Evaluation of C-Reactive Protein and Computer-Aided Analysis of Chest X-rays as Tuberculosis Triage Tests at Health Facilities in Lesotho and South Africa

S. Bosman, I. Ayakaka, J. Muhairwe, M. Kamele, A. van Heerden, T. Madonsela, N. Labhardt, G. Sommer, J. Bremerich, T. Zoller, K. Murphy, B. van Ginneken, A. Keter, B. Jacobs, M. Bresser, A. Signorell, T. Glass, L. Lynen and K. Reither

Clinical Infectious Diseases 2024.

DOI

Abstract

Background

To improve tuberculosis case-finding, rapid, non-sputum triage tests need to be developed according to the World Health Organization target product profile (TPP) (>90% sensitivity, >70% specificity). We prospectively evaluated and compared artificial intelligence-based, computer-aided detection software, CAD4TBv7, and C-reactive protein assay (CRP) as triage tests at health facilities in Lesotho and South Africa.

Methods

Adults (>=18 years) presenting with >=1 of the 4 cardinal tuberculosis symptoms were consecutively recruited between February 2021 and April 2022. After informed consent, each participant underwent a digital chest X-ray for CAD4TBv7 and a CRP test. Participants provided 1 sputum sample for Xpert MTB/RIF Ultra and Xpert MTB/RIF and 1 for liquid culture. Additionally, an expert radiologist read the chest X-rays via teleradiology. For primary analysis, a composite microbiological reference standard (ie, positive culture or Xpert Ultra) was used.

Results

We enrolled 1392 participants, 48% were people with HIV and 24% had previously tuberculosis. The receiver operating characteristic curve for CAD4TBv7 and CRP showed an area under the curve of .87 (95% CI: .84-.91) and .80 (95% CI: .76-.84), respectively. At thresholds corresponding to 90% sensitivity, specificity was 68.2% (95% CI: 65.4-71.0%) and 38.2% (95% CI: 35.3-41.1%) for CAD4TBv7 and CRP, respectively. CAD4TBv7 detected tuberculosis as well as an expert radiologist. CAD4TBv7 almost met the TPP criteria for tuberculosis triage.

Conclusions

CAD4TBv7 is accurate as a triage test for patients with tuberculosis symptoms from areas with a high tuberculosis and HIV burden. The role of CRP in tuberculosis triage requires further research.

Clinical Trials Registration

Clinicaltrials.gov identifier: NCT04666311.