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Publications

Journal Article Preprint Epublish 7 citations

PubMed: 40166571 DOI: 10.1101/2025.03.20.25324205

The long-term risk of tuberculosis among individuals with Xpert Ultra "trace" screening results: a longitudinal follow-up study.

medRxiv

Authors: Joowhan Sung, Mariam Nantale, Annet Nalutaaya, Patrick Biché, James Mukiibi, Joab Akampurira, Rogers Kiyonga, Francis Kayondo, Michael Mukiibi, Caitlin Visek, Caleb E Kamoga, David W Dowdy, Achilles Katamba, Emily A Kendall

Affiliations

  • Johns Hopkins University School of Medicine, Division of Infectious Diseases, Baltimore, MD, USA.
  • Uganda Tuberculosis Implementation Research Consortium, Walimu, Kampala, Uganda.
  • Johns Hopkins Bloomberg School of Public Health, Department of Epidemiology, Baltimore, MD, USA.
  • Makerere University College of Health Science, Department of Internal Medicine, Clinical Epidemiology and Biostatistics Unit, Kampala, Uganda.

Abstract

Background

Systematic screening for tuberculosis using Xpert Ultra generates "trace" results of uncertain significance. Additional microbiological testing in this context is often negative, but untreated individuals might still progress to culture-positive disease. We aimed to estimate the two-year risk of tuberculosis among screening participants with trace-positive sputum.

Methods

We screened 31,505 people for tuberculosis in Uganda using sputum Xpert Ultra as an initial test, through event-based and door-to-door screening. We enrolled 128 participants with trace-positive sputum (PWTS), 139 Ultra-negative controls into a prospective cohort, and 110 Ultra-positive (>trace) controls for cross-sectional comparison. All participants underwent extensive initial evaluation, and untreated PWTS and negative controls were followed with re-testing for up to 24 months. We estimated cumulative hazards of tuberculosis among PWTS versus negative controls, using two definitions of tuberculosis: one incorporating clinician judgment (primary) and one based strictly on microbiological results (secondary). We then compared hazards between subgroups of PWTS.

Findings

Of 128 PWTS, 79 (62%) were male and 19 (15%) HIV-positive. Forty-five (35%) PWTS were recommended for treatment upon enrollment, eight lost to follow-up within three months, and 75 followed for median 706 (interquartile range 344-714) days, of whom 19 were recommended for treatment during follow-up. The cumulative hazard of tuberculosis among PWTS not treated at baseline was 0.24 (95% confidence interval: 0.15-0.40) at one year and 0.33 (0.21-0.54) at two years, versus 0.03 (0.01-0.10) at two years for negative controls. Hazards were similar for microbiologically defined tuberculosis (0.36 [0.22-0.58] at 2 years). Tuberculosis diagnosis during follow-up was strongly associated with abnormal baseline chest X-ray (hazard ratio 14.6 [3.3-63.8]) but not with baseline symptoms.

Interpretation

Individuals with trace-positive sputum during screening have a substantial two-year risk of tuberculosis, even when extensive initial evaluations do not confirm disease. Treatment should be considered for most screening participants with trace-positive sputum and abnormal chest imaging.

Funding

National Institutes of Health and Gates Foundation.

MeSH

Research Design, Incidence, Follow-Up Studies, Sputum, Tuberculosis, Therapeutics