The impact of diabetes mellitus on tuberculosis recurrence in Eastern China: a retrospective cohort study.

BACKGROUND: The comorbidity of tuberculosis (TB) and diabetes mellitus (DM) is a significant global public health issue. This study aims to explore the recurrence risk and related factors of active pulmonary TB, specifically focusing on the impact of DM. METHODS: A retrospective cohort study was conducted in Lianyungang City, Jiangsu Province, Eastern China by recruiting 12,509 individuals with newly diagnosed pulmonary TB between 2011 and 2019. The Cox proportional hazards models were performed to identify risk factors of recurrence and assess the association between DM and recurrence. The hazard ratio (HR) and 95% confidence interval (CI) were used to estimate the strength of the association. RESULTS: After a median follow-up period of 5.46 years, we observed 439 recurrent cases (incident recurrence rate: 6.62 per 1000 person-years). Males (HR: 1.30, 95% CI: 1.03-1.64), patients aged ≥ 60 years (HR: 1.39, 95% CI: 1.15-1.70), DM (HR: 2.40, 95% CI: 1.68-3.45), and etiologic positivity in the initial episode (HR: 2.42, 95% CI: 2.00-2.92) had a significantly increased risk of recurrence. CONCLUSIONS: Recurrence of pulmonary TB patients who have completed treatment, especially those who also suffer from DM, should be a concern. Enhanced follow-up and targeted surveillance of these high-risk groups are needed.

Environment pollutants exposure affects the endogenous activation of within-host Mycobacterium tuberculosis.

OBJECTIVE: Epidemiological studies have linked ambient pollutants with tuberculosis (TB) risk, but the association has not been fully understood. Here, for the first time, we applied whole-genome sequencing (WGS) to assess the reproductive state of Mycobacterium tuberculosis (MTB) by profiling the mutation rate of MTB (MTBMR) during within-host endogenous reactivated progression, intending to dissect the actual effects of ambient pollutants on the endogenous reactivation. METHODS: We conducted a retrospective cohort study on bacteriologically confirmed TB patients and followed them for relapse in Jiangsu and Sichuan Province, China. Endogenous and exogenous activation were distinguished by WGS of the pathogen. The average concentration of air pollution was estimated by considering a lag of 0-1 to 0-12 months. We applied a generalized additive model with a Poisson function to evaluate the relationships between ambient pollutants exposure and MTBMR. RESULTS: In the single-pollutant adjusted models, the maximum effect for PM10 (MTBMR increase: 81.87%, 95% CI: 38.38, 139.03) and PM2.5 (MTBMR increase: 73.91%, 95% CI: 22.17, 147.55) was observed at a lag of 0-12 months for every 10 µg/m³ increase. For SO2, the maximum effect was observed at lag 0-8 months, with MTBMR increasing by 128.06% (95% CI: 45.92, 256.44); and for NO2, the maximum effect was observed at lag 0-9 months, with MTBMR increasing by 124.02% (95% CI: 34.5, 273.14). In contrast, the O3 concentration was inversely associated with MTBMR, and the maximum reduction of MTBMR was 6.18% (95% CI: -9.24, -3.02) at a lag of 0-9 months. Similar results were observed for multi-pollutant models. CONCLUSIONS: Increased exposure to ambient pollutants (PM10, PM2.5, SO2, and NO2) contributed to a faster MTBMR, indicating that MTB exhibits increased reproductive activity, thus accelerating within-host endogenous reactivation. O3 exposure could decrease the MTBMR, suggesting that MTB exerts low reproductive activity by inhibiting within-host endogenous activation.

Serum LDL-C/HDL-C ratio and the risk of carotid plaques: a longitudinal study.

BACKGROUND: Dyslipidemia contributes to an increased risk of carotid atherosclerosis. However, the association between the ratio of low-density lipoprotein cholesterol (LDL-C) to high-density lipoprotein cholesterol (HDL-C) and carotid plaque formation has not been well documented. This study aims to assess the role of LDL-C/HDL-C in the risk of carotid plaque formation in a Chinese population. METHODS: We followed 2,191 participants who attended the annual routine health examination. Cox proportional hazards regression, restricted cubic spline (RCS), and subgroup analysis were applied to evaluate the association between the LDL-C/HDL-C ratio and carotid plaques. The hazard ratio (HR) and 95% confidence interval (CI) were used to estimate the strength of the association. RESULTS: Among 2,191 participants, 388 had incident carotid plaques detected, with a median follow-up time of 1.05 years. Compared with subjects younger than 45 years, those aged 45 to 59 years (HR: 2.00, 95% CI: 1.55-2.58) and over 60 years (HR: 3.36, 95% CI: 2.47-4.58) had an increased risk of carotid plaque formation. Males (HR: 1.26, 95% CI: 1.01-1.56), diabetes (HR: 1.46, 95% CI: 1.06-2.01) and a high LDL-C/HDL-C ratio (HR: 1.22, 95% CI: 1.07-1.38) were significantly linked with the occurrence of carotid plaques. After adjusting for potential confounding factors, we observed that a high LDL-C/HDL-C ratio promoted carotid plaque events (HR: 1.30, 95% CI: 1.12-1.50). The RCS analysis revealed a significant nonlinear association. The association was stronger among females (P-interaction < 0.05). CONCLUSION: A high LDL-C/HDL-C ratio could accelerate the occurrence of carotid plaques. Older men with diabetes and dyslipidemia are the critical target population. Women may be more likely to benefit from lipid-lowering interventions and thus avoid carotid plaque formation.

Association of ABO blood group and antituberculosis drug-induced liver injury: A case-control study from a Chinese Han population.

WHAT IS KNOWN AND OBJECTIVE: Antituberculosis drug-induced liver injury (ATLI) is a serious adverse drug reaction, and its pathogenic mechanism is still largely unknown. Rifampin (RIF) has been reported to cause haemolysis due to the production of drug-dependent antibodies, and haemolysis results in an increased level of free haem, which affects the function of hepatocytes. Blood group determinants can act as specific receptor sites for drug-antibody complexes, causing erythrocyte destruction in the presence of RIF. RIF-induced immune haemolysis may be a potential mechanism for ATLI. Thus, the study aimed to explore the role of ABO blood group systems in Chinese ATLI patients. METHODS: A 1:4 matched case-control study was conducted among 146 ATLI cases and 584 controls. Multivariable conditional logistic regression and Cox proportional regression were used to estimate the association between ABO blood group and risk of ATLI by odds ratio (OR), hazards ratio (HR) and 95% confidence intervals (CIs), and liver disease history and taking hepatoprotectant were used as covariates. RESULTS AND DISCUSSION: Patients in the A, B, AB and non-O blood groups had a significantly higher risk of ATLI than those in the O blood group (OR = 1.832, 95% CI: 1.126-2.983, P = .015; OR = 1.751, 95% CI: 1.044-2.937, P = .034; OR = 2.059, 95% CI: 1.077-3.938, P = .029; OR = 1.822, 95% CI: 1.173-2.831, P = .007, respectively). After considering the time of ALTI occurrence, similar results were found in the A, B, AB and non-O blood groups (HR = 1.676, 95% CI: 1.072-2.620, P = .024; HR = 1.620, 95% CI: 1.016-2.584, P = .043; HR = 2.010, 95% CI: 1.130-3.576, P = .018; HR = 1.701, 95% CI: 1.138-2.542, P = .010, respectively). Furthermore, subgroup analysis also detected a significant association between ABO blood group and ATLI in patients taking RIF (P < .05). However, no significant difference was observed in patients not taking RIF (P > .05). WHAT IS NEW AND CONCLUSION: The present study is the first to evaluate the role of ABO blood group systems in Chinese ATLI cases. Based on the present matched case-control study, the ABO blood group may be associated with susceptibility to ATLI in the Chinese antituberculosis population, especially in patients with blood groups A, B and AB who are taking RIF.

Association of FAM65B, AGBL4, and CUX2 genetic polymorphisms with susceptibility to antituberculosis drug-induced hepatotoxicity: validation study in a Chinese Han population.

OBJECTIVE: Antituberculosis (anti-TB) drug-induced hepatotoxicity (ATDH) is a serious adverse drug reaction, and its pathogenic mechanism has not been elucidated thoroughly to date. A recent genome-wide association study reported that seven single-nucleotide polymorphisms (SNPs) in the family with sequence similarity 65, member B gene (FAM65B), ATP/GTP-binding protein-like 4 gene (AGBL4), and cut-like homeobox 2 gene (CUX2) were associated strongly with ATDH in Ethiopian patients. We validated this relationship in a Chinese Han anti-TB treatment population. PATIENTS AND METHODS: A 1 : 2 matched case-control study was carried out of 235 ATDH cases and 470 controls. Multivariate conditional logistic regression analysis was used to estimate the association between genotypes and risk of ATDH by odds ratios with 95% confidence intervals, and weight and hepatoprotectant use were used as covariates. RESULTS: Patients with a polymorphism at rs10946737 in the FAM65B gene were at an increased risk of moderate and severe liver injury under the dominant model (adjusted odds ratio=2.147, 95% confidence interval: 1.067-4.323, P=0.032). No other genotypes or genetic risk scores were found to be significantly related to ATDH. CONCLUSION: This is the first study to explore and validate the relationships between seven SNPs in the FAM65B, AGBL4, and CUX2 genes and ATDH in a Chinese population. On the basis of this case-control study, SNP rs10946737 in FAM65B may be associated with susceptibility to ATDH in Chinese Han anti-TB treatment patients. Further research is warranted to explain the role of the FAM65B gene and its contribution toward individual differences in susceptibility to ATDH.

Relevance of NAT2 genotype to anti-tuberculosis drug-induced hepatotoxicity in a Chinese Han population.

BACKGROUND: Anti-tuberculosis drug-induced hepatotoxicity (ATDH) is a serious adverse drug reaction. The slow acetylator status of N-acetyl transferase 2 (NAT2) is a well-established risk factor for ATDH. One novel tagging single nucleotide polymorphism (tagging SNP), rs1495741, in NAT2 has been found to be highly predictive of the NAT2 phenotype. The present study aimed to validate the relationships between tagging SNP rs1495741 and ATDH in a Chinese Han population. METHODS: A 1:2 matched case-control study was conducted using 235 ATDH cases and 470 controls. Conditional or unconditional logistic regression analysis was used to estimate the association between genotypes and the risk of ATDH according to the odds ratio (OR) with a 95% confidence interval (CI). RESULTS: Patients carrying the AA genotype of tagging SNP rs1495741 were at higher risk of ATDH than those carrying the GG genotype (OR = 1.653, 95% CI = 1.050-2.601; p = 0.030). Subgroup analysis suggested that the AA genotype was a risk factor for ATDH in patients aged older than 50 years (OR = 2.486, 95% CI = 1.313-4.706; p = 0.005), weighing over 50 kg (OR = 1.757, 95% CI = 1.016-3.038; p = 0.044) or using a hepatoprotectant (OR = 1.611, 95% CI = 1.009-2.572; p = 0.046). Tagging SNP rs1495741 was not a significant risk factor for moderate and severe hepatotoxicity but appears to be relevant to risk of mild hepatotoxicity specifically. CONCLUSIONS: The present study is the first to validate the relationships between the tagging SNP rs1495741 and ATDH in a Chinese population. Based on this case-control study, the NAT2 rs1495741 polymorphism is a risk factor for mild but not more severe ATDH in Chinese Han patients.

Possible association of HMOX1 and NQO1 polymorphisms with anti-tuberculosis drug-induced liver injury: A matched case-control study.

WHAT IS KNOWN AND OBJECTIVE: Reactive metabolites from anti-tuberculosis (anti-TB) drugs can result in abnormal accumulation of reactive oxygen species (ROS), which plays an important role in anti-TB drug-induced liver injury (ATLI). Liver cells could keep the production of ROS in balance by antioxidant activities. The heme oxygenase 1, encoded by the HMOX1 gene and NADH:quinone oxidoreductase 1, encoded by the NQO1 gene are crucial mediators of cellular defense against ROS. The present study aimed to investigate the associations between HMOX1 and NQO1 polymorphisms and ATLI in Chinese anti-TB treatment population. METHODS: A matched case-control study was conducted using 314 ATLI cases and 628 controls. Multivariate conditional logistic regression analysis was used to estimate the association between genotypes and risk of ATLI by the odds ratios (ORs) with 95% confidence intervals (CIs), with weight and use of hepatoprotectant as covariates. RESULTS AND DISCUSSION: Patients carrying the GG genotype at rs2071748 in HMOX1 were at a higher risk of ATLI than those with the AA genotype (adjusted OR = 1.503, 95% CI: 1.005-2.249, P = 0.047), and significant differences were also found under the recessive (P = 0.015) and additive (P = 0.045) models. Subgroup analysis confirmed the relationship in mild hepatotoxicity cases under the recessive and additive models (adjusted OR = 1.714, 95% CI: 1.169-2.513, P = 0.006; adjusted OR = 1.287, 95% CI: 1.015-1.631, P = 0.037, respectively). WHAT IS NEW AND CONCLUSION: This is the first study to explore the relationship between HMOX1, NQO1 polymorphisms and ATLI in Chinese anti-TB treatment population. Based on a matched case-control study, genetic polymorphisms of HMOX1 may be associated with susceptibility to ATLI in the Chinese population.

Ambient air pollution contributed to pulmonary tuberculosis in China.

Published studies on outdoor air pollution and tuberculosis risk have shown heterogeneous results. Discrepancies in prior studies may be partially explained by the limited geographic scope, diverse exposure times, and heterogeneous statistical methods. Thus, we conducted a multi-province, multi-city time-series study to comprehensively investigate this issue. We selected 67 districts or counties from all geographic regions of China as study sites. We extracted data on newly diagnosed pulmonary tuberculosis (PTB) cases, outdoor air pollutant concentrations, and meteorological factors in 67 sites from January 1, 2014 to December 31, 2019. We utilized a generalized additive model to evaluate the relationship between ambient air pollutants and PTB risk. Between 2014 and 2019, there were 172,160 newly diagnosed PTB cases reported in 67 sites. With every 10-µg/m3 increase in SO2, NO2, PM10, PM2.5, and 1-mg/m3 in CO, the PTB risk increased by 1.97% [lag 0 week, 95% confidence interval (CI): 1.26, 2.68], 1.30% (lag 0 week, 95% CI: 0.43, 2.19), 0.55% (lag 8 weeks, 95% CI: 0.24, 0.85), 0.59% (lag 10 weeks, 95% CI: 0.16, 1.03), and 5.80% (lag 15 weeks, 95% CI: 2.96, 8.72), respectively. Our results indicated that ambient air pollutants were positively correlated with PTB risk, suggesting that decreasing outdoor air pollutant concentrations may help to reduce the burden of tuberculosis in countries with a high burden of tuberculosis and air pollution.

Inactivated COVID-19 vaccine booster dose shortened the viral shedding time of patients infected with the Omicron variant BA.2.

OBJECTIVES: We assessed the effect of inactivated COVID-19 vaccine boosting immunization on the viral shedding time for patients infected with the Omicron variant BA.2. METHODS: We performed a real-world study by analyzing the outbreak data of patients infected with the COVID-19 Omicron variant BA.2 from March to May 2022 in Shanghai, China. Patients were categorized into three groups, including not fully vaccinated (zero and one dose), fully vaccinated (two doses), and booster-vaccinated (three doses). RESULTS: A total of 4443 patients infected with COVID-19 were included in the analysis. The proportion of viral shedding within 14 days in the three groups was 94.7%, 95.5%, and 96.7%, respectively (P <0.001). After adjusting for sex, age, underlying conditions, and clinical symptoms, the booster vaccination had a 29% increased possibility (hazard ratio: 1.29, 95% confidence interval: 1.18-1.41) of no detectable viral shedding within 14 days, whereas the fully vaccinated group had an 11% increased possibility of no detectable viral shedding (hazard ratio: 1.11, 95% confidence interval: 1.01-1.23). The effect of booster vaccination was more significant in males, the elderly, and people with underlying conditions or symptomatic infections. CONCLUSION: Our study confirmed that the booster vaccination could significantly shorten the viral shedding time of patients infected with the Omicron variant BA.2.

Air pollutants in bronchoalveolar lavage fluid and pulmonary tuberculosis: A mediation analysis of gene-specific methylation.

Particulate matter (PM) exposure could alter the risk of tuberculosis, but the underlying mechanism is still unclear. We enrolled 132 pulmonary tuberculosis (PTB) patients and 30 controls. Bronchoalveolar lavage fluid samples were collected from all participants to detect organochlorine pesticides, polycyclic aromatic hydrocarbons, metal elements, and DNA methylation of immunity-related genes. We observed that γ-HCH, Bap, Sr, Ag, and Sn were related to an increased risk of PTB, while Cu and Ba had a negative effect. IFN-γ, IL-17A, IL-2, and IL-23 had a higher level in the PTB group, while IL-4 was lower. The methylation of 18 CpG sites was statistically associated with PTB risk. The methylation at the IL-4_06_121 site showed a significant mediating role on γ-HCH, Sr, and Sn. Our study suggests that PM exposure can increase the risk of tuberculosis by affecting DNA methylation and cytokine expression.