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 darkskinned
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.