Cumulative TB disease burden following sputum Xpert Ultra 'Trace' results in clinical settings: Results from a multi-site observational clinical study.

Λεπτομέρειες βιβλιογραφικής εγγραφής
Τίτλος:	Cumulative TB disease burden following sputum Xpert Ultra 'Trace' results in clinical settings: Results from a multi-site observational clinical study.
Συγγραφείς:	Dalmat RR; Department of Global Health, University of Washington, Seattle, Washington, USA., Visek C; Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA., Budiawan E; Department of Global Health, University of Washington, Seattle, Washington, USA., Stein G; Department of Global Health, University of Washington, Seattle, Washington, USA., Nalutaaya A; Uganda Tuberculosis Implementation Research Consortium, Walimu, Kampala, Uganda., Mukiibi J; Uganda Tuberculosis Implementation Research Consortium, Walimu, Kampala, Uganda., Nantale M; Uganda Tuberculosis Implementation Research Consortium, Walimu, Kampala, Uganda., Biché P; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA., Sung J; Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA., Magcaba Z; Umkhuseli Innovation and Research Management, Pietermaritzburg, South Africa., Ngcobo N; Umkhuseli Innovation and Research Management, Pietermaritzburg, South Africa., Morton JF; Department of Global Health, University of Washington, Seattle, Washington, USA., Lenn M; Department of Global Health, University of Washington, Seattle, Washington, USA., Aucock S; Umkhuseli Innovation and Research Management, Pietermaritzburg, South Africa., Shapiro AE; Department of Global Health, University of Washington, Seattle, Washington, USA.; Department of Medicine, University of Washington, Seattle, Washington, USA.; Department of Epidemiology, University of Washington, Seattle, Washington, USA., Steadman A; Global Health Labs, Inc., Bellevue, WA USA., Draper R; Umkhuseli Innovation and Research Management, Pietermaritzburg, South Africa.; Department of Internal Medicine, Harry Gwala Regional Hospital, University of KwaZulu-Natal, Pietermaritzburg, South Africa., Ganguloo A; Umkhuseli Innovation and Research Management, Pietermaritzburg, South Africa.; Department of Internal Medicine, Harry Gwala Regional Hospital, University of KwaZulu-Natal, Pietermaritzburg, South Africa., Wilson D; Umkhuseli Innovation and Research Management, Pietermaritzburg, South Africa.; Department of Internal Medicine, Harry Gwala Regional Hospital, University of KwaZulu-Natal, Pietermaritzburg, South Africa., Katamba A; Uganda Tuberculosis Implementation Research Consortium, Walimu, Kampala, Uganda.; Clinical Epidemiology & Biostatistics Unit, Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda., Kendall EA; Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA., Drain PK; Department of Global Health, University of Washington, Seattle, Washington, USA.; Department of Medicine, University of Washington, Seattle, Washington, USA.; Department of Epidemiology, University of Washington, Seattle, Washington, USA.
Πηγή:	MedRxiv : the preprint server for health sciences [medRxiv] 2025 Jul 15. Date of Electronic Publication: 2025 Jul 15.
Τύπος έκδοσης:	Journal Article; Preprint
Γλώσσα:	English
Στοιχεία περιοδικού:	Country of Publication: United States NLM ID: 101767986 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: medRxiv Subsets: PubMed not MEDLINE
Περίληψη:	Background: Highly sensitive molecular tests, like Xpert Ultra, are reshaping TB diagnosis-detecting paucibacillary TB but sometimes creating uncertainty when they detect DNA in extremely low quantities that may not signal disease. This ambiguity also complicates the evaluation of novel diagnostic strategies. We sought to monitor adults with a 'Trace' result on an Xpert Ultra test to estimate the risk of tuberculosis disease up to 24 months later. Methods: We conducted a multi-site clinical observational study in South Africa and Uganda, where we enrolled ambulatory participants aged >=15 years with a sputum Xpert Ultra Trace result who had not yet initiated TB treatment. All participants underwent comprehensive clinical evaluation and repeated, standard sputum TB testing. Clinicians deferred treatment recommendations if TB status remained uncertain after evaluation. Untreated participants were followed regularly until TB diagnosis and/or treatment initiation. We estimated cumulative incidence of TB disease, defined by three reference standards. Results: Of 311 participants with Trace results (50% male, 57% PLHIV, 37% treated for TB within the last 5 years), 24% were positive for TB within 12 months by culture, 37% by sputum Xpert or culture, and 54% by culture or clinical diagnosis. After excluding those diagnosed with TB at baseline, patients identified at baseline as having recent TB history, abnormal chest x-ray, or positive tongue swab, had higher risk of TB diagnosis (hazard ratios: 2.6, 2.4, 4.5, respectively) during follow-up. This hazard was highest in the first three months after the negative baseline evaluation (0.22 [95% CI: 0.19-0.26] per person-month) and decreased to 0.01 [95% CI: 0-0.02] per person-month in both the 3-6 and 6-12-month intervals. Conclusion: Approximately half of adults and adolescents with a sputum Trace result were diagnosed with TB disease within twelve months. Although most TB diagnoses were made within 3 months, risk remained higher than estimated population incidence rates through the follow-up period. Individuals with sputum Trace results should receive close clinical monitoring, despite initial clinical treatment decision.
Competing Interests:	AES has received funding from Merck as a clinical trials investigator for work unrelated to this study. PKD reports receiving research funding, paid to his institution, from the US National Institutes of Health, US Centers for Disease Control and Prevention, Bill and Melinda Gates Foundation, Abbott Laboratories, and InBios International; and scientific advisory board (SAB) and/or consulting fees from Abbott Diagnostics, Abbvie, Cepheid, InBios International, PATH, OraSure, Revvity, Roche and Quidel. All authors declare no conflicts of interest.
References:	Clin Infect Dis. 2024 May 15;78(5):1313-1320. (PMID: 38306491) Eur J Case Rep Intern Med. 2020 Jul 06;7(10):001737. (PMID: 33083351) J Clin Microbiol. 2018 Feb 22;56(3):. (PMID: 29305538) Int J Infect Dis. 2022 Jan;114:115-123. (PMID: 34740802) Public Health Action. 2022 Mar 21;12(1):28-33. (PMID: 35317531) PLoS One. 2022 Aug 12;17(8):e0272997. (PMID: 35960758) Int J Mycobacteriol. 2021 Jan-Mar;10(1):101-103. (PMID: 33707382) Clin Microbiol Rev. 2018 Jul 18;31(4):. (PMID: 30021818) Lancet Infect Dis. 2018 Jan;18(1):76-84. (PMID: 29198911) Clin Infect Dis. 2026 Mar 20;:. (PMID: 41858248) Clin Infect Dis. 2023 May 3;76(9):1594-1603. (PMID: 36610730) Clin Infect Dis. 2016 Apr 15;62(8):995-1001. (PMID: 26908793) Cochrane Database Syst Rev. 2014 Jan 21;(1):CD009593. (PMID: 24448973) mBio. 2017 Aug 29;8(4):. (PMID: 28851844) Lancet Infect Dis. 2026 Feb;26(2):203-212. (PMID: 41072452)
Grant Information:	K23 AI185268 United States AI NIAID NIH HHS; R01 HL153611 United States HL NHLBI NIH HHS
Contributed Indexing:	Keywords: GeneXpert; Trace; Tuberculosis; diagnostics; paucibacillary
Entry Date(s):	Date Created: 20250812 Date Completed: 20250914 Latest Revision: 20260322
Update Code:	20260322
PubMed Central ID:	PMC12338891
DOI:	10.1101/2025.07.14.25331384
PMID:	40791690
Βάση Δεδομένων:	MEDLINE

Περιγραφή
DOI:	10.1101/2025.07.14.25331384