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Group-specific component (Gc) variants of vitamin D binding protein differ in their affinity for vitamin D metabolites that modulate antimycobacterial immunity. We conducted studies to determine whether Gc genotype associates with susceptibility to tuberculosis (TB). The following subjects were recruited into case-control studies: in the UK, 123 adult TB patients and 140 controls, all of Gujarati Asian ethnic origin; in Brazil, 130 adult TB patients and 78 controls; and in South Africa, 281 children with TB and 182 controls. Gc genotypes were determined and their frequency was compared between cases versus controls. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were obtained retrospectively for 139 Gujarati Asians, and case-control analysis was stratified by vitamin D status. Interferon (IFN)-gamma release assays were also performed on 36 Gujarati Asian TB contacts. The Gc2/2 genotype was strongly associated with susceptibility to active TB in Gujarati Asians, compared with Gc1/1 genotype (OR 2.81, 95% CI 1.19-6.66; p = 0.009). This association was preserved if serum 25(OH)D was <20 nmol.L(-1) (p = 0.01) but not if serum 25(OH)D was > or =20 nmol.L(-1) (p = 0.36). Carriage of the Gc2 allele was associated with increased PPD of tuberculin-stimulated IFN-gamma release in Gujarati Asian TB contacts (p = 0.02). No association between Gc genotype and susceptibility to TB was observed in other ethnic groups studied.

Background: Tuberculosis is increasing in London, especially in those recently entering the UK from an area of high incidence. Screening through the port of arrival scheme has a poor yield and has been considered discriminatory., Methods: A study was undertaken to compare the yield and costs of screening new entrants in a hospital based new entrants' clinic (1262 referrals from the port of arrival), general practice (1311 new registrations), and centres for the homeless (267 individuals) using a symptom questionnaire and tuberculin testing if indicated. Clinical outcome measures were cases of tuberculosis, tuberculin reactors requiring chemoprophylaxis and BCG vaccinations. Cost outcomes were cost per individual screened and cost per individual per case of tuberculosis prevented., Results: Verbal screening limited tuberculin testing to 16% of those in general practice; most were tested at the other two locations. Intervention (BCG vaccination, chemoprophylaxis or treatment) occurred in 27% of those who received tuberculin testing. Attendance for screening was 17% of the port of arrival notifications (63% had registered with a GP), 54% in primary care, and 67% in the homeless (42% registered with a GP). Costs for screening an individual in general practice, hostels for the homeless, and the new entrants' clinic were 1.26 pounds sterling, 13.17 pounds sterling and 96.36 pounds sterling, respectively, while the cost per person screened per case of tuberculosis prevented was 6.32 pounds sterling, 23.00 pounds sterling, and 10.00 pounds sterling, respectively. The benefit of screening was highly sensitive to the number of cases of tuberculosis identified and case holding during treatment., Conclusion: Screening for tuberculosis in primary care is feasible and could replace hospital screening of new arrivals for those registered with a GP.