SUMMARY: Tuberculosis (TB) is the leading infectious cause of mortality worldwide, due in part to a limited understanding of its clinical pathogenic spectrum of infection and disease. Historically, scientific research, diagnostic testing, and drug treatment have focused on addressing one of two disease states: latent TB infection or active TB disease. Recent research has clearly demonstrated that human TB infection, from latent infection to active disease, exists within a continuous spectrum of metabolic bacterial activity and antagonistic immunological responses. This revised understanding leads us to propose two additional clinical states: incipient and subclinical TB. The recognition of incipient and subclinical TB, which helps divide latent and active TB along the clinical disease spectrum, provides opportunities for the development of diagnostic and therapeutic interventions to prevent progression to active TB disease and transmission of TB bacilli. In this report, we review the current understanding of the pathogenesis, immunology, clinical epidemiology, diagnosis, treatment, and prevention of both incipient and subclinical TB, two emerging clinical states of an ancient bacterium.

Worldwide increases in global migration and trade have been making communicable diseases a concern throughout the world and have highlighted the connections in health and medicine among and between continents. Physicians in developed countries are now expected to have a broader knowledge of tropical disease and newly emerging infections, while being culturally sensitive to the increasing number of international travelers and ethnic minority populations. Exposing medical students to these global health issues encourages students to enter primary care medicine, obtain public health degrees, and practice medicine among the poor and ethnic minorities. In addition, medical students who have completed an international clinical rotation often report a greater ability to recognize disease presentations, more comprehensive physical exam skills with less reliance on expensive imaging, and greater cultural sensitivity. American medical students have become increasingly more interested and active in global health, but medical schools have been slow to respond. The authors review the evidence supporting the benefits of promoting more global health teaching and opportunities among medical students. Finally, the authors suggest several steps that medical schools can take to meet the growing global health interest of medical students, which will make them better physicians and strengthen our medical system.

Increasing international travel and migration have contributed to globalization of diseases. Physicians today must understand the global burden and epidemiology of diseases, the disparities and inequities in global health systems, and the importance of cross-cultural sensitivity. To meet these needs, resident physicians across all specialties have expressed growing interest in global health training and international clinical rotations. More residents are acquiring international experience, despite inadequate guidance and support from most accreditation organizations and residency programs. Surveys of global health training, including international clinical rotations, highlight the benefits of global health training as well as the need for a more coordinated approach. In particular, international rotations broaden a resident’s medical knowledge, reinforce physical examination skills, and encourage practicing medicine among underserved and multicultural populations. As residents recognize these personal and professional benefits, a strong majority of them seek to gain international clinical experience. In conclusion, with feasible and appropriate administrative steps, all residents can receive global health training and be afforded the accreditation and programmatic support to participate in safe international rotations. The next steps should address accreditation for international rotations and allowance for training away from continuity clinics by residency accreditation bodies, and stipend and travel support for six or more weeks of call-free elective time from residency programs.

Most diagnostic tests for tuberculosis (TB) rely on sputum samples, which are difficult to obtain and have low sensitivity in immunocompromised patients, patients with disseminated TB, and children, delaying treatment initiation. The World Health Organization (WHO) calls for the development of a rapid, biomarker-based, non-sputum test capable of detecting all forms of TB at the point-of-care to enable immediate treatment initiation. Lipoarabinomannan (LAM) is the only WHO-endorsed TB biomarker that can be detected in urine, an easily collected sample. This status update discusses the characteristics of LAM as a biomarker, describes the performance of first-generation urine LAM tests and reasons for slow uptake, and presents considerations for developing the next generation of more sensitive and impactful tests. Next-generation urine LAM tests have the potential to reach adult and pediatric patients regardless of HIV status or site of infection and facilitate global TB control. Implementation and scale-up of existing LAM tests and development of next-generation assays should be prioritized.