Vitamin D Deficiency and TB | CDC EID

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Volume 16, Number 5–May 2010
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Vitamin D Deficiency and Tuberculosis Progression
Najeeha Talat, Sharon Perry, Julie Parsonnet, Ghaffar Dawood, and Rabia Hussain
Author affiliations: Aga Khan University, Karachi, Pakistan (N. Talat, R. Hussain); Stanford University School of Medicine, Stanford, California, USA (S. Perry, J. Parsonnet); and Masoomeen General Hospital, Karachi, Pakistan (G. Dawood)

Suggested citation for this article

Abstract
To assess the association between vitamin D deficiency and tuberculosis disease progression, we studied vitamin D levels in a cohort of tuberculosis patients and their contacts (N = 129) in Pakistan. Most (79%) persons showed deficiency. Low vitamin D levels were associated with a 5-fold increased risk for progression to tuberculosis.
Deficiency of vitamin D (25-hydroxycholecalciferol) has long been implicated in activation of tuberculosis (TB) (1). Serum levels of vitamin D in TB patients are lower than in healthy controls (2,3). Paradoxically, prolonged treatment of TB also causes a decline in serum vitamin D levels (2). Several studies have suggested that vitamin D is a potent immunomodulator of innate immune responses (4,5) by acting as a cofactor for induction of antimycobacterial activity (6). Of the 22 countries that have the highest TB incidence, Pakistan ranks eighth. In a previous study in Karachi, we observed that active disease developed in 7 (6.4%) of 109 TB case-contacts within 2 years (7). In the present study, we
explored the role of vitamin D deficiency in TB disease progression within this cohort.

The Study
Household contacts (n = 109) of 20 patients with recently diagnosed sputum-positive pulmonary TB (index case-patients) were enrolled at Masoomeen General Hospital, in Karachi during 2001–2004 for a TB household cohort study (7). Blood samples were collected at baseline and at 6, 12, and 24 months follow-up. Visiting health workers reviewed clinical charts every 3 months for the first 24 months and at a final home study visit during November 2007–January 2008 (45–74 months from baseline). Persons with secondary cases were referred to a consultant at Masoomeen General Hospital for additional investigation, including assessment of physical signs and symptoms, laboratory tests, chest radiographs, and sputum smear microscopy (7). For the present study, 129 de-identified, plasma samples preserved at –70°C from the baseline visit were shipped to Stanford University (Stanford, CA, USA) for analysis of vitamin D levels. Total circulating serum 25[OH] vitamin D was measured with ELISA by using the Immuno Diagnostic System Ltd (IDS, Fountain Hill, AZ, USA). All protocols were followed according to manufacturer's instructions. Each test was run in duplicate, with mean absorbance computed from the average for 2 wells normalized to a zero calibrator well. Levels of vitamin D in test samples were derived by fitting a 2-parameter logistic curve to 6 standard levels and expressed as ng/mL (1 nmol/L × 0.4 = 1 ng/mL). All R2 values were >95%. The assay detection range was 6–360 nmol/L (2.4–144 ng/mL). Levels in 1 person were below the detection limit and were excluded from analysis. The ethical review committees of Aga Khan and Stanford universities approved the study protocol.

We used Kaplan-Meier analysis to evaluate the association of vitamin D levels with outcome of TB disease in 100 household contacts completing >1 follow-up visit. Vitamin D levels in the cohort were classified in population-based tertiles (low, middle, high). We used SAS version 9.3 (SAS Institute, Cary, NC, USA) for statistical analyses.

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Suggested Citation for this Article
Talat N, Perry S, Parsonnet J, Dawood G, Hussai R. Vitamin D deficiency and tuberculosis progression. Emerg Infect Dis [serial on the Internet]. 2010 May [date cited]. http://www.cdc.gov/EID/content/16/5/853.htm

DOI: 10.3201/eid1605.091693