Diagnostic Utility of Xpert MTB RIF in Extra-pulmonary Tuberculosis.

Background:

Most studies of Xpert MTB RIF in EPTB (extra-pulmonary tuberculosis) have used culture as the comparative gold standard, but culture may be negative in most patients with EPTB. We evaluated the test against a composite reference standard (CRS) for diagnosis of TB composed of smear microscopy, mycobacterial culture, clinical findings, histology/cytology, site-specific imaging and response after 3 months of anti-tuberculous therapy (ATT).

Methods:

Retrospective study between January and June 2015. Patients above 18 years of age with suspected EPTB tested with site specific Xpert MTB RIF.

Results:

625 patients were tested for EPTB with Xpert MTB RIF during the study period. Of these,431 patients were excluded (283- alternate diagnoses, 84- missing medical records, 64- no follow up). 194 patients diagnosed with confirmed /probable TB were analysed. 22 of the 194 patients (11.3%) had received ATT before evaluation.

Table 1: Sensitivity of smear, culture and Xpert MTB RIF

Sample	Smear +	Culture +	Xpert +
Body fluids (33)	0/33 (0%)	8/33 (24.2%)	8/33 (24.2%)
Pus (24)	3/20 (15%)	12/20 (60%)	23/24 (95.8%)
CSF (14)	0/14 (0%)	2 /12 (16 .7%)	7/14 (50%)
Tissue (123)	16/119 (13.4%)	37/107 (34.6%)	104/123 (84.6%)
Total (194)	19 /186 (10.2%)	59/172 (34.3%)	142/194 (73.2%)

 

Table 2: Sensitivity of Xpert MTB RIF according to culture negative and culture positive status

Xpert +	Fluid	Pus	CSF	Tissue	Total
Culture negative	2/25 (8%)	12/12 (100%)	5/12 (41.7%)	68/86 (79.1%)	87/135 (64.4%)
Culture positive	6/8 (75%)	11/12 (91.7%)	2/2 (100%)	36/37 (97.3%)	55/59 (93.2%)
Total	8/33 (24.2%)	23/24 (95.8%)	7/14 (50%)	104/123 (84.6%)	142/194 (73.2%)

Mean time to culture positivity was 18.2 days (5-36 days). Rifampicin resistance (RIF R) was detected by Xpert MTB RIF in 8 cases, of which 1 case was sensitive on phenotypic drug susceptibility testing (DST). RIF R was indeterminate in 1 case. Phenotypic DST was done in 30 of the 59 culture positive cases (50.8%). Concordance with DST was seen in 29 cases (96.7%) and discordance in 1(3.3%).

Conclusion:

Except for body fluids, Xpert MTB RIF was more sensitive than smears and cultures in all EPTB specimens including CSF, when a composite reference standard for TB was used. Xpert MTB helped to confirm the diagnosis in 64.4% of culture negative EPTB.These findings support WHO guidelines recommending the routine use of Xpert MTB in the diagnosis of EPTB.