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 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.
| Original language | English (US) |
|---|---|
| Article number | e0206119 |
| Journal | PLoS One |
| Volume | 13 |
| Issue number | 10 |
| DOIs | |
| State | Published - Oct 1 2018 |
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ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Agricultural and Biological Sciences(all)
Cite this
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; Nalwanga, Priscilla Bbosa; 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; Cattamanchi, Adithya.
In: PLoS One, Vol. 13, No. 10, e0206119, 01.10.2018.Research output: Contribution to journal › Article
}
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
AU - Cattamanchi, Adithya
PY - 2018/10/1
Y1 - 2018/10/1
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
VL - 13
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 10
M1 - e0206119
ER -