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Published ahead of print on December 7, 2006, doi:10.1164/rccm.200610-1439OC

Am. J. Respir. Crit. Care Med., Volume 175, Number 5, March 2007, 514-520

A more recent version of this article appeared on March 1, 2007
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Submitted on October 9, 2006
Accepted on December 7, 2006

The Effect of HIV-1 Infection on T cell Based and Skin Test Detection of Tuberculosis Infection

Molebogeng Xheeda Rangaka1, Katalin A Wilkinson1, Ronnett Seldon2, Gilles Van Cutsem3, Graeme Ayton Meintjes2, Chelsea Morroni4, Priscilla Mouton2, Lavanya Diwakar2, Tom G Connell2, Gary Maartens5, and Robert J Wilkinson6*

1 Institute of Infectious Diseases and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa; Wright Fleming Institute, Wellcome Trust Center for Research in Clinical Tropical Medicine and Department of Infectious Diseases Epidemiology, Imperial College London, London, United Kingdom, 2 Institute of Infectious Diseases and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa, 3 Khayelitsha site B, Medicins Sans Frontieres, South Africa, 4 School of Public Health, University of Cape Town, Cape Town, South Africa, 5 Institute of Infectious Diseases and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa; Division of Pharmacology, University of Cape Town, Cape Town, South Africa, 6 Institute of Infectious Diseases and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa; Wright Fleming Institute, Wellcome Trust Center for Research in Clinical Tropical Medicine and Department of Infectious Diseases Epidemiology, Imperial College London, London, United Kingdom; Department of Medicine, University of Cape Town, Cape Town, South Africa

* To whom correspondence should be addressed. E-mail: r.j.wilkinson{at}imperial.ac.uk.

Rationale Two forms of the Interferon-gamma release assay (IFNGRA) to detect tuberculosis infection are available but neither has been evaluated in comparable HIV infected and uninfected persons in a high tuberculosis incidence environment. Objective To compare the ability of the T-Spot.TB, QuantiFERON®TB Gold and the Mantoux test to identify latent tuberculosis in HIV infected and uninfected persons Methods A cross-sectional study of 160 healthy adults without active tuberculosis attending a voluntary counselling and testing centre for HIV infection in Khayelitsha: a deprived urban South African community with HIV antenatal seroprevalence of 33% and a tuberculosis incidence of 1612/100,000. Measurements and main results One hundred and sixty (74 HIV+ and 86 HIV-) persons were enrolled. A lower proportion of Mantoux results were positive in HIV infected compared to HIV uninfected (p<0.01). By contrast, the proportion of IFNGRA positive was not significantly different in HIV infected persons for the T-Spot.TB (52% versus 59%, p=0.41) or the QuantiFERON®TB Gold (43% and 46%, p=0.89). Fair agreement between the Mantoux (5/10mm cut-offs) and IFNGRA was seen in HIV infected people ({kappa}=0.52-0.6). By contrast poor agreement between the Mantoux and QuantiFERON®TB Gold was observed in the HIV uninfected group ({kappa}=0.07-0.30, depending upon Mantoux cut-off). The pattern was similar for T-Spot.TB ({kappa}=0.18-0.24). Interpretation IFNGRA sensitivity appears relatively unimpaired by moderately advanced HIV infection. However agreement between the tests and with the Mantoux varied from poor to fair. This highlights the need for prospective studies to determine which test may predict the subsequent risk of tuberculosis.


Key words: Diagnostic techniques and procedures, Antigens, Interferons, ESAT-6 protein, CFP-10 protein




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