Whole Genome Sequence-Based Analyses of Drug Resistance Characteristics, Genetic Diversity, and Transmission Dynamics of Drug-Resistant Mycobacterium tuberculosis in Urumqi City.

Objective: This study aims to analyze the drug resistance spectrum, genetic diversity, and transmission dynamics to provide a basis for the prevention and control of drug-resistant (DR) tuberculosis (TB) epidemics. Methods: This retrospective study is based on routine national drug resistance surveillance. The demographic, epidemiological, and clinical information on DR-TB patients from 2016 to 2021 was collected and used for phenotypic drug susceptibility testing and whole-genome sequencing. Results: It was indicated that L2.2.1 was the dominant lineage in Urumqi. The drug resistance spectrum in Urumqi was narrow, which means more drug combinations can be used for clinical treatment. Furthermore, mutations identification of drug-resistance gene katG, rpoB, embA/B, rrs, rpsL, eis, gyrA/B, folC and tryA are important for clinical drug use. However, mutations in cross-resistance genes rrs have limited guidance for clinical selection of KM, CPM and AK. Moreover, there is an increased risk of cluster transmission of DR-TB, and the difference in clustering rate among L2, L3, and L4 was not statistically significant (χ2 = 2.6410, p = 0.2670). Conclusion: In the Urumqi, DR-TB has a complex prevalence state, a narrow drug resistance spectrum, and a high clustering rate and burden of drug resistance. To reduce the burden of DR-TB, related research should be strengthened, and the development of prevention, control, and treatment strategies should be accelerated.

Association Studies of Serum Levels of TNF- α, IL-10, IFN-γ and CXCL 5 with Latent Tuberculosis Infection in Close Contacts.

Purpose: Early recognition and treatment of latent tuberculosis infection(LTBI) is key to tuberculosis(TB) prevention. However, the emergence of LTBI is influenced by a combination of factors, of which the role of individual immune cytokines remains controversial. The aim of this study is to explore the influencing factors of LTBI and their effects with cytokines on LTBI. Patients and Methods: Close contacts of tuberculosis in Urumqi City from 2021 to 2022 were selected for the study to conduct a field survey. It used logistic regression model to analyse the influencing factors of LTBI, principal component analysis to extract a composite indicators of cytokines, and structural equation modelling to explore the direct and indirect effects of cytokines and influencing factors on LTBI. Results: LTBI infection rate of 33.3% among 288 TB close contacts. A multifactorial Logistic model showed that factors influencing LTBI included education, daily contact hours, eating animal liver, and drinking coffee (P<0.05); After controlling for confounding factors and extracting composite indicators of cytokines using principal component analysis, CXCL5 and IFN-γ is a protective factor for LTBI(OR=0.572, P=0.047), IL-10 and TNF-α is a risk factor for LTBI(OR=2.119, P=0.010); Structural equation modelling shows drinking coffee, eating animal liver, daily contact hours, and IL-10 and TNF-α had direct effects on LTBI and educations had indirect effects on LTBI(P<0.05). Conclusion: IL-10 and TNF-α are involved in the immune response and are directly related to LTBI. By monitoring the cytokine levels of TB close contacts and paying attention to their dietary habits and exposure, we can detect and intervene in LTBI at an early stage and control their progression to TB.

eDOTS: Improving the Treatment of Pulmonary Tuberculosis in Xinjiang, China.

Purpose: To increase pulmonary tuberculosis (PTB) treatment adherence in Xinjiang Region, an electronic DOTS (eDOTS) system developed was applied and evaluated. Methods: An eDOTS system comprised electronic medicine boxes, mobile phones and a central processing platform. Between April and June 2016, persons with active PTB (PAPTB) were recruited from villages and a city and were prescribed a six-month course of antibiotics using either DOTS or eDOTS. Treatment adherence rate and chest X-ray digital radiography (DR) score were used to evaluate usefulness of eDOTS. Results: A total 167 PAPTB were recruited with 81 participants from villages and 86 from neighbourhoods. Of the 81 village patients, 43 (53%) used eDOTS and 38 (47%) used DOTS. Among the 86 patients from neighbourhoods, 50 (58%) used eDOTS and 36 (42%) used DOTS. After 6 months of treatment, the average treatment compliance of the village patients who used eDOTS were 47.0%±20.5% compared to 26.7%±21.1% who used DOTS (t=-4.475, p<0.001). The patients using eDOTS from both the villages and city had significantly lower X-ray DR scores than the patients using DOTS by 1.81 points, 95% CI (0.72-2.90) and 1.05 points, 95% CI (0.15-1.95), respectively. Conclusion: eDOTS is an effective means of managing the treatment of active PTB patients through daily reminding and monitoring of patient compliance. Ease of contact with doctors and special education programs encouraged PAPTB to complete their treatment course as required.

Alterations in the Gut Microbiome of Individuals With Tuberculosis of Different Disease States.

Objective: There is evidence that the gut microbiota play a regulatory role in the occurrence and progression of tuberculosis. The purpose of the current study was to explore the alterations in gut microbiome under different tuberculosis disease stages in the Uyghur population, clarify the composition of microbial taxonomy, search for microbial biomarkers and provide innovative ideas for individual immune prevention and for control strategies. Design: A case-control study of Uyghur individuals was performed using 56 cases of pulmonary tuberculosis (PTB), 36 cases of latent tuberculosis infection (LTBI) and 50 healthy controls (HC), from which stool samples were collected for 16S rRNA gene sequencing. Results: The results showed that the alpha diversity indexes of the PTB group were lower than those of the other two groups (P <0.001), while only observed species were different between LTBI and HC (P <0.05). Beta diversity showed differences among the three groups (P = 0.001). At the genus level, the relative abundance of Bifidobacterium and Bacteroides increased, while Roseburia and Faecalibacterium decreased in the PTB group, when compared with the other two groups, but the changes between the LTBI and HC groups were not significant. The classifier in the test set showed that the ability of the combined genus to distinguish between each two groups was 81.73, 87.26, and 86.88%, respectively, and the validation efficiency was higher than that of a single screened genus. Conclusion: The gut microbiota of PTB patients was significantly disordered compared with LTBI and HC, while the changes of LTBI and HC were not significant. In the future, gut microbiota could be used as a non-invasive biomarker to assess disease activity.

The association between SLC11A1 gene polymorphism and treatment failure of pulmonary tuberculosis / 预防医学

Objective@#To analyze the association between recombinant solute carrier family 11, member 1 ( SLC11A1 ) rs17235409 polymorphism and treatment failure of pulmonary tuberculosis, so as to provide the basis for the prevention and treatment of pulmonary tuberculosis.@*Methods@#The patients with pulmonary tuberculosis registered for treatment at the Urumqi Center for Disease Control and Prevention in 2019 was recruited and collected demographic, clinical and treatment information from National Infectious Diseases Reporting System. The polymorphism of SLC11A1 rs17235409 was detected by multiple ligase chain reaction and Hardy-Weinberg balance test was performed. The multivariate logistic regression analysis was conducted for the association between rs17235409 and the treatment outcome of tuberculosis.@*Results@#A total of 731 cases of pulmonary tuberculosis patients were enrolled, and 37 cases failed, with a failure rate of 5.06%. The failure rate of the patients with G/A was 8.55%, with G/G was 4.23%. The results of multivariate logistic regression analysis showed that the patients with G/A were more likely to fail in the treatment than those with G/G ( OR=2.213, 95%CI: 1.041-4.702 ). The males with G/A were more likely to fail in the treatment than those with G/G ( OR=2.547, 95%CI: 1.021-6.356 ). @*Conclusion@#The rs17235409 polymorphism of SLC11A1 is associated with the failure of tuberculosis treatment, and the patients with G/A are more likely to fail.

A study on the relationship between air pollution and pulmonary tuberculosis based on the general additive model in Wulumuqi, China.

OBJECTIVE: This study aimed to explore the impact of atmospheric pollutants on the incidence of tuberculosis (TB), and provide new ideas for the prevention and control of TB in the future. METHODS: It explored the relationship between air pollutants and meteorological factors, as well as between air pollutants and heating through Spearman correlation analysis and rank sum test. Additionally, it analyzed the relationship between air pollutants and TB incidence using the general additive model. Statistical analysis results at the p<0.05 level were considered significant. RESULTS: Three months after exposure to air pollutants (PM2.5, SO2, NO2, and CO) TB incidence increased. However, TB incidence increased 9 months after exposure to PM10. The single pollutant model showed when concentrations of PM2.5, PM10, SO2, NO2, CO, and O3 increased by 1µg/m3 (or 1mg/m3), the number of TB cases increased by 0.09%, 0.08%, 0.58%, 0.42%, 6.9%, and 0.57%, respectively. The optimal multi-pollutant model was a two-factor model (PM10+NO2). CONCLUSION: Air pollutants including PM2.5, PM10, SO2, NO2, CO, and O3 increased the risk of TB. Few studies have been conducted in this area of research, especially regarding the mechanism. The results of this study should contribute to the understanding of TB incidence and prompt additional research.