Theron G., Peter J., Calligaro G., Meldau R., Hanrahan C., Khalfey H., Matinyenya B., Muchinga T., Smith L., Pandie S., Lenders L., Patel V., Mayosi B.M., Dheda K.
Lung Infection and Immunity Unit, Department of Medicine, University of Cape Town, Cape Town, South Africa; Johns Hopkins Bloomberg School of Public Health, Department of Epidemiology, Baltimore, MD, United States; Department of Medicine, Groote Schuur Hospital, University of Cape Town, South Africa; Department of Neurology, University of KwaZulu Natal, South Africa; Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa
Theron, G., Lung Infection and Immunity Unit, Department of Medicine, University of Cape Town, Cape Town, South Africa; Peter, J., Lung Infection and Immunity Unit, Department of Medicine, University of Cape Town, Cape Town, South Africa; Calligaro, G., Lung Infection and Immunity Unit, Department of Medicine, University of Cape Town, Cape Town, South Africa; Meldau, R., Lung Infection and Immunity Unit, Department of Medicine, University of Cape Town, Cape Town, South Africa; Hanrahan, C., Johns Hopkins Bloomberg School of Public Health, Department of Epidemiology, Baltimore, MD, United States; Khalfey, H., Lung Infection and Immunity Unit, Department of Medicine, University of Cape Town, Cape Town, South Africa; Matinyenya, B., Lung Infection and Immunity Unit, Department of Medicine, University of Cape Town, Cape Town, South Africa; Muchinga, T., Lung Infection and Immunity Unit, Department of Medicine, University of Cape Town, Cape Town, South Africa; Smith, L., Lung Infection and Immunity Unit, Department of Medicine, University of Cape Town, Cape Town, South Africa; Pandie, S., Department of Medicine, Groote Schuur Hospital, University of Cape Town, South Africa; Lenders, L., Lung Infection and Immunity Unit, Department of Medicine, University of Cape Town, Cape Town, South Africa; Patel, V., Department of Neurology, University of KwaZulu Natal, South Africa; Mayosi, B.M., Department of Medicine, Groote Schuur Hospital, University of Cape Town, South Africa; Dheda, K., Lung Infection and Immunity Unit, Department of Medicine, University of Cape Town, Cape Town, South Africa, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa
The determinants of Xpert MTB/RIF sensitivity, a widely used PCR test for the diagnosis of tuberculosis (TB) are poorly understood. We compared culture time-to-positivity (TTP; a surrogate of bacterial load), MTB/RIF TB-specific and internal positive control (IPC)-specific C T values, and clinical characteristics in patients with suspected TB who provided expectorated (n = 438) or induced sputum (n = 128), tracheal aspirates (n = 71), bronchoalveolar lavage fluid (n = 152), pleural fluid (n = 76), cerebral spinal fluid (CSF; n = 152), pericardial fluid (n = 131), or urine (n = 173) specimens. Median bacterial load (TTP in days) was the strongest associate of MTB/RIF positivity in each fluid. TTP correlated with C T values in pulmonary specimens but not extrapulmonary specimens (Spearman's coefficient 0.5043 versus 0.1437; p = 0.030). Inhibition affected a greater proportion of pulmonary specimens than extrapulmonary specimens (IPC C T > 34: 6% (47/731) versus 1% (4/381; p < 0.0001). Pulmonary specimens had greater load than extrapulmonary specimens [TTPs (interquartile range) of 11 (7-16) versus 22 (18-33.5) days; p < 0.0001]. HIV-infection was associated with a decreased likelihood of MTB/RIF-positivity in pulmonary specimens but an increased likelihood in extrapulmonary specimens. Mycobacterial load, which displays significant variation across different body compartments, is the main determinant of MTB/RIF-positivity rather than PCR inhibition. MTB/RIF C T is a poor surrogate of load in extrapulmonary specimens.