Thorax doi:10.1136

Vitamin D deficiency and TB disease phenotype

Published Online First 23 September 2015

Background
Extrapulmonary TB is increasingly common, yet the determinants of the wide clinical spectrum of TB are poorly understood.

Methods
surveillance data (Birmingham, UK: 1980–2009 and USA Centers for Disease Control: 1993–2008) to identify demographic factors associated with extrapulmonary TB. 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 extra pulmonary 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 extra pulmonary 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 extra pulmonary 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
This study identifies vitamin D deficiency as a probable risk factor for extra pulmonary dissemination in TB, which may account for the associations of dark-skinned ethnicity and female gender with
extra pulmonary disease.
The 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.

G Mohan.