Asymptomatic Tuberculosis Across the Disease Spectrum: A Scoping Review of Epidemiology, Diagnosis, and Public Health Implications

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Abstract
Background: Tuberculosis (TB) remains a leading infectious cause of death globally. While control strategies have traditionally prioritized symptomatic cases, growing evidence highlights the substantial burden of asymptomatic or subclinical TB, microbiologically confirmed disease without classical symptoms, posing challenges for detection, treatment, and elimination efforts. Methods: We conducted a scoping review in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. We selected epidemiological studies, prevalence surveys, modeling analyses, and recent World Health Organization (WHO) guidance to summarize the current understanding of asymptomatic TB. We examined definitions, diagnostic approaches, transmission potential, natural history, and public health implications, with special focus on vulnerable populations. Results: Prevalence surveys reveal that up to 30%–50% of bacteriologically confirmed TB cases may be asymptomatic at diagnosis, many of whom remain undetected under symptom-based screening. A substantial fraction of these individuals is smear positive, underscoring their potential role in community transmission. Despite clinical silence, radiographic and molecular studies demonstrate ongoing lung pathology and immune activation, with 20%–30% progressing to symptomatic disease within 2 years. Diagnostic challenges include low bacillary burden and inability to expectorate sputum, though innovations, such as computer-aided radiography, sputum pooling, and host transcriptomic biomarkers, are advancing detection. Conclusions: Asymptomatic TB represents a hidden but consequential component of the TB disease spectrum. Recognition and integration of this stage into TB control frameworks are essential for accurate burden estimation, timely treatment, and achievement of elimination targets. Future efforts must focus on scalable diagnostics, biomarker validation, and equitable screening strategies tailored to vulnerable populations.
Funding Information
  • Fundação Oswaldo Cruz
  • National Institutes of Health (66560)
  • Conselho Nacional de Desenvolvimento Científico e Tecnológico (U01AI174268)
  • Department of Biotechnology, Government of West Bengal
  • Indian Council of Medical Research
  • National Institute of Allergy and Infectious Diseases
  • Office of AIDS Research
  • CRDF Global
  • South African Medical Research Council (G-202403-71788)

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