Blood-based host biomarker diagnostics in active case finding for pulmonary tuberculosis: A diagnostic case-control...

Area of Science:

• Infectious disease diagnostics
• Tuberculosis screening
• Point-of-care testing

Background:

• Scalable tuberculosis (TB) screening strategies are crucial for high-burden populations.
• The World Health Organization prioritizes non-sputum-based triage tests for TB detection.
• Correction of TB screening methods is needed in resource-limited settings.

Purpose of the Study:

• To evaluate the diagnostic accuracy of point-of-care C-reactive protein (CRP) and a novel host-response assay (Xpert-MTB-HR) as TB triage tests.
• To assess these tests against World Health Organization Target Product Profile (TPP) benchmarks in a high TB-burden setting.
• To compare the performance of CRP and Xpert-MTB-HR in identifying active TB cases among incarcerated individuals.

Main Methods:

• A diagnostic case-control study was conducted in two Brazilian prisons.
• Participants underwent sputum-based TB testing (Xpert MTB/RIF and culture) and blood tests for CRP and Xpert-MTB-HR.
• Receiver operating characteristic curves were used to evaluate assay performance, focusing on sensitivity and specificity benchmarks.

Main Results:

• The study included 100 TB cases and 200 controls.
• Xpert-MTB-HR (AUC 0.84) demonstrated higher accuracy than CRP (AUC 0.79).
• Neither test met the TPP benchmark of 70% specificity at 90% sensitivity. However, Xpert-MTB-HR showed high sensitivity for individuals with high sputum bacillary load.

Conclusions:

• CRP and Xpert-MTB-HR assays did not meet TPP benchmarks for TB triage in this high-burden prison setting.
• Xpert-MTB-HR showed promise for detecting TB in individuals with significant bacterial burden.
• Further development of non-sputum-based TB triage tests is warranted.