Cartridge-based nucleic acid amplification test in drug-resistant Mycobacterium tuberculosis as compared to solid cultures: Is it time to look beyond cartridge-based nucleic acid amplification test?

Abstract

Background: There is a need to study the performance, validity, and accuracy of cartridge-based nucleic acid amplification test (CB-NAAT) for accessing drug resistance among pulmonary tuberculosis (TB) compared with the solid culture drug susceptibility test (DST). Methods: Patients with symptoms of cough for more than 2 weeks with anyone symptoms such as night sweats, fever, and unintentional weight loss were studied. Cases with previously diagnosed drug-resistant pulmonary TB by sputum CB-NAAT having constitutional symptoms but not on any ATT for a minimum of 2 months were also included in the study. The patient's information, including age, immune surveillance status, clinical features, and chest X-rays, were recorded. Each sputum sample was divided into three aliquots and tested for smear microscopy, liquid culture (LC), and genotypic DST. Results of all three diagnostic modalities were compared with CB-NAAT reports. Results: Of 236 patients with sputum-positive CB-NAAT (n = 236), 49.4% (n = 117) were rifampicin resistant, while 50. 4% (n = 119) were rifampicin sensitive. The genotypic DST assays carried out of all enrolled patients showed that 76.3% (n = 181) patients were resistant to one or more first-line antitubercular drugs (FL ATTs) or second-line (SL) ATTs, while 23.7% (n = 55) patients were sensitive to all ATTs. Among all the study participants, 56.4% (n = 133) of patients had sputum smear-positive by ZN stain, while 88.6% (n = 209) showed growth on LC (BACTEC) media. On concordant analysis of CB-NAAT with DST assays, we found that among 119 CB-NAAT rifampicin-sensitive patients, 66 patients were drug-resistant (DR) TB to any of the FL or SL ATTs. The sensitivity, specificity, positive predictive value, and negative predictive value of CB-NAAT for detecting rifampicin resistance on sputum for pulmonary TB when compared with the gold-standard DST assays were 97.67%, 76.67%, 70.59%, and 98.29%, respectively. Conclusions: This study found that the use of rapid molecular technique (CB-NAAT) in screening DRTB at the community level is suboptimal compared to the gold-standard solid culture method. Although CB-NAAT's sensitivity in detecting DR pulmonary TB is significantly higher, the specificity is lower in that population who have received ATT earlier.

Keywords

• cartridge-based nucleic acid amplification test
• line probe assays
• liquid cultures
• multidrug-resistant tuberculosis
• solid cultures
• sputum microscopy