Tuberculosis (TB) remains a leading cause of infectious-disease-related morbidity and mortality worldwide, including in low-incidence, high-income countries, where cases increasingly cluster among vulnerable populations. In these settings, persistent diagnostic and treatment delays, rather than a lack of therapeutic options, drive preventable morbidity, ongoing transmission, and inappropriate antimicrobial use. We argue that TB antimicrobial stewardship must extend beyond treatment adherence and resistance containment to encompass the entire diagnostic continuum. Emerging evidence demonstrating a substantial burden of subclinical and asymptomatic TB challenges symptom-based diagnostic paradigms and reveals an underrecognized “asymptomatic delay”, during which radiologic or microbiologic disease is present but undetected. Failure to identify TB during this interval represents a critical stewardship failure, perpetuating empirical broad-spectrum antibiotic exposure while allowing disease progression and transmission. We review diagnostic challenges across the early clinical spectrum of pulmonary and extrapulmonary TB in low-incidence settings, with particular emphasis on migrants and other high-risk populations disproportionately affected by structural and healthcare system barriers. We propose a stewardship-oriented framework integrating targeted screening, enhanced clinical vigilance, front-loaded and parallel diagnostic pathways, and early referral to specialized TB centers. Explicit incorporation of asymptomatic delay into TB diagnostic frameworks can strengthen system accountability, reduce inappropriate antibiotic use, improve patient outcomes, and accelerate progress toward TB elimination in high-income, low-incidence countries.
Benevento et al. (Thu,) studied this question.