Performance of WHO-Endorsed Rapid Tests for Detection of Susceptibility to First-Line Drugs in Patients with Pulmonary Tuberculosis in Bangladesh

Abstract

The fast and accurate detection of susceptibility in drugs is a major challenge for a successful tuberculosis (TB) control programme. This study evaluated the performance of WHO-endorsed rapid diagnostic tools, such as BACTEC MGIT 960 SIRE (MGIT SIRE), GenoType MTBDRplus (MTBDRplus) and Xpert MTB/RIF (Xpert), for detecting susceptibility to first-line anti-TB drugs among pulmonary TB patients in Bangladesh. A total of 825 sputum samples with results from drug susceptibility testing (DST) against first-line anti-TB drugs in the MGIT SIRE, MTBDRplus and Xpert assays were evaluated and compared with the gold standard proportion susceptibility method of the Lowenstein–Jensen (LJ) medium. The overall sensitivities of MGIT SIRE were 97.6%, 90.0%, 61.3% and 44.9%, while specificities were 89.9%, 94.5%, 91.3% and 92.2% for detection of susceptibility to isoniazid (INH), rifampicin (RIF), streptomycin (STR) and ethambutol (EMB), respectively. For MTBDRplus, the sensitivities were 88.0% and 88.7%, and the specificities were 97.4% and 97.8% for the detection of susceptibility to INH and RIF, respectively. Xpert demonstrated a sensitivity and specificity of 94.8% and 99.5%, respectively, for the detection of RIF susceptibility. All tests performed significantly better in retreated TB patients compared with primary TB cases. For detection of RIF and INH susceptibility, all three assays showed almost perfect agreement with the LJ method, although MGIT SIRE exhibited low agreement for STR and EMB. Considering the high performance, shorter turnaround time and ease of use, molecular-based approaches Xpert and MTBDRplus can be widely implemented throughout the country for the rapid detection of drug-resistant TB.

A precision overview of genomic resistance screening in isolates ofMycobacterium tuberculosisusing web-based bioinformatics tools

“…Mutations in katG, kasA, inhA, fabG1 genes and the oxyR-ahpC intergenic region are associated with conferring resistance to isoniazid (44,62,63), thus ethA/R mutations are associated with ethionamide resistance (48,64,65). Our results were in concordance with previous studies (44,63,66) due to the higher prevalence of mutations in katG (88.8%). Furthermore, it has been shown that mutations in the ahpC promoter conferred resistance by compensatory mechanism (67,68) like L427P in the katG gene (69,70).…”

Comparative genomics of drug-resistant strains of Mycobacterium tuberculosis in Ecuador

“…In the case of the first-line drug in Mtb treatment, mutations in the 81-bp rifampicin resistance determining region (RRDR) of the rpoB gene, also known as a hotspot region, have been accurate predictors of rifampicin resistance in many studies [69][70][71]. On the other hand, it has been established that INH resistance, predominantly mediated through loss of catalase-peroxidase activity via mutations in katG, produces high-level resistant strains [18,72,73]. Finally, in ethambutol, most resistance-related genes are located on the embB, embC, and upstream of the embA [74,75].…”

“…In 2015, due to drug resistance rising worldwide, the WHO proposed expanding rapid testing and detection of cases as one of the five high-priority actions to tackle the global DR-TB crisis [15]. As part of these actions, some molecular biology-based diagnostic methods have been applied in a clinical setting for their versatility and speed, including variants of Xpert MTB/RIF and Geno-Type MTBDRplus [16][17][18][19]. Although these methods are rapid and straightforward, Mtb continuously evolves through the genomic acquisition of single nucleotide polymorphisms (SNPs), insertions, and deletions (indels), impacting the ability to discriminate strains without the classic regions used for resistance detection [20].…”

Drug Resistance and Molecular Characteristics of Mycobacterium tuberculosis: A Single Center Experience

“…Tuberculosis (TB) disease is a chronic infectious disease caused by Mycobacterium tuberculosis (MTB). Globally, there were an estimated 9.9 million new cases of MTB in 2020 [1], and about half a million of these cases were multidrug-resistant TB (MDR-TB) [2]. The emergency of drug-resistant TB (DR-TB) has threatened global public health efforts to control TB [3,4].…”