Xpert MTB/RIF Test for Diagnosing Childhood Pulmonary TB
We enrolled 255 (92.7%) of 275 eligible study participants and described data for 250 study participants. (See Figure 1) All the 250 study participants had sputum cultures (both LJ and MGIT) and Xpert MTB/RIF tests conducted. The median age was 36 months (IQR 16 – 74.5) and 41.6% were HIV positive. The study participant characteristics are as shown in Table 1.
(Enlarge Image)
Figure 1.
Study profile.
Fifteen children (6%, 95% CI 3.4- 9.7) had a positive sputum smear for acid fast bacilli. There were thirty five children (14%, 95% CI 9.9 – 18.9) with a positive sputum culture for MTB and thirty five children (14%, 95% CI 9.9 – 18.9) with a positive Xpert MTB/RIF test. Two (5.7% 95% CI 0.6 – 19.1) of the 35 children with a positive MTB/RIF test had rifampicin resistance detected. We documented a positive Xpert MTB/RIF test in 14 of the 15 (93.3%, 95% CI 68.1 - 99.8) positive smears. Twelve (34.3%) of the children with a positive sputum culture were HIV positive while thirteen children (37.1%) with a positive Xpert MTB/RIF test were HIV positive. There was no statistically significant difference in the positivity rate for the Xpert MTB/RIF results between HIV positive and negative children. We documented a positive Xpert MTB/RIF test in 9.5% (4 of 42), 9.9% (13 of 131), and 23.4% (18 of 77) of children aged < 1 year, 1 – 5 years, and > 5 years respectively. Three children (3/35, 8.6%) had MTB growth on LJ media and MOTT on MGIT media. Two of the three children had a positive Xpert MTB/RIF test.
Thirteen sputum cultures (5.2%, 95% CI 2.8 – 8.7%) were classified as contaminated while 2 Xpert MTB/RIF test results (0.8%, 95% CI 0.1 – 2.9) were indeterminate. While the median time to detection was 49.5 days (IQR 38.4–61.2) for LJ and 6 days (IQR 5 – 11.5) for MGIT culture, it was 2 hours for the Xpert MTB/RIF test.
Chest radiographs for 235 study participants were reviewed and classified as probable TB (80/235, 34% (95% CI 28–40.5)); possible TB (96/235, 40.9% (95% CI 34.5–47.4)), and TB unlikely (46/235, 19.6% (95% CI 14.7–25.2)). Thirteen of 235 (5.5%, 95% CI 3–9.3) radiograph reviews were inconclusive in that all the three reviewers did not agree. Fifteen chest radiographs were not reviewed as these children were lost to follow up before the radiographs were taken.
For diagnostic accuracy, we excluded data from 15 children (13 contaminated culture and 2 indeterminate MTB/RIF test results) and analysed 235 records. The Xpert MTB/RIF test identified MTB in 27 of the 34 culture confirmed cases demonstrating a sensitivity of 79.4% (95% CI 63.2 – 89.7) and 7 of 201 culture negative cases, a specificity of 96.5% (95% CI 93 – 98.3). More diagnostic parameters are shown in Table 2. Fourteen of the 34 culture positives were smear positive (41.2%, 95% CI 24.6 – 59.3). The Xpert MTB/RIF test identified twice as many cases as the smear microscopy (79.4% Vs 41.2%). The Xpert MTB/RIF test identified 13 of 14 smear positive-culture positive (93%, 95% CI 66–99.8) and 14 of 20 smear negative -culture positive cases (70%, 95% CI 46–88). Twenty one of 221 (9.5%, 95% CI 6 – 14.2) negative smears were Xpert MTB/RIF positive. The Xpert MTB/RIF test had a sensitivity of 93.3% (95% CI 70.2 – 98.8) and specificity of 94.8% (95% CI 85.9 – 98.2) among children aged 5 years and above. The sensitivity and specificity of the Xpert MTB/RIF test was 68.2% (95% CI 46 – 84.6) and 97.2% (95% CI 93 – 98.9) respectively among children aged 5 years and below. The clinical characteristics which were independently associated with a positive Xpert MTB/RIF test included age > 5 years, a positive history of TB contact, and a positive tuberculin test (Table 3).
Results
Descriptive Statistics
We enrolled 255 (92.7%) of 275 eligible study participants and described data for 250 study participants. (See Figure 1) All the 250 study participants had sputum cultures (both LJ and MGIT) and Xpert MTB/RIF tests conducted. The median age was 36 months (IQR 16 – 74.5) and 41.6% were HIV positive. The study participant characteristics are as shown in Table 1.
(Enlarge Image)
Figure 1.
Study profile.
Fifteen children (6%, 95% CI 3.4- 9.7) had a positive sputum smear for acid fast bacilli. There were thirty five children (14%, 95% CI 9.9 – 18.9) with a positive sputum culture for MTB and thirty five children (14%, 95% CI 9.9 – 18.9) with a positive Xpert MTB/RIF test. Two (5.7% 95% CI 0.6 – 19.1) of the 35 children with a positive MTB/RIF test had rifampicin resistance detected. We documented a positive Xpert MTB/RIF test in 14 of the 15 (93.3%, 95% CI 68.1 - 99.8) positive smears. Twelve (34.3%) of the children with a positive sputum culture were HIV positive while thirteen children (37.1%) with a positive Xpert MTB/RIF test were HIV positive. There was no statistically significant difference in the positivity rate for the Xpert MTB/RIF results between HIV positive and negative children. We documented a positive Xpert MTB/RIF test in 9.5% (4 of 42), 9.9% (13 of 131), and 23.4% (18 of 77) of children aged < 1 year, 1 – 5 years, and > 5 years respectively. Three children (3/35, 8.6%) had MTB growth on LJ media and MOTT on MGIT media. Two of the three children had a positive Xpert MTB/RIF test.
Thirteen sputum cultures (5.2%, 95% CI 2.8 – 8.7%) were classified as contaminated while 2 Xpert MTB/RIF test results (0.8%, 95% CI 0.1 – 2.9) were indeterminate. While the median time to detection was 49.5 days (IQR 38.4–61.2) for LJ and 6 days (IQR 5 – 11.5) for MGIT culture, it was 2 hours for the Xpert MTB/RIF test.
Chest radiographs for 235 study participants were reviewed and classified as probable TB (80/235, 34% (95% CI 28–40.5)); possible TB (96/235, 40.9% (95% CI 34.5–47.4)), and TB unlikely (46/235, 19.6% (95% CI 14.7–25.2)). Thirteen of 235 (5.5%, 95% CI 3–9.3) radiograph reviews were inconclusive in that all the three reviewers did not agree. Fifteen chest radiographs were not reviewed as these children were lost to follow up before the radiographs were taken.
Diagnostic Test Results
For diagnostic accuracy, we excluded data from 15 children (13 contaminated culture and 2 indeterminate MTB/RIF test results) and analysed 235 records. The Xpert MTB/RIF test identified MTB in 27 of the 34 culture confirmed cases demonstrating a sensitivity of 79.4% (95% CI 63.2 – 89.7) and 7 of 201 culture negative cases, a specificity of 96.5% (95% CI 93 – 98.3). More diagnostic parameters are shown in Table 2. Fourteen of the 34 culture positives were smear positive (41.2%, 95% CI 24.6 – 59.3). The Xpert MTB/RIF test identified twice as many cases as the smear microscopy (79.4% Vs 41.2%). The Xpert MTB/RIF test identified 13 of 14 smear positive-culture positive (93%, 95% CI 66–99.8) and 14 of 20 smear negative -culture positive cases (70%, 95% CI 46–88). Twenty one of 221 (9.5%, 95% CI 6 – 14.2) negative smears were Xpert MTB/RIF positive. The Xpert MTB/RIF test had a sensitivity of 93.3% (95% CI 70.2 – 98.8) and specificity of 94.8% (95% CI 85.9 – 98.2) among children aged 5 years and above. The sensitivity and specificity of the Xpert MTB/RIF test was 68.2% (95% CI 46 – 84.6) and 97.2% (95% CI 93 – 98.9) respectively among children aged 5 years and below. The clinical characteristics which were independently associated with a positive Xpert MTB/RIF test included age > 5 years, a positive history of TB contact, and a positive tuberculin test (Table 3).
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