Effect of Introducing Xpert MTB/RIF to Test and Treat Individuals at Risk of Multidrug-Resistant Tuberculosis in Kazakhstan: A Prospective Cohort Study

Abstract

BackgroundXpert MTB/RIF (Xpert) was piloted in Kazakhstan to detect tuberculosis (TB) and rifampicin resistance (RR-)TB among individuals at risk of multidrug-resistant (MDR-) TB. This study assessed the performance of Xpert compared to conventional diagnostic methods, RR-TB case detection among various risk groups, treatment initiation and time to diagnosis and treatment.MethodsEligible individuals were tested with Xpert, smear microscopy, culture and drug-susceptibility testing (DST) at the national TB reference laboratory and three provincial laboratories. Data was collected prospectively from August 2012 to May 2013 from routine laboratory and treatment registers.ResultsA total of 5,611 Xpert tests were performed mostly targeting contacts of MDR-TB patients, ‘other’ presumptive MDR-TB patients, and retreatment cases (26%, 24% and 22%, respectively). Compared to phenotypic DST, the positive predictive value of Xpert to detect RR-TB was 93.1% and 96.4% and the negative predictive value was 94.6% and 92.7% using solid and liquid culture media, respectively. RR-TB detection was highest among (former) prisoners, retreatment cases, people living with HIV/AIDS (PLWHA), and TB patients with positive smears after intensive phase of treatment (59%, 58%, 54% and 53% among TB positives, respectively). 88.9% of RR-TB patients were registered to have started second-line TB treatment. Median time to diagnosis with Xpert was 0.0 days (IQR 0.0-1.0), time from diagnosis to start of first-line treatment 3.0 days (IQR 1.0-7.0), and to start of second-line treatment 7.0 days (IQR 4.0-16).ConclusionsCompared to conventional culture and DST, Xpert had a shorter result turn-around-time and excellent concordance to detect RR-TB. Time from sputum collection to start of second-line treatment was reduced to one week. The yield of Xpert could be maximized by increasing referrals from penitentiary and HIV centers to TB centers.

Diagnostic performance and impact of routinely implemented Xpert® MTB/RIF assay in a setting of high incidence of drug-resistant TB in Odessa Oblast, Ukraine

“…In our study, rifampicin resistance was detected in a total of 1289/ 3167 individual sputum specimens, translating into rifampicin resistance rates in the study population of 40.7%. Sensitivity of the assay for detection of rifampicin resistance in our study was very good (93.4%; 1212/1298), with overall specificity of 95.9% (1792/ 1869), which is consistent with earlier reports from similar settings [18,24]. Relatively minor discrepancies between Xpert MTB/RIF and phenotypic DST results (n ¼ 163; 5.1%) could be explained by the heteroresistance associated with a differential growth of drugsensitive and drug-resistant populations of M. tuberculosis coexisting in original sputum specimens, as well as by possible clerical and reporting errors.…”

“…In Ukraine, the introduction of the Xpert MTB/RIF assay started in 2013. Formal protocols specifying categories of patients having access to rapid molecular TB diagnosis [10], as well as the availability of the electronic national TB register [14], created means for systematic implementation of new diagnostic methods and monitoring of accurate treatment outcomes, but data on performance, clinical outcomes and cost effectiveness of the rapid molecular assays in Ukraine are so far limited [9,11,13,18]. Although the study cohort cannot be considered fully representativeddue to the retrospective nature of the study and the lack of information on whether selection of patients for rapid diagnostics was in full agreement with the National guidelines [10]dour results on rifampicin resistance are in agreement with high overall rates of MDR-TB in Ukraine [1].…”

Clinical Outcomes of Patients With Drug-Resistant Tuberculous Meningitis Treated With an Intensified Antituberculosis Regimen

“…We could not establish whether fluoroquinolones improved outcomes from INH-R TBM when added later in treatment based on DST, but our findings underscore the necessity for improved early drug resistance detection. The use of rapid molecular testing of pulmonary TB by Xpert MTB/RIF has facilitated early diagnosis of rifampicin resistance and second-line treatment initiation [ 22 ]. Xpert MTB/RIF has been recommended by the World Health Organization for direct use on CSF as the initial diagnostic test [ 21 , 23 ]; however, isoniazid resistance cannot be detected by the current Xpert cartridge.…”

Outcomes of Community-Based Systematic Screening of Household Contacts of Patients with Multidrug-Resistant Tuberculosis in Myanmar

“…Studies have shown that Xpert MTB/RIF can detect up to 59% additional TB cases when compared to sputum smear microscopy [16][17][18]. It can also detect RR-TB as well as reduce the turnaround time from sample collection to diagnosis and treatment [19]. Inadequate access or lack of access to Xpert MTB/RIF machines was one of the main barriers for Xpert MTB/RIF testing for all eligible patients.…”