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PLoS One. 2018 Oct 23;13(10):e0206119. doi: 10.1371/journal.pone.0206119. eCollection 2018.

Diagnostic performance of blood inflammatory markers for tuberculosis screening in people living with HIV.

Author information

1
Division of Pulmonary and Critical Care Medicine, University of California San Francisco and Zuckerberg San Francisco General Hospital, San Francisco, California, United States of America.
2
Curry International Tuberculosis Center, University of California San Francisco, San Francisco, California, United States of America.
3
Department of Pathology and Laboratory Medicine, University of California at Davis, Sacramento, California, United States of America.
4
Division of Infectious Diseases, Oregon Health & Science University, Portland, Oregon, United States of America.
5
Epidemiology Programs, Oregon Health & Science University-Portland State University School of Public Health, Portland, Oregon, United States of America.
6
Division of HIV, Infectious Diseases, and Global Medicine, Department of Medicine, University of California San Francisco and Zuckerberg San Francisco General Hospital, San Francisco, California, United States of America.
7
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America.
8
Department of Medicine, School of Medicine, Makerere University, Kampala, Uganda.
9
Division of Respiratory Medicine, Department of Medicine, Mulago Hospital, Kampala, Uganda.
10
Department of Medicine, Mulago Hospital, Makerere University, Kampala, Uganda.
11
Infectious Diseases Research Collaboration, Kampala, Uganda.
12
International Multidisciplinary Programme to Address Lung Health and TB in Africa, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
13
Infectious Diseases Institute, Department of Research, Makerere College Health Sciences, Makerere University, Kampala, Uganda.
14
Department of Biochemistry, College of Natural Sciences, Makerere University, Kampala, Uganda.
15
Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut, United States of America.
16
Section of Pulmonary, Critical Care, and Sleep Medicine, Yale School of Medicine, New Haven, Connecticut, United States of America.

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.

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