Diagnostic Performance of Blood Inflammatory Markers for Tuberculosis Screening in People Living with HIV

Authors

Katherine Farr, University of California San Francisco
Resmi Ravindran, University of California at Davis
Luke Strnad, OHSU-PSU School of Public HealthFollow
Emily Chang, University of California San Francisco
Leah H. Chaisson, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
Christina Yoon, University of California San Francisco
William Worodria, Makerere University, Kampala, Uganda
Alfred Andama, Makerere University, Kampala, Uganda
Irene Ayakaka, Infectious Diseases Research Collaboration, Kampala, Uganda
Priscilla Bbosa Nalwanga, Infectious Diseases Research Collaboration, Kampala, Uganda
multiple additional authors

Published In

Plos One

Document Type

Article

Publication Date

2018

Subjects

HIV -- Case studies, HIV -- Clinical trials

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.

Description

Copyright (c) 2018 The Authors

This work is licensed under a Creative Commons Attribution 4.0 International License.

Locate the Document

• https://doi-org.proxy.lib.pdx.edu/10.1371/journal.pone.0206119

DOI

10.1371/journal.pone.0206119

Persistent Identifier

https://archives.pdx.edu/ds/psu/33696

Citation Details

Farr, K., Ravindran, R., Strnad, L., Chang, E., Chaisson, L. H., Yoon, C., ... & Byanyima, P. (2018). Diagnostic performance of blood inflammatory markers for tuberculosis screening in people living with HIV. PloS one, 13(10), e0206119.