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
Byron W P Reeve PhD, Gcobisa Ndlangalavu PhD, Hridesh Mishra PhD, Zaida Palmer MSc, Happy Tshivhula PhD, Loren Rockman BSc (Hons), Selisha Naidoo MSc, Desiree L Mbu MSc, Charissa C Naidoo PhD, Brigitta Derendinger PhD, Prof Gerhard Walzl MD PhD, Stephanus T Malherbe MD PhD, Prof Paul D van Helden PhD, Fred C Semitala MD, Christina Yoon MD, Rishi K Gupta MRCP PhD, Prof Mahdad Noursadeghi FRCP PhD, Prof Robin M Warren PhD, Prof Grant Theron PhD
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引用次数: 0
Abstract
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). 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. 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] 77% [68–85; 80/104]; p>0·99] but higher specificity (64% [61–68; 445/696] 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] 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. 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. South African Medical Research Council, EDCTP2, US National Institutes of Health–National Institute of Allergy and Infectious Diseases.
期刊介绍:
The Lancet Global Health is an online publication that releases monthly open access (subscription-free) issues.Each issue includes original research, commentary, and correspondence.In addition to this, the publication also provides regular blog posts.
The main focus of The Lancet Global Health is on disadvantaged populations, which can include both entire economic regions and marginalized groups within prosperous nations.The publication prefers to cover topics related to reproductive, maternal, neonatal, child, and adolescent health; infectious diseases (including neglected tropical diseases); non-communicable diseases; mental health; the global health workforce; health systems; surgery; and health policy.