Microscopic observation drug susceptibility assay (MODS) for early diagnosis of tuberculosis in children

Abstract

MODS is a novel liquid culture based technique that has been shown to be effective and rapid for early diagnosis of tuberculosis (TB). We evaluated the MODS assay for diagnosis of TB in children in Viet Nam. 217 consecutive samples including sputum (n = 132), gastric fluid (n = 50), CSF (n = 32) and pleural fluid (n = 3) collected from 96 children with suspected TB, were tested by smear, MODS and MGIT. When test results were aggregated by patient, the sensitivity and specificity of smear, MGIT and MODS against "clinical diagnosis" (confirmed and probable groups) as the gold standard were 28.2% and 100%, 42.3% and 100%, 39.7% and 94.4%, respectively. The sensitivity of MGIT and MODS was not significantly different in this analysis (P = 0.5), but MGIT was more sensitive than MODS when analysed on the sample level using a marginal model (P = 0.03). The median time to detection of MODS and MGIT were 8 days and 13 days, respectively, and the time to detection was significantly shorter for MODS in samples where both tests were positive (P<0.001). An analysis of time-dependent sensitivity showed that the detection rates were significantly higher for MODS than for MGIT by day 7 or day 14 (P<0.001 and P = 0.04), respectively. MODS is a rapid and sensitive alternative method for the isolation of M.tuberculosis from children.

Figure 1. Patient recruitment and assignment of patients to ‘confirmed’, ‘probable’, or ‘TB unlikely’ groups.

Figure 2. MODS positive in relation to Smear and MGIT, by patient.

* This patient was deemed a false positive due to H37Rv (the positive control strain) identification by spoligotyping.

Figure 3. Detection rates of Smear, MGIT and MODS in relation to TB treatment.

P values for comparison of detection rates between MODS and MGIT. * TAT: Turn around time.

Figure 4. Time-dependent sensitivity of smear, MODS and MGIT.

In the 73 samples which were both MGIT and MODS positive, the time dependent sensitivities of MODS were higher than MGIT on both day 7 (P<0.001) and day 14 (P = 0.04).

Figure 5. Time to MGIT positive and MODS positive in relation to smear grade.

Filled dots are samples positive by either MGIT or MODS, lines are scatter plot smoothers. Both MGIT and MODS had a negative Spearman rank correlation with smear grade (P<0.001).

Figure 6. Position of contamination observed in MODS Plates.

C. Positive control (H₃₇Rv), S. Sample, F. Contaminated with fungi, Rv. Contaminated with H37Rv, Rv(4). Four experiments contaminated with H37Rv at this position.