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

Abstract

BackgroundXpert MTB/RIF was introduced as a screening test for all presumptive tuberculosis cases in primary health services in Cape Town, South Africa.Study AimTo 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.MethodsThe 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.ResultsThe 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.ConclusionMDR-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.

MTBDR plus and MTBDR sl Assays: Absence of Wild-Type Probe Hybridization and Implications for Detection of Drug-Resistant Tuberculosis

“…Molecular-based tests, however, can produce results in Ͻ1 day (5,(8)(9)(10)(11)(12). The WHO has endorsed line probe hybridization and molecular beacon assays for the detection of drug resistance in highincidence settings (13).…”

Xpert MTB/RIF assay for the diagnosis of pulmonary tuberculosis in children: A systematic review and meta-analysis

“…Studies of adults have reported shortcomings and delays in health systems and diagnostic pathways that affect the impact of Xpert on timely treatment initiation and patient outcomes. [32][33][34] Costs for health systems, as well as for patients, have to be taken into account during consideration of the use of a new diagnostic, but no data were provided in the studies included. Additional data are needed to improve use of Xpert (panel).…”

MDR-TB screening in a setting with molecular diagnostic techniques: Who got tested, who didn’t and why?

“…Among the MDR-TB patients started on treatment, the median time to initiation of treatment was high, at 79 days (n = 5). In the Delhi, India, study 10 (a setting with LPA), the median time to initiate treatment was 37 days, and in South Africa, 14 a setting where Xpert ® MTB/RIF (Cepheid, Sunnyvale, CA, USA) is available, it was 17 days. The delay in our study is unacceptable, and steps are urgently needed to ensure the early initiation of treatment and break the chain of transmission.…”

“…tive models for tracking, including the use of mobile phone reminders 14 and electronic patient registers. 15 2 Health system strengthening: this would include training and re-sensitising the staff of the general health care delivery system, especially DMC laboratory technicians, and developing a mechanism for sputum transport from the DMC to the IRL.…”