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越南胡志明市感染人类免疫缺陷病毒患者的耐药性和传播。

Drug Resistance and Transmission among Human Immunodeficiency Virus-Infected Patients in Ho Chi Minh City, Vietnam.

机构信息

National Institute of Hygiene and Epidemiology, Hanoi, Vietnam.

Sydney Medical School and Marie Bashir Institute for Infectious Diseases and Biosecurity, The University of Sydney, Sydney, Australia.

出版信息

Am J Trop Med Hyg. 2018 Dec;99(6):1397-1406. doi: 10.4269/ajtmh.18-0185.

Abstract

Vietnam has a high burden of tuberculosis (TB) and multidrug-resistant (MDR) TB, but drug resistance patterns and TB transmission dynamics among TB/human immunodeficiency virus (HIV) coinfected patients are not well described. We characterized 200 isolates from TB/HIV coinfected patients diagnosed at the main TB referral hospital in Ho Chi Minh City, Vietnam. Phenotypic drug susceptibility testing (DST) for first-line drugs, spoligotyping, and 24-locus mycobacterial interspersed repetitive unit (MIRU-24) analysis was performed on all isolates. The 24-locus mycobacterial interspersed repetitive unit clusters and MDR isolates were subjected to whole genome sequencing (WGS). Most of the TB/HIV coinfected patients were young (162/174; 93.1% aged < 45 years) males (173; 86.5% male). Beijing (98; 49.0%) and Indo-Oceanic (70; 35.0%) lineage strains were most common. Phenotypic drug resistance was detected in 84 (42.0%) isolates, of which 17 (8.5%) were MDR; three additional MDR strains were identified on WGS. Strain clustering was reduced from 84.0% with spoligotyping to 20.0% with MIRU-24 typing and to 13.5% with WGS. Whole genome sequencing identified five additional clusters, or members of clusters, not recognized by MIRU-24. In total, 13 small (two to three member) WGS clusters were identified, with less clustering among drug susceptible (2/27; 7.4%) than among drug-resistant strains (25/27; 92.6%). On phylogenetic analysis, strains from TB/HIV coinfected patients were interspersed among strains from the general community; no major clusters indicating transmission among people living with HIV were detected. Tuberculosis/HIV coinfection in Vietnam was associated with high rates of drug resistance and limited genomic evidence of ongoing transmission among HIV-infected patients.

摘要

越南的结核病(TB)和耐多药结核病(MDR-TB)负担沉重,但结核病/人类免疫缺陷病毒(HIV)合并感染患者的耐药模式和结核病传播动态尚未得到充分描述。我们对来自越南胡志明市主要结核病转诊医院的 200 例结核病/HIV 合并感染患者的分离株进行了特征描述。对所有分离株进行了一线药物表型药物敏感性试验(DST)、 spoligotyping 和 24 位位基因间隔重复单元(MIRU-24)分析。对 24 位位基因间隔重复单元聚类和 MDR 分离株进行了全基因组测序(WGS)。大多数结核病/HIV 合并感染患者为年轻男性(174 例中有 162 例,年龄<45 岁,占 93.1%)。北京(98 例,占 49.0%)和印度-印度洋(70 例,占 35.0%)谱系菌株最为常见。在 84 例(42.0%)分离株中检测到表型药物耐药性,其中 17 例(8.5%)为 MDR;通过 WGS 鉴定了另外 3 株 MDR 菌株。 spoligotyping 从 84.0%降低到 MIRU-24 分型的 20.0%,再到 WGS 的 13.5%。全基因组测序鉴定了 5 个额外的聚类,或 MIRU-24 无法识别的聚类成员。共有 13 个小(两到三个成员)WGS 聚类,药物敏感株(27 株中的 2 株,7.4%)的聚类少于耐药株(27 株中的 25 株,92.6%)。在系统发育分析中,来自结核病/HIV 合并感染患者的菌株散布在来自普通社区的菌株之间;未检测到提示 HIV 感染者之间传播的主要聚类。越南的结核病/艾滋病合并感染与耐药率高和 HIV 感染者之间传播的有限基因组证据有关。

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