Urine-Xpert Ultra for the diagnosis of tuberculosis in people living with HIV: a prospective, multicentre, diagnostic accuracy study.

Autor:	Sossen B; Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa., Székely R; FIND, Geneva, Switzerland., Mukoka M; Public Health Group, Malawi-Liverpool-Wellcome Programme, Blantyre, Malawi; Department of Pathology, Kamuzu University of Health Sciences, Blantyre, Malawi., Muyoyeta M; Centre for Infectious Diseases Research in Zambia, Lusaka, Zambia., Nakabugo E; Infectious Diseases Institute, Makerere University, Kampala, Uganda., Hella J; Ifakara Health Institute, Dar es Salaam, Tanzania., Van Nguyen H; National Lung Hospital, Ha Noi, Viet Nam., Ubolyam S; HIV-NAT, Thai Red Cross AIDS Research Centre, Bangkok, Thailand; Center of Excellence in Tuberculosis, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand., Erkosar B; FIND, Geneva, Switzerland., Vermeulen M; Wellcome Center for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa., Centner CM; Division of Medical Microbiology, University of Cape Town, Cape Town, South Africa; National Health Laboratory Service, Groote Schuur Hospital, Cape Town, South Africa., Nyangu S; Centre for Infectious Diseases Research in Zambia, Lusaka, Zambia., Sanjase N; Centre for Infectious Diseases Research in Zambia, Lusaka, Zambia., Sasamalo M; Ifakara Health Institute, Dar es Salaam, Tanzania., Dinh HT; National Lung Hospital, Ha Noi, Viet Nam., Ngo TA; Viet Tiep Hospital, Hai Phong, Viet Nam., Manosuthi W; Bamrasnaradura Infectious Diseases Institute, Nonthaburi, Thailand., Jirajariyavej S; Taksin Hospital, Bangkok, Thailand., Nguyen NV; National Lung Hospital, Ha Noi, Viet Nam., Avihingsanon A; HIV-NAT, Thai Red Cross AIDS Research Centre, Bangkok, Thailand; Center of Excellence in Tuberculosis, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand., Kerkhoff AD; Division of HIV, Infectious Diseases, and Global Medicine, Zuckerberg San Francisco General Hospital and Trauma Center, University of California San Francisco, San Francisco, CA, USA., Denkinger CM; FIND, Geneva, Switzerland; Division of Infectious Disease and Tropical Medicine, Heidelberg University Hospital, Heidelberg, Germany; Faculty of Medicine, Heidelberg University, Heidelberg, Germany; German Centre for infection Research (DZIF), partner site Heidelberg University Hospital, Heidelberg, Germany., Reither K; Swiss Tropical and Public Health Institute, Allschwil, Switzerland; University of Basel, Basel, Switzerland., Nakiyingi L; Infectious Diseases Institute, Makerere University, Kampala, Uganda., MacPherson P; Public Health Group, Malawi-Liverpool-Wellcome Programme, Blantyre, Malawi; School of Health and Wellbeing, University of Glasgow, Glasgow, UK; Clinical Research Department, London School of Hygiene & Tropical Medicine, London, UK., Meintjes G; Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa; Wellcome Center for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa., Ruhwald M; FIND, Geneva, Switzerland. Electronic address: morten.ruhwald@finddx.org.
Jazyk:	angličtina
Zdroj:	The Lancet. Global health [Lancet Glob Health] 2024 Dec; Vol. 12 (12), pp. e2024-2034.
DOI:	10.1016/S2214-109X(24)00357-7
Abstrakt:	Background: Diagnostic delays for tuberculosis are common, with high resultant mortality. Urine-Xpert Ultra (Cepheid) could improve time to diagnosis of tuberculosis disease and rifampicin resistance. We previously reported on lot-to-lot variation of the Fujifilm SILVAMP TB LAM. In this prespecified secondary analysis of the same cohort, we aimed to determine the diagnostic yield and accuracy of Urine-Xpert Ultra for tuberculosis in people with HIV, compared with an extended microbiological reference standard (eMRS) and composite reference standard (CRS) and also compared with Determine TB LAM Ag (AlereLAM, Abbott). Methods: In this prospective, multicentre, diagnostic accuracy study, we recruited consecutive inpatients and outpatients (aged ≥18 years) with HIV from 13 hospitals and clinics in seven countries (Malawi, South Africa, Tanzania, Thailand, Uganda, Viet Nam, and Zambia). Patients with no isoniazid preventive therapy in the past 6 months and fewer than three doses of tuberculosis treatment in the past 60 days were included. Reference and index testing was performed in real time. The primary outcome of this secondary analysis was the diagnostic yield and accuracy of Urine-Xpert Ultra compared with the eMRS and CRS. Diagnostic accuracy was compared with AlereLAM and diagnostic yield was compared with both AlereLAM and Sputum-Xpert Ultra. This study was registered with ClinicalTrials.gov, NCT04089423, and is complete. Findings: Between Dec 13, 2019, and Aug 5, 2021, 3528 potentially eligible individuals were screened and 1731 were enrolled, of whom 1602 (92·5%) were classifiable by the eMRS (median age 40 years [IQR 33-48], 838 [52·3%] of 1602 were female, 764 [47·7%] were male, 937 [58·5%] were outpatients, 665 [41·5%] were inpatients, median CD4 count was 374 cells per μL [IQR 138-630], and 254 [15·9%] had microbiologically confirmed tuberculosis). Against eMRS as reference, sensitivities of Urine-Xpert Ultra and AlereLAM were 32·7% (95% CI 27·2-38·7) and 30·7% (25·4-36·6) and specificities were 98·0% (97·1-98·6) and 90·4% (88·7-91·8), respectively. Against CRS as reference, sensitivities of Urine-Xpert Ultra and AlereLAM were 21·1% (95% CI 17·6-25·1), and 30·5% (26·4-34·9), and specificities were 99·1% (98·3-99·6) and 95·1% (93·5-96·3), respectively. The combination of Sputum-Xpert Ultra with AlereLAM or Urine-Xpert Ultra diagnosed 202 (77·1%) and 204 (77·9%) of 262 eMRS-positive participants, respectively, in incompletely overlapping groups; combining all three tests diagnosed 214 (81·7%) of 262 eMRS-positive participants INTERPRETATION: Urine-Xpert Ultra could offer promising clinical utility in addition to AlereLAM and Sputum-Xpert Ultra. In inpatient settings where both AlereLAM and Urine-Xpert Ultra are possible, both should be offered to support rapid diagnosis and treatment. Funding: Global Health Innovative Technology Fund, KfW Development Bank, Commonwealth of Australia represented by the Department of Foreign Affairs and Trade, and the Netherlands Enterprise Agency. Competing Interests: Declaration of interests RS, BE, CMD, and MR are or were employed by FIND, the global alliance for diagnostics, at the time of the study; FIND is a not-for-profit foundation that supports the evaluation of publicly prioritised tuberculosis assays and the implementation of WHO-approved (guidance and prequalification) assays using donor grants; FIND has product evaluation agreements with several private sector companies that design diagnostics for tuberculosis and other diseases; these agreements strictly define FIND's independence and neutrality with regard to these private sector companies. CMD reports funding from the US National Institutes of Health for the R2D2 project (1U01AI152087-01). All other authors declare no competing interests. (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)
Databáze:	MEDLINE
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