Comparing Tuberculosis Diagnostic Yield in Smear/Culture and Xpert® MTB/RIF-Based Algorithms Using a Non-Randomised Stepped-Wedge Design

Abstract

Setting: Primary health services in Cape Town, South Africa.

Study aim: To compare tuberculosis (TB) diagnostic yield in an existing smear/culture-based and a newly introduced Xpert® MTB/RIF-based algorithm.

Methods: TB diagnostic yield (the proportion of presumptive TB cases with a laboratory diagnosis of TB) was assessed using a non-randomised stepped-wedge design as sites transitioned to the Xpert® based algorithm. We identified the full sequence of sputum tests recorded in the electronic laboratory database for presumptive TB cases from 60 primary health sites during seven one-month time-points, six months apart. Differences in TB yield and temporal trends were estimated using a binomial regression model.

Results: TB yield was 20.9% (95% CI 19.9% to 22.0%) in the smear/culture-based algorithm compared to 17.9% (95%CI 16.4% to 19.5%) in the Xpert® based algorithm. There was a decline in TB yield over time with a mean risk difference of -0.9% (95% CI -1.2% to -0.6%) (p<0.001) per time-point. When estimates were adjusted for the temporal trend, TB yield was 19.1% (95% CI 17.6% to 20.5%) in the smear/culture-based algorithm compared to 19.3% (95% CI 17.7% to 20.9%) in the Xpert® based algorithm with a risk difference of 0.3% (95% CI -1.8% to 2.3%) (p = 0.796). Culture tests were undertaken for 35.5% of smear-negative compared to 17.9% of Xpert® negative low MDR-TB risk cases and for 82.6% of smear-negative compared to 40.5% of Xpert® negative high MDR-TB risk cases in respective algorithms.

Conclusion: Introduction of an Xpert® based algorithm did not produce the expected increase in TB diagnostic yield. Studies are required to assess whether improving adherence to the Xpert® negative algorithm for HIV-infected individuals will increase yield. In light of the high cost of Xpert®, a review of its role as a screening test for all presumptive TB cases may be warranted.

Fig 1. Testing protocols in the smear/culture and Xpert^® based TB diagnostic algorithms in PHC facilities in Cape Town.

The diagram shows the simplified sequence of TB diagnostic tests recommended in each algorithm and the action taken based on test results. Low MDR-TB risk was defined as ≤four weeks previous TB treatment and high MDR-TB risk as >four weeks previous TB treatment, from congregate settings or with a known MDR-TB contact. Abbreviations: TB—tuberculosis, LPA—line probe assay, DST—drug susceptibility testing, HIV—human immunodeficiency virus, MTB—mycobacterium tuberculosis, PHC—primary health care.

Fig 2. A non-randomised stepped-wedge evaluation of TB yield in five PHC groups as they transitioned from the smear/culture to the Xpert^® based algorithms in Cape Town.

This figure shows the TB diagnostic algorithm in place in 5 groups of PHC sites over the seven time-points (T1 to T7) used in the analysis. All sites initially had a smear/culture-based algorithm in place. The Xpert-based algorithm was introduced in August 2011 in Group A, in October 2011 in Group B, in February 2012 in Group C, in October 2012 in Group D and in February 2013 in Group E. With the exception of one PHC site, the groups represent all the sites within a sub-district. Abbreviations: TB—tuberculosis, PHC—primary health care.

Fig 3. TB yield in the smear/culture and Xpert^® based algorithms at PHC sites in Cape Town by time-point.

The graph shows the proportion of presumptive cases identified with TB (and 95% confidence intervals) in the smear/culture and Xpert-based algorithms as PHC sites changed from the former to the latter over seven time points (T1 to T7). Estimates derived from the binomial regression analysis were adjusted for clustering of cases at PHC sites. Time points were as follows: T1 = November 2010, T2 = May 2011. T3 = November 2011, T4 = May 2012, T5 = November 2012, T6 = May 2013, T7 = November 2013. Abbreviations: TB—tuberculosis, PHC—primary health care, CI—confidence interval.