TY - JOUR
T1 - Xpert MTB/RIF as a measure of sputum bacillary burden
T2 - Variation by HIV status and immunosuppression
AU - Hanrahan, Colleen F.
AU - Theron, Grant
AU - Bassett, Jean
AU - Dheda, Keertan
AU - Scott, Lesley
AU - Stevens, Wendy
AU - Sanne, Ian
AU - Van Rie, Annelies
N1 - Copyright:
Copyright 2014 Elsevier B.V., All rights reserved.
PY - 2014/6/1
Y1 - 2014/6/1
N2 - Rationale: Xpert MTB/RIF cycle threshold values are a measure of sputum mycobacterial burden. Data on the impact of HIV infection and immunosuppression on this measure are limited. Objectives: Examine the impact of HIV status and level of immunosuppression on the distribution of mean cycle threshold values, and the correlation of cycle threshold values and smear microscopy grade with time to culture positivity. Methods: Paired sputum samples from 2,406 individuals with suspected pulmonary tuberculosis in South Africa were tested by Xpert MTB/RIF, concentrated smear microscopy, and liquid culture to quantify bacterial burden using cycle threshold values, smear grading, and time to culture positivity. Measurements and Main Results: Cycle threshold values were lower in HIV-uninfected versus HIV-infected individuals (22.9 vs. 26.6; P < 0.001). Among HIV-infected, CD4 count was an independent predictor of cycle threshold value, with an average increase of 1.50 cycles for CD4 count greater than or equal to 200 (P 0.071) and 3.66 cycles for CD4 count less than 200 (P < 0.001) compared with HIV-uninfected individuals. Correlation between cycle threshold value and time to culture positivity was similar to that between smear status and time to culture positivity (both Spearman ρ 0.58). The strength of correlation between measures decreased as the level of immunosuppression increased. A cycle threshold value cutoff of 28 had good predictive value for smear positivity. Conclusions: We observed decreasing bacillary burden with increasing level of immunosuppression as measured by Xpert MTB/RIF cycle threshold values. A cycle threshold value of 28 can be used as a measure of bacterial burden and smear status in a high HIV burden setting.
AB - Rationale: Xpert MTB/RIF cycle threshold values are a measure of sputum mycobacterial burden. Data on the impact of HIV infection and immunosuppression on this measure are limited. Objectives: Examine the impact of HIV status and level of immunosuppression on the distribution of mean cycle threshold values, and the correlation of cycle threshold values and smear microscopy grade with time to culture positivity. Methods: Paired sputum samples from 2,406 individuals with suspected pulmonary tuberculosis in South Africa were tested by Xpert MTB/RIF, concentrated smear microscopy, and liquid culture to quantify bacterial burden using cycle threshold values, smear grading, and time to culture positivity. Measurements and Main Results: Cycle threshold values were lower in HIV-uninfected versus HIV-infected individuals (22.9 vs. 26.6; P < 0.001). Among HIV-infected, CD4 count was an independent predictor of cycle threshold value, with an average increase of 1.50 cycles for CD4 count greater than or equal to 200 (P 0.071) and 3.66 cycles for CD4 count less than 200 (P < 0.001) compared with HIV-uninfected individuals. Correlation between cycle threshold value and time to culture positivity was similar to that between smear status and time to culture positivity (both Spearman ρ 0.58). The strength of correlation between measures decreased as the level of immunosuppression increased. A cycle threshold value cutoff of 28 had good predictive value for smear positivity. Conclusions: We observed decreasing bacillary burden with increasing level of immunosuppression as measured by Xpert MTB/RIF cycle threshold values. A cycle threshold value of 28 can be used as a measure of bacterial burden and smear status in a high HIV burden setting.
KW - Diagnostics
KW - South Africa
KW - Tuberculosis
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U2 - 10.1164/rccm.201312-2140OC
DO - 10.1164/rccm.201312-2140OC
M3 - Article
C2 - 24786895
AN - SCOPUS:84901811250
VL - 189
SP - 1426
EP - 1434
JO - American Journal of Respiratory and Critical Care Medicine
JF - American Journal of Respiratory and Critical Care Medicine
SN - 1073-449X
IS - 11
ER -