Recent advances in the development and deployment of antituberculosis drugs have been underpinned by an improved understanding of their pharmacokinetic-pharmacodynamic behavior in the complex context of tuberculosis disease in the host. New information from novel technologies has helped to clarify aspects of drug distribution and action, which contribute to the critical clinical phenomena of persistence and resistance in Mycobacterium tuberculosis (Mtb), while effective integration of these data through quantitative pharmacology tools has facilitated more rational decision-making in preclinical and clinical drug development. This new framework permits a much more extensive and efficient evaluation of the space of novel and repurposed multidrug regimens in tuberculosis with the expectation of accelerating the arrival of even shorter, safer, and more effective treatments in the clinic.
Post-tuberculosis lung disease (PTLD) is an increasingly recognized consequence of pulmonary tuberculosis (TB) disease, affecting millions of survivors worldwide and imposing substantial clinical, functional, and socioeconomic burdens. This narrative review synthesizes current evidence across epidemiology, definitions, clinical phenotypes, assessment, and management, with dedicated consideration of children and adolescents. PTLD is common: Studies report abnormal spirometry in ∼60% of TB survivors and persistent, activity-limiting dyspnea in a sizeable minority. Outcomes are generally worse in low- and middle-income settings. The 2019 international consensus definition-"evidence of chronic respiratory abnormality attributable at least in part to prior TB"-has catalyzed research and service development; a newer research definition proposes a structured, three-domain approach (symptoms, radiology, lung function) and introduces "post-TB lung abnormality" for single-domain findings. PTLD encompasses heterogeneous patterns, including fibrosis, cavitation with chronic pulmonary aspergillosis risk, bronchiectasis, airflow obstruction, tracheobronchial stenosis, pleural disease, vascular complications, and pulmonary hypertension. Assessment should integrate symptom review, exercise capacity, oximetry, spirometry (with Global Lung Initiative [GLI] reference standards), and context-appropriate imaging, alongside targeted microbiology and echocardiography where indicated. Evidence for disease-modifying therapy remains limited; however, pulmonary rehabilitation improves function and symptoms, and selected patients may benefit from inhaled bronchodilators or surgical interventions. A "treatable traits" framework-spanning pulmonary, extrapulmonary, and behavioral risk domains-offers a pragmatic, person-centered strategy while high-quality trials mature. In children, TB during critical periods of lung development confers lasting functional and growth impacts, underscoring the need for age-specific screening and follow-up. We outline key research priorities: embedding PTLD outcomes in TB trials, standardizing measurement, elucidating mechanisms, evaluating host-directed therapies, and integrating post-TB care into routine health services.
Tuberculosis (TB) care and prevention have long relied on the assumption that individuals with the disease will seek care once they become aware of symptoms. However, national prevalence surveys show that nearly half of bacteriologically confirmed TB cases report no symptoms at screening, challenging this paradigm. The World Health Organization (WHO) now recognizes asymptomatic TB as part of the disease spectrum and promotes symptom-agnostic screening strategies to identify and treat these individuals. Evidence suggests that asymptomatic TB could be contributing to transmission, although further research is needed. While defining symptom status remains imprecise, individuals with asymptomatic TB present distinct diagnostic and treatment challenges. Asymptomatic pulmonary TB typically involves more limited disease, lower bacillary burden, and difficulty producing sputum, reducing the sensitivity of current sputum-based tests. Novel diagnostic approaches, including alternative sampling and molecular tools, are under development. Treatment uptake and adherence are another concern, as individuals feel well and derive no immediate symptomatic benefit, increasing the risk of poor initiation and completion. Addressing these gaps through improved diagnostics, shorter and better-tolerated regimens, and enhanced treatment support is essential. Recognizing and targeting asymptomatic TB is critical to interrupt transmission and accelerate progress toward global TB elimination.
Although the airborne route of Mycobacterium tuberculosis has been known for more than 60 years, and suspected long before that, there remains controversy over exactly how transmission occurs and how to prevent it. From an infectious particle perspective, the Wells-Riley equation simplifies understanding the interrelationship of some but not all relevant factors, and many assumptions are made that we know are untrue, like steady-state, well-mixed conditions, uniform virulence of infectious particles, and uniform susceptibility of exposed hosts. The source strength of infectious individuals is an important unknown factor. Retrospectively, the infection rate is used to calculate the infectious dose generation rate (quanta/h). A recent controversy is the importance of presymptomatic tuberculosis (TB) and quiet breathing as opposed to cough-generated aerosol. Early effective treatment rapidly reduces infectiousness from known and presymptomatic cases but requires active screening of high-risk populations. Environmental controls are essential for reducing transmission from presymptomatic and unsuspected cases. While masks for patients and respirators for healthcare workers are valuable in high-risk situations before appropriate treatment begins, their effectiveness is limited.
