Christina Yoon1, J Lucian Davis, Laurence Huang, Conrad Muzoora, Helen Byakwaga, Colin Scibetta, David R Bangsberg, Payam Nahid, Fred C Semitala, Peter W Hunt, Jeffrey N Martin, Adithya Cattamanchi. 1. *Division of Pulmonary and Critical Care Medicine, Department of Medicine, †Curry International Tuberculosis Center, and ‡HIV/AIDS Division, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, CA; §Department of Medicine, Mbarara University of Science and Technology, Mbarara, Uganda; ‖Department of Epidemiology and Biostatistics, University of California, San Francisco, CA; ¶Department of Internal Medicine, University of California, San Francisco, CA; **Center for Global Health, Massachusetts General Hospital, Harvard Medical School, Boston, MA; ††Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard Medical School, Boston, MA; and ‡‡Department of Medicine, Makerere University, Kampala, Uganda.
Abstract
BACKGROUND: Symptom-based tuberculosis screening identifies less than one-third of eligible HIV-infected patients as candidates for isoniazid preventive therapy (IPT). We evaluated whether testing for C-reactive protein (CRP) improves patient selection for IPT. METHODS: We measured CRP levels (normal <10 mg/L) using a point-of-care (POC) assay on stored serum samples from HIV-infected Ugandan adults initiating antiretroviral therapy. We assessed diagnostic accuracy in reference to baseline tuberculosis status adjudicated by an expert committee and calculated net reclassification improvement to quantify the incremental discriminatory benefit of POC-CRP in determining IPT eligibility compared to the World Health Organization (WHO) symptom screen. RESULTS: Of 201 patients (median CD4 cell count, 137 cells/μL; interquartile range, 83-206), 5 (2.5%) had tuberculosis. Compared to the WHO symptom screen, POC-CRP had similar sensitivity (100% vs. 80%, P = 0.30) but greater specificity (21% vs. 87%, P < 0.0001) for tuberculosis. If based on the WHO symptom screen, no patients with tuberculosis but only 42 of 196 patients without tuberculosis would have been considered IPT eligible. If POC-CRP were used instead, 1 patient with tuberculosis (reclassification of cases, -20%; P = 0.32) and 129 patients without tuberculosis (reclassification of noncases, +66%; P < 0.001) would have been reclassified as IPT eligible, a net reclassification improvement of 46% (P = 0.03). In addition, POC-CRP testing would have reduced the proportion of patients without active tuberculosis requiring confirmatory tuberculosis testing (87% vs. 21%, P < 0.0001). CONCLUSIONS: POC-CRP testing increased more than 4-fold the proportion of HIV-infected adults immediately identified as IPT eligible and decreased the proportion of patients requiring referral for further tuberculosis diagnostic testing. POC-CRP testing could substantially improve implementation of tuberculosis screening guidelines.
BACKGROUND: Symptom-based tuberculosis screening identifies less than one-third of eligible HIV-infectedpatients as candidates for isoniazid preventive therapy (IPT). We evaluated whether testing for C-reactive protein (CRP) improves patient selection for IPT. METHODS: We measured CRP levels (normal <10 mg/L) using a point-of-care (POC) assay on stored serum samples from HIV-infected Ugandan adults initiating antiretroviral therapy. We assessed diagnostic accuracy in reference to baseline tuberculosis status adjudicated by an expert committee and calculated net reclassification improvement to quantify the incremental discriminatory benefit of POC-CRP in determining IPT eligibility compared to the World Health Organization (WHO) symptom screen. RESULTS: Of 201 patients (median CD4 cell count, 137 cells/μL; interquartile range, 83-206), 5 (2.5%) had tuberculosis. Compared to the WHO symptom screen, POC-CRP had similar sensitivity (100% vs. 80%, P = 0.30) but greater specificity (21% vs. 87%, P < 0.0001) for tuberculosis. If based on the WHO symptom screen, no patients with tuberculosis but only 42 of 196 patients without tuberculosis would have been considered IPT eligible. If POC-CRP were used instead, 1 patient with tuberculosis (reclassification of cases, -20%; P = 0.32) and 129 patients without tuberculosis (reclassification of noncases, +66%; P < 0.001) would have been reclassified as IPT eligible, a net reclassification improvement of 46% (P = 0.03). In addition, POC-CRP testing would have reduced the proportion of patients without active tuberculosis requiring confirmatory tuberculosis testing (87% vs. 21%, P < 0.0001). CONCLUSIONS: POC-CRP testing increased more than 4-fold the proportion of HIV-infected adults immediately identified as IPT eligible and decreased the proportion of patients requiring referral for further tuberculosis diagnostic testing. POC-CRP testing could substantially improve implementation of tuberculosis screening guidelines.
Authors: Patrick M Bossuyt; Johannes B Reitsma; David E Bruns; Constantine A Gatsonis; Paul P Glasziou; Les M Irwig; David Moher; Drummond Rennie; Henrica C W de Vet; Jeroen G Lijmer Journal: Ann Intern Med Date: 2003-01-07 Impact factor: 25.391
Authors: R A M Breen; O Leonard; F M R Perrin; C J Smith; S Bhagani; I Cropley; M C I Lipman Journal: Int J Tuberc Lung Dis Date: 2008-01 Impact factor: 2.373
Authors: Adrienne E Shapiro; Ting Hong; Sabina Govere; Hilary Thulare; Mahomed-Yunus Moosa; Afton Dorasamy; Carole L Wallis; Connie L Celum; Jacques Grosset; Paul K Drain Journal: AIDS Date: 2018-08-24 Impact factor: 4.177
Authors: C Yoon; L H Chaisson; S M Patel; I E Allen; P K Drain; D Wilson; A Cattamanchi Journal: Int J Tuberc Lung Dis Date: 2017-09-01 Impact factor: 2.373
Authors: Jayant V Rajan; Fred C Semitala; Tejas Mehta; Mark Seielstad; Lani Montalvo; Alfred Andama; Lucy Asege; Martha Nakaye; Jane Katende; Sandra Mwebe; Moses R Kamya; Christina Yoon; Adithya Cattamanchi Journal: Clin Infect Dis Date: 2019-06-18 Impact factor: 9.079
Authors: Lelia H Chaisson; Fred C Semitala; Sandra Mwebe; Jane Katende; Lucy Asege; Martha Nakaye; Alfred O Andama; Elly Atuhumuza; Moses Kamya; Adithya Cattamanchi; Christina Yoon Journal: AIDS Date: 2022-06-22 Impact factor: 4.632
Authors: Lelia H Chaisson; Fred C Semitala; Lucy Asege; Sandra Mwebe; Jane Katende; Martha Nakaye; Alfred O Andama; Carina Marquez; Elly Atuhumuza; Moses Kamya; Adithya Cattamanchi; Christina Yoon Journal: AIDS Date: 2019-04-01 Impact factor: 4.177