A Comparison of Multidrug-Resistant Tuberculosis Treatment Commencement Times in MDRTBPlus Line Probe Assay and Xpert® MTB/RIF-Based Algorithms in a Routine Operational Setting in Cape Town

Background: Xpert MTB/RIF was introduced as a screening test for all presumptive tuberculosis cases in primary health services in Cape Town, South Africa. Study Aim: To compare multidrug-resistant tuberculosis (MDR-TB) treatment commencement times in MDRTBPlus Line Probe Assay and Xpert MTB/RIF-based algorithms in a routine operational setting. Methods: The study was undertaken in 10 of 29 high tuberculosis burden primary health facilities, selected through stratified random sampling. An observational study was undertaken as facilities transitioned to the Xpert MTB/RIF-based algorithm. MDR-TB diagnostic data were collected from electronic laboratory records and treatment data from clinical records and registers. Kaplan Meier time-to-event analysis was used to compare treatment commencement time, laboratory turnaround time and action delay between algorithms. A facility-level paired analysis was done: the median time-to-event was estimated per facility in each algorithm and mean differences between algorithms compared using a paired t-test. Cox proportional hazards regression was used to assess the effect of patient-level variables on treatment commencement time. The difference between algorithms was compared using the hazard ratio. Results: The median treatment commencement time in the Xpert MTB/RIF-based algorithm was 17 days (95% CI 13 to 22 days), with a median laboratory turnaround time (to result available in the laboratory) of <1 day (95% CI<1 to 1 day). There was a decrease of 25 days (95% CI 17 to 32 days, p<0.001) in median MDR-TB treatment commencement time in the Xpert MTB/RIF-based algorithm. We found no significant effect on treatment commencement times for the patient-level variables assessed. Conclusion: MDR-TB treatment commencement time was significantly reduced in the Xpert MTB/RIF-based algorithm. Changes in the health system may have contributed. However, an unacceptable level of delay remains. Health system and patient factors contributing to delay need to be evaluated and addressed to optimise test benefits.