV传播的关键区域。这项研究为识别HCV传播热点提供了依据。
