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

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Farr, Katherine, Ravindran, Resmi, Strnad, Luke, Chang, Emily, Chaisson,, Lelia H, Yoon, Christina, Worodria, William, Andama, Alfred, Ayakaka, Irene ORCID: https://orcid.org/0000-0003-1051-5684, Nalwanga, Priscilla Bbosa, Byanyima, Patrick, Kalema, Nelson, Kaswabuli, Sylvia, Katagira, Winceslaus, Aman, Kyomugisha Denise, Tumwine,, Nuwagaba Wallen, Sanyu, Ingvar, Ssebunya, Robert, Davis, J. Lucian, Huang, Laurence, Khan, Imran H and Cattamanchi, Adithya (2018) 'Diagnostic performance of blood inflammatory markers for tuberculosis screening in people living with HIV'. PLoS ONE, Vol 13, Issue 10, e0206119.

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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.

Item Type: Article
Subjects: WC Communicable Diseases > Virus Diseases > Acquired Immunodeficiency Syndrome. HIV Infections > WC 503 Acquired immunodeficiency syndrome. HIV infections
WC Communicable Diseases > Virus Diseases > Acquired Immunodeficiency Syndrome. HIV Infections > WC 503.1 Diagnosis
WC Communicable Diseases > Virus Diseases > Acquired Immunodeficiency Syndrome. HIV Infections > WC 503.6 Prevention and control
WF Respiratory System > Tuberculosis > WF 200 Tuberculosis (General)
Faculty: Department: Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI): https://doi.org/10.1371/journal.pone.0206119
Depositing User: Stacy Murtagh
Date Deposited: 25 Oct 2018 16:29
Last Modified: 07 Nov 2018 09:07
URI: https://archive.lstmed.ac.uk/id/eprint/9508

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