Early detection of multidrug- and pre-extensively drug-resistant tuberculosis from smear-positive sputum by direct sequencing

BMC Infectious Diseases

Research Article

Weihua Wang¹  Peng Peng¹  Jun Chen²  Youyi Rao²  Yi Ren²  Lifeng Chen²  Yixiang Du³ 

[1] Department of Internal Medicine, Wuhan Institute for Tuberculosis Control, Wuhan Pulmonary Hospital, 430030, Wuhan, China;Department of Laboratory Medicine, Wuhan Institute for Tuberculosis Control, Wuhan Pulmonary Hospital, 430030, Wuhan, China;Department of Tuberculosis Control, Wuhan Institute for Tuberculosis Control, Wuhan Pulmonary Hospital, 430030, Wuhan, China;

关键词: Mycobacterium tuberculosis;    MDR-TB;    Pre-XDR-TB;    Rifampicin;    Isoniazid;    Fluoroquinolone;   

DOI  :  10.1186/s12879-017-2409-6

 received in 2016-04-04, accepted in 2017-04-19,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundEmergence of multidrug- and extensively drug-resistant tuberculosis (M/XDR-TB) is a major hurdle for TB control programs especially in developing countries like China. Resistance to fluoroquinolones is high among MDR-TB patients. Early diagnosis of MDR/pre-XDR-TB is essential for lowering transmission of drug-resistant TB and adjusting the treatment regimen.MethodsSmear-positive sputum specimens (n = 186) were collected from Wuhan Institute for Tuberculosis Control. The DNA was extracted from the specimens and run through a Sanger sequencing assay to detect mutations associated with MDR/pre-XDR-TB including the rpoB core region for rifampicin (RIF) resistance; katG and inhA promoter for isoniazid (INH) resistance; and gyrA for fluoroquinolone (FQ) resistance. Sequencing data were compared to phenotypic Lowenstein-Jensen (L-J) proportion method drug susceptibility testing (DST) results for performance analysis.ResultsBy comparing the mutation data with phenotypic results, the detection rates of MDR-TB and pre-XDR-TB were 84.31% (43/51) and 83.33% (20/24), respectively. The sequencing assay illustrated good sensitivity for the detection of resistance to RIF (96.92%), INH (86.89%), FQ (77.50%). The specificities of the assay were 98.35% for RIF, 99.20% for INH, and 97.26% for FQ.ConclusionsThe sequencing assay is an efficient, accurate method for detection of MDR-TB and pre-XDR-TB from clinical smear-positive sputum specimens, should be considered as a supplemental method for obtaining early DST results before the availability of phenotypic DST results. This could be of benefit to early diagnosis, adjusting the treatment regimen and controlling transmission of drug-resistant TB.

【 授权许可】

CC BY   
© The Author(s). 2017