Utility of interferon-gamma ELISPOT assay responses in highly tuberculosis-exposed patients with advanced HIV infection in South Africa

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dc.contributor.authorLawn, Stephenen_ZA
dc.contributor.authorBangani, Nonzwakazien_ZA
dc.contributor.authorVogt, Monicaen_ZA
dc.contributor.authorBekker, Linda-Gailen_ZA
dc.contributor.authorBadri, Motasimen_ZA
dc.contributor.authorNtobongwana, Marjorieen_ZA
dc.contributor.authorDockrell, Hazelen_ZA
dc.contributor.authorWilkinson, Roberten_ZA
dc.contributor.authorWood, Robinen_ZA
dc.date.accessioned2015-10-12T10:51:51Z
dc.date.available2015-10-12T10:51:51Z
dc.date.issued2007en_ZA
dc.description.abstractBACKGROUND:Interferon-gamma (IFN-gamma) ELISPOT assays incorporating Mycobacterium tuberculosis-specific antigens are useful in the diagnosis of tuberculosis (TB) or latent infection. However, their utility in patients with advanced HIV is unknown. We studied determinants of ELISPOT responses among patients with advanced HIV infection (but without active TB) living in a South African community with very high TB notification rates. METHODS: IFN-gamma responses to ESAT-6 and CFP-10 in overnight ELISPOT assays and in 7-day whole blood assays (WBA) were compared in HIV-infected patients (HIV+, n = 40) and healthy HIV-negative controls (HIV-, n = 30) without active TB. Tuberculin skin tests (TSTs) were also done. RESULTS: ELISPOTs, WBAs and TSTs were each positive in >70% of HIV- controls, reflecting very high community exposure to M. tuberculosis. Among HIV+ patients, quantitative WBA responses and TSTs (but not the proportion of positive ELISPOT responses) were significantly impaired in those with CD4 cell counts <100 cells/mul compared to those with higher counts. In contrast, ELISPOT responses (but not WBA or TST) were strongly related to history of TB treatment; a much lower proportion of HIV+ patients who had recently completed treatment for TB (n = 19) had positive responses compared to those who had not been treated (11% versus 62%, respectively; P < 0.001). Multivariate analysis confirmed that ELISPOT responses had a strong inverse association with a history of recent TB treatment (adjusted OR = 0.06, 95%CI = 0.10-0.40, P < 0.01) and that they were independent of CD4 cell count and viral load. Among HIV+ individuals who had not received TB treatment both the magnitude and proportion of positive ELISPOT responses (but not TST or WBA) were similar to those of HIV-negative controls. CONCLUSION: The proportion of positive ELISPOT responses in patients with advanced HIV infection was independent of CD4 cell count but had a strong inverse association with history of TB treatment. This concurs with the previously documented low TB risk among patients in this cohort with a history of recent treatment for TB. These data suggest ELISPOT assays may be useful for patient assessment and as an immuno-epidemiological research tool among patients with advanced HIV and warrant larger scale prospective evaluation.en_ZA
dc.identifier.apacitationLawn, S., Bangani, N., Vogt, M., Bekker, L., Badri, M., Ntobongwana, M., ... Wood, R. (2007). Utility of interferon-gamma ELISPOT assay responses in highly tuberculosis-exposed patients with advanced HIV infection in South Africa. <i>BMC Infectious Diseases</i>, http://hdl.handle.net/11427/14168en_ZA
dc.identifier.chicagocitationLawn, Stephen, Nonzwakazi Bangani, Monica Vogt, Linda-Gail Bekker, Motasim Badri, Marjorie Ntobongwana, Hazel Dockrell, Robert Wilkinson, and Robin Wood "Utility of interferon-gamma ELISPOT assay responses in highly tuberculosis-exposed patients with advanced HIV infection in South Africa." <i>BMC Infectious Diseases</i> (2007) http://hdl.handle.net/11427/14168en_ZA
dc.identifier.citationLawn, S. D., Bangani, N., Vogt, M., Bekker, L. G., Badri, M., Ntobongwana, M., ... & Wood, R. (2007). Utility of interferon-γ ELISPOT assay responses in highly tuberculosis-exposed patients with advanced HIV infection in South Africa. BMC infectious diseases, 7(1), 99.en_ZA
dc.identifier.ris TY - Journal Article AU - Lawn, Stephen AU - Bangani, Nonzwakazi AU - Vogt, Monica AU - Bekker, Linda-Gail AU - Badri, Motasim AU - Ntobongwana, Marjorie AU - Dockrell, Hazel AU - Wilkinson, Robert AU - Wood, Robin AB - BACKGROUND:Interferon-gamma (IFN-gamma) ELISPOT assays incorporating Mycobacterium tuberculosis-specific antigens are useful in the diagnosis of tuberculosis (TB) or latent infection. However, their utility in patients with advanced HIV is unknown. We studied determinants of ELISPOT responses among patients with advanced HIV infection (but without active TB) living in a South African community with very high TB notification rates. METHODS: IFN-gamma responses to ESAT-6 and CFP-10 in overnight ELISPOT assays and in 7-day whole blood assays (WBA) were compared in HIV-infected patients (HIV+, n = 40) and healthy HIV-negative controls (HIV-, n = 30) without active TB. Tuberculin skin tests (TSTs) were also done. RESULTS: ELISPOTs, WBAs and TSTs were each positive in >70% of HIV- controls, reflecting very high community exposure to M. tuberculosis. Among HIV+ patients, quantitative WBA responses and TSTs (but not the proportion of positive ELISPOT responses) were significantly impaired in those with CD4 cell counts <100 cells/mul compared to those with higher counts. In contrast, ELISPOT responses (but not WBA or TST) were strongly related to history of TB treatment; a much lower proportion of HIV+ patients who had recently completed treatment for TB (n = 19) had positive responses compared to those who had not been treated (11% versus 62%, respectively; P < 0.001). Multivariate analysis confirmed that ELISPOT responses had a strong inverse association with a history of recent TB treatment (adjusted OR = 0.06, 95%CI = 0.10-0.40, P < 0.01) and that they were independent of CD4 cell count and viral load. Among HIV+ individuals who had not received TB treatment both the magnitude and proportion of positive ELISPOT responses (but not TST or WBA) were similar to those of HIV-negative controls. CONCLUSION: The proportion of positive ELISPOT responses in patients with advanced HIV infection was independent of CD4 cell count but had a strong inverse association with history of TB treatment. This concurs with the previously documented low TB risk among patients in this cohort with a history of recent treatment for TB. These data suggest ELISPOT assays may be useful for patient assessment and as an immuno-epidemiological research tool among patients with advanced HIV and warrant larger scale prospective evaluation. DA - 2007 DB - OpenUCT DO - 10.1186/1471-2334-7-99 DP - University of Cape Town J1 - BMC Infectious Diseases LK - https://open.uct.ac.za PB - University of Cape Town PY - 2007 T1 - Utility of interferon-gamma ELISPOT assay responses in highly tuberculosis-exposed patients with advanced HIV infection in South Africa TI - Utility of interferon-gamma ELISPOT assay responses in highly tuberculosis-exposed patients with advanced HIV infection in South Africa UR - http://hdl.handle.net/11427/14168 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/14168
dc.identifier.urihttp://dx.doi.org/10.1186/1471-2334-7-99
dc.identifier.vancouvercitationLawn S, Bangani N, Vogt M, Bekker L, Badri M, Ntobongwana M, et al. Utility of interferon-gamma ELISPOT assay responses in highly tuberculosis-exposed patients with advanced HIV infection in South Africa. BMC Infectious Diseases. 2007; http://hdl.handle.net/11427/14168.en_ZA
dc.language.isoengen_ZA
dc.publisherBiomed Central Ltden_ZA
dc.publisher.departmentDesmond Tutu HIV Centreen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an Open Access article distributed under the terms of the Creative Commons Attribution Licenseen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/2.0en_ZA
dc.sourceBMC Infectious Diseasesen_ZA
dc.source.urihttp://www.biomedcentral.com/bmcinfectdis/en_ZA
dc.subject.otherTuberculosisen_ZA
dc.subject.otherHIVen_ZA
dc.subject.otherDiagnosisen_ZA
dc.subject.otherScreeningen_ZA
dc.titleUtility of interferon-gamma ELISPOT assay responses in highly tuberculosis-exposed patients with advanced HIV infection in South Africaen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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