Department of Biomedical and Clinical Sciences L Sacco, Infectious Diseases and Tropical Medicine Chair, University of Milan, Milan, Italy.
Infect Genet Evol. 2013 Jul;17:223-30. doi: 10.1016/j.meegid.2013.04.003. Epub 2013 Apr 18.
More than 20 million hepatitis C virus (HCV) carriers live in the countries of the Eastern Mediterranean. We determined HCV genotype distribution among chronically infected patients in Montenegro and investigated the phylodynamics and phylogeography of the most represented HCV subtypes. The HCV-NS5b sequences of the Montenegrin patients were compared with sequences isolated in different known localities of the Mediterranean area, Europe and Asia. A Bayesian approach was used in order to allow the simultaneous estimate of the evolutionary rate, time-scaled phylogeny, demography and ancestral spatial status. The most frequent HCV subtypes among the Montenegrin patients, were 1b (34.7%) and 3a (24.7%), but there was also a significant prevalence of 1a and 4d (19.5%). Subtype 3a was significantly more frequent among younger patients and intravenous drug users (IDUs), whereas subtype 1b was more frequently associated with iatrogenic exposure and older ages. The spatio-temporal analysis of the epidemic suggested that HCV-1b penetrated Europe at the beginning of the XX century, probably through Greece and Cyprus and in the 1920s reached Montenegro, where there was an exponential increase in the effective number of infections between the 1950s and 1970s. The phylogeographic and phylodynamic analysis of HCV 3a showed that its most probable origin was in the Indian sub-continent (Pakistan in our reconstruction) about 300years ago. The evolutionary dynamics analysis showed that HCV-3a reached Montenegro more recently in the late 1970s and underwent multi-phasic growth still persisting. Our data suggest multiple introduction of HCV subtypes in the area, supported by different causes of dispersion: adverse social conditions and unsafe medical practices for HCV-1b and i.v. drug use for HCV-3a.
超过 2000 万丙型肝炎病毒 (HCV) 携带者生活在地中海东部国家。我们确定了黑山慢性感染患者的 HCV 基因型分布，并研究了最具代表性的 HCV 亚型的系统发育动力学和系统地理学。将黑山患者的 HCV-NS5b 序列与在地中海地区、欧洲和亚洲不同已知地点分离的序列进行了比较。采用贝叶斯方法同时估计进化率、时间尺度系统发育、人口统计学和祖先的空间状态。黑山患者中最常见的 HCV 亚型为 1b（34.7%）和 3a（24.7%），但 1a 和 4d 也有显著的流行率（19.5%）。3a 亚型在年轻患者和静脉吸毒者（IDUs）中更为常见，而 1b 亚型则与医源性暴露和年龄较大有关。流行的时空分析表明，HCV-1b 于 20 世纪初通过希腊和塞浦路斯进入欧洲，并于 20 世纪 20 年代到达黑山，在 20 世纪 50 年代至 70 年代期间，有效感染人数呈指数增长。HCV 3a 的系统地理学和系统发育分析表明，其最可能的起源地是大约 300 年前的印度次大陆（我们重建中的巴基斯坦）。进化动力学分析表明，HCV-3a 于 20 世纪 70 年代末最近到达黑山，并经历了多阶段增长，至今仍在持续。我们的数据表明，HCV 亚型的多种传入与不同的传播原因有关：HCV-1b 是由于不良的社会条件和不安全的医疗实践，而 HCV-3a 则是由于静脉内药物使用。
