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- Title
Diagnostic performance of blood inflammatory markers for tuberculosis screening in people living with HIV.
- Authors
Farr, Katherine; Ravindran, Resmi; Strnad, Luke; Chang, Emily; Chaisson, Lelia H.; Yoon, Christina; Worodria, William; Andama, Alfred; Ayakaka, Irene; Bbosa Nalwanga, Priscilla; Byanyima, Patrick; Kalema, Nelson; Kaswabuli, Sylvia; Katagira, Winceslaus; Aman, Kyomugisha Denise; Musisi, Emmanuel; Tumwine, Nuwagaba Wallen; Sanyu, Ingvar; Ssebunya, Robert; Davis, J. Lucian
- Abstract
Background: Approaches to screening for active tuberculosis (TB) among people living with HIV are inadequate, leading to missed diagnoses and poor implementation of preventive therapy. Methods: Consecutive HIV-infected adults hospitalized at Mulago Hospital (Kampala, Uganda) between June 2011 and July 2013 with a cough ≥ 2 weeks were enrolled. Patients underwent extensive evaluation for pulmonary TB. Concentrations of 43 cytokines/chemokines were measured at the same time point as C-reactive protein (CRP) in banked plasma samples using commercially-available multiplex kits. Advanced classification algorithms were used to rank cytokines/chemokines for their ability to identify TB, and to model the specificity of the top-ranked cytokines/chemokines individually and in combination with sensitivity constrained to ≥ 90% as recommended for TB screening. Results: The median plasma level of 5 biomarkers (IL-6, INF-γ, MIG, CRP, IL-18) was significantly different between patients with and without TB. With sensitivity constrained to 90%, all had low specificity with IL-6 showing the highest specificity (44%; 95% CI 37.4–49.5). Biomarker panels were found to be more valuable than any biomarker alone. A panel combining IFN-γ and IL-6 had the highest specificity (50%; 95% CI 46.7–53.3). Sensitivity remained high (>85%) for all panels among sputum smear-negative TB patients. Conclusions: Direct measurement of unstimulated plasma cytokines/chemokines in peripheral blood is a promising approach to TB screening. Cytokine/chemokine panels retained high sensitivity for smear-negative TB and achieved improved specificity compared to individual cytokines/chemokines. These markers should be further evaluated in outpatient settings where most TB screening occurs and where other illnesses associated with systematic inflammation are less common.
- Subjects
TUBERCULOSIS; HIV-positive persons; PREVENTIVE medicine; CYTOKINES; CHEMOKINES
- Publication
PLoS ONE, 2018, Vol 13, Issue 10, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0206119