Yaws re-emergence and bacterial drug resistance selection after mass administration of azithromycin: a genomic epidemiology investigation
Yaws re-emergence and bacterial drug resistance selection after mass administration of azithromycin: a genomic epidemiology investigation
复制标题
DOI：
10.1016/s2666-5247(20)30113-0
复制
发表时间：
2020-10-01
期刊：
影响因子：
38.2
通讯作者：
Mitja, Oriol
中科院分区：
文献类型：
--
作者：
Beale, Mathew A.;Noguera-Julian, Marc;Mitja, Oriol
在一项评估世卫组织使用大规模阿奇霉素治疗根除雅司病战略的纵向研究中，我们观察到以单一JG8序列型为主的雅司病病例再次出现，并出现耐阿奇霉素的梅毒螺旋体亚种pertenue （ttp pertenue）。在这里，我们使用研究期间收集的样本分析细菌种群的基因组变化。方法对2013年4月1日至2016年11月1日在巴布亚新几内亚利希尔岛采集的37例患者皮肤病变拭子提取的DNA进行全细菌基因组测序。我们制作了系统发育图，并将其与时空信息相关联，以调查新病例的来源和5个大环内酯耐药病例的出现。我们使用监测样本的深度扩增子测序来评估少数大环内酯耐药人群的存在。研究结果表明，重新出现的JG8序列类型由3个具有不同时空特征的细菌亚系组成。在5名具有耐药性肺结核的患者中，我们从3名患者中恢复了基因组，没有发现变异。深度测序显示，治疗前，指标患者具有固定的大环内酯敏感基因型，而治疗后样本具有固定的耐药基因型，4例接触病例中有3例也是如此。在本研究中，雅司病病例的再次出现是多系性的，表明有多种流行病学来源。然而，鉴于耐药病例的基因组和流行病学联系以及耐药等位基因在一般人群中的罕见性，在本研究中，阿奇霉素耐药性可能只进化了一次，随后继续传播。版权所有(C) 2020作者。Elsevier Ltd.出版。
Background In a longitudinal study assessing the WHO strategy for yaws eradication using mass azithromycin treatment, we observed resurgence of yaws cases with dominance of a single JG8 sequence type and emergence of azithromycin-resistant Treponema pallidum subspecies pertenue (T p pertenue). Here, we analyse genomic changes in the bacterial population using samples collected during the study.Methods We did whole bacterial genome sequencing directly on DNA extracted from 37 skin lesion swabs collected from patients on Lihir Island, Papua New Guinea, between April 1, 2013, and Nov 1, 2016. We produced phylogenies and correlated these with spatiotemporal information to investigate the source of new cases and the emergence of five macrolide-resistant cases. We used deep amplicon sequencing of surveillance samples to assess the presence of minority macrolide-resistant populations.Findings We recovered 20 whole T p pertenue genomes, and phylogenetic analysis showed that the re-emerging JG8 sequence type was composed of three bacterial sublineages characterised by distinct spatiotemporal patterns. Of five patients with resistant T p pertenue, all epidemiologically linked, we recovered genomes from three and found no variants. Deep sequencing showed that before treatment, the index patient had fixed macrolide-sensitive T p pertenue, whereas the post-treatment sample had a fixed resistant genotype, as did three of four contact cases.Interpretation In this study, re-emergence of yaws cases was polyphyletic, indicating multiple epidemiological sources. However, given the genomic and epidemiological linkage of resistant cases and the rarity of resistance alleles in the general population, azithromycin resistance is likely to have evolved only once in this study, followed by onward dissemination. Copyright (C) 2020 The Author(s). Published by Elsevier Ltd.