title: Acquired immunodeficiencies and tuberculosis: focus on HIV/AIDS and diabetes mellitus.
abstract: The spread of human immunodeficiency virus (HIV) infection within Africa led to marked increases in numbers of cases of tuberculosis (TB), and although the epidemic peaked in 2006, there were still 1.8 million new cases in 2013, with 29.2 million prevalent cases. Half of all TB cases in Africa are in those with HIV co-infection. A brief review of the well-documented main immunological mechanisms of HIV-associated increased susceptibility to TB is presented. However, a new threat is facing TB control, which presents itself in the form of a rapid increase in the number of people living with type II diabetes mellitus (T2DM), particularly in areas that are already hardest hit by the TB epidemic. T2DM increases susceptibility to TB threefold, and the TB burden attributable to T2DM is 15%. This review addresses the much smaller body of research information available on T2DM-TB, compared to HIV-TB comorbidity. We discuss the altered clinical presentation of TB in the context of T2DM comorbidity, changes in innate and adaptive immune responses, including lymphocyte subsets and T-cell phenotypes, the effect of treatment of the different comorbidities, changes in biomarker expression and genetic predisposition to the respective morbidities, and other factors affecting the comorbidity. Although significant gains have been made in improving our understanding of the underlying mechanisms of T2DM-associated increased susceptibility, knowledge gaps still exist that require urgent attention.
authors.affiliation: DST/NRF Centre of Excellence for Biomedical Tuberculosis Research and MRC Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
authors.forename: Katharina
authors.initials: K
authors.lastname: Ronacher
authors.forename: Simone A
authors.initials: SA
authors.lastname: Joosten
authors.forename: Reinout
authors.initials: R
authors.lastname: van Crevel
authors.forename: Hazel M
authors.initials: HM
authors.lastname: Dockrell
authors.forename: Gerhard
authors.initials: G
authors.lastname: Walzl
authors.forename: Tom H M
authors.initials: TH
authors.lastname: Ottenhoff
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000453:epidemiology / Q000276:immunology*; D056704:Adaptive Immunity; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D015415:Biomarkers; D060085:Coinfection; D021821:Communicable Diseases, Emerging; D015897:Comorbidity; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000453:epidemiology; D004198:Disease Susceptibility; D020022:Genetic Predisposition to Disease; D054884:Host-Pathogen Interactions / Q000235:genetics / Q000276:immunology; D006801:Humans; D054019:Immune Reconstitution Inflammatory Syndrome / Q000150:complications / Q000209:etiology; D007113:Immunity, Innate; D016867:Immunocompromised Host; D014376:Tuberculosis / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology* / Q000628:therapy
chemical_list: D015415:Biomarkers
keywords: HIV; tuberculosis; type II diabetes mellitus