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

    European respiratory review, 06/2023, Letnik: 32, Številka: 168
    Journal Article

    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 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). 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. 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 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 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. CRP sets the standard for tuberculosis screening among outpatient PLHIV. The choice between using CRP at 5 mg·L cut-off or in a CPM depends on available resources.