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Screening toll-like receptor markers to predict latent tuberculosis infection and subsequent tuberculosis disease in a Chinese population.

ABSTRACT: BACKGROUND: We investigated whether polymorphisms in the toll-like receptor genes or gene-gene interactions are associated with susceptibility to latent tuberculosis infection (LTBI) or subsequent pulmonary tuberculosis (PTB) in a Chinese population. METHODS: Two matched case-control studies were undertaken. Previously reported polymorphisms in the toll-like receptors (TLRs) were compared between 422 healthy controls (HC) and 205 LTBI patients and between 205 LTBI patients and 109 PTB patients, to assess whether these polymorphisms and their interactions are associated with LTBI or PTB. A PCR-based restriction fragment length polymorphism analysis was used to detect genetic polymorphisms in the TLR genes. Nonparametric multifactor dimensionality reduction (MDR) was used to analyze the effects of interactions between complex disease genes and other genes or environmental factors. RESULTS: Sixteen markers in TLR1, TLR2, TLR4, TLR6, TLR8, TLR9, and TIRAP were detected. In TLR2, the frequencies of the CC genotype (OR?=?2.262; 95% CI: 1.433-3.570) and C allele (OR?=?1.566; 95% CI: 1.223-1.900) in single-nucleotide polymorphism (SNP) rs3804100 were significantly higher in the LTBI group than in the HC group, whereas the GA genotype of SNP rs5743708 was associated with PTB (OR?=?6.087; 95% CI: 1.687-21.968). The frequencies of the GG genotype of SNP rs7873784 in TLR4 (OR?=?2.136; 95% CI: 1.312-3.478) and the CC genotype of rs3764879 in TLR8 (OR?=?1.982; 95% CI: 1.292-3.042) were also significantly higher in the PTB group than in the HC group. The TC genotype frequency of SNP rs5743836 in TLR9 was significantly higher in the LTBI group than in the HC group (OR?=?1.664; 95% CI: 1.201-2.306). An MDR analysis of gene-gene and gene-environment interactions identified three SNPs (rs10759932, rs7873784, and rs10759931) that predicted LTBI with 84% accuracy (p?=?0.0004) and three SNPs (rs3804100, rs1898830, and rs10759931) that predicted PTB with 80% accuracy (p?=?0.0001). CONCLUSIONS: Our results suggest that genetic variation in TLR2, 4, 8 and 9, implicating TLR-related pathways affecting the innate immunity response, modulate LTBI and PTB susceptibility in Chinese.

SUBMITTER: Wu L

PROVIDER: S-EPMC4421918 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Screening toll-like receptor markers to predict latent tuberculosis infection and subsequent tuberculosis disease in a Chinese population.

Wu Linlin L Hu Yi Y Li Dange D Jiang Weili W Xu Biao B

BMC medical genetics 20150401

<h4>Background</h4>We investigated whether polymorphisms in the toll-like receptor genes or gene-gene interactions are associated with susceptibility to latent tuberculosis infection (LTBI) or subsequent pulmonary tuberculosis (PTB) in a Chinese population.<h4>Methods</h4>Two matched case-control studies were undertaken. Previously reported polymorphisms in the toll-like receptors (TLRs) were compared between 422 healthy controls (HC) and 205 LTBI patients and between 205 LTBI patients and 109 P ...[more]

PMID: 25928077

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Project description:BackgroundIn Australia, demand for specialist infectious diseases services exceeds capacity to provide timely management of latent tuberculosis infection (LTBI) in areas of high refugee and asylum seeker settlement. A model for treating LTBI patients in primary care has been developed and piloted in a refugee-focused primary health service (Monash Health Refugee Health and Wellbeing [MHRHW]) and a universal primary care clinic. This study reports on the development and evaluation of the model, focusing on the model feasibility, and barriers and enablers to its success.MethodsA convergent mix-methods design was used to evaluate the model for treating LTBI patients in primary care, where a prospective cohort study of patients commencing treatment either at MHRHW or the universal primary care clinic determined the model feasibility, while focus groups with clinicians directly involved in treating these patients explored barriers and enablers to sustainability and success of the model.ResultsFrom January 2017 to April 2018, 65 patients with confirmed LTBI presented at participating clinics. Treatment was accepted by 31 (48%) patients, of whom 15(48%) were treated at MHRHW and 16 (52%) at the universal primary care clinic. The 6-months' treatment completion rate was higher at MHRHW compared to the universal primary care clinic (14 (93%) compared to 9 (56%) respectively, p = 0.0373). Reasons for non-completion included adverse reaction, opting out and relocation. At the completion of the pilot, 15 clinicians participated in two focus groups. Clinicians identified barriers and enablers for successful LTBI management at patient, provider, organisational and clinical levels. While barriers for treatment completion and adherence were consistent across the two pilot sites, enablers, such as resources to facilitate patient education and follow-up, were available only at MHRHW.ConclusionScreening and management of LTBI patients can be achieved within the primary care setting, considerate of barriers and enablers at patient, provider, organisational and clinical levels. Upscaling of a primary care response to the management of LTBI will require supporting primary care clinics with resources to employ dedicated clinical staff for patient education, follow-up communication and monitoring medication adherence.

Project description:ObjectivesTo estimate the number needed to screen (NNS) and the number needed to treat (NNT) to prevent one tuberculosis (TB) case in the Norwegian immigrant latent tuberculosis infection (LTBI) screening programme and to explore the effect of delay of LTBI treatment initiation.DesignPopulation-based, prospective cohort study.ParticipantsImmigrants to Norway.OutcomeIncident TB.MethodsWe obtained aggregated data on immigration to Norway in 2008-2011 and used data from the Norwegian Surveillance System for Infectious Diseases to assess the number of TB cases arising in this cohort within 5 years after arrival. We calculated the average NNS and NNT for immigrants from the top 10 source countries for TB in Norway and by estimated TB incidence rates in source countries. We explored the sensitivity of these estimates with regard to test performance, treatment efficacy and treatment adherence using an extreme value approach, and assessed the effects of emigration, time to TB diagnosis (to define incident TB) and intervention timing.ResultsNNS and NNT were overall high, with substantial variation. NNT showed numerically stronger negative correlation with TB notification rate in Norway (-0.75 [95% CI -1.00 to -0.44]) than with the WHO incidence rate (IR) (-0.32 [95% CI -0.93 to 0.29]). NNT was affected substantially by emigration and the definition of incident TB. Estimates were lowest for Somali (NNS 99 [70-150], NNT 27 [19-41]) and highest for Thai immigrants (NNS 585 [413-887], NNT 111 [79-116]). Implementing LTBI treatment in immigrants sooner after arrival may improve the effectiveness of the programme.ConclusionUsing TB notifications in Norway, rather than IR in source countries, would improve targeting of immigrants for LTBI management. However, the overall high NNT is a concern and challenges the scale-up of preventive LTBI treatment for significant public health impact. Better data are urgently needed to monitor and evaluate NNS and NNT in countries implementing LTBI screening.

Project description:BackgroundThe World Health Organization recommends that systematic testing and screening of latent tuberculosis infection (LTBI) among the incarcerated population "should be considered", though based on evidence of either low or very low quality. However, in Japan, a TB middle-burden country, systematic screening for LTBI in correctional facilities is currently not conducted. As part of a larger study to determine the cost-effectiveness of LTBI screening in correctional facilities in Japan, this study was conducted to determine the situation of LTBI, including treatment outcome, among the incarcerated population in Japan, and provide the essential data for cost-effectiveness analysis.MethodA cross-sectional study was conducted between 2017 and 2018 with public health centers which have one or more correctional facilities under their jurisdiction. Questionnaire surveys were sent to collect information on their policy of managing LTBI patients notified from correctional facilities, including whether or not there was a standardized procedure for initiating LTBI treatment, and also to collect sociodemographic information and treatment outcome of LTBI patients who were notified from the respective correctional facilities in 2015 and 2016.ResultsThe survey was sent to a total of 163 public health centers, out of which 133 (81.6%) responded. 8 of the 133 public health centers actively guided the correctional facilities regarding LTBI treatment initiation through a standardized procedure, while 115 either had not established such procedure or were unaware of how LTBI treatment was being initiated in the correctional facilities. A total of 91 LTBI patients were notified from the correctional facilities in 2015 and 2016, and the information of 89 were available for analysis. 82 were males, and 83 were Japan-born. Treatment outcome was known for 88 patients, of which 70 had completed treatment. Of the 18 who did not complete the treatment, 15 had been lost to follow-up upon release from the facilities. Among those who had been released whilst on treatment, the proportion of those who completed the treatment was higher in those patients who received pre-release visit by a public health nurse, than those who did not.ConclusionsLTBI treatment was often being initiated without consideration for the patients' prison term. The treatment completion rate within jail was high, indicating the possibility that incarcerated population can benefit for LTBI treatment. On the other hand, the completion rate decreased significantly among those who had been released while still on treatment. In order to optimize the benefit, initiation of LTBI must carefully be considered upon the patient's prison term, as well as coordination among the relevant organizations to ensure continuity of care after release.

Dataset Information

Screening toll-like receptor markers to predict latent tuberculosis infection and subsequent tuberculosis disease in a Chinese population.

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Screening toll-like receptor markers to predict latent tuberculosis infection and subsequent tuberculosis disease in a Chinese population.

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