title: Viewpoint: Scientific dogmas, paradoxes and mysteries of latent Mycobacterium tuberculosis infection.
abstract: Worldwide, there are nearly 10 million new cases of active TB and 1.8 million associated deaths every year. WHO estimates that one-third of the world's population is infected with Mycobacterium tuberculosis (Mtb), forming a huge latent Mtb global reservoir. This renders the prospect of ever eliminating Mtb from the human race almost impossible. Several controversial issues regarding host-pathogen interactions and existing prevention and eradication strategies for latent Mtb infections need to be critically re-examined. In this viewpoint, widely held assumptions on Mtb latency and isoniazid monotherapy and chemoprophylaxis are challenged. We highlight the need for future research to resolve these issues and to develop evidence-based strategies for better understanding of equilibrium and escape of Mtb in the human body, eventually leading to global recommendations for elimination of the latent Mtb state through informed policy and practice. Until such strategies and policies are realized, WHO and TB experts will have to settle for global TB control rather than eradication.
authors.affiliation: Department of Infection, University College London Medical School, London, UK. a.zumla@ucl.ac.uk
authors.forename: Alimuddin
authors.initials: A
authors.lastname: Zumla
authors.forename: Rifat
authors.initials: R
authors.lastname: Atun
authors.forename: Markus
authors.initials: M
authors.lastname: Maeurer
authors.forename: Peter
authors.initials: P
authors.lastname: Mwaba
authors.forename: Zhenkun
authors.initials: Z
authors.lastname: Ma
authors.forename: Justin
authors.initials: J
authors.lastname: O'Grady
authors.forename: Matthew
authors.initials: M
authors.lastname: Bates
authors.forename: Keertan
authors.initials: K
authors.lastname: Dheda
authors.forename: Michael
authors.initials: M
authors.lastname: Hoelscher
authors.forename: John
authors.initials: J
authors.lastname: Grange
mesh_terms: D000995:Antitubercular Agents / Q000627:therapeutic use; D019317:Evidence-Based Medicine / Q000379:methods; D014943:Global Health; D054884:Host-Pathogen Interactions; D006801:Humans; D007538:Isoniazid / Q000627:therapeutic use; D055985:Latent Tuberculosis / Q000453:epidemiology / Q000382:microbiology / Q000628:therapy*; D009626:Terminology as Topic
chemical_list: D000995:Antitubercular Agents; D007538:Isoniazid