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