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Abstract
Blood based methods of identifying tuberculosis infections in high HIV/TB incidence areas
M. Rangaka1, K. Wilkinson1, M. Shey2, R. Seldon1, P. Mouton2, G. van Cutsem3, E. Goemare3, G. Meintjes4, G. Maartens5, R. Wilkinson6, Mycobacterial Immunology Group
1Institute of Infectious Diseases and Molecular Medicine, Mycobacterial Immunology Group, Cape Town, South Africa, 2Institute of Infectious Diseases and Molecular Medicine, Mycobacterial Immunology Unit, Cape Town, South Africa, 3Medecins Sans Frontieres-Cape Town, Ubuntu Clinic, Site B, Cape Town, South Africa, 4GF Jooste Hospital, Department of Infectious Disease Medicine, Cape Town, South Africa, 5Groote Schuur Hospital, Department of Pharmacology, Cape Town, South Africa, 6Wellcome Trust/Institute of Infectious Diseases and Molecular Medicine, Mycobacterial Immunology Unit, Cape Town, South Africa
Background: TB infection in the HIV-infected presents unique diagnostic challenges.The aim of this study was to determine in vitro reactivity to Mycobacterium tuberculosis antigens in healthy people with and without HIV infection as well as to compare in vitro reactivity with PPD TST (mantoux).
Methods: In a cross-sectional design, 80 people, similar numbers being HIV-infected and uninfected, were recruited for a study that has 80% power to detect a 25% difference (or > 99% power to detect a 40% difference) in RD1 positivity at 5% significance level. The study was conducted at Ubuntu Clinic in Khayelitsha, Cape Town. VCT was the entry point for recruitment. Active TB was exclusory. Skin testing and phlebotomoy for laboratory assays were done on the first visit. Skin reactions were measured 48-72hours later. Diluted whole blood was cultured for 72 hours in the presence of various antigens of M. tb. The Interferon-gamma content of supernatants was determined by ELISA. HIV-infected participants with reactions >5mm were offered isoniazid.
Results:
 [Percentage with positive responses by TST]
 [Median IFN-gamma responses]
Conclusions: Compared to HIV uninfected, the recall response to PPD in HIV-infected people is impaired. By contrast, the responses to antigens secreted by dividing M. tuberculosis are well preserved. This has implications for immunodiagnosis: There is a role for RD1 assays in the HIV context and these tests may identify more people for TB prophylaxis. HIV may not quite be the Achilles’ heel of T cell based assays!
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