Cari Stek1,2,3, Jozefien Buyze1, Joris Menten1, Charlotte Schutz2,3, Friedrich Thienemann2, Lisette Blumenthal2, Gary Maartens2,3, Tom Boyles3, Robert J Wilkinson2,3,4,5, Graeme Meintjes2,3, Lutgarde Lynen1. 1. Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium. 2. Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa. 3. Department of Medicine, University of Cape Town, Cape Town, South Africa. 4. Department of Medicine, Imperial College London, London, United Kingdom; and. 5. The Francis Crick Institute, London, United Kingdom.
Abstract
BACKGROUND: The diagnosis of paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) relies on characteristic clinical features synthesized as the International Network for the Study of HIV-associated IRIS (INSHI) case definition. There is no confirmatory laboratory test. SETTING: Site B HIV-TB clinic in Khayelitsha, Cape Town, South Africa. METHODS: Using data of participants with HIV-associated tuberculosis starting antiretroviral treatment from a prospective trial evaluating prednisone for TB-IRIS prevention, we applied latent class analysis to model a gold standard for TB-IRIS. The model-predicted probability of TB-IRIS for each participant was used to assess the performance of the INSHI case definition and compare its diagnostic accuracy with several adapted case definitions. RESULTS: Data for this analysis were complete for 217 participants; 41% developed TB-IRIS. Our latent class model included the following parameters: respiratory symptoms; night sweats; INSHI major criteria 1, 2, and 4; maximum C-reactive protein >90 mg/L; maximum heart rate >120/min; maximum temperature >37.7°C; and preantiretroviral therapy CD4 count <50 cells/µL. The model estimated a TB-IRIS incidence of 43% and had optimal goodness of fit (χ2 = 337, P = 1.0). The INSHI case definition displayed a sensitivity of 0.77 and a specificity of 0.86. Replacing all the minor INSHI criteria with objectives measures (C-reactive protein elevation, fever, and/or tachycardia) resulted in a definition with better diagnostic accuracy, with a sensitivity of 0.89 and a specificity of 0.88. CONCLUSION: The INSHI case definition identifies TB-IRIS with reasonable accuracy. Amending the case definition by replacing INSHI minor criteria with objective variables improved sensitivity without loss of specificity.
BACKGROUND: The diagnosis of paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) relies on characteristic clinical features synthesized as the International Network for the Study of HIV-associated IRIS (INSHI) case definition. There is no confirmatory laboratory test. SETTING: Site B HIV-TB clinic in Khayelitsha, Cape Town, South Africa. METHODS: Using data of participants with HIV-associated tuberculosis starting antiretroviral treatment from a prospective trial evaluating prednisone for TB-IRIS prevention, we applied latent class analysis to model a gold standard for TB-IRIS. The model-predicted probability of TB-IRIS for each participant was used to assess the performance of the INSHI case definition and compare its diagnostic accuracy with several adapted case definitions. RESULTS: Data for this analysis were complete for 217 participants; 41% developed TB-IRIS. Our latent class model included the following parameters: respiratory symptoms; night sweats; INSHI major criteria 1, 2, and 4; maximum C-reactive protein >90 mg/L; maximum heart rate >120/min; maximum temperature >37.7°C; and preantiretroviral therapy CD4 count <50 cells/µL. The model estimated a TB-IRIS incidence of 43% and had optimal goodness of fit (χ2 = 337, P = 1.0). The INSHI case definition displayed a sensitivity of 0.77 and a specificity of 0.86. Replacing all the minor INSHI criteria with objectives measures (C-reactive protein elevation, fever, and/or tachycardia) resulted in a definition with better diagnostic accuracy, with a sensitivity of 0.89 and a specificity of 0.88. CONCLUSION: The INSHI case definition identifies TB-IRIS with reasonable accuracy. Amending the case definition by replacing INSHI minor criteria with objective variables improved sensitivity without loss of specificity.
Authors: P K Drain; L Mayeza; P Bartman; R Hurtado; P Moodley; S Varghese; G Maartens; G G Alvarez; D Wilson Journal: Int J Tuberc Lung Dis Date: 2014-01 Impact factor: 2.373
Authors: Graeme Meintjes; Cari Stek; Lisette Blumenthal; Friedrich Thienemann; Charlotte Schutz; Jozefien Buyze; Raffaella Ravinetto; Harry van Loen; Amy Nair; Amanda Jackson; Robert Colebunders; Gary Maartens; Robert J Wilkinson; Lutgarde Lynen Journal: N Engl J Med Date: 2018-11-15 Impact factor: 91.245
Authors: Graeme Meintjes; Stephen D Lawn; Fabio Scano; Gary Maartens; Martyn A French; William Worodria; Julian H Elliott; David Murdoch; Robert J Wilkinson; Catherine Seyler; Laurence John; Maarten Schim van der Loeff; Peter Reiss; Lut Lynen; Edward N Janoff; Charles Gilks; Robert Colebunders Journal: Lancet Infect Dis Date: 2008-08 Impact factor: 25.071