Bourhy Hervé, Nakouné Emmanuel, Hall Matthew, Nouvellet Pierre, Lepelletier Anthony, Talbi Chiraz, Watier Laurence, Holmes Edward C, Cauchemez Simon, Lemey Philippe, Donnelly Christl A, Rambaut Andrew
Institut Pasteur, Unit Lyssavirus Dynamics and Host Adaptation, WHO Collaborating Centre for Reference and Research on Rabies, Paris, France.
Institut Pasteur de Bangui, Bangui, République Centrafricaine.
PLoS Pathog. 2016 Apr 8;12(4):e1005525. doi: 10.1371/journal.ppat.1005525. eCollection 2016 Apr.
The development of novel approaches that combine epidemiological and genomic data provides new opportunities to reveal the spatiotemporal dynamics of infectious diseases and determine the processes responsible for their spread and maintenance. Taking advantage of detailed epidemiological time series and viral sequence data from more than 20 years reported by the National Reference Centre for Rabies of Bangui, the capital city of Central African Republic, we used a combination of mathematical modeling and phylogenetic analysis to determine the spatiotemporal dynamics of rabies in domestic dogs as well as the frequency of extinction and introduction events in an African city. We show that although dog rabies virus (RABV) appears to be endemic in Bangui, its epidemiology is in fact shaped by the regular extinction of local chains of transmission coupled with the introduction of new lineages, generating successive waves of spread. Notably, the effective reproduction number during each wave was rarely above the critical value of 1, such that rabies is not self-sustaining in Bangui. In turn, this suggests that rabies at local geographic scales is driven by human-mediated dispersal of RABV among sparsely connected peri-urban and rural areas as opposed to dispersion in a relatively large homogenous urban dog population. This combined epidemiological and genomic approach enables development of a comprehensive framework for understanding disease persistence and informing control measures, indicating that control measures are probably best targeted towards areas neighbouring the city that appear as the source of frequent incursions seeding outbreaks in Bangui.
结合流行病学和基因组数据的新方法的发展,为揭示传染病的时空动态以及确定其传播和维持的过程提供了新机会。利用中非共和国首都班吉国家狂犬病参考中心报告的20多年来详细的流行病学时间序列和病毒序列数据,我们结合数学建模和系统发育分析,以确定家犬中狂犬病的时空动态以及非洲一个城市中灭绝和引入事件的频率。我们表明,尽管犬狂犬病病毒(RABV)在班吉似乎是地方病,但其流行病学实际上是由当地传播链的定期灭绝以及新谱系的引入所塑造的,从而产生连续的传播波。值得注意的是,每一波期间的有效繁殖数很少高于临界值1,因此狂犬病在班吉无法自我维持。反过来,这表明在当地地理尺度上,狂犬病是由人类介导的RABV在稀疏连接的城郊和农村地区之间传播驱动的,而不是在相对较大的同质城市犬群中传播。这种结合流行病学和基因组的方法能够建立一个全面的框架来理解疾病的持续存在并为控制措施提供信息,这表明控制措施可能最好针对城市周边那些似乎是在班吉引发疫情的频繁入侵源的地区。