Ochang Ernest A, Udoh Ubong A, Emanghe Ubleni E, Tiku Gerald O, Offor Jonah B, Odo Micheal, Nkombe Emmanuel, Owuna Oju E, Obeten Sunday M, Meremikwu Martin M
Department of Medical Microbiology and Parasitology, University of Calabar, Calabar, CRS, Nigeria.
Department of Medical Microbiology and Parasitology, University of Calabar, Calabar, CRS, Nigeria.
Int J Mycobacteriol. 2016 Dec;5 Suppl 1:S145-S146. doi: 10.1016/j.ijmyco.2016.09.007. Epub 2016 Oct 21.
OBJECTIVE/BACKGROUND: World Health Organization tuberculosis (TB) indices from 2014 to 2016 showed that Nigeria had the 6th highest prevalence, 4th highest incidence, and the highest mortality rate globally. In efforts to improve TB care, the XpertMTB/Rif (GeneXpert) technology, Cepheid, Sunnyvale, California, USA, which has revolutionized TB detection with concomitant rifampicin-resistance molecular detection, was introduced in Cross River State, South-South Nigeria, in 2014. The GeneXpert uses molecular beacons to detect five overlapping 81-bp regions in the rpoB gene known as the Rifampicin Resistant Determinant Region (RRDR). These probes are represented as Probe A (507-511), Probe B (512-518), Probe C (518-523), Probe D (523-529), and Probe E (529-533). Mutations in this region have been shown to account for about 93% of resistance to rifampicin, which is the most important drug in tuberculosis treatment. The objective of this study was to determine the frequency of rifampicin resistance and the commonly associated probes for various rpoB gene mutations within the 81-bp RRDR of Mycobacterium tuberculosis in Cross River State, Nigeria.
We collated and analyzed data from the 10 Xpert MTB/Rif sites in Cross River State from June 2014 to June 2016 and determined the frequency of mutations associated with different probes designated A-E, which represent the RRDR of rpoB gene. All centers use XpertMTB/Rif version G4.
In total, 973 tuberculosis cases were detected from 4671 cases tested. Rif resistance was detected in 6.0% (58/973) of cases. Probe E mutations were the most common, seen in 60.3% (35/58); followed by Probe D, 17.2% (10/58); and Probe B, 13.8% (8/58). Probe A occurred in 3.4% (2/58). No Probe C mutation was seen. Multiple mutation combinations involving probes B and D occurred in 3.4% (2/58), while one isolate had triple site mutations involving A, D, and E. One isolate that at initial testing showed a Probe A mutation displayed a Probe D mutation when tested in another site prior to treatment enrollment.
In our setting, 6.0% of tuberculosis isolates are rifampicin resistant. Mutations associated with probe E commonly due to codon 531 are the most predominant cause of rifampicin resistance. Mutations at probe C (codons 518-523) were uncommon. A change in mutation may have occurred in one of the patients.
目的/背景：世界卫生组织2014年至2016年的结核病（TB）指标显示，尼日利亚的患病率全球第六高、发病率全球第四高、死亡率全球最高。为努力改善结核病护理，2014年在尼日利亚南南地区的克罗斯河州引入了Xpert MTB/Rif（GeneXpert）技术（美国加利福尼亚州森尼韦尔市的塞菲德公司生产），该技术彻底改变了结核病检测方式，并能同时进行利福平耐药性分子检测。GeneXpert使用分子信标检测rpoB基因中五个重叠的81碱基对区域，这些区域被称为利福平耐药决定区（RRDR）。这些探针分别表示为探针A（507 - 511）、探针B（512 - 518）、探针C（518 - 523）、探针D（523 - 529）和探针E（529 - 533）。该区域的突变已被证明约占对利福平耐药性的93%，利福平是结核病治疗中最重要的药物。本研究的目的是确定尼日利亚克罗斯河州结核分枝杆菌81碱基对RRDR内利福平耐药的频率以及各种rpoB基因突变常见的相关探针。
我们整理并分析了2014年6月至2016年6月克罗斯河州10个Xpert MTB/Rif检测点的数据，确定了与代表rpoB基因RRDR的不同探针A - E相关的突变频率。所有中心均使用G4版Xpert MTB/Rif。
在检测的4671例病例中，共检测出973例结核病病例。6.0%（58/973）的病例检测出利福平耐药。探针E突变最为常见，占60.3%（35/58）；其次是探针D，占17.2%（10/58）；探针B占13.8%（8/58）。探针A出现的比例为3.4%（2/58）。未发现探针C突变。涉及探针B和D的多重突变组合占3.4%（2/58），而有一株分离株有涉及A、D和E的三位点突变。有一株分离株在初始检测时显示探针A突变，但在治疗登记前于另一个检测点检测时显示探针D突变。
在我们的研究环境中，6.0%的结核分枝杆菌分离株对利福平耐药。通常由密码子531导致的与探针E相关的突变是利福平耐药的最主要原因。探针C（密码子518 - 523）处的突变不常见。其中一名患者可能发生了突变变化。
