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Vitamin D deficiency and TB disease phenotype

journal contribution
posted on 29.09.2015, 09:52 by Manish Pareek, J. Innes, S. Sridhar, L. Grass, D. Connell, G. Woltmann, M. Wiselka, A. R. Martineau, O. Min Kon, M. Dedicoat, A. Lalvani
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.

Funding

MP is an NIHR Academic Clinical Lecturer in Infectious Diseases. His PhD was funded by a Medical Research Council Capacity Building Studentship. AL is a Wellcome Senior Research Fellow in Clinical Science and NIHR Senior Investigator. This work was supported by the NIHR Health Protection Research Unit in Respiratory Infections, Imperial College London. The funding bodies played no role in data collection, analysis or interpretation. They were not involved in the decision to submit the paper for publication. None of the authors have been paid to write this article by a pharmaceutical company or other agency. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.

History

Citation

Thorax, 2015, 70 (12), pp. 1171-1180

Author affiliation

/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/School of Medicine/Department of Infection, Immunity and Inflammation

Version

AM (Accepted Manuscript)

Published in

Thorax

Volume

70

Issue

12

Pagination

1171-1180

Publisher

BMJ Publishing Group, British Thoracic Society (BTS)

issn

0040-6376

eissn

1468-3296

Acceptance date

14/04/2015

Copyright date

2015

Available date

23/09/2015

Notes

Supplementary Data This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content. Data supplement 1 - Online supplement https://thorax.bmj.com/highwire/filestream/174837/field_highwire_adjunct_files/0/thoraxjnl-2014-206617supp.pdf

Language

en

Publisher version

https://thorax.bmj.com/content/70/12/1171