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Urgent Implementation in a Hospital Setting of a Strategy To Rule Out Secondary Cases Caused by Imported Extensively Drug-Resistant Mycobacterium tuberculosis Strains at Diagnosis

机译:在医院中紧急实施一项策略以排除诊断中输入的广泛耐药结核分枝杆菌菌株引起的继发病例

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摘要

Current migratory movements require new strategies for rapidly tracking the transmission of high-risk imported Mycobacterium tuberculosis strains. Whole-genome sequencing (WGS) enables us to identify single-nucleotide polymorphisms (SNPs) and therefore design PCRs to track specific relevant strains. However, fast implementation of these strategies in the hospital setting is difficult because professionals working in diagnostics, molecular epidemiology, and genomics are generally at separate institutions. In this study, we describe the urgent implementation of a system that integrates genomics and molecular tools in a genuine high-risk epidemiological alert involving 2 independent importations of extensively drug resistant (XDR) and pre-XDR Beijing M. tuberculosis strains from Russia into Spain. Both cases involved commercial sex workers with long-standing tuberculosis (TB). The system was based on strain-specific PCRs tailored from WGS data that were transferred to the local node that was managing the epidemiological alert. The optimized tests were available for prospective implementation in the local node 33 working days after receiving the primary cultures of the XDR strains and were applied to all 42 new incident cases. An interpretable result was obtained in each case (directly from sputum for 27 stain-positive cases) and corresponded to the amplification profiles for strains other than the targeted pre-XDR and XDR strains, which made it possible to prospectively rule out transmission of these high-risk strains at diagnosis.
机译:当前的迁徙运动需要新的策略来快速追踪高风险进口结核分枝杆菌菌株的传播。全基因组测序(WGS)使我们能够鉴定单核苷酸多态性(SNP),因此可以设计PCR来跟踪特定的相关菌株。但是,由于在诊断,分子流行病学和基因组学领域的专业人员通常在不同的机构工作,因此很难在医院中快速实施这些策略。在这项研究中,我们描述了在真正的高风险流行病学警报中将基因组学和分子工具整合在一起的系统的紧急实施情况,涉及从俄罗斯到西班牙的两次独立进口的广泛耐药性(XDR)和XDR之前的北京结核分枝杆菌菌株。 。这两个案例都涉及具有长期结核病(TB)的商业性工作者。该系统基于根据WGS数据量身定制的特定菌株PCR,这些PCR数据已转移到管理流行病学警报的本地节点。在接受XDR菌株的原代培养后的33个工作日内,优化的测试可用于本地节点的预期实施,并且已应用于所有42个新的事件病例。在每种情况下均可获得可解释的结果(直接从痰液中的27个染色阳性病例中获得),并且与除目标XDR前和XDR菌株以外的菌株的扩增曲线相对应,从而有可能前瞻性地排除了这些高XDR菌株的传播诊断时出现高风险菌株。

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