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Original article
Vitamin D deficiency and TB disease phenotype
  1. Manish Pareek1,2,3,4,
  2. John Innes5,
  3. Saranya Sridhar2,
  4. Lisa Grass2,
  5. David Connell2,
  6. Gerrit Woltmann6,
  7. Martin Wiselka4,
  8. Adrian R Martineau7,
  9. Onn Min Kon8,
  10. Martin Dedicoat5,
  11. Ajit Lalvani2,8
  1. 1Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, UK
  2. 2Tuberculosis Research Centre, National Heart and Lung Institute, Imperial College London, London, UK
  3. 3Department of Infectious Disease Epidemiology, Imperial College London, London, UK
  4. 4Department of Infection and Tropical Medicine, University Hospitals Leicester NHS Trust, Leicester, UK
  5. 5Department of Infection and Tropical Medicine, Heart of England NHS Foundation Trust, Bordesley Green East, Birmingham, UK
  6. 6Department of Respiratory Medicine, Institute for Lung Health, University Hospitals Leicester NHS Trust, Leicester, UK
  7. 7Centre for Primary Care and Public Health, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
  8. 8Tuberculosis Service, Department of Chest and Allergy Clinic, St. Mary's Hospital, Imperial College Healthcare NHS Trust, London, UK
  1. Correspondence to Professor Ajit Lalvani, a.lalvani{at}


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.

  • Tuberculosis

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