title: Vitamin D deficiency and TB disease phenotype.
abstract: BACKGROUND
  Extrapulmonary TB is increasingly common, yet the determinants of the wide clinical spectrum of TB are poorly understood.
  
  
  METHODS
  We examined surveillance data (Birmingham, UK: 1980-2009 and USA Centers for Disease Control: 1993-2008) to identify demographic factors associated with extrapulmonary TB. We then directly tested association of these factors and serum 25-hydroxycholecalciferol (25(OH)D) concentration with extrapulmonary TB by multivariable analysis in a separate UK cohort.
  
  
  RESULTS
  Data were available for 10,152 and 277,013 TB cases for Birmingham and US, respectively. Local-born individuals of white ethnicity had a lower proportion of extrapulmonary disease when compared with local-born non-whites (p<0.0001); both groups had a lower proportion of extrapulmonary disease when compared with foreign-born non-whites (p<0.0001). In a separate UK cohort (n=462), individuals with extrapulmonary TB had lower mean serum 25(OH)D concentration than those with pulmonary TB (11.4 vs 15.2 nmol/L, respectively, p=0.0001). On multivariable analysis, vitamin D deficiency was strongly associated with extrapulmonary TB independently of ethnicity, gender and other factors. Doubling in serum 25(OH)D concentration conferred substantially reduced risk of extrapulmonary disease (OR 0.55, 95% CI 0.41 to 0.73).
  
  
  CONCLUSIONS
  We identify vitamin D deficiency as a probable risk factor for extrapulmonary dissemination in TB, which may account for the associations of dark-skinned ethnicity and female gender with extrapulmonary disease. Our findings implicate vitamin D status in Mycobacterium tuberculosis containment in vivo and, given the high prevalence of deficiency, may inform development of novel TB prevention strategies.
authors.affiliation: Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, UK Tuberculosis Research Centre, National Heart and Lung Institute, Imperial College London, London, UK Department of Infectious Disease Epidemiology, Imperial College London, London, UK Department of Infection and Tropical Medicine, University Hospitals Leicester NHS Trust, Leicester, UK.
authors.forename: Manish
authors.initials: M
authors.lastname: Pareek
authors.affiliation: Department of Infection and Tropical Medicine, Heart of England NHS Foundation Trust, Bordesley Green East, Birmingham, UK.
authors.forename: John
authors.initials: J
authors.lastname: Innes
authors.affiliation: Tuberculosis Research Centre, National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: Saranya
authors.initials: S
authors.lastname: Sridhar
authors.affiliation: Tuberculosis Research Centre, National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: Lisa
authors.initials: L
authors.lastname: Grass
authors.affiliation: Tuberculosis Research Centre, National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: David
authors.initials: D
authors.lastname: Connell
authors.affiliation: Department of Respiratory Medicine, Institute for Lung Health, University Hospitals Leicester NHS Trust, Leicester, UK.
authors.forename: Gerrit
authors.initials: G
authors.lastname: Woltmann
authors.affiliation: Department of Infection and Tropical Medicine, University Hospitals Leicester NHS Trust, Leicester, UK.
authors.forename: Martin
authors.initials: M
authors.lastname: Wiselka
authors.affiliation: Centre for Primary Care and Public Health, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
authors.forename: Adrian R
authors.initials: AR
authors.lastname: Martineau
authors.affiliation: Tuberculosis Service, Department of Chest and Allergy Clinic, St. Mary's Hospital, Imperial College Healthcare NHS Trust, London, UK.
authors.forename: Onn Min
authors.initials: OM
authors.lastname: Kon
authors.affiliation: Department of Infection and Tropical Medicine, Heart of England NHS Foundation Trust, Bordesley Green East, Birmingham, UK.
authors.forename: Martin
authors.initials: M
authors.lastname: Dedicoat
authors.affiliation: Tuberculosis Research Centre, National Heart and Lung Institute, Imperial College London, London, UK Tuberculosis Service, Department of Chest and Allergy Clinic, St. Mary's Hospital, Imperial College Healthcare NHS Trust, London, UK.
authors.forename: Ajit
authors.initials: A
authors.lastname: Lalvani
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012307:Risk Factors; D014397:Tuberculosis, Pulmonary / Q000453:epidemiology* / Q000208:ethnology / Q000235:genetics* / Q000276:immunology; D014808:Vitamin D Deficiency / Q000453:epidemiology*; D055815:Young Adult
keywords: Tuberculosis