The diagnostic utility of line probe assays for multidrug-resistant tuberculosis

Abstract

Owing to the burden of multidrug-resistant tuberculosis, molecular techniques have been approved by the WHO for the rapid diagnosis of the same. The objectives of this prospective, diagnostic study, conducted at Christian Medical College, a tertiary care center in South India, were to compare the performance of line probe assay (GenoTypeMTBDRplus) with culture, as well as the Xpert MTB/Rif assay on sputum samples. Ninety-one consecutive suspects of multidrug-resistant pulmonary tuberculosis patients from January 2013 to June 2013 were enrolled in this study and the results of line probe assay compared to culture and Xpert MTB/Rif. Compared to culture, the assay demonstrated a sensitivity and specificity of 81.5% (95%CI 67.4-91.1%) and 87.5% (95%CI 71-96.5%) for the detection of tuberculosis, with sensitivity and specificity of 100% (95%CI 85.2-100%) and 93.8% (95%CI 69.8-99.8%), respectively, for rifampicin resistance. For isoniazid resistance, sensitivity and specificity were 89.3% (95%CI 71.8-97.7%) and 100% (95%CI 71.5-100%), respectively. Compared to Xpert MTB/Rif assay, the assay showed a sensitivity of 80% (95%CI 68.2-88.9%) and specificity of 100% (95%CI 85.8-100%) for the detection of tuberculosis a sensitivity of 94.3% (95%CI 80.8-99.3%) and specificity of 94.1% (95%CI 71.3-99.9%) for rifampicin resistance was attained. This assay performed well on smear positive samples, but poorly on smear negative and scanty samples, and can serve as a rapid diagnostic tool, particularly in isoniazid monoresistant cases of tuberculosis, which are not diagnosed by Xpert MTB/Rif.

A Comparative Evaluation of the New Genexpert MTB/RIF Ultra and other Rapid Diagnostic Assays for Detecting Tuberculosis in Pulmonary and Extra Pulmonary Specimens

“…Ninan et al . (2016) reported similar sensitivity rates (67%) in smear negative samples for LPA in their study as observed herein with SN-CP specimens, with our LPA also showing a sensitivity of 66.67% 22 . However our LPA sensitivity was a little lower than that reported by Meaza et al .…”

Diagnostic utility of a line probe assay for multidrug resistant-TB in smear-negative pulmonary tuberculosis

“…The aim of our study was to evaluate the utility of the latest version of LPA for the diagnosis of sputum smear-negative PTB patients. Almost similar sensitivity (66.7%) with high specificity (92.3%) was observed in a study conducted by Ninan et al [ 15 ] for the detection of MTB with MGIT-960 culture as reference standard. Another study conducted by Meaza et al [ 16 ] showed both higher sensitivity (77.8%) and specificity (97.9%).…”

“…Moreover, in our study, we used larger volumes of decontaminated sputum sample (1 mL) as compared to that recommended by the manufacturer (0.5 mL). This might have resulted in higher detection rates of MTB by LPA from the previous studies conducted by Ninan et al [ 15 ] and Meaza et al [ 16 ]; however, it warrants validation in future studies and the possible re-evaluation of the assay’s methodology.…”

<p>Efficacy Of Line Probe Assay In Detection Of Drug-Resistant Pulmonary Tuberculosis In Comparison With GeneXpert And Phenotypic Methods In Iran And Genetic Analysis Of Isolates By MIRU-VNTR</p>

“…The detection of dead bacilli by molecular technique may have resulted to false positive results. Hence, when a new test is assayed against culturing method as a reference standard, it can show false positive results 14,21. Two cases were reported as false negative by LPA method, which these cases were reported “very low” by GeneXpert MTB/RIF and were grown in culture.…”

“…This method also known as line probe assay (LPA) is based on polymerase chain reaction (PCR) and hybridization assay. Specific gene for MTB complex, mutations in rpoB for RIF resistance, katG for high-level INH resistance, and inhA for low-level INH resistance are detected directly from clinical samples by LPA method 14. However, because of strain diversity and various types of mutations in drug-resistant MTB, LPA assay needs to be studied particularly in developing countries.…”