Clinical Evaluation of the Enhanced Gen-Probe Amplified Mycobacterium Tuberculosis Direct Test for Rapid Diagnosis of Tuberculosis in Prison Inmates

Abstract

The reliability of the enhanced Amplified Mycobacterium Tuberculosis Direct Test (E-MTD; Gen-Probe, Inc., San Diego, Calif.) for rapid diagnosis of pulmonary tuberculosis (TB) was evaluated by testing 1,004 respiratory specimens from 489 Texas prison inmates. Results were compared to those of mycobacterial culture (BACTEC TB 460 and Middlebrook 7H11 biplates), smear for acid-fast bacilli (AFB; auramine O), and clinical course. After chart review, three patients (nine specimens) who were on antituberculosis therapy before the study began were excluded from final analysis. Of the remaining 995 specimens, 21 were AFB smear positive: 13 grew Mycobacterium tuberculosis complex (MTBC), 6 grew nontuberculous mycobacteria, and 2 (from two patients diagnosed with TB and started on therapy after the study began) were culture negative. Twenty-eight specimens (20 patients) were positive for MTBC by culture and E-MTD. Seven specimens (seven patients) were positive by culture alone; three were from patients who had other E-MTD-positive specimens, two were false-positive cultures, and two were false-negative E-MTD results. Eight specimens were positive by E-MTD only; four specimens (four patients) were false-positive E-MTD results, and four specimens were from two patients with earlier E-MTD-positive specimens that grew MTBC. Thus, there were 22 patients with TB (10 smear positive and 12 smear negative). The sensitivity and specificity of the AFB smear for diagnosis of TB, by patient, were 45.5 and 98.9%, respectively. After resolving discrepancies, these same values for E-MTD were 90.9 and 99.1% overall, 100 and 100% for the smear-positive patients, and 83.3 and 99.1% for the smear-negative patients. Excluding the one smear-negative patient whose E-MTD-negative, MTBC culture-positive specimen contained inhibitory substances, the sensitivity of E-MTD was 95.2% overall and 90.9% in smear-negative patients. The specificity and positive predictive value of E-MTD can be improved, without altering other performance characteristics, by modifying the equivocal zone recommended by the manufacturer. These data suggest that E-MTD is a reliable method for rapid diagnosis of pulmonary TB, irrespective of the AFB smear result. Guidelines for the most appropriate use of E-MTD with smear-negative patients are needed.

PCR-based diagnostics for infectious diseases: uses, limitations, and future applications in acute-care settings

“…Nonetheless, recent studies suggest that more widespread use of these assays may significantly affect patient management, clinical outcomes, and cost efficacy. 56,57 Potential yet unrealised applications of the assay for use in acute-care settings include earlier informed decision-making for appropriate use of isolation beds in high prevalence sites, regional outbreaks, or where isolation beds are scarce. The use of this and other PCR-based diagnostics in these settings, however, will have to be balanced against costs, expertise, and time associated with routine around-the-clock availability of testing, as discussed in more detail below.…”

What is the optimal approach for using a direct amplification test in the routine diagnosis of pulmonary tuberculosis? A preliminary assessment

“…The potential advantage of using a more sensitive NAA test such as the enhanced MTB direct test (General-Probe Inc), which has sensitivities of up to 83.3% in smear-negative patients and was recently approved by the FDA for use in smear-negative specimens, needs further evaluation. 8,14,18 Thus, the cost-effectiveness of the different NAA tests needs to be formally validated in relevant clinical settings with prospective studies involving large numbers of patients and careful, a priori definition of pretest risks. In particular, the risks and consequences of not treating smear-negative cases who are also NAA testnegative need to be further evaluated.…”

Evaluation of the BDProbeTec strand displacement amplification assay in comparison with the AMTD II direct test for rapid diagnosis of tuberculosis

“…Overall, the clinical performances of the BDProbeTec MTB and AMTD-II assays appeared to be similar in terms of both sensitivity (96.1% for both tests) and specificity (100% for the former and 97.1% for the latter). Positive and negative predictive values for AMTD-II were 92.6% and 98.5%, with corresponding values for BDProbe- [6,8,9,12,13,[16][17][18].…”

“…The amplification target is the internal region of IS6110, an insertion sequence that exists in multiple copies in the genome of the M. tuberculosis complex [14,15]. Both assays have elevated sensitivity (> 90%) and specificity (> 99%) [6,[8][9][10][16][17][18].…”

“…The BDProbeTec MTB and AMTD-II tests were performed as recommended by the manufacturers. Positive and negative amplification controls were included in each AMTD-II run [6,8,9,12,13,[16][17][18]. Preliminary assessment of both nucleic acid amplification-based assays indicated a lower detection limit of ‡ 20 M. tuberculosis ATCC 25177 cells ⁄ mL.…”