TY - JOUR
T1 - Simultaneous measurement of antigen-induced CXCL10 and IFN-γ enhances test sensitivity for bovine TB detection in cattle
AU - Coad, Michael
AU - Doyle, Mairead
AU - Steinbach, Sabine
AU - Gormley, Eamonn
AU - Vordermeier, Martin
AU - Jones, Gareth
N1 - Funding Information:
The authors would like to acknowledge the following: the staff of the APHA Animal Services Unit for their dedication to animal welfare; the Department of Agriculture, Food and the Marine for providing the samples from Ireland and Tara Fitzsimmons and Kevina McGill for processing these samples. The work was funded by the UK Department for Environment, Food and Rural Affairs (DEFRA projects SE3266 and SE3268) and by the Irish Department of Agriculture, Food and the Marine .
Funding Information:
The authors would like to acknowledge the following: the staff of the APHA Animal Services Unit for their dedication to animal welfare; the Department of Agriculture, Food and the Marine for providing the samples from Ireland and Tara Fitzsimmons and Kevina McGill for processing these samples. The work was funded by the UK Department for Environment, Food and Rural Affairs (DEFRA projects SE3266 and SE3268) and by the Irish Department of Agriculture, Food and the Marine.
Publisher Copyright:
© 2019
PY - 2019/3/1
Y1 - 2019/3/1
N2 - Bovine tuberculosis (BTB) is a disease of economic and zoonotic importance caused mainly by Mycobacterium bovis. In addition to the tuberculin skin test, an interferon-gamma (IFN-γ) release assay (IGRA) blood test has been incorporated in the BTB control programs of numerous countries as an ancillary test to the skin test. A potential disadvantage of the IGRA assay is that it relies solely on the measurement of a single readout (i.e. IFN-γ) for the detection of BTB. In this study we have assessed the practical use of CXCL10 as an additional biomarker for the diagnosis of BTB in the setting of the current testing approach alongside IGRA. To do so, we have assessed both IFN-γ and CXCL10 readouts in blood cultures from a variety of different BTB cattle groups stimulated with standard tuberculin reagents and also with more specific defined antigens (ESAT-6, CFP-10 and Rv3615c). When using a tuberculin based whole blood assay, CXCL10 alone could not substitute for IFN-γ as the analyte measured in the test without reducing the sensitivity of detecting BTB animals. However, when used as an additional test readout, CXCL10 identified BTB animals that failed to induce IFN-γ responses. When tested in non-infected animals, the use of the dual biomarker system had the potential to lower overall test specificity, however this could be overcome by raising the cut-off values for CXCL10 test positivity. Taken together, the results demonstrate that in particular settings, measurement of CXCL10 has the potential to complement the current use of IFN-γ in blood assays to maximise the detection of BTB.
AB - Bovine tuberculosis (BTB) is a disease of economic and zoonotic importance caused mainly by Mycobacterium bovis. In addition to the tuberculin skin test, an interferon-gamma (IFN-γ) release assay (IGRA) blood test has been incorporated in the BTB control programs of numerous countries as an ancillary test to the skin test. A potential disadvantage of the IGRA assay is that it relies solely on the measurement of a single readout (i.e. IFN-γ) for the detection of BTB. In this study we have assessed the practical use of CXCL10 as an additional biomarker for the diagnosis of BTB in the setting of the current testing approach alongside IGRA. To do so, we have assessed both IFN-γ and CXCL10 readouts in blood cultures from a variety of different BTB cattle groups stimulated with standard tuberculin reagents and also with more specific defined antigens (ESAT-6, CFP-10 and Rv3615c). When using a tuberculin based whole blood assay, CXCL10 alone could not substitute for IFN-γ as the analyte measured in the test without reducing the sensitivity of detecting BTB animals. However, when used as an additional test readout, CXCL10 identified BTB animals that failed to induce IFN-γ responses. When tested in non-infected animals, the use of the dual biomarker system had the potential to lower overall test specificity, however this could be overcome by raising the cut-off values for CXCL10 test positivity. Taken together, the results demonstrate that in particular settings, measurement of CXCL10 has the potential to complement the current use of IFN-γ in blood assays to maximise the detection of BTB.
KW - Bovine tuberculosis
KW - CXCL10
KW - Diagnostic test
KW - Bacterial Proteins/immunology
KW - Enzyme-Linked Immunosorbent Assay/veterinary
KW - Interferon-gamma Release Tests/veterinary
KW - Mycobacterium bovis/immunology
KW - Tuberculin Test/veterinary
KW - United Kingdom
KW - Chemokine CXCL10/blood
KW - Tuberculosis, Bovine/diagnosis
KW - Animals
KW - Cattle
KW - Sensitivity and Specificity
KW - Biomarkers/blood
KW - Antigens, Bacterial/immunology
KW - Serologic Tests/veterinary
KW - Interferon-gamma/blood
UR - http://www.scopus.com/inward/record.url?scp=85059664712&partnerID=8YFLogxK
U2 - 10.1016/j.vetmic.2019.01.007
DO - 10.1016/j.vetmic.2019.01.007
M3 - Article
C2 - 30827373
AN - SCOPUS:85059664712
SN - 0378-1135
VL - 230
SP - 1
EP - 6
JO - Veterinary Microbiology
JF - Veterinary Microbiology
ER -
