The impact of expanded testing for multidrug resistant tuberculosis using genotype [correction of geontype] MTBDRplus in South Africa: an observational cohort study

Abstract

Introduction: Globally, multidrug resistant tuberculosis (MDR-TB) remains underdiagnosed. The Genotype MTBDRplus®, a rapid drug susceptibility testing (DST) assay used to detect resistance to isoniazid and rifampicin in the diagnosis of MDR-TB, has good diagnostic accuracy, but its impact on patient outcomes in routine practice is unproven. We assessed the clinical impact of routine DST using MTBDRplus in a single health district in South Africa.

Methods: Data were collected on all adult pulmonary TB patients registered at 25 public health clinics in the periods before and after introduction of an expanded DST algorithm using MTBDRplus version 1.0.

Results: We collected data on 1176 TB patients before implementation and 1177 patients afterwards. In the before period, measured MDR-TB prevalence among new cases was 0.7% (95% CI1.4-3.1%), and among retreatment cases 6.2% (95% CI:3.5-8.8%), versus 3.7% (95% CI:2.4-5.0, p<0.01) and 6.6% (95% CI:3.8-9.4%, p = 0.83) respectively after MTBDRplus introduction. The median times from sputum collection to MDR treatment in the before and after periods were 78 days (IQR:52-93) and 62 days (IQR:32-86, p = 0.05), respectively. Among MDR-TB cases, 27% (95%CI:10-44) in the before period converted sputum cultures to negative by 8 months following treatment initiation, while 52% (95%CI:38-66) converted in the intervention period (p = 0.04).

Conclusions: The expanded use of MTBDRplus DST resulted in a substantial increase in the proportion of new cases identified as MDR-TB; though time to MDR treatment was reduced, it was still over two months. Culture conversion for MDR-TB patients improved after introduction of MTBDRplus. This work illustrates the mixture of successes and challenges resulting from increased access to rapid DST in a setting with a high TB burden.

Figure 1. DST algorithm by study period.

An illustration of the DST algorithm in the Before LPA period (A) and the After LPA period (B). Abbreviations: DST, drug susceptibility testing; LPA, line probe assay; TB, tuberculosis; MDR-TB, multidrug resistant tuberculosis.

Figure 2. DST by patient category and study period.

A breakdown of whether DST was performed or not, by study period (Before and After LPA) and patient category (New versus Retreatment). Abbreviations: LPA, MTBDRplus line probe assay; DST, drug susceptibility testing.

Figure 3. Time to treatment and drug susceptibility test turnaround times by study period.

An illustration of critical events in the time to MDR treatment and DST turnaround. Abbreviations: DST, drug susceptibility testing; LPA, MTBDRplus line probe assay; MDR, multi-drug resistant tuberculosis; IQR, inter-quartile range.

Figure 4. Time to MDR treatment among MDR-TB patients, by study period.

Kaplan-Meir curves for time from initial sputum collection to MDR treatment by study period, including a modeled Before LPA period where the number of MDR-TB cases during the Before LPA period was augmented to match that observed during the After LPA period. Abbreviations: LPA, MTBDRplus line probe assay; MDR, multidrug resistant tuberculosis.

Figure 5. All-cause mortality by 8 months following initial registration among all MDR patients, by study period.

Kaplan-Meir curves for time from initial TB case registration to death by all causes among all MDR patients, by study period. Abbreviation: LPA, MTBDRplus line probe assay.