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Lancet Infect. Dis., Oct 07 2025, S1473-3099(25)00536-5 | https://doi.org/10.1016/S1473-3099(25)00536-5
Long-term risk of tuberculosis among individuals with Xpert Ultra trace screening results in Uganda: a longitudinal follow-up study
Joowhan Sung MD a,b, Mariam Nantale MPH b, Annet Nalutaaya MS b, Patrick Biché MPH c, James Mukiibi b, Joab Akampurira b, Rogers Kiyonga b, Francis Kayondo b, Michael Mukiibi b, Caitlin Visek MD a, Caleb E Kamoga b, Prof David W Dowdy MD b,c, Achilles Katamba PhD b,d, Emily A Kendall MD a,b,c
aDivision of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD, USA
bUganda Tuberculosis Implementation Research Consortium, Walimu, Kampala, Uganda
cJohns Hopkins Bloomberg School of Public Health, Department of Epidemiology, Baltimore, MD, USA
dMakerere University College of Health Science, Department of Internal Medicine, Clinical Epidemiology and Biostatistics Unit, Kampala, Uganda
Correspondence to: Dr Joowhan Sung
aDivision of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD, USA
bUganda Tuberculosis Implementation Research Consortium, Walimu, Kampala, Uganda
cJohns Hopkins Bloomberg School of Public Health, Department of Epidemiology, Baltimore, MD, USA
dMakerere University College of Health Science, Department of Internal Medicine, Clinical Epidemiology and Biostatistics Unit, Kampala, Uganda
Correspondence to: Dr Joowhan Sung
Abstract
Background: Systematic screening for tuberculosis using Xpert Ultra can generate 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 2-year risk of tuberculosis among screened participants with trace-positive sputum (PWTS).
Methods: In this longitudinal follow-up study, we conducted Ultra-based systematic screening for tuberculosis in Kampala, Uganda, from Feb 2, 2021, to April 27, 2024, enrolling PWTS as well as participants who were Ultra-positive or Ultra-negative controls. Recruitment occurred primarily through community-based screening events and door-to-door screening. Ultra sputum testing was offered to individuals aged 15 years or older who were not on active tuberculosis treatment, regardless of their symptoms. All PWTS, as well as age-matched and sex-matched participants with negative screening results and consecutive participants with positive screening results, were recruited. Participants underwent extensive initial evaluation, and untreated PWTS and negative-control participants were followed up with re-testing for up to 24 months. Our primary outcome was the cumulative hazard of tuberculosis among PWTS, using two definitions of tuberculosis: one incorporating clinician judgement and one strictly microbiological. We then compared hazards between PWTS and negative-control participants. We also assessed whether the presence of symptoms or chest x-ray abnormalities at baseline were associated with tuberculosis diagnosis during follow-up in PWTS.
Findings: 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 PWTS and 139 age-matched and sex-matched control participants who were Ultra-negative (negative-control participants) into prospective cohorts and 110 control participants who were Ultra-positive (more than trace) for cross-sectional comparison. Of 128 PWTS, 79 (62%) were male, 49 (38%) were female, and 19 (15%) were HIV positive; 45 (35%) were recommended for treatment upon enrolment, eight (6%) were lost to follow-up within 3 months, and 75 (56%) were followed up for a median of 706 days (IQR 344-714), of whom 19 (25%) were recommended for treatment during follow-up. The cumulative hazard of tuberculosis among PWTS not treated at baseline was 0·24 (95% CI 0·15-0·40) at 1 year and 0·33 (0·21-0·54) at 2 years, versus 0·03 (0·01-0·10) at 2 years for negative-control participants. Hazards were similar for microbiologically defined tuberculosis (0·36 [95% CI 0·22-0·58] for PWTS vs 0·02 [0·01-0·10] for negative-control participants at 2 years). Tuberculosis diagnosis during follow-up was strongly associated with atypical baseline chest x-ray (ie, interpreted by radiologists as having any abnormality; hazard ratio 14·6 [95% CI 3·3-63·8]) but not with baseline symptoms (cough, fever, night sweats, or weight loss).
Interpretation: Individuals with trace-positive sputum during screening have a substantial 2-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 atypical chest imaging.
Methods: In this longitudinal follow-up study, we conducted Ultra-based systematic screening for tuberculosis in Kampala, Uganda, from Feb 2, 2021, to April 27, 2024, enrolling PWTS as well as participants who were Ultra-positive or Ultra-negative controls. Recruitment occurred primarily through community-based screening events and door-to-door screening. Ultra sputum testing was offered to individuals aged 15 years or older who were not on active tuberculosis treatment, regardless of their symptoms. All PWTS, as well as age-matched and sex-matched participants with negative screening results and consecutive participants with positive screening results, were recruited. Participants underwent extensive initial evaluation, and untreated PWTS and negative-control participants were followed up with re-testing for up to 24 months. Our primary outcome was the cumulative hazard of tuberculosis among PWTS, using two definitions of tuberculosis: one incorporating clinician judgement and one strictly microbiological. We then compared hazards between PWTS and negative-control participants. We also assessed whether the presence of symptoms or chest x-ray abnormalities at baseline were associated with tuberculosis diagnosis during follow-up in PWTS.
Findings: 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 PWTS and 139 age-matched and sex-matched control participants who were Ultra-negative (negative-control participants) into prospective cohorts and 110 control participants who were Ultra-positive (more than trace) for cross-sectional comparison. Of 128 PWTS, 79 (62%) were male, 49 (38%) were female, and 19 (15%) were HIV positive; 45 (35%) were recommended for treatment upon enrolment, eight (6%) were lost to follow-up within 3 months, and 75 (56%) were followed up for a median of 706 days (IQR 344-714), of whom 19 (25%) were recommended for treatment during follow-up. The cumulative hazard of tuberculosis among PWTS not treated at baseline was 0·24 (95% CI 0·15-0·40) at 1 year and 0·33 (0·21-0·54) at 2 years, versus 0·03 (0·01-0·10) at 2 years for negative-control participants. Hazards were similar for microbiologically defined tuberculosis (0·36 [95% CI 0·22-0·58] for PWTS vs 0·02 [0·01-0·10] for negative-control participants at 2 years). Tuberculosis diagnosis during follow-up was strongly associated with atypical baseline chest x-ray (ie, interpreted by radiologists as having any abnormality; hazard ratio 14·6 [95% CI 3·3-63·8]) but not with baseline symptoms (cough, fever, night sweats, or weight loss).
Interpretation: Individuals with trace-positive sputum during screening have a substantial 2-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 atypical chest imaging.
논문정보
- Research article
- 2025년 10월 (BRIC 등록일 2025-12-03)
- 국외 연구진
- 의약학 > 감염의학
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