Frequent suboptimal thermocycler ramp rate usage negatively impacts MTBDR sl performance for second-line drug resistant tuberculosis diagnosis

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Abstract
Strengthening the detection of second-line drug-resistance is a key tuberculosis (TB) control priority. The performance of MTBDR plus , a multidrug-resistant (MDR)-TB assay is reduced when suboptimal ramp rates are used. We investigated ramp rate’s effect on MTBDR sl ; the most widely-used molecular second-line drug-resistant TB assay. We tested 52 smear-negative Xpert MTB/RIF Ultra-positive sputa and a Mycobacterium tuberculosis ( Mtb ) dilution series at manufacturer-recommended (2.2°C/s) or most common suboptimal ramp rate (4.0°C/s; identified via an earlier survey). Mtb- complex DNA (TUB-band)-positivity, indeterminate rates, fluoroquinolone- and second-line injectable-resistance accuracy, banding differences and, separately, inter-reader variability were assessed. 39% of re-surveyed laboratories (5/13) did not use the manufacturer-recommended MTBDR sl ramp rate. On sputum, this ramp rate improved indeterminates vs. 4.0°C/s (0/52 vs. 7/51; p=0.006), false drug-resistance calls (0/104 vs. 6/102; p=0.013), and incorrect banding calls (0/1300 vs. 55/1275; psl performance. Ramp rate correction will improve second-line drug-resistant TB diagnoses. Laboratories must ensure the optimal manufacturer-recommended ramp rate is used.
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