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埃塞俄比亚东北部结核分枝杆菌感染的表型和基因型药物敏感性谱及相关因素

Phenotypic and genotypic drug sensitivity profiles of Mycobacterium tuberculosis infection and associated factors in northeastern Ethiopia.

作者信息

Gashaw Fikru, Erko Berhanu, Mekonnen Yalemtsehay, Yenew Bazezew, Amare Misikir, Gumi Balako, Ameni Gobena

机构信息

Aklilu Lemma Institute of Pathobiology, Addis Ababa University, P.O. Box 1176, Addis Ababa, Ethiopia.

Department of Microbial, Cellular and Molecular Biology, College of Natural Sciences, Addis Ababa University, P.O. Box 1176, Addis Ababa, Ethiopia.

出版信息

BMC Infect Dis. 2021 Mar 12;21(1):261. doi: 10.1186/s12879-021-05961-8.

Abstract

BACKGROUND

Tuberculosis is a devastating and a deadly disease despite the novel advances in its diagnostic tools and drug therapy. Drug resistant Mycobacterium contributes a great share to tuberculosis mortality. Status of drug resistance and patients' awareness toward the disease is unknown in northeastern Ethiopia. Thus, the aim of this study was to determine the phenotypic and genotypic drug sensitivity patterns and associated factors in Oromia Special Zone and Dessie Town, northeastern Ethiopia.

METHODS

In a cross-sectional study, 384 smear positive tuberculosis cases were recruited and Löwenstein-Jensen culture was done. The performance of GenoTypic MTBDRplus assay using the conventional BACTEC MGIT 960 as a "gold standard" was determined. Drug resistant strains were identified using spoligotyping. Pearson Chi-square test was used to determine the association of drug sensitivity test and tuberculosis type, lineages, dominant strains and clustering of the isolates.

RESULTS

The 384 smear positive Mycobacterium samples were cultured on LJ media of which 29.2% (112/384) as culture positive. A fair agreement was found between MTBDRplus assay and the conventional MGIT test in detecting the Mycobacterium tuberculosis with sensitivity, specificity, positive and negative predictive value of 94.2, 30.2, 68.4 and 76.5%, respectively. Among LJ culture positive samples 95 of them gave valid result for MTBDRplus assay and 16.8% (16/95) as drug resistant. Similarly, MGIT subculture was made for the 112 isolates and 69 of them gave positive result with 15.9% (11/69) as drug resistant. Cohen's kappa value showed almost a perfect agreement between the two testing methods in detecting rifampicin (sensitivity 100% and specificity 98.3%) and multi-drug resistance (sensitivity 83.3% and specificity 100%). Spoligotyping identified 76.5% (13/17) of the drug resistant isolates as Euro-American and family 33 as the predominant family. Significant association was observed between drug resistant isolates and the dominant strains (χ2: 34.861; p = 0.040) of the Mycobacterium.

CONCLUSION

Higher magnitude of drug resistance was found in the study area. The GenoTypic MDRTBplus assay had an acceptable drug sensitivity testing performance.

摘要

背景

尽管结核病在诊断工具和药物治疗方面有了新进展,但它仍然是一种具有毁灭性的致命疾病。耐药性分枝杆菌在结核病死亡率中占很大比例。埃塞俄比亚东北部地区的耐药状况以及患者对该疾病的认知情况尚不清楚。因此,本研究的目的是确定埃塞俄比亚东北部奥罗米亚特别区和德西镇结核分枝杆菌的表型和基因型药敏模式及相关因素。

方法

在一项横断面研究中,招募了384例涂片阳性肺结核病例并进行罗氏培养。以传统的BACTEC MGIT 960作为“金标准”,评估基因分型MTBDRplus检测方法的性能。使用间隔寡核苷酸分型法鉴定耐药菌株。采用Pearson卡方检验确定药敏试验与结核类型、谱系、优势菌株及分离株聚类之间的关联。

结果

384份涂片阳性分枝杆菌样本在罗氏培养基上培养,其中29.2%(112/384)培养阳性。MTBDRplus检测方法与传统MGIT检测方法在检测结核分枝杆菌方面具有较好的一致性,其灵敏度、特异度、阳性预测值和阴性预测值分别为94.2%、30.2%、68.4%和76.5%。在罗氏培养阳性样本中,95份样本MTBDRplus检测结果有效,其中16.8%(16/95)耐药。同样,对112株分离株进行MGIT传代培养,69株培养阳性,其中15.9%(11/69)耐药。Cohen's kappa值显示,两种检测方法在检测利福平(灵敏度100%,特异度98.3%)和多药耐药(灵敏度83.3%,特异度100%)方面几乎完全一致。间隔寡核苷酸分型法鉴定出76.5%(13/17)的耐药分离株为欧美型,33型为主要类型。耐药分离株与分枝杆菌的优势菌株之间存在显著关联(χ2:34.861;p = 0.040)。

结论

研究地区发现较高水平的耐药情况。基因分型MDRTBplus检测方法具有可接受的药敏检测性能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a132/7953820/14ce169e4909/12879_2021_5961_Fig1_HTML.jpg

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