Diagnostic Value of GeneChip for Detection of Resistant Mycobacterium tuberculosis in Patients with Differing Treatment Histories

Abstract

The increasing burden of drug-resistant tuberculosis (TB) poses an escalating threat to national TB control programs. To assist appropriate treatment for TB patients, accurate and rapid detection of drug resistance is critical. The GeneChip test is a novel molecular tool for the diagnosis of TB drug resistance. Performance-related data on GeneChip are limited, and evaluation in new and previously treated TB cases has never been performed. We evaluated the diagnostic performance of GeneChip in detecting resistance to rifampin (RMP) and isoniazid (INH) and in detecting multidrug-resistant tuberculosis (MDR-TB) in comparison with standard drug susceptibility testing (DST) and compared the results in a group of previously treated and newly detected TB patients in an urban area in southeastern China. One thousand one hundred seventy-three (83.8%) new cases and 227 (16.2%) previously treated cases were collected between January 2011 and September 2013. The GeneChip showed a specificity of 97.8% and a sensitivity of 94.8% for detection of RMP resistance and 97.3% and 70.9%, respectively, for INH resistance in new cases. For previously treated cases, the overall sensitivity, specificity, and agreement rate are 94.6%, 91.3%, and 92.1%, respectively, for detection of RMP resistance and 69.7%, 95.4%, and 86.8%, respectively, for INH resistance. The sensitivity and specificity of MDR-TB were 81.8% and 99.0% in new cases and 77.8% and 93.4% in previously treated cases, respectively. The GeneChip system provides a simple, rapid, reliable, and accurate clinical assay for the detection of TB drug resistance, and it is a potentially important diagnostic tool in a high-prevalence area. T uberculosis (TB) is an infectious disease caused by the bacillusMycobacterium tuberculosis and remains a major global health problem. In 2012, the World Health Organization (WHO) estimated an incidence of 8.6 million new TB cases and 1.3 million TB deaths (just under 1.0 million among HIV-negative people and 0.3 million HIV-associated TB deaths) (1).The emergence of drug-resistant TB (especially multidrug-resistant TB [MDR-TB], defined as resistance to both rifampin [RMP] and isoniazid [INH]) represents a serious threat to TB control efforts worldwide. Globally, 3.6% of new TB cases and 20.2% of previously treated cases are estimated to have MDR-TB (1, 2). Acid-fast bacillus (AFB) smear microscopy is the most common method for diagnosing TB. However, low sensitivity and an inability to detect smear-negative pulmonary cases limit the usefulness of this technique (3, 4). Diagnosis based on culture is the reference standard, but results take weeks to obtain. Conventional drug susceptibility testing (DST) can provide definitive results, but this approach is time-consuming and usually requires several weeks to produce susceptibility profiles, which can lead to inadequate treatment and further acquired drug resistance during this period (5, 6). Therefore, highly sensitive and specific, easy-toapply, quick, and cost-effective methods are needed in the ...

GeneChip analysis of resistant Mycobacterium tuberculosis with previously treated tuberculosis in Changchun

“…The overall sensitivity, specificity, agreement rate, PPV, NPV, and kappa values were 83.1, 98.7, 93.9, 96.6, 92.9% and 0.85 for detecting M. tuberculosis RFP resistance, respectively; 79.9, 99.6, 93.1, 98.8, 91.1% and 0.84 for detecting M. tuberculosis INH resistance, respectively; and 74.1, 99.8, 93.6, 99.2, 92.4% and 0.81 for detecting MDR-TB, respectively. These results were consistent with those reported by Guo, Y. et al, Pang, Y. et al, Tang, P et al, and Zhu, L. et al [ 10 , 19 – 21 ]. However, compared with the MeltPro TB assay method in detection of TB drug resistance [ 22 , 23 ].…”

Diagnostic Performance of GeneChip for the Rapid Detection of Drug-Resistant Tuberculosis in Different Subgroups of Patients

“… 26 , 27 Therefore, the characteristics of cases should not be ignored when evaluating the performance of GeneChip. 24 , 28 In the current study, we observed that sex, age, treatment history, treatment failure outcome, and place of residence were significantly associated with the diagnostic value of GeneChip.…”

“… 21 Another study in China reported that GeneChip performed better in newly treated cases in detecting RIF resistance, INH resistance, and MDR-TB. 24 However, few studies have evaluated the performance of GeneChip in subgroups of patients with different characteristics.…”

Advances in the application of molecular diagnostic techniques for the detection of infectious disease pathogens (Review)

“…Ma et al (82) developed and evaluated a solid-phase chip for the simultaneous detection of 15 types of bacteria directly from respiratory tract specimens of patients with pneumonia, thus reducing detection time, facilitating the early administration of antimicrobial drugs and preventing bacterial resistance caused by empirical antibiotic treatment. Recent studies have shown that the CapitalBio DNA chip (CapitalBio Corporation) can detect the resistance of MTB to rifampicin and isoniazid, and the corresponding gene mutations within 6 h, which is quicker and more accurate than traditional bacterial culture and drug susceptibility tests (83)(84)(85). Currently, a number of automatic detection platforms based on solid-phase chips are entering the market.…”