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Clinical Trial
. 2024 Nov 22;79(5):1293-1302.
doi: 10.1093/cid/ciae378.

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

Shannon Bosman  1 , Irene Ayakaka  2 , Josephine Muhairwe  3 , Mashaete Kamele  2 , Alastair van Heerden  1   4 , Thandanani Madonsela  1 , Niklaus D Labhardt  5   6 , Gregor Sommer  6   7   8 , Jens Bremerich  6   7 , Thomas Zoller  9 , Keelin Murphy  10 , Bram van Ginneken  10 , Alfred K Keter  11 , Bart K M Jacobs  11 , Moniek Bresser  6   12 , Aita Signorell  6   12 , Tracy R Glass  6   12 , Lutgarde Lynen  11 , Klaus Reither  6   12
Affiliations
Clinical Trial

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

Shannon Bosman et al. Clin Infect Dis. .

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.

Keywords: C-reactive protein; chest X-ray; computer-aided detection; triage test; tuberculosis.

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Conflict of interest statement

Potential conflicts of interest. B. v. G. reports that his group received royalties from Delft Imaging Systems and that he holds shares in Thirona. K. R., B. v. G., A. v. H., A. S., K. M., L. L., T. Z., B. K. M. J., S. B., T. M., and M. K. report support related to this work from the European and Developing Countries Clinical Trials Partnership 2 (EDCTP2). K. R. reports grants unrelated to this work from EDCTP2 and Horizon 2020, as well as unpaid participation on a data safety monitoring board or scientific advisory board for evaluation of new TB diagnostics. S. B. reports a grant unrelated to this work from the National Institutes of Health (NIH) and travel support from MSD. T. M. reports travel support from MSD. N. D. L. reports support for travel from ViiV Healthcare and Gilead Sciences Sarl as well as for attending a board meeting from ViiV Healthcare and Pharming. S. B. and T. M. report travel support from MSD. The other authors report no potential conflict of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

Graphical Abstract
Graphical Abstract
https://tidbitapp.io/tidbits/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-cd20af86-fe13-42f5-9a51-4733a4788d7b?utm_campaign=tidbitlinkshare&utm_source=ITP
Figure 1.
Figure 1.
Study flow diagram. Abbreviation: CAD, computer-aided detection.
Figure 2.
Figure 2.
CAD4TBv7, CRP and expert radiologist performance. Composite microbiological reference standard (culture or Xpert Ultra). 95% CIs calculated by bootstrapping. Expert radiologist point estimates are generated by choosing different reading thresholds—that is, cases classified as highly probable tuberculosis (left point estimate), highly probable or possible tuberculosis (middle point estimate), or highly probable or possible tuberculosis or abnormal but not tuberculosis (right point estimate). Abbreviations: AUROC, area under the receiver operating characteristic curve; CI, confidence interval; CRP, C-reactive protein.
Figure 3.
Figure 3.
Venn diagram of participants with positive composite reference standard and CAD4TBv7 and CRP above the threshold. Only participants with results from all 3 tests are shown. Abbreviation: CRP, C-reactive protein.
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References

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