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Diagnostic accuracy of WHO screening criteria to guide lateral-flow lipoarabinomannan testing among HIV-positive inpatients: A systematic review and individual participant data meta-analysis

Dhana, Ashar; Hamada, Yohhei; Kengne, Andre P; Kerkhoff, Andrew D; Broger, Tobias; Denkinger, Claudia M; Rangaka, Molebogeng X; ... Maartens, Gary; + view all (2022) Diagnostic accuracy of WHO screening criteria to guide lateral-flow lipoarabinomannan testing among HIV-positive inpatients: A systematic review and individual participant data meta-analysis. Journal of Infection , 85 (1) pp. 40-48. 10.1016/j.jinf.2022.05.010. Green open access

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Abstract

BACKGROUND: WHO recommends urine lateral-flow lipoarabinomannan (LF-LAM) testing with AlereLAM in HIV-positive inpatients only if screening criteria are met. We assessed the performance of WHO screening criteria and alternative screening tests/strategies to guide LF-LAM testing and compared diagnostic accuracy of the WHO AlereLAM algorithm (WHO screening criteria → AlereLAM) with AlereLAM and FujiLAM (a novel LF-LAM test). METHODS: We searched MEDLINE, Embase, and Cochrane Library from Jan 1, 2011 to March 1, 2020 for studies among adult/adolescent HIV-positive inpatients regardless of tuberculosis signs and symptoms. The reference standards were 1) AlereLAM or FujiLAM for screening tests/strategies and 2) culture or Xpert for AlereLAM/FujiLAM. We determined proportion of inpatients eligible for AlereLAM using WHO screening criteria; assessed accuracy of WHO criteria and alternative screening tests/strategies to guide LF-LAM testing; compared accuracy of WHO AlereLAM algorithm with AlereLAM/FujiLAM in all; and determined diagnostic yield of AlereLAM, FujiLAM, and Xpert MTB/RIF (Xpert). We estimated pooled proportions with a random-effects model, assessed diagnostic accuracy using random-effects bivariate models, and assessed diagnostic yield descriptively. FINDINGS: We obtained data from all 5 identified studies (n=3,504). The pooled proportion of inpatients eligible for AlereLAM using WHO criteria was 93% (95%CI 91, 95). Among screening tests/strategies to guide LF-LAM testing, WHO criteria, C-reactive protein (≥5 mg/L), and CD4 count (<200 cells/μL) had high sensitivities but low specificities; cough (≥2 weeks), haemoglobin (<8 g/dL), body mass index (<18.5 kg/m2), lymphadenopathy, and WHO-defined danger signs had higher specificities but suboptimal sensitivities. AlereLAM in all had the same sensitivity (62%) and specificity (88%) as WHO AlereLAM algorithm. Sensitivity of FujiLAM and AlereLAM was 69% and 48%, while specificity was 48% and 96%, respectively. Diagnostic yield of sputum Xpert was 29-41%, AlereLAM was 39-76%, and urine Xpert was 35-62%. In one study, FujiLAM diagnosed 80% of tuberculosis cases (vs 39% for AlereLAM), and sputum Xpert combined with AlereLAM, urine Xpert, or FujiLAM diagnosed 69%, 81%, and 92% of all cases, respectively. INTERPRETATION: WHO criteria and alternative screening tests/strategies have limited utility in guiding LF-LAM testing, suggesting that AlereLAM testing in all HIV-positive medical inpatients be implemented. Routine FujiLAM may improve tuberculosis diagnosis. FUNDING: None.

Type: Article
Title: Diagnostic accuracy of WHO screening criteria to guide lateral-flow lipoarabinomannan testing among HIV-positive inpatients: A systematic review and individual participant data meta-analysis
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.jinf.2022.05.010
Publisher version: https://doi.org/10.1016/j.jinf.2022.05.010
Language: English
Additional information: This version is the author accepted manuscript. // This research was funded, in part, by the Wellcome Trust (203135/Z/16/Z; 214321/Z/18/Z). For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission.
Keywords: Tuberculosis, Human immunodeficiency virus, Inpatient, Screening, Sensitivity, Specificity, Diagnosis, LAM, Lipoarabinomannan
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute for Global Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute for Global Health > Infection and Population Health
URI: https://discovery.ucl.ac.uk/id/eprint/10149133
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