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

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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