Diagnostic performance of blood inflammatory markers for tuberculosis screening in people living with HIV
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Date
2018
Journal Title
Journal ISSN
Volume Title
Publisher
PLoS ONE
Abstract
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.
Description
Keywords
Blood inflammatory markers, Tuberculosis screening, HIV
Citation
Farr K, Ravindran R, Strnad L, Chang E, Chaisson LH, Yoon C, et al. (2018) Diagnostic performance of blood inflammatory markers for tuberculosis screening in people living with HIV. PLoS ONE 13(10): e0206119. https://doi.org/ 10.1371/journal.pone.0206119