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Association of Fok1 VDR polymorphism with Vitamin D and its associated molecules in pulmonary tuberculosis patients and their household contacts.

ABSTRACT: Status of Fok I VDR polymorphism along with vitamin D, Vitamin D receptor (VDR), and cathelicidin levels in Tuberculosis (TB) patients compared to household contacts and implication of these findings in susceptibility to TB is not known. 150 active TB patients, 150 household contacts and 150 healthy controls were recruited from North Indian population. Fok1 VDR polymorphism was studied by polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP).VDR mRNA and protein levels were studied using quantitative real time PCR (q rt PCR) and enzyme linked immunosorbent assay (ELISA) respectively. Cathelicidin and Vitamin D levels were measured using ELISA and chemiluminescence immunoassay (CLIA) respectively. Significant association was found between Fok1 polymorphism and susceptibility to TB (P?

SUBMITTER: Panda S

PROVIDER: S-EPMC6813333 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Association of Fok1 VDR polymorphism with Vitamin D and its associated molecules in pulmonary tuberculosis patients and their household contacts.

Panda Sudhasini S Tiwari Ambrish A Luthra Kalpana K Sharma S K SK Singh Archana A

Scientific reports 20191024 1

Status of Fok I VDR polymorphism along with vitamin D, Vitamin D receptor (VDR), and cathelicidin levels in Tuberculosis (TB) patients compared to household contacts and implication of these findings in susceptibility to TB is not known. 150 active TB patients, 150 household contacts and 150 healthy controls were recruited from North Indian population. Fok1 VDR polymorphism was studied by polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP).VDR mRNA and protein levels w ...[more]

PMID: 31649297

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Project description:The World Health Organization (WHO) recently changed its guidance for tuberculosis (TB) preventive treatment (TPT) recommending TPT for all pulmonary TB (PTB) exposed household contacts (HHC) to prevent incident TB disease (iTBD), regardless of TB infection (TBI) status. However, this recommendation was conditional as the strength of evidence was not strong. We assessed risk factors for iTBD in recently-exposed adult and pediatric Indian HHC, to determine which HHC subgroups might benefit most from TPT. We prospectively enrolled consenting HHC of adult PTB patients in Pune and Chennai, India. They underwent clinical, microbiologic and radiologic screening for TB disease (TBD) and TBI, at enrollment, 4-6, 12 and 24 months. TBI testing was performed by tuberculin skin test (TST) and Quantiferon®- Gold-in-Tube (QGIT) assay. HHC without baseline TBD were followed for development of iTBI and iTBD. Using mixed-effect Poisson regression, we assessed baseline characteristics including TBI status, and incident TBI (iTBI) using several TST and/or QGIT cut-offs, as potential risk factors for iTBD. Of 1051 HHC enrolled, 42 (4%) with baseline TBD and 12 (1%) with no baseline TBI test available, were excluded. Of the remaining 997 HHC, 707 (71%) had baseline TBI (TST #x2265; 5 mm or QGIT #x2265; 0.35 IU/ml). Overall, 20 HHC (2%) developed iTBD (12 cases/1000 person-years, 95%CI: 8-19). HIV infection (aIRR = 29.08, 95% CI: 2.38-355.77, p = 0.01) and undernutrition (aIRR = 6.16, 95% CI: 1.89-20.03, p = 0.003) were independently associated with iTBD. iTBD was not associated with age, diabetes mellitus, smoking, alcohol, and baseline TBI, or iTBI, regardless of TST (#x2265; 5 mm, #x2265; 10 mm, #x2265; 6 mm increase) or QGIT (#x2265; 0.35 IU/ml, #x2265; 0.7 IU/ml) cut-offs. Given the high overall risk of iTBD among recently exposed HHCs, and the lack of association between TBI status and iTBD, our findings support the new WHO recommendation to offer TPT to all HHC of PTB patients residing in a high TB burden country such as India, and do not suggest any benefit of TBI testing at baseline or during follow-up to risk stratify recently-exposed HHC for TPT.

Project description:BackgroundThe End TB Strategy calls for systematic screening of selected high-risk groups including contacts of tuberculosis (TB) cases to facilitate early TB case detection. Contact investigation is not usually routinely practiced in low TB burden countries, such as Ghana, with consequent paucity of data on the yield of TB case detection from such interventions. This study's objective was to document the outcomes and feasibility of implementing contact investigation activities under programmatic conditions in Ghana.MethodsRetrospective analyses were conducted of abstracted data from the National TB Program, following a contact investigation intervention for TB cases diagnosed in 10 facilities in Accra from June 2010 to December 2014. Various proportions and yield from number of contacts needed to screen (NNS) and number needed to test (NNT) to detect a TB case were assessed.ResultsOverall, out of the 8519 listed contacts of 3267 index cases, 8166 (96%) were screened and 614 (7.5%) were identified as presumptive TB. Out of these, 438 (71%) underwent sputum smear microscopy/evaluation and 53 TB cases were diagnosed. Of these, 56.6% were males, and 49% had sputum smear-positive TB, 38% had sputum smear-negative TB, and 7% had extra-pulmonary TB. The NNS and NNT to detect a TB case of all forms were 154 and 8, respectively. The proportion of TB cases with contacts listed and proportion of contacts screened annually were 88-96% and 83-100%, respectively. The proportion of presumptive TB cases tested and proportion of TB cases diagnosed among contacts tested that were 100% and 36%, respectively, in 2010 dropped to 40% and 14%, respectively, by 2014.ConclusionsThe study demonstrates that contact identification and prioritization components of a contact investigation were feasible, but overall yield of TB cases may have been lower due to the declining rate of clinical evaluation of presumptive TB contacts over time. Addressing barriers to accessing appropriate diagnostic tests may enhance yield from contact investigation in Ghana.

Dataset Information

Association of Fok1 VDR polymorphism with Vitamin D and its associated molecules in pulmonary tuberculosis patients and their household contacts.

Publications

Association of Fok1 VDR polymorphism with Vitamin D and its associated molecules in pulmonary tuberculosis patients and their household contacts.

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