European Respiratory Review (Jun 2023)

Clinical utility of WHO-recommended screening tools and development and validation of novel clinical prediction models for pulmonary tuberculosis screening among outpatients living with HIV: an individual participant data meta-analysis

  • Ashar Dhana,
  • Rishi K. Gupta,
  • Yohhei Hamada,
  • Andre P. Kengne,
  • Andrew D. Kerkhoff,
  • Christina Yoon,
  • Adithya Cattamanchi,
  • Byron W.P. Reeve,
  • Grant Theron,
  • Gcobisa Ndlangalavu,
  • Robin Wood,
  • Paul K. Drain,
  • Claire J. Calderwood,
  • Mahdad Noursadeghi,
  • Tom Boyles,
  • Graeme Meintjes,
  • Gary Maartens,
  • David A. Barr

DOI
https://doi.org/10.1183/16000617.0021-2023
Journal volume & issue
Vol. 32, no. 168

Abstract

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Background: The World Health Organization (WHO) recommends that outpatient people living with HIV (PLHIV) undergo tuberculosis screening with the WHO four-symptom screen (W4SS) or C-reactive protein (CRP) (5 mg·L−1 cut-off) followed by confirmatory testing if screen positive. We conducted an individual participant data meta-analysis to determine the performance of WHO-recommended screening tools and two newly developed clinical prediction models (CPMs). Methods: Following a systematic review, we identified studies that recruited adult outpatient PLHIV irrespective of tuberculosis signs and symptoms or with a positive W4SS, evaluated CRP and collected sputum for culture. We used logistic regression to develop an extended CPM (which included CRP and other predictors) and a CRP-only CPM. We used internal–external cross-validation to evaluate performance. Results: We pooled data from eight cohorts (n=4315 participants). The extended CPM had excellent discrimination (C-statistic 0.81); the CRP-only CPM had similar discrimination. The C-statistics for WHO-recommended tools were lower. Both CPMs had equivalent or higher net benefit compared with the WHO-recommended tools. Compared with both CPMs, CRP (5 mg·L−1 cut-off) had equivalent net benefit across a clinically useful range of threshold probabilities, while the W4SS had a lower net benefit. The W4SS would capture 91% of tuberculosis cases and require confirmatory testing for 78% of participants. CRP (5 mg·L−1 cut-off), the extended CPM (4.2% threshold) and the CRP-only CPM (3.6% threshold) would capture similar percentages of cases but reduce confirmatory tests required by 24, 27 and 36%, respectively. Conclusions: CRP sets the standard for tuberculosis screening among outpatient PLHIV. The choice between using CRP at 5 mg·L−1 cut-off or in a CPM depends on available resources.