TY - JOUR
T1 - Evaluation of multi-antigen serological screening for active tuberculosis among people living with HIV
AU - Jaganath, Devan
AU - Rajan, Jayant
AU - Yoon, Christina
AU - Ravindran, Resmi
AU - Andama, Alfred
AU - Asege, Lucy
AU - Mwebe, Sandra Z.
AU - Katende, Jane
AU - Nakaye, Martha
AU - Semitala, Fred C.
AU - Khan, Imran H.
AU - Cattamanchi, Adithya
PY - 2020/6
Y1 - 2020/6
N2 - Better triage tests for screening tuberculosis (TB) disease are needed for people living with HIV (PLHIV). We performed the first evaluation of a previously-validated 8-antigen serological panel to screen PLHIV for pulmonary TB in Kampala, Uganda. We selected a random 1:1 sample with and without TB (defined by sputum culture) from a cohort of PLHIV initiating antiretroviral therapy. We used a multiplex microbead immunoassay and an ensemble machine learning classifier to determine the area under the receiver operating characteristic curve (AUC) for Ag85A, Ag85B, Ag85C, Rv0934-P38, Rv3881, Rv3841-BfrB, Rv3873, and Rv2878c. We then assessed the performance with the addition of four TB-specific antigens ESAT-6, CFP-10, Rv1980-MPT64, and Rv2031-HSPX, and every antigen combination. Of 262 participants (median CD4 cell-count 152 cells/μL [IQR 65–279]), 138 (53%) had culture-confirmed TB. The 8-antigen panel had an AUC of 0.53 (95% CI 0.40–0.66), and the additional 4 antigens did not improve performance (AUC 0.51, 95% CI 0.39–0.64). When sensitivity was restricted to ≥90% for the 8- and 12-antigen panel, specificity was 2.2% (95% CI 0–17.7%) and 8.1% (95% CI 0–23.9%), respectively. A three-antigen combination (Rv0934-P38, Ag85A, and Rv2031-HSPX) outperformed both panels, with an AUC of 0.60 (95% CI 0.48–0.73), 90% sensitivity (95% CI 78.2–96.7%) and 29.7% specificity (95% CI 15.9–47%). The multi-antigen panels did not achieve the target accuracy for a TB triage test among PLHIV. We identified a new combination that improved performance for TB screening in an HIV-positive sample compared to an existing serological panel in Uganda, and suggests an approach to identify novel antigen combinations specifically for screening TB in PLHIV.
AB - Better triage tests for screening tuberculosis (TB) disease are needed for people living with HIV (PLHIV). We performed the first evaluation of a previously-validated 8-antigen serological panel to screen PLHIV for pulmonary TB in Kampala, Uganda. We selected a random 1:1 sample with and without TB (defined by sputum culture) from a cohort of PLHIV initiating antiretroviral therapy. We used a multiplex microbead immunoassay and an ensemble machine learning classifier to determine the area under the receiver operating characteristic curve (AUC) for Ag85A, Ag85B, Ag85C, Rv0934-P38, Rv3881, Rv3841-BfrB, Rv3873, and Rv2878c. We then assessed the performance with the addition of four TB-specific antigens ESAT-6, CFP-10, Rv1980-MPT64, and Rv2031-HSPX, and every antigen combination. Of 262 participants (median CD4 cell-count 152 cells/μL [IQR 65–279]), 138 (53%) had culture-confirmed TB. The 8-antigen panel had an AUC of 0.53 (95% CI 0.40–0.66), and the additional 4 antigens did not improve performance (AUC 0.51, 95% CI 0.39–0.64). When sensitivity was restricted to ≥90% for the 8- and 12-antigen panel, specificity was 2.2% (95% CI 0–17.7%) and 8.1% (95% CI 0–23.9%), respectively. A three-antigen combination (Rv0934-P38, Ag85A, and Rv2031-HSPX) outperformed both panels, with an AUC of 0.60 (95% CI 0.48–0.73), 90% sensitivity (95% CI 78.2–96.7%) and 29.7% specificity (95% CI 15.9–47%). The multi-antigen panels did not achieve the target accuracy for a TB triage test among PLHIV. We identified a new combination that improved performance for TB screening in an HIV-positive sample compared to an existing serological panel in Uganda, and suggests an approach to identify novel antigen combinations specifically for screening TB in PLHIV.
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U2 - 10.1371/journal.pone.0234130
DO - 10.1371/journal.pone.0234130
M3 - Article
C2 - 32497095
AN - SCOPUS:85086007884
VL - 15
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 6
M1 - e0234130
ER -