Prolonged tuberculosis-associated immune reconstitution inflammatory syndrome: characteristics and risk factors

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dc.contributor.advisorMeintjes, Graemeen_ZA
dc.contributor.authorBana, Tasnim Mohammeden_ZA
dc.date.accessioned2016-01-21T11:07:48Z
dc.date.available2016-01-21T11:07:48Z
dc.date.issued2015en_ZA
dc.descriptionIncludes bibliographical referencesen_ZA
dc.description.abstractBackground: In a proportion of patients with HIV-associated tuberculosis who develop paradoxical immune reconstitution inflammatory syndrome (IRIS), the clinical course of IRIS is prolonged necessitating substantial health care utilization for diagnostic and therapeutic interventions. This phenomenon has not been systematically studied to date. We aimed to determine the proportion of patients with prolonged TB-IRIS, as well as the clinical characteristics and risk factors for prolonged TB-IRIS. Methods: We pooled data from two prospective observational studies and a randomized controlled trial that enrolled patients with paradoxical TB-IRIS using the same diagnostic approach and clinical case definitions in Cape Town, South Africa. Prolonged TB-IRIS was defined as TB-IRIS symptoms lasting > 90 days. Risk factors for TB-IRIS were analysed using Wilcoxon rank sum test, Fisher's exact test, multivariate logistic regression and Cox proportional hazards model. In a separate set of analyses, risk factors for relapsing after a 4-week course of prednisone for treatment of TB-IRIS were analysed. Results: Two-hundred and sixteen patients with TB-IRIS were included. The median duration of TB-IRIS symptoms was 71.0 days (IQR=41.0-113.2). In 73/181 patients with sufficient follow-up (40.3%) IRIS duration was > 90 days. Six patients (3.3%) had IRIS duration > 1 year, mainly with nodal involvement. In univariate logistic regression analysis, the following were significantly associated with IRIS duration > 90 days: lymph node involvement at initial TB diagnosis (p=0.02), drug-resistant TB (p=0.02), lymph node TB-IRIS (p=0.0005) and not being hospitalized at time of TB-IRIS diagnosis (p=0.004). The association with lymph node TB-IRIS (p=0.02) and hospitalization status (p=0.05) remained significant in the multivariate logistic regression model. In the Cox proportional hazards model, IRIS lymph node involvement was independently associated with lower hazards of IRIS resolution (HR 0.55, 95%CI=0.38-0.78). In univariate analysis those patients with lesser reductions in liver function abnormalities during prednisone treatment had a higher risk of relapse after stopping prednisone, but no significant associations remained in multivariate analysis. Conclusions: Around 40% of patients with TB-IRIS have symptoms for more than 90 days. Lymph node IRIS involvement is an independent risk factor for a prolonged course and in the small proportion of patients (3%) with symptoms more than one year this usually manifests with lymph node involvement. Whether earlier recognition and treatment of lymph node TB-IRIS could reduce the risk of prolonged TB-IRIS needs to be evaluated. Trial registration: The randomized controlled trial was registered with Current Controlled Trials ISRCTN21322548.en_ZA
dc.identifier.apacitationBana, T. M. (2015). <i>Prolonged tuberculosis-associated immune reconstitution inflammatory syndrome: characteristics and risk factors</i>. (Thesis). University of Cape Town ,Faculty of Health Sciences ,Institute of Infectious Disease and Molecular Medicine. Retrieved from http://hdl.handle.net/11427/16480en_ZA
dc.identifier.chicagocitationBana, Tasnim Mohammed. <i>"Prolonged tuberculosis-associated immune reconstitution inflammatory syndrome: characteristics and risk factors."</i> Thesis., University of Cape Town ,Faculty of Health Sciences ,Institute of Infectious Disease and Molecular Medicine, 2015. http://hdl.handle.net/11427/16480en_ZA
dc.identifier.citationBana, T. 2015. Prolonged tuberculosis-associated immune reconstitution inflammatory syndrome: characteristics and risk factors. University of Cape Town.en_ZA
dc.identifier.ris TY - Thesis / Dissertation AU - Bana, Tasnim Mohammed AB - Background: In a proportion of patients with HIV-associated tuberculosis who develop paradoxical immune reconstitution inflammatory syndrome (IRIS), the clinical course of IRIS is prolonged necessitating substantial health care utilization for diagnostic and therapeutic interventions. This phenomenon has not been systematically studied to date. We aimed to determine the proportion of patients with prolonged TB-IRIS, as well as the clinical characteristics and risk factors for prolonged TB-IRIS. Methods: We pooled data from two prospective observational studies and a randomized controlled trial that enrolled patients with paradoxical TB-IRIS using the same diagnostic approach and clinical case definitions in Cape Town, South Africa. Prolonged TB-IRIS was defined as TB-IRIS symptoms lasting > 90 days. Risk factors for TB-IRIS were analysed using Wilcoxon rank sum test, Fisher's exact test, multivariate logistic regression and Cox proportional hazards model. In a separate set of analyses, risk factors for relapsing after a 4-week course of prednisone for treatment of TB-IRIS were analysed. Results: Two-hundred and sixteen patients with TB-IRIS were included. The median duration of TB-IRIS symptoms was 71.0 days (IQR=41.0-113.2). In 73/181 patients with sufficient follow-up (40.3%) IRIS duration was > 90 days. Six patients (3.3%) had IRIS duration > 1 year, mainly with nodal involvement. In univariate logistic regression analysis, the following were significantly associated with IRIS duration > 90 days: lymph node involvement at initial TB diagnosis (p=0.02), drug-resistant TB (p=0.02), lymph node TB-IRIS (p=0.0005) and not being hospitalized at time of TB-IRIS diagnosis (p=0.004). The association with lymph node TB-IRIS (p=0.02) and hospitalization status (p=0.05) remained significant in the multivariate logistic regression model. In the Cox proportional hazards model, IRIS lymph node involvement was independently associated with lower hazards of IRIS resolution (HR 0.55, 95%CI=0.38-0.78). In univariate analysis those patients with lesser reductions in liver function abnormalities during prednisone treatment had a higher risk of relapse after stopping prednisone, but no significant associations remained in multivariate analysis. Conclusions: Around 40% of patients with TB-IRIS have symptoms for more than 90 days. Lymph node IRIS involvement is an independent risk factor for a prolonged course and in the small proportion of patients (3%) with symptoms more than one year this usually manifests with lymph node involvement. Whether earlier recognition and treatment of lymph node TB-IRIS could reduce the risk of prolonged TB-IRIS needs to be evaluated. Trial registration: The randomized controlled trial was registered with Current Controlled Trials ISRCTN21322548. DA - 2015 DB - OpenUCT DP - University of Cape Town LK - https://open.uct.ac.za PB - University of Cape Town PY - 2015 T1 - Prolonged tuberculosis-associated immune reconstitution inflammatory syndrome: characteristics and risk factors TI - Prolonged tuberculosis-associated immune reconstitution inflammatory syndrome: characteristics and risk factors UR - http://hdl.handle.net/11427/16480 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/16480
dc.identifier.vancouvercitationBana TM. Prolonged tuberculosis-associated immune reconstitution inflammatory syndrome: characteristics and risk factors. [Thesis]. University of Cape Town ,Faculty of Health Sciences ,Institute of Infectious Disease and Molecular Medicine, 2015 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/16480en_ZA
dc.language.isoengen_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.subject.otherMedicineen_ZA
dc.titleProlonged tuberculosis-associated immune reconstitution inflammatory syndrome: characteristics and risk factorsen_ZA
dc.typeMaster Thesis
dc.type.qualificationlevelMasters
dc.type.qualificationnameMMeden_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceThesisen_ZA
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