Despite being preventable and curable, tuberculosis (TB) remains the leading cause of death from a single infectious agent globally. In 2024, an estimated 10.7 million people developed TB, yet only 8.3 million were diagnosed, reflecting significant diagnostic gaps. These “missing millions” underscore systemic weaknesses within the TB pathology value chain, defined here as the sequence of processes from patient identification and specimen collection through testing, result reporting, linkage to treatment and monitoring. This review highlights key challenges and opportunities across each step of this chain, with a focus on diagnostic bottlenecks and innovations to improve accessibility, efficiency, and patient-centred care. Sputum remains the primary diagnostic specimen, but it presents barriers for individuals unable to expectorate, such as children and people with HIV. Additional specimens, including stool (for adults), urine (for molecular testing), blood, breath, saliva and oral rinse, show promise, but require further validation. Laboratory constraints, particularly in transport logistics and result turnaround times, contribute to diagnostic delays and patient attrition. While molecular tests and next-generation sequencing have improved TB detection and drug resistance profiling, their decentralization remains limited by infrastructural and financial barriers. Digital tools for result reporting and patient tracking show promise but need broader integration. Near point-of-care technologies and novel diagnostics tailored to regional needs can close critical gaps, reduce loss to follow-up, and support earlier treatment initiation. Ultimately, strengthening the TB diagnostic value chain requires coordinated investments, innovative technologies, and policy frameworks that support equitable access to timely diagnosis and care, particularly in high-burden settings.
David et al. (Tue,) studied this question.