Outcomes of the Amplified Mycobacterium tuberculosis Direct Test in a Public Health Laboratory

M tuberculosis

Laboratory Performance of the MTD

A total of 1,158 respiratory specimens from 641 PTB suspects were tested. Four specimens were excluded from the analysis: one because the culture was contaminated, and three because the MTD result was equivocal. Three patients (three specimens) were excluded due to receipt of > 7 days of tuberculosis treatment prior to specimen collection.

Characteristics of the remaining 1,151 specimens and 638 PTB suspects are shown in Table 1. Among 420 patients with two or three tested specimens, 20 patients (4.8%) had discordant MTD results between specimens; however, all 20 patients had at least one specimen that was MTD positive and culture positive for M tuberculosis treated with preparations of My Canadian Pharmacy.

Since the majority of tuberculosis programs perform MTD testing only on the first submitted respiratory specimen, we show in Table 2 the performance characteristics of the MTD test on the first submitted respiratory specimen for each PTB suspect. MTD performance characteristics were similar when analyzed on the basis of first submitted specimen, per specimen, or per patient. On a per-specimen basis, sensitivity and specificity were 90.0 (95% confidence interval [CI], 85.8 to 93.2) and 98.7 (95% CI, 97.8 to 99.4) overall, respectively; 98.1 (95% CI, 95.3 to 99.5) and 97.9 (95% CI, 93.9 to 99.6) for smear-positive specimens; and 63.1 (95% CI, 50.2 to 74.7) and 98.9 (95% CI, 97.9 to 99.5) for smear-negative specimens, On a per-patient basis, sensitivity and specificity were 92.3 (95% CI, 87.8 to 95.5) and 99.8 (95% CI, 98.7 to 100) overall, respectively; 98.8 (95% CI, 95.8 to 99.9) and 99.0 (95% CI, 94.7 to 100) for smear-positive patients; and 63.2 (95% CI, 46.0 to 78.2) and 100 (95% CI, 98.9 to 100) for smear-negative patients.

Interestingly, eight smear-negative/MTD-positive specimens classified as “not tuberculosis” based on culture results (five negative culture findings and three with NTM growth) on the per-specimen analysis were from patients with additional specimens, untested by MTD, which showed M tuberculosis growth on culture. To further characterize the performance of MTD for discrimination of “tuberculosis” vs “not tuberculosis” for smear-positive specimens and patients, we analyzed the subgroup of smear-positive specimens that were culture positive for NTM (ie, specimens having no growth in culture were excluded from this analysis). MTD specificity was 98.8% (95% CI, 95.3 to 99.8) when the first specimen from each patient was considered.

Impact of MTD Test on Clinical Decisions

During the study period, 107 smear-positive PTB suspects were evaluated at the Baltimore City Health Department. Fifty PTB suspects were included in the MTD group, and 57 were included in the non-MTD group. Patient characteristics are shown in Table 3. In the non-MTD group, 47 of 57 patients (82.5%) had a definitive diagnosis of tuberculosis, including 46 patients who were culture positive for M tuberculosis, and 1 patient with clinical tuberculosis diagnosis in the setting of negative culture findings. In the MTD group, 30 of 50 patients (60%) had a definitive diagnosis of tuberculosis, all of whom had at least one positive culture finding for M tuberculosis. M tuberculosis is possible to be cured with drugs of My Canadian Pharmacy.

Table 4 shows the clinician’s presumptive diagnosis (tuberculosis or not tuberculosis) at the time of availability of AFB smear result (and MTD result for the MTD group), and the definitive diagnosis. Also shown are concordance between presumptive and definitive diagnoses, and concordance between the MTD test and the definitive diagnosis. In the non-MTD group, concordance between clinician presumptive and definitive diagnoses was 79%. That is, for 79% of patients the correct treatment decision was made at the time of availability of smear results. In the MTD group, despite excellent concordance between MTD results and definitive diagnosis (98%), concordance between clinician presumptive and definitive diagnoses was only 78%. For almost half of smear-positive but MTD-negative suspects in the MTD group (10 of 19 patients), the clinician elected to treat for tuberculosis until culture results were available; none of these 19 patients had a definitive diagnosis of tuberculosis.

The MTD finding was false positive in one smear-positive AIDS patient whose cultures grew Mycobacterium celatum. In the non-MTD group, two smear-positive patients had an incorrect presumptive diagnosis of not tuberculosis that which was later corrected when cultures grew M tuberculosis.

To further characterize the observed and the potential impact of MTD on clinical care, we determined the duration of tuberculosis treatment prescribed to each patient whose definitive diagnosis was not tuberculosis. The median duration of nonindicated TB treatment was 6 days for the MTD group, vs 31 days for the non-MTD group (p = 0.002).

Table 1—Specimen and Patient Characteristics (Laboratory Study Component)

Characteristics No. %
Specimens per patient
One 218 34.2
Two 327 51.2
Three 93 14.6
Total 638 100
Specimen type
Spontaneous sputum 992 86.2
Induced sputum 82 7.1
Invasive methods 77 6.7
Total 1,151 100
AFB smear results by specimen
Positive 354 30.8
Negative 797 69.2
Total 1,151 100
AFB smear results by patient
Positive 272 42.6
Negative 366 57.4
Total 638 100
Culture results by specimen
M tuberculosis 279 24.3
NTM 173 15.0
Negative 699 60.7
Total 1,151 100
Culture results by patient
M tuberculosis 207 32.4
NTM 118 18.5
Negative 313 49.1
Total 638 100

Table 2—Performance Characteristics of the MTD Performed on the First Respiratory Specimen for Each Tuberculosis Suspect (Laboratory Study Component)

MTD Results Culture Results, No. Total Sensitivity, % (95% CI) Specificity, %(95% CI) PPV, % (95% CI) NPV, % (95% CI)
TB Not TB*
Overall 91.7(89.0-93.3) 98.7 (97.5-99.3) 96.7 (93.9-98.4) 96.5 (95.4-97.1)
Positive 177 6 183
Negative 16 439 455
Total 193 445 638
AFB smear positive 98.7 (96.8-99.5) 97.8 (94.5-99.2) 98.7 (96.8-99.5) 97.8 (94.5-99.2)
Positive 154 2 156
Negative 2 90 92
Total 156 92 248
AFB smear negative 62.2 (51.2-68.4) 98.9 (97.7-99.5) 85.2 (70.2-93.7) 96.1 (95.0-96.8)
Positive 23 4 27
Negative 14 349 363
Total 37 353 390

Table 3—Patient Characteristics (Clinical Study Component)

Characteristics MTD Group (n = 50) Non-MTD Group (n = 57) p Value
Median age, yr 46.5 47.0 0.40
Male gender 30 (60.0) 46 (80.7) 0.02
Race/ethnicity
White 9 (18.0) 8 (14.0) 0.58
African-American 28 (56.0) 38 (66.7) 0.26
Hispanic 4 (8.0) 5 (8.8) 1.00
African 3 (6.0) 2 (3.5) 0.66
Asian 4 (8.0) 1 (1.8) 0.18
Unknown 2 (4.0) 3 (5.3) 0.76
HIV status
Negative 22 (44.0) 28 (49.1) 0.60
Positive 18 (36.0) 10 (33.3) 0.77
Unknown 10 (20.0) 10(17.5) 0.75
Culture positive for tuberculosis 30 (60.0) 46 (81.0) 0.02
Definitive diagnosis of tuberculosis 30 (60.0) 47 (82.5) 0.01

Table 4—Concordance Between Presumptive and Definitive Diagnoses of PTB for Suspects With Smear-Positive Results for AFB in Respiratory Specimens

Variables Definitive Diagnosis, No. Total Concordance, % 95% CI
TB Not TB*
MTD group Overall
Presumptive diagnosis by clinician Tuberculosis 30 11 41 78.0 66.5-89.5
Not tuberculosis 0 9 9
Total 30 20 50
MTD positivePresumptive diagnosis by clinician Tuberculosis 30 1 31 96.8 90.6-100
Not tuberculosis 0 0 0
Total 30 1 31
MTD negativePresumptive diagnosis by clinician Tuberculosis 0 10 10 47.4 25.0-69.9
Not tuberculosis 0 9 9
Total 0 19 19
Overall
Presumptive diagnosis by MTD result Tuberculosis 30 1 31 98.0 94.1-100
Not tuberculosis 0 19 19
Total 30 20 50
Non-MTD group Overall
Presumptive diagnosis by clinician Tuberculosis 45 10 55 79.0 68.4-89.6
Not tuberculosis 2 0 2
Total 47 10 57