Vogler Amy J, Andrianaivoarimanana Voahangy, Telfer Sandra, Hall Carina M, Sahl Jason W, Hepp Crystal M, Centner Heather, Andersen Genevieve, Birdsell Dawn N, Rahalison Lila, Nottingham Roxanne, Keim Paul, Wagner David M, Rajerison Minoarisoa
The Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, Arizona, United States of America.
Plague Research Unit, Institut Pasteur de Madagascar, Antananarivo, Madagascar.
PLoS Negl Trop Dis. 2017 Sep 5;11(9):e0005887. doi: 10.1371/journal.pntd.0005887. eCollection 2017 Sep.
Yersinia pestis appears to be maintained in multiple, geographically separate, and phylogenetically distinct subpopulations within the highlands of Madagascar. However, the dynamics of these locally differentiated subpopulations through time are mostly unknown. To address that gap and further inform our understanding of plague epidemiology, we investigated the phylogeography of Y. pestis in Madagascar over an 18 year period.
METHODOLOGY/PRINCIPAL FINDINGS: We generated whole genome sequences for 31 strains and discovered new SNPs that we used in conjunction with previously identified SNPs and variable-number tandem repeats (VNTRs) to genotype 773 Malagasy Y. pestis samples from 1995 to 2012. We mapped the locations where samples were obtained on a fine geographic scale to examine phylogeographic patterns through time. We identified 18 geographically separate and phylogenetically distinct subpopulations that display spatial and temporal stability, persisting in the same locations over a period of almost two decades. We found that geographic areas with higher levels of topographical relief are associated with greater levels of phylogenetic diversity and that sampling frequency can vary considerably among subpopulations and from year to year. We also found evidence of various Y. pestis dispersal events, including over long distances, but no evidence that any dispersal events resulted in successful establishment of a transferred genotype in a new location during the examined time period.
CONCLUSIONS/SIGNIFICANCE: Our analysis suggests that persistent endemic cycles of Y. pestis transmission within local areas are responsible for the long term maintenance of plague in Madagascar, rather than repeated episodes of wide scale epidemic spread. Landscape likely plays a role in maintaining Y. pestis subpopulations in Madagascar, with increased topographical relief associated with increased levels of localized differentiation. Local ecological factors likely affect the dynamics of individual subpopulations and the associated likelihood of observing human plague cases in a given year in a particular location.
鼠疫耶尔森菌似乎在马达加斯加高地多个地理上分离且系统发育上不同的亚种群中维持存在。然而，这些局部分化的亚种群随时间的动态变化大多未知。为填补这一空白并进一步增进我们对鼠疫流行病学的理解，我们调查了18年间马达加斯加鼠疫耶尔森菌的系统地理学。
方法/主要发现：我们生成了31个菌株的全基因组序列，并发现了新的单核苷酸多态性（SNP），我们将其与先前鉴定的SNP和可变数目串联重复序列（VNTR）结合使用，对1995年至2012年的773份马达加斯加鼠疫耶尔森菌样本进行基因分型。我们在精细地理尺度上绘制了样本采集地点，以研究随时间的系统地理模式。我们识别出18个地理上分离且系统发育上不同的亚种群，它们表现出空间和时间稳定性，在近二十年的时间里一直存在于相同地点。我们发现地形起伏较大的地理区域与更高水平的系统发育多样性相关，并且亚种群之间以及不同年份的采样频率可能有很大差异。我们还发现了各种鼠疫耶尔森菌传播事件的证据，包括远距离传播，但没有证据表明在所研究的时间段内，任何传播事件导致转移的基因型在新地点成功定殖。
结论/意义：我们的分析表明，鼠疫耶尔森菌在局部地区持续的地方性传播循环是马达加斯加鼠疫长期维持的原因，而非大规模流行传播的反复发生。景观可能在维持马达加斯加鼠疫耶尔森菌亚种群方面发挥作用，地形起伏增加与局部分化水平提高相关。当地生态因素可能影响各个亚种群的动态以及在特定年份特定地点观察到人类鼠疫病例的相关可能性。
