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

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 (CT)] as an alternate point-of-care measure of bacillary burden are limited. This study assessed the correlation (Spearman's) between CT, 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 CT and TTP (ρ0.50). In multivariate analyses, lower CT (higher bacillary load) was associated with negative HIV serostatus and low BMI. A smear positivity rule-out (95% sensitivity) CT 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 CT values correlate well with smear, both in HIV positive and negative individuals, and that CT cut-offs might be broadly applicable to multiple settings. Studies to directly assess the association of CT with infectiousness are needed.