Reeve, BWP; Ndlangalavu, G; Mishra, H; Palmer, Z; Tshivhula, H; Rockman, L; Naidoo, S; ... Theron, G; + view all Reeve, BWP; Ndlangalavu, G; Mishra, H; Palmer, Z; Tshivhula, H; Rockman, L; Naidoo, S; Mbu, DL; Naidoo, CC; Derendinger, B; Walzl, G; Malherbe, ST; van Helden, PD; Semitala, FC; Yoon, C; Gupta, RK; Noursadeghi, M; Warren, RM; Theron, G; - view fewer (2024) Point-of-care C-reactive protein and Xpert MTB/RIF Ultra for tuberculosis screening and diagnosis in unselected antiretroviral therapy initiators: a prospective, cross-sectional, diagnostic accuracy study. The Lancet Global Health , 12 (5) e793-e803. 10.1016/S2214-109X(24)00052-4.

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Abstract

Background: Tuberculosis, a major cause of death in people living with HIV, remains challenging to diagnose. Diagnostic accuracy data are scarce for promising triage and confirmatory tests such as C-reactive protein (CRP), sputum and urine Xpert MTB/RIF Ultra (Xpert Ultra), and urine Determine TB LAM Ag (a lateral flow lipoarabinomannan [LF-LAM] test), without symptom selection. We evaluated novel triage and confirmatory tests in ambulatory people with HIV initiating antiretroviral therapy (ART). Methods: 897 ART-initiators were recruited irrespective of symptoms and sputum induction offered. For triage (n=800), we evaluated point-of-care blood-based CRP testing, compared with the WHO-recommended four-symptom screen (W4SS). For sputum-based confirmatory testing (n=787), we evaluated Xpert Ultra versus Xpert MTB/RIF (Xpert). For urine-based confirmatory testing (n=732), we evaluated Xpert Ultra and LF-LAM. We used a sputum culture reference standard. Findings: 463 (52%) of 897 participants were female. The areas under the receiver operator characteristic curves for CRP was 0·78 (95% CI 0·73–0·83) and for number of W4SS symptoms was 0·70 (0·64–0·75). CRP (≥10 mg/L) had similar sensitivity to W4SS (77% [95% CI 68–85; 80/104] vs 77% [68–85; 80/104]; p>0·99] but higher specificity (64% [61–68; 445/696] vs 48% [45–52; 334/696]; p<0·0001]; reducing unnecessary confirmatory testing by 138 (95% CI 117–160) per 1000 people and number-needed-to-test from 6·91 (95% CI 6·25–7·81) to 4·87 (4·41–5·51). Sputum samples with Xpert Ultra, which required induction in 49 (31%) of 158 of people (95% CI 24–39), had higher sensitivity than Xpert (71% [95% CI 61–80; 74/104] vs 56% [46–66; 58/104]; p<0·0001). Of the people with one or more confirmatory sputum or urine test results that were positive, the proportion detected by Xpert Ultra increased from 45% (26–64) to 66% (46–82) with induction. Programmatically done haemoglobin, triage test combinations, and urine tests showed comparatively worse results. Interpretation: CRP is a more specific triage test than W4SS in those initiating ART. Sputum induction improves diagnostic yield. Sputum samples with Xpert Ultra is a more accurate confirmatory test than with Xpert. Funding: South African Medical Research Council, EDCTP2, US National Institutes of Health–National Institute of Allergy and Infectious Diseases.

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