Sethi S, Yadav R, Singh S, Khaneja R, Aggarwal A, Agarwal P, Behera D
Department of Medical Microbiology, Post Graduate Institute of Medical education and Research, Chandigarh, India.
State TB Cell, State TB Office, Chandigarh, India.
Lett Appl Microbiol. 2017 Nov;65(5):373-380. doi: 10.1111/lam.12787. Epub 2017 Sep 27.
Multidrug resistant tuberculosis (MDR-TB) is rising and the World Health Organization has recommended the line probe assay (LPA) for screening. In this study we assess LPA at a tertiary care centre from North India in 1758 samples from suspected MDR-TB cases. All smear-positive and/or Mycobacterium tuberculosis culture confirmed cases (n = 1170) were subjected to the GenoType-MTBDR assay. Amongst these the majority were retreatment cases, smear-positive at diagnosis (n = 637). An MDR prevalence of 7·8% was observed with the highest cases reported amongst MDR contacts (33·3%). The most common rifampicin resistance encoding mutation seen overall and in individual patient groups was H531L (53·3%). A higher prevalence of H526D mutation was observed in retreatment cases, smear-positive at 4 months of anti-tubercular therapy vs other patient groups (P = 0·052). The most common mutation encoding isoniazid resistance was S315T1 in the katG (79·9%) and C-15T in the inhA gene (91·1%). Thirty rifampicin and nine isoniazid resistant isolates had wild type gene deletion but no detectable mutation by LPA. Although LPA is a practical and rapid screening method for most mutations expected to result in MDR-TB, we observed that it only detects the known major mutations in specific genes. Such studies can provide the knowledge required to formulate customized strips based on prevalent mutations in our region and in specific patient groups.
To the best of our knowledge this is the largest study evaluating the GenoType-MTBDR line probe assay from India. We have studied the prevalence of mutations encoding rifampicin and isoniazid resistance in different patient groups based on criteria for multidrug resistance (MDR) suspicion. The translational impact of this study is in the design of customized country- or region-wise line probe assay strips. The identification of a few mutations in particular patient groups and the detection of wild type deletion mutants with no observable mutations both point toward the need for such customization enabling us to combat the rising trend of MDR tuberculosis.
耐多药结核病（MDR-TB）病例数正在上升，世界卫生组织已推荐使用线性探针分析（LPA）进行筛查。在本研究中，我们在印度北部的一家三级医疗中心对1758份疑似耐多药结核病病例样本进行了LPA评估。所有涂片阳性和/或结核分枝杆菌培养确诊的病例（n = 1170）均接受了GenoType-MTBDR分析。其中大多数为复治病例，诊断时涂片阳性（n = 637）。耐多药患病率为7.8%，在耐多药接触者中报告的病例数最高（33.3%）。总体及各患者组中最常见的利福平耐药编码突变是H531L（53.3%）。与其他患者组相比，在抗结核治疗4个月时涂片阳性的复治病例中，H526D突变的患病率更高（P = 0.052）。编码异烟肼耐药的最常见突变是katG基因中的S315T1（79.9%）和inhA基因中的C-15T（91.1%）。30株利福平耐药和9株异烟肼耐药菌株存在野生型基因缺失，但LPA未检测到突变。虽然LPA是一种针对大多数预计会导致耐多药结核病的突变的实用且快速的筛查方法，但我们观察到它仅能检测特定基因中的已知主要突变。此类研究可为根据我们地区及特定患者组中的流行突变制定定制化检测条提供所需知识。
据我们所知，这是评估来自印度的GenoType-MTBDR线性探针分析的最大规模研究。我们根据耐多药（MDR）怀疑标准研究了不同患者组中利福平和异烟肼耐药编码突变的患病率。本研究的转化影响在于设计定制化的国家或地区层面的线性探针分析检测条。在特定患者组中鉴定出一些突变以及检测到无明显突变的野生型缺失突变体均表明需要进行此类定制，以使我们能够应对耐多药结核病病例数上升的趋势。
