Correlation of Xpert MTB/RIF with measures to assess Mycobacterium tuberculosis bacillary burden in high HIV burden areas of Southern Africa

Abstract

Traditionally, smear microscopy has been used as a point-of-care measure of bacillary burden in tuberculosis patients to inform infection control and contact tracing. Xpert MTB/RIF has the potential to replace smear. However, data to support the use of its quantitative output [cycle threshold (C_T)] as an alternate point-of-care measure of bacillary burden are limited. This study assessed the correlation (Spearman's) between C_T, smear, culture time-to-positivity (TTP), and clinical factors in patients with Xpert-positive sputum from Mozambique (n = 238) and South Africa (n = 462). Mean CT and smear grade correlated well (ρ0.72); compared to TTP and smear (ρ0.61); and mean C_T and TTP (ρ0.50). In multivariate analyses, lower C_T (higher bacillary load) was associated with negative HIV serostatus and low BMI. A smear positivity rule-out (95% sensitivity) C_T cut-off of 28.0 was identified, with 54.1% specificity, 2.07 positive likelihood ratio, 0.09 negative likelihood ratio and 79.0% correctly classified. Cut-offs were higher for HIV positive compared to HIV negative individuals for any set sensitivity level. This study suggests Xpert C_T values correlate well with smear, both in HIV positive and negative individuals, and that C_T cut-offs might be broadly applicable to multiple settings. Studies to directly assess the association of C_T with infectiousness are needed.

Figure 1

(A) Boxplot of mean cycle threshold (C_T) – (average of positive Xpert MTB/RIF probes) according to smear grade and (B) Correlation between mean cycle threshold (C_T) and time to culture positivity (TTP) in days.

Figure 2

ROC curve analysis showing sensitivity for differing mean cycle threshold (C_T) – (average of positive Xpert MTB/RIF probes) values as a test for smear positivity.