Author:
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Beynon, Fenella; Theron, Grant; Respeito, Durval; Mambuque, Edson; Saavedra, Belén; Bulo, Helder; Sanz, Sergi; Dheda, Keertan; García-Basteiro, Alberto L.
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Abstract:
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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 (rho0.72); compared to TTP and smear (rho0.61); and mean CT
and TTP (rho0.50). 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. |