Didelot Xavier, Eyre David W, Cule Madeleine, Ip Camilla L C, Ansari M Azim, Griffiths David, Vaughan Alison, O'Connor Lily, Golubchik Tanya, Batty Elizabeth M, Piazza Paolo, Wilson Daniel J, Bowden Rory, Donnelly Peter J, Dingle Kate E, Wilcox Mark, Walker A Sarah, Crook Derrick W, Peto Tim E A, Harding Rosalind M
Genome Biol. 2012 Dec 21;13(12):R118. doi: 10.1186/gb-2012-13-12-r118.
The control of Clostridium difficile infection is a major international healthcare priority, hindered by a limited understanding of transmission epidemiology for these bacteria. However, transmission studies of bacterial pathogens are rapidly being transformed by the advent of next generation sequencing.
Here we sequence whole C. difficile genomes from 486 cases arising over four years in Oxfordshire. We show that we can estimate the times back to common ancestors of bacterial lineages with sufficient resolution to distinguish whether direct transmission is plausible or not. Time depths were inferred using a within-host evolutionary rate that we estimated at 1.4 mutations per genome per year based on serially isolated genomes. The subset of plausible transmissions was found to be highly associated with pairs of patients sharing time and space in hospital. Conversely, the large majority of pairs of genomes matched by conventional typing and isolated from patients within a month of each other were too distantly related to be direct transmissions.
Our results confirm that nosocomial transmission between symptomatic C. difficile cases contributes far less to current rates of infection than has been widely assumed, which clarifies the importance of future research into other transmission routes, such as from asymptomatic carriers. With the costs of DNA sequencing rapidly falling and its use becoming more and more widespread, genomics will revolutionize our understanding of the transmission of bacterial pathogens.
艰难梭菌感染的控制是一项重大的国际医疗保健重点工作，但由于对这些细菌的传播流行病学了解有限而受到阻碍。然而，随着下一代测序技术的出现，细菌病原体的传播研究正在迅速变革。
在此，我们对牛津郡四年内出现的486例艰难梭菌病例的全基因组进行了测序。我们表明，我们能够以足够的分辨率估计细菌谱系共同祖先的时间，以区分直接传播是否合理。基于连续分离的基因组，我们估计宿主内进化速率为每年每个基因组1.4个突变，并据此推断时间深度。发现可能传播的子集与在医院共享时间和空间的患者对高度相关。相反，通过传统分型匹配且在彼此一个月内从患者中分离出的绝大多数基因组对，其亲缘关系过于遥远，不可能是直接传播。
我们的结果证实，有症状的艰难梭菌病例之间的医院内传播对当前感染率的贡献远低于广泛假设的情况，这明确了未来对其他传播途径（如来自无症状携带者）进行研究的重要性。随着DNA测序成本迅速下降且其应用越来越广泛，基因组学将彻底改变我们对细菌病原体传播的理解。
