Reversion and conversion of Mycobacterium tuberculosis IFN-gamma ELISpot results during anti-tuberculous treatment in HIV-infected children

dc.contributor.authorConnell, Tomen_ZA
dc.contributor.authorDavies, Mary-Annen_ZA
dc.contributor.authorJohannisen, Christineen_ZA
dc.contributor.authorWood, Kathrynen_ZA
dc.contributor.authorPienaar, Sandyen_ZA
dc.contributor.authorWilkinson, Katalinen_ZA
dc.contributor.authorWilkinson, Roberten_ZA
dc.contributor.authorZar, Heatheren_ZA
dc.contributor.authorBeatty, Daviden_ZA
dc.contributor.authorNicol, Marken_ZA
dc.contributor.authorCurtis, Nigelen_ZA
dc.contributor.authorEley, Brianen_ZA
dc.date.accessioned2015-11-11T11:57:16Z
dc.date.available2015-11-11T11:57:16Z
dc.date.issued2010en_ZA
dc.description.abstractBACKGROUND: Recent interest has focused on the potential use of serial interferon gamma (IFN-gamma) release assay (IGRA) measurements to assess the response to anti-tuberculous (TB) treatment. The kinetics of IFN-gamma responses to Mycobacterium tuberculosis (MTB) antigens in HIV-infected children during treatment have not however been previously investigated. METHODS: IFN-gamma responses to the MTB antigens, ESAT-6, CFP-10 and PPD were measured by an enzyme-linked immunospot assay (IFN-gamma ELISpot) at presentation and at one, two and six months after starting anti-tuberculous treatment in HIV-infected children with definite or probable TB. Responses at different time points were compared using a Mann-Whitney U test with paired data analysed using the Wilcoxon signed rank test. A Fisher's exact or Chi-squared test was used to compare proportions when test results were analysed as dichotomous outcomes. RESULTS: Of 102 children with suspected TB, 22 (21%) had definite TB and 24 (23%) probable TB. At least one follow up IFN-gamma ELISpot assay result was available for 31 (67%) of the 46 children. In children with definite or probable TB in whom the IFN-gamma ELISpot assay result was positive at presentation, anti-tuberculous treatment was accompanied by a significant decrease in both the magnitude of the IFN-gamma response to individual or combined MTB-specific antigens (ESAT-6 median 110 SFCs/106 PBMC (IQR 65-305) at presentation vs. 15 (10-115) at six months, p = 0.04; CFP-10 177 (48-508) vs. 20 (5-165), p = 0.004, ESAT-6 or CFP-10 median 250 SFCs/106 PBMC (IQR 94-508) vs. 25 (10-165), p = 0.004) and in the proportion of children with a positive IFN-gamma ELISpot assay (Fisher's exact test: ESAT-6 15/0 vs 5/11, p = 0.0002, CFP-10 22/0 vs 8/17, p = 0.0001, ESAT-6 or CFP-10 22/0 vs. 9/17, p= 0.002). However almost half of the children had a positive IFN-gamma ELISpot assay after six months of anti-tuberculous treatment. In addition, there was conversion of the IFN-gamma ELISpot assay result during anti-tuberculous therapy in six of 12 children in whom the initial IFN-gamma ELISpot assay was negative. CONCLUSIONS: In HIV-infected children with definite or probable TB, anti-tuberculosis treatment is accompanied by a reduction in the magnitude of the IFN-gamma ELISpot response to MTB-antigens. However, serial IFN-gamma ELISpot measurements appear to have limited clinical utility in assessing a successful response to anti-tuberculous treatment in HIV infected children.en_ZA
dc.identifier.apacitationConnell, T., Davies, M., Johannisen, C., Wood, K., Pienaar, S., Wilkinson, K., ... Eley, B. (2010). Reversion and conversion of Mycobacterium tuberculosis IFN-gamma ELISpot results during anti-tuberculous treatment in HIV-infected children. <i>BMC Infectious Diseases</i>, http://hdl.handle.net/11427/14868en_ZA
dc.identifier.chicagocitationConnell, Tom, Mary-Ann Davies, Christine Johannisen, Kathryn Wood, Sandy Pienaar, Katalin Wilkinson, Robert Wilkinson, et al "Reversion and conversion of Mycobacterium tuberculosis IFN-gamma ELISpot results during anti-tuberculous treatment in HIV-infected children." <i>BMC Infectious Diseases</i> (2010) http://hdl.handle.net/11427/14868en_ZA
dc.identifier.citationConnell, T. G., Davies, M. A., Johannisen, C., Wood, K., Pienaar, S., Wilkinson, K. A., ... & Eley, B. (2010). Reversion and conversion of Mycobacterium tuberculosis IFN-γ ELISpot results during anti-tuberculous treatment in HIV-infected children. BMC infectious diseases, 10(1), 138.en_ZA
dc.identifier.ris TY - Journal Article AU - Connell, Tom AU - Davies, Mary-Ann AU - Johannisen, Christine AU - Wood, Kathryn AU - Pienaar, Sandy AU - Wilkinson, Katalin AU - Wilkinson, Robert AU - Zar, Heather AU - Beatty, David AU - Nicol, Mark AU - Curtis, Nigel AU - Eley, Brian AB - BACKGROUND: Recent interest has focused on the potential use of serial interferon gamma (IFN-gamma) release assay (IGRA) measurements to assess the response to anti-tuberculous (TB) treatment. The kinetics of IFN-gamma responses to Mycobacterium tuberculosis (MTB) antigens in HIV-infected children during treatment have not however been previously investigated. METHODS: IFN-gamma responses to the MTB antigens, ESAT-6, CFP-10 and PPD were measured by an enzyme-linked immunospot assay (IFN-gamma ELISpot) at presentation and at one, two and six months after starting anti-tuberculous treatment in HIV-infected children with definite or probable TB. Responses at different time points were compared using a Mann-Whitney U test with paired data analysed using the Wilcoxon signed rank test. A Fisher's exact or Chi-squared test was used to compare proportions when test results were analysed as dichotomous outcomes. RESULTS: Of 102 children with suspected TB, 22 (21%) had definite TB and 24 (23%) probable TB. At least one follow up IFN-gamma ELISpot assay result was available for 31 (67%) of the 46 children. In children with definite or probable TB in whom the IFN-gamma ELISpot assay result was positive at presentation, anti-tuberculous treatment was accompanied by a significant decrease in both the magnitude of the IFN-gamma response to individual or combined MTB-specific antigens (ESAT-6 median 110 SFCs/106 PBMC (IQR 65-305) at presentation vs. 15 (10-115) at six months, p = 0.04; CFP-10 177 (48-508) vs. 20 (5-165), p = 0.004, ESAT-6 or CFP-10 median 250 SFCs/106 PBMC (IQR 94-508) vs. 25 (10-165), p = 0.004) and in the proportion of children with a positive IFN-gamma ELISpot assay (Fisher's exact test: ESAT-6 15/0 vs 5/11, p = 0.0002, CFP-10 22/0 vs 8/17, p = 0.0001, ESAT-6 or CFP-10 22/0 vs. 9/17, p= 0.002). However almost half of the children had a positive IFN-gamma ELISpot assay after six months of anti-tuberculous treatment. In addition, there was conversion of the IFN-gamma ELISpot assay result during anti-tuberculous therapy in six of 12 children in whom the initial IFN-gamma ELISpot assay was negative. CONCLUSIONS: In HIV-infected children with definite or probable TB, anti-tuberculosis treatment is accompanied by a reduction in the magnitude of the IFN-gamma ELISpot response to MTB-antigens. However, serial IFN-gamma ELISpot measurements appear to have limited clinical utility in assessing a successful response to anti-tuberculous treatment in HIV infected children. DA - 2010 DB - OpenUCT DO - 10.1186/1471-2334-10-138 DP - University of Cape Town J1 - BMC Infectious Diseases LK - https://open.uct.ac.za PB - University of Cape Town PY - 2010 T1 - Reversion and conversion of Mycobacterium tuberculosis IFN-gamma ELISpot results during anti-tuberculous treatment in HIV-infected children TI - Reversion and conversion of Mycobacterium tuberculosis IFN-gamma ELISpot results during anti-tuberculous treatment in HIV-infected children UR - http://hdl.handle.net/11427/14868 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/14868
dc.identifier.urihttp://dx.doi.org/10.1186/1471-2334-10-138
dc.identifier.vancouvercitationConnell T, Davies M, Johannisen C, Wood K, Pienaar S, Wilkinson K, et al. Reversion and conversion of Mycobacterium tuberculosis IFN-gamma ELISpot results during anti-tuberculous treatment in HIV-infected children. BMC Infectious Diseases. 2010; http://hdl.handle.net/11427/14868.en_ZA
dc.language.isoengen_ZA
dc.publisherBioMed Central Ltden_ZA
dc.publisher.departmentInstitute of Infectious Disease and Molecular Medicineen_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.holder2010 Connell et al; licensee BioMed Central Ltd.en_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.otherMycobacterium tuberculosisen_ZA
dc.subject.otherPaediatrics and Child Healthen_ZA
dc.subject.otherHIV-infected childrenen_ZA
dc.titleReversion and conversion of Mycobacterium tuberculosis IFN-gamma ELISpot results during anti-tuberculous treatment in HIV-infected childrenen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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