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

  • Author(s): Farr, Katherine
  • Ravindran, Resmi
  • Strnad, Luke
  • Chang, Emily
  • Chaisson, Lelia H
  • Yoon, Christina
  • Worodria, William
  • Andama, Alfred
  • Ayakaka, Irene
  • Bbosa Nalwanga, Priscilla
  • Byanyima, Patrick
  • Kalema, Nelson
  • Kaswabuli, Sylvia
  • Katagira, Winceslaus
  • Aman, Kyomugisha Denise
  • Musisi, Emmanuel
  • Tumwine, Nuwagaba Wallen
  • Sanyu, Ingvar
  • Ssebunya, Robert
  • Davis, J Lucian
  • Huang, Laurence
  • Khan, Imran H
  • Cattamanchi, Adithya
  • et al.
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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