Use the Clue Box and fill in the blanks.
1. The disease caused by the deficiency of Vitamin A is
2.
The name of the vaccine used against tuberculosis is
3. The disease caused due to the deficiency of Vitamin D is
4. Hameorrhage is caused due to the deficiency of
5. The greatest disease carrier insect is
Coronary thrombosis is a
7. The infectious agent that can reproduce only in living cells is
The fat soluble vitamins are
The drug obtained from the cinchona tree is
10. The bite of an infected tse-tse fly causes
11. The disease that affects the lungs is
12. The throat is affected by
13. The part of the human body affected by jaundice is the
14. The disease that affects the teeth and gums is
15. Joints are affected by
16. The lens used to correct long sight is
17. Nerves are affected by
18. AIDS occurs due to the contamination of
19. The herb which cures colds and coughs is
20. Lack of iodine causes
Answers
Answer:
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.
Keywords: Vitamin D, tuberculosis, household contacts, bacteria, Pakistan, dispatch
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.
Median vitamin D level for the 128 cohort participants was 9.1 ng/mL (interquatrile range [IQR] 5.3–14.7); levels were 9.6 ng/mL (IQR 5.8–19.1) for 100 disease-free contacts, 7.9 ng/mL (IQR 4.7–10.3) for 20 TB index case-patients, 4.6 ng/mL (IQR 4.0–5.2) for 2 co-prevalent TB case-patients who were receiving antituberculous treatment at recruitment, and 5.1 ng/mL (IQR 3.4–14.3) in 6 household contacts with a history of TB treatment (2–10 years) (Figure 1, panel A). In the 100 disease-free household contacts, vitamin D levels were significantly higher than in the 28 participants with a history of TB diagnosis at baseline (p = 0.02; Mann-Whitney U test) (Figure 1, panel B). Median vitamin D levels were significantly lower in the 74 female patients than in the 54 male patients (7.8 vs. 11.9, Mann-Whitney U test, p = 0.0004) (Figure 1, panel C). When we stratified the cohort by vitamin D level, 79% had deficient (<20 ng/mL), 14% had insufficient (20–30 ng/mL), and 7% had sufficient (>30 ng/mL) levels of vitamin D (Table).