Vitamin D deficiency and TB disease phenotype

Manish Pareek, John Innes, Saranya Sridhar, Lisa Grass, David Connell, Gerrit Woltmann, Martin Wiselka, Adrian R. Martineau, Onn Min Kon, Martin Dedicoat, Ajit Lalvani (Lead / Corresponding author)

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    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.

    Original languageEnglish
    Pages (from-to)1171-1180
    Number of pages10
    JournalThorax
    Volume70
    Issue number12
    Early online date23 Sep 2015
    DOIs
    Publication statusPublished - Dec 2015

    Keywords

    • Adolescent
    • Adult
    • Female
    • Humans
    • Immunity, Innate
    • Male
    • Middle Aged
    • Phenotype
    • Risk Factors
    • Tuberculosis, Pulmonary/epidemiology
    • Vitamin D Deficiency/epidemiology
    • Young Adult

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  • Cite this

    Pareek, M., Innes, J., Sridhar, S., Grass, L., Connell, D., Woltmann, G., Wiselka, M., Martineau, A. R., Kon, O. M., Dedicoat, M., & Lalvani, A. (2015). Vitamin D deficiency and TB disease phenotype. Thorax, 70(12), 1171-1180. https://doi.org/10.1136/thoraxjnl-2014-206617