Revisiting the timetable of tuberculosisBMJ 2018; 362 doi: https://doi.org/10.1136/bmj.k2738 (Published 23 August 2018) Cite this as: BMJ 2018;362:k2738
- Marcel A Behr, professor of medicine1,
- Paul H Edelstein, professor of pathology and laboratory medicine23,
- Lalita Ramakrishnan, professor of immunology and infectious diseases3
- 1McGill International TB Centre, Infectious Diseases and Immunity in Global Health Program, McGill University Health Centre Research Institute, Montreal H4A 3J1, Canada
- 2Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
- 3Molecular Immunity Unit, Department of Medicine, University of Cambridge, MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK
- Correspondence to: L Ramakrishnan
Between a quarter and a third of the world’s population are estimated to be latently infected with Mycobacterium tuberculosis.1 The 2018 World Health Organization resource page for tuberculosis (TB) states: “On average, 5-10% of those who are infected will develop active TB disease over their lifetime.” Other authorities use terms such as “dormant” or “alive but inactive” (supplementary box 1).
Because “reactivated” TB is contagious, eradicating latent infection is a cornerstone of global TB control2 and achieving a better understanding of latent infection is deemed a research priority.34 The word latent has both biological and medical definitions. The biological concept of latency is that of a resting stage, hidden until circumstances are suitable for development. The medical definition is simply a pathological process in which symptoms are not yet manifest. The TB clinical community has long used the apposition of latent TB infection and reactivation, clearly applying the biological definition.
The importance attached to latency is reflected in a major push from research funding agencies to understand the biology and epidemiology of latent TB infection and to develop drugs that specifically treat latent infection, aiming for global TB eradication (supplementary box 2). Multiple longitudinal epidemiological studies, however, show that the majority of TB disease manifests soon after infection, with disease rarely occurring more than two years after infection. (We use the term “remote infection” to describe infection preceding active TB by more than two years.) The vast burden of global TB is, therefore, from recently transmitted infection. Only in countries with a low TB burden, where ongoing transmission is minimal, is TB from remote infection a …