TY - JOUR
T1 - Diagnostic performance of blood inflammatory markers for tuberculosis screening in people living with HIV
AU - Farr, Katherine
AU - Ravindran, Resmi
AU - Strnad, Luke
AU - Chang, Emily
AU - Chaisson, Lelia H.
AU - Yoon, Christina
AU - Worodria, William
AU - Andama, Alfred
AU - Ayakaka, Irene
AU - Nalwanga, Priscilla Bbosa
AU - Byanyima, Patrick
AU - Kalema, Nelson
AU - Kaswabuli, Sylvia
AU - Katagira, Winceslaus
AU - Aman, Kyomugisha Denise
AU - Musisi, Emmanuel
AU - Tumwine, Nuwagaba Wallen
AU - Sanyu, Ingvar
AU - Ssebunya, Robert
AU - Davis, J. Lucian
AU - Huang, Laurence
AU - Khan, Imran H.
AU - Cattamanchi, Adithya
N1 - Publisher Copyright:
© 2018 Farr et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2018/10
Y1 - 2018/10
N2 - 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 specificityof 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-?, 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-? 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.
AB - 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 specificityof 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-?, 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-? 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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U2 - 10.1371/journal.pone.0206119
DO - 10.1371/journal.pone.0206119
M3 - Article
C2 - 30352099
AN - SCOPUS:85055601804
SN - 1932-6203
VL - 13
JO - PloS one
JF - PloS one
IS - 10
M1 - e0206119
ER -