A recent study by Boehme et al. (8
) successfully showed the use of the Xpert test for point-of-care treatment in low-income countries for the detection of RIF resistance in pulmonary TB cases. Along with high specificity, the study showed a sensitivity of 90% for smear-negative pulmonary TB cases. Since we were one of the sites evaluating the test, we decided to also evaluate its utility for paucibacillary extrapulmonary specimens. The test identified 83% (125/150 specimens) of all “confirmed TB” cases, including 64% (38/59) of smear-negative TB cases. It was also observed that the Xpert test detected TB in 80% (103/129) of the samples from “probable TB” cases, whose cultures were negative but who had positive radiological tests and/or positive histology/cytology reports, while some of the patients were already on antitubercular treatment at the point of enrollment in the study.
The specificity of the Xpert test (99.6%) was found to be similar to that reported by Boehme et al. (8
). In the case of extrapulmonary specimens, the sensitivities of smear (51%) and culture (53%), though comparable, were found to be low in comparison with that of the Xpert test (81%); and the average TTP of culture is 25 days for MGIT only. Culture is seen to have a low sensitivity in cases of smear-positive patients (n
= 57, smear positive, culture negative), because 80% (45/57) of the patients were on ATT for various periods of time ranging from 4 to 6 months when enrolled in the study, and 16% (9/57) of the patients had completed their treatment regimen. Thus, both groups of patients were expected to become culture negative.
The low of sensitivity of culture (53%) in comparison with that of the Xpert test (81%) against the CRS can be explained as follows: (i) 78% (104/133) of culture negative, Xpert-positive patients were on antitubercular treatment for various periods of time when enrolled in the study; (ii) the paucibacillary nature of extrapulmonary specimens with a tendency of M. tuberculosis to form clumps leads to an uneven distribution of the bacilli; (iii) there is loss of viable bacilli during NALC-NaOH processing (due to decanting supernatant steps), unlike Xpert processing, wherein the entire volume of the processed specimen is used; and (iv) the Xpert sample reagent has a better homogenization and liquefaction efficiency than NALC-NaOH processing.
The study shows that the Xpert test has true diagnostic potential with good sensitivity (86 to 100%) for specimens such as synovial, pericardial, and peritoneal fluids; pus; and fine-needle aspirates and moderate sensitivity (63 to 73%) for tissues, lymph nodes, and pleural fluid but poor sensitivity (29%) in the case of CSF, at least in this small number of samples. A preprocessing step (concentrating the specimen by centrifuging it at high speed and then using the pellet for processing) might be required to increase the sensitivity for paucibacillary specimen types such as CSF. There is a need to evaluate and confirm the utility of this tool on a large sample size with specimens such as CSF, other body fluids, and urine, which are easier to obtain.
Finally, not only M. tuberculosis detection but also rapidly determining the patient's MDR status is of prime importance in bringing to an end the spread of MDR-TB and decreasing mortality. Conventional DST results take at least 2 months from the time when the culture is inoculated. Faster methods that allow MDR regimens to be started early are urgently needed. Conventional procedures are laborious and require high-infrastructure laboratories and trained personnel, a luxury that is available only in a few reference centers and not in resource-limited settings or decentralized laboratory settings, where they are most required.
The high cost of this sophisticated technology is offset to an extent by the rapid turnaround time, similar to that of smear microscopy (<2 h), with less biohazard risk and only minimal training needed (22
In conclusion, the GeneXpert MTB/RIF test not only has good sensitivity and specificity for the diagnosis of TB and detection of RIF resistance in EPTB but also perfectly fits the requirements of the Indian health care setting.