Evaluation of indirect drug susceptibility testing using the MODS assay for the detection of XDR-TB in China

Zk, Huang; Luo, Qiong; Gl, Xiong; Wt, Li; Xu, Xiaowei; Jm, Li

doi:10.5588/ijtld.13.0736

Cited by 3 publications

(1 citation statement)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The major strengths of the MODS assay is that it is a rapid (10 days quicker than MGIT DST), cheap, non-commercial assay that can be used to detect M/XDR-TB directly from processed sputum with inexpensive, readily purchased supplies or commercial kits [ 19 , 35 – 37 ]. Concerns over biohazard risk associated with daily readings of MODS have been eliminated by modifying the procedure to seal plates after inoculation to contain the infectious organisms.…”

Section: Discussionmentioning

confidence: 99%

Performance Comparison of Three Rapid Tests for the Diagnosis of Drug-Resistant Tuberculosis

et al. 2015

View full text Add to dashboard Cite

BackgroundThe aim of this study was to compare the performance of several recently developed assays for the detection of multi- and extensively drug-resistant tuberculosis (M/XDR-TB) in a large, multinational field trial.MethodsSamples from 1,128 M/XDR-TB suspects were examined by Line Probe Assay (LPA), Pyrosequencing (PSQ), and Microscopic Observation of Drug Susceptibility (MODS) and compared to the BACTEC MGIT960 reference standard to detect M/XDR-TB directly from patient sputum samples collected at TB clinics in India, Moldova, and South Africa.ResultsSpecificity for all three assays was excellent: 97–100% for isoniazid (INH), rifampin (RIF), moxifloxacin (MOX) and ofloxacin (OFX) and 99–100% for amikacin (AMK), capreomycin (CAP) and kanamycin (KAN) resistance. Sensitivities were lower, but still very good: 94–100% for INH, RIF, MOX and OFX, and 84–90% for AMK and CAP, but only 48–62% for KAN. In terms of agreement, statistically significant differences were only found for detection of RIF (MODS outperformed PSQ) and KAN (MODS outperformed LPA and PSQ) resistance. Mean time-to-result was 1.1 days for LPA and PSQ, 14.3 days for MODS, and 24.7 days for MGIT.ConclusionsAll three rapid assays evaluated provide clinicians with timely detection of resistance to the drugs tested; with molecular results available one day following laboratory receipt of samples. In particular, the very high specificity seen for detection of drug resistance means that clinicians can use the results of these rapid tests to avoid the use of toxic drugs to which the infecting organism is resistant and develop treatment regiments that have a higher likelihood of yielding a successful outcome.

show abstract

Section: Discussionmentioning

confidence: 99%

Performance Comparison of Three Rapid Tests for the Diagnosis of Drug-Resistant Tuberculosis

et al. 2015

View full text Add to dashboard Cite

show abstract

A Systematic Review of Mutations Associated with Isoniazid Resistance Points to Lower Diagnostic Sensitivity for Common Mutations and Increased Incidence of Uncommon Mutations in Clinical Strains of Mycobacterium tuberculosis

Valafar

2020

Preprint

View full text Add to dashboard Cite

Molecular testing is rapidly becoming integral to the global tuberculosis (TB) control effort. Uncommon mechanisms of resistance can escape detection by these platforms and lead to the development of Multi-Drug Resistant (MDR) strains. This article is a systematic review of published articles that reported isoniazid (INH) resistance-conferring mutations between September-2013 and December-2019. The aims were to catalogue mutations associated with INH resistance, estimate their global prevalence and co-occurrence, and their utility in molecular diagnostics. The genes commonly associated with INH resistance, katG, inhA, fabG1, and the intergenic region oxyR-ahpC were considered in this review. In total, 52 articles were included describing 5,632 INHR clinical isolates from 31 countries. The three most frequently mutated loci continue to be katG315 (4,100), inhA-15 (786), and inhA-8 (105). However, the diagnostic value of inhA-8 is far lower than previously thought, only appearing in 25 (0.4%) INHR isolates that lacked a mutation at the first two loci. Importantly, of the four katG loci recommended by the previous systematic review for diagnostics, only katG315 was observed in our INHR isolates. This indicates continued evolution and regional differences in INH resistance. We have identified 58 loci (common to both systematic reviews) in three genomic regions as a reliable basis for molecular diagnostics. We also catalogue mutations at 49 new loci associated with INH resistance. Including all observed mutations provides a cumulative sensitivity of 85.1%. The most disconcerting is the remaining 14.9% of isolates that harbor an unknown mechanism of resistance, will escape molecular detection, and likely convert to MDR-TB, further complicating treatment. Integrating the information cataloged in this and other similar studies into current diagnostic tools is essential for combating the emergence of MDR-TB. Exclusion of this information will lead to an unnatural selection which will result in eradication of the common but propagation of the uncommon mechanisms of resistance, leading to ineffective global treatment policy and a need for region-specific regiments. Finally, the observance of many low-frequency resistance-conferring mutations point to an advantage of platforms that consider regions rather than specific loci for detection of resistance.

show abstract

Systematic Review of Mutations Associated with Isoniazid Resistance Points to Continuing Evolution and Subsequent Evasion of Molecular Detection, and Potential for Emergence of Multidrug Resistance in Clinical Strains of Mycobacterium tuberculosis

Valafar

2021

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Molecular testing is rapidly becoming an integral component of global tuberculosis (TB) control. Uncommon mechanisms of resistance escape detection by these platforms and undermine our ability to contain outbreaks. This article is a systematic review of published articles that reported isoniazid (INH) resistance-conferring mutations between September 2013 and December 2019. The genes katG, inhA, fabG1, and the intergenic region oxyR’-ahpC were considered in this review. Fifty-two articles were included describing 9,306 clinical isolates (5,804 INHR, 3,502 INHS) from 31 countries. The three most frequently mutated loci continue to be katG315 (4,271), inhA-15 (787), and inhA-8 (106). However, the diagnostic value of inhA-8 is far lower than previously thought, only appearing in 25 (0.4%) INHR isolates lacking the first two mutations. We catalogued 45 new loci (29 katG, nine inhA, seven ahpC) associated with INH resistance and identified 59 loci (common to this and previous reviews) as a reliable basis for molecular diagnostics. Including all observed mutations provides a cumulative sensitivity of 85.6%. In 14.4% of resistant isolates no mechanism of resistance was detected, making them likely to escape molecular detection, and in case of mono INH resistance likely to convert to MDR-TB. Integrating the information cataloged in this study into current diagnostic tools is essential for combating the emergence of MDR-TB, and its exclusion can lead to an unintended selection against common mechanisms and to diversifying evolution. Observation of many low-frequency resistance-conferring mutations points to an advantage of WGS for diagnostics. Finally, we provide five recommendations for future diagnostic platforms.

show abstract

Evaluation of indirect drug susceptibility testing using the MODS assay for the detection of XDR-TB in China

Abstract: The MODS assay offers a simple, rapid, economical and feasible method for the detection of M. tuberculosis resistance to first- and second-line drugs in resource-limited settings.

Cited by 3 publications

References 0 publications

Performance Comparison of Three Rapid Tests for the Diagnosis of Drug-Resistant Tuberculosis

Performance Comparison of Three Rapid Tests for the Diagnosis of Drug-Resistant Tuberculosis

A Systematic Review of Mutations Associated with Isoniazid Resistance Points to Lower Diagnostic Sensitivity for Common Mutations and Increased Incidence of Uncommon Mutations in Clinical Strains of Mycobacterium tuberculosis

Systematic Review of Mutations Associated with Isoniazid Resistance Points to Continuing Evolution and Subsequent Evasion of Molecular Detection, and Potential for Emergence of Multidrug Resistance in Clinical Strains of Mycobacterium tuberculosis

Contact Info

Product

Resources

About