title: Convergence of a diabetes mellitus, protein energy malnutrition, and TB epidemic: the neglected elderly population.
abstract: On a global scale, nearly two billion persons are infected with Mycobacterium tuberculosis. From this vast reservoir of latent tuberculosis (TB) infection, a substantial number will develop active TB during their lifetime, with some being able to transmit TB or Multi-drug- resistant (MDR) TB to others. There is clinical evidence pointing to a higher prevalence of infectious diseases including TB among individuals with Diabetes Mellitus (DM). Furthermore, ageing and diabetes mellitus may further aggravate protein-energy malnutrition (PEM), which in turn impairs T-lymphocyte mediated immunologic defenses, thereby increasing the risk of developing active TB and compromising TB treatment. This article aims to a) highlight synergistic mechanisms associated with immunosenescence, DM and PEM in relation to the development of active TB and b) identify nutritional, clinical and epidemiological research gaps.
  
  
  
  To explore the synergistic relationship between ageing, DM, tuberculosis and PEM, a comprehensive review was undertaken. The MEDLINE and the Google Scholar databases were searched for articles published from 1990 to March 2015, using different MESH keywords in various combinations.
  
  
  
  Ageing and DM act synergistically to reduce levels of interferon gamma (IFN- γ), thereby increasing susceptibility to TB, for which cell mediated immunity (CMI) plays an instrumental role. These processes can set in motion a vicious nutritional cycle which can predispose to PEM, further impairing the CMI and consequently limiting host defenses. This ultimately transforms the latent TB infection into active disease. A clinical diagnostic algorithm and clinical guidelines need to be established for this population.
  
  
  
  Given the increase in ageing population with DM and PEM, especially in resource-poor settings, these synergistic tripartite interactions must be examined if a burgeoning TB epidemic is to be averted. Implementation of a comprehensive, all-encompassing approach to curb transmission is clearly indicated. To this end, clinical, nutritional and epidemiological research gaps must be addressed without a delay.
authors.affiliation: International Centre for Reproductive health, Ghent University, LSHTM Alumni, Ghent, Belgium. soniasimonemenon@gmail.com.|CDC Foundation, Atlanta, USA. soniasimonemenon@gmail.com.
authors.forename: Sonia
authors.initials: S
authors.lastname: Menon
authors.affiliation: LSHTM Alumni, Beirut, Lebanon.
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Rossi
authors.affiliation: Department of Social and Preventive Medicine, Laval University-Faculty of Medicine, Quebec, Canada.
authors.forename: Leon
authors.initials: L
authors.lastname: Nshimyumukiza
authors.affiliation: Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Canada.
authors.forename: Aibibula
authors.initials: A
authors.lastname: Wusiman
authors.affiliation: Department of Clinical Pharmacy, Saints Cyril and Methodius University of Skopje (Alumni), Skopje, Republic of Macedonia.
authors.forename: Natasha
authors.initials: N
authors.lastname: Zdraveska
authors.affiliation: Médecins Sans Frontières, Paris, France.
authors.forename: Manal Shams
authors.initials: MS
authors.lastname: Eldin
mesh_terms: D000367:Age Factors; D000368:Aged; D048909:Diabetes Complications / Q000453:epidemiology* / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology; D058872:Epidemics; D014943:Global Health; D006801:Humans; D007111:Immunity, Cellular; D011502:Protein-Energy Malnutrition / Q000150:complications / Q000453:epidemiology* / Q000276:immunology / Q000503:physiopathology; D014376:Tuberculosis / Q000150:complications / Q000453:epidemiology* / Q000276:immunology / Q000503:physiopathology