Chinese Tuberculosis Patients Research Articles

Clinical features, immunologic parameter and treatment outcome of Chinese tuberculosis patients with or without DM.

The coexistence of diabetes mellitus (DM) and pulmonary tuberculosis (PTB) poses a significant health concern globally, with their convergence presenting a considerable challenge to healthcare systems. Previous research has highlighted that comorbidities can mutually influence and exacerbate immune disorders. However, there is a paucity of data on the impact of DM on immunological features and treatment responses in the TB population in China. From January 2020 to June 2022, 264 cases of pulmonary tuberculosis patients (82 DM patients and 182 non-DM patients) hospitalized in our center were selected. 80 patients with TB with DM (TB-DM) and 80 patients with TB without DM (TB-NDM) were enrolled into the final analysis by propensity score matching for age, gender and involved lung field at a ratio of 1:1. The clinical characteristics, immunological features and treatment response were compared between the two groups. After propensity score matching, no differences in the general features such as age gender, involved lung field, the incidence of retreatment and WBC count were found between the two groups. Compared to TB-NDM group, the TB-DM group exhibited a higher positive rate of sputum smear and incidence of cavitary lesions. Immunological features analysis revealed that the TB-DM patients had higher levels of TNF-α [pg/ml; 8.56 (7.08-13.35) vs. 7.64 (6.38-10.14) p = 0.033] and IL-8 [pg/ml; 25.85 (11.63-58.40) vs. 17.56 (6.44-39.08) p = 0.003] but lower CD8+ T lymphocyte count [cells/mm3; 334.02 (249.35-420.71) VS 380.95 (291.73-471.25) p = 0.038]. However, there was no significant difference in serum IL-6 concentration and CD4+ T lymphocyte count between the two groups. After 2 months of anti-tuberculosis treatment, 39 (24.4%) cases had suboptimal treatment response, including 23 (28.7%) TB-DM patients and 16 (20%) TB-NDM patients. There was no difference in suboptimal response rate (SRR) was found between the two groups (p = 0.269). The multivariate logistic regression analysis indicated that retreatment for TB [AOR: 5.68 (95%CI: 2.01-16.08), p = 0.001], sputum smear positivity [AOR: 8.01 (95%CI: 2.62-24.50), p = 0.001] were associated with SRR in all participants, and in TB-DM group, only sputum smear positivity [AOR: 16.47 (1.75-155.12), p = 0.014] was positive with SRR. DM is a risk factor for pulmonary cavity formation and sputum smear positivity in TB population. Additionally, TB-DM patients is characterized by enhanced cytokine responses and decreased CD8+ T lymphocytes. The retreatment for TB and sputum smear positivity were associated with the occurrence of suboptimal treatment response.

Prevalence and genetic basis of Mycobacterium tuberculosis resistance to pretomanid in China

BackgroundPretomanid is a key component of new regimens for the treatment of drug-resistant tuberculosis (TB) which are being rolled out globally. However, there is limited information on the prevalence of pre-existing resistance to the drug.MethodsTo investigate pretomanid resistance rates in China and its underlying genetic basis, as well as to generate additional minimum inhibitory concentration (MIC) data for epidemiological cutoff (ECOFF)/breakpoint setting, we performed MIC determinations in the Mycobacterial Growth Indicator Tube™ (MGIT) system, followed by WGS analysis, on 475 Mycobacterium tuberculosis (MTB) isolated from Chinese TB patients between 2013 and 2020.ResultsWe observed a pretomanid MIC distribution with a 99% ECOFF equal to 0.5 mg/L. Of the 15 isolates with MIC values > 0.5 mg/L, one (MIC = 1 mg/L) was identified as MTB lineage 1 (L1), a genotype previously reported to be intrinsically less susceptible to pretomanid, two were borderline resistant (MIC = 2–4 mg/L) and the remaining 12 isolates were highly resistant (MIC ≥ 16 mg/L) to the drug. Five resistant isolates did not harbor mutations in the known pretomanid resistant genes.ConclusionsOur results further support a breakpoint of 0.5 mg/L for a non-L1 MTB population, which is characteristic of China. Further, our data point to an unexpected high (14/475, 3%) pre-existing pretomanid resistance rate in the country, as well as to the existence of yet-to-be-discovered pretomanid resistance genes.

SLC2A9 Gene Polymorphism Is Associated with Elevated Serum Uric Acid Caused by Pyrazinamide

What Is Known and Objective. Elevated serum uric acid (SUA) is one of the most common adverse reactions during the administration of pyrazinamide, but patients exhibit significant individual differences. This study aimed to evaluate the relationship between gene polymorphisms and pyrazinamide-induced SUA elevation in Han Chinese tuberculosis patients. Methods. Tuberculosis patients treated with pyrazinamide were genotyped for the following three candidate genes: SLC22A12, SLC2A9, and ABCG2. Patients were divided into low-risk and high-risk groups according to the change of SUA after treatment. Intergroup comparisons were performed on clinical characteristics, allele and genotype frequencies, and haplotype distributions, and logistic regression analysis was used to explore the relevant risk factors. Results. In total, 143 patients were enrolled, including 83 in the high-risk groups and 60 in the low-risk groups. We observed a significant association between SLC2A9 polymorphism and pyrazinamide-induced SUA elevation. The G allele was significantly lower in the high-risk group than in the low-risk group (27.7% vs. 48.3%, OR = 0.410, 95% CI: 0.250–0.671, p < 0.001 ). Patients with the GA and GG genotypes were less likely to have SUA elevation than those with the AA genotype (OR = 0.125, 95% CI: 0.053–0.293, p < 0.001 and OR = 0.252, 95% CI: 0.074–0.851, p = 0.026 , respectively). Regarding SLC2A9 rs13129697, the frequency of the G allele was significantly lower in the high-risk group than in the low-risk group (26.1% vs. 40.8%, OR = 0.531, 95% CI: 0.312–0.842, p = 0.008 ). In the low-risk group, the proportion of patients with the TG genotype was significantly higher than that with the TT genotype (81.7% vs. 18.3%, OR = 0.279, 95% CI: 0.127–0.611, p = 0.001 ). Haplotype analysis revealed that patients with the SLC2A9 (rs1014290–rs13129697) GG haplotype had lower risk of SUA elevation than those with the AT haplotype (27.11% vs. 63.25%, p = 0.005 ). Furthermore, logistic regression analysis showed that drinking history was an independent risk factor for elevated SUA caused by PZA (OR = 3.943, 95% CI = 1.18–13.175, p = 0.026 ) and that the rs1014290 GA genotype might be a protective factor (OR = 0.094, 95% CI = 0.023–0.386, p = 0.001 ) after correction. What Is New and Conclusion. We found that SLC2A9 genetic polymorphisms were associated with elevated SUA caused by pyrazinamide. The G>A variant of rs1014290 and drinking history might be risk factors.

The relationship between relative telomere length and anti-tuberculosis drug-induced hepatitis : A case-control study

Anti-tuberculosis drug-induced hepatitis (AT-DIH) is a common and serious adverse drug reaction of tuberculosis treatment. Evidence demonstrated that many factors could affect the occurrence of AT-DIH, such as ageing, smoking, alcohol, oxidative stress, etc., while these factors could also promote telomere shortening. Therefore, relative telomere length (RTL) is indirectly related to the occurrence of AT-DIH. The present study aimed to explore and validate this relationship in Chinese tuberculosis patients. A 1:4 matched case-control study was undertaken using 202 AT-DIH cases and 808 controls. Logistic regression models were used to estimate the association between RTL and AT-DIH with odds ratios (ORs) and 95% confidence intervals (CIs). The area under receiver operating characteristic curve (AUC) was calculated to estimate the discriminative performance for distinguishing AT-DIH cases from controls. The average RTL in AT-DIH cases was significantly shorter than that in controls (1.24 vs. 1.46, P=0.002). Patients with longer RTL were at a reduced risk of AT-DIH (OR=0.79, 95% CI: 0.66-0.94, P=0.009), and a dose-response relationship also existed between RTL and lower AT-DIH risk (P for trend=0.012). Under the optimal RTL cut-off value of 1.22, the corresponding AUCs were 0.57 (95% CI: 0.53-0.62, P=0.001) in the univariate model and 0.62 (95% CI: 0.57-0.66, P<0.001) in the multivariate model. This study showed that the shorter the RTL, the higher the risk of AT-DIH during an anti-tuberculosis treatment. The short RTL could potentially serve as a risk factor or a predictive test of the hepatotoxic risk associated with anti-tuberculosis treatments.

Poor diet quality evaluated with the China Healthy Diet Index in Chinese tuberculosis patients.

The purpose of this study was to compare and evaluate the diet quality of tuberculosis patients and healthy adults by using the China Healthy Diet Index (CHDI) and to provide guidance for the diet of tuberculosis patients in the future. A case-control study of 1241 patients and 1241 healthy individuals matchedfor sex and age. The CHDI was used to score the overall diet quality of patients in the casegroup and the control group. The CHDI score of tuberculosis patients was 61.61 and that of healthy controls was 63.97. After adjustment for confounders, participants with >80 on CHDI were 73.5% less likely to develop tuberculosis than participants with <51 (OR: 0.265, 95% CI: 0.086, 0.813, p < 0.05). In the original model, the CHDI scores in the highest range were inversely associated with tuberculosis risk compared with the lowest range (OR: 0.687, 95% CI: 0.420,1.122, p < 0.001). After adjusting for confounders, the CHDI score was significantly associated with a reduced risk of tuberculosis (OR: 0.265, 95% CI: 0.086, 0.813, p < 0.001). After adjusting for confounders, a high-quality diet was positively correlated with anti-tuberculosis treatment outcomes (OR:0.957, 95% CI: 0.918,0.998, p = 0.039). Compared with healthy adults, tuberculosis patients have poor diet quality with unreasonable diet structure. The insufficient intake of whole grains, vegetables, beans, aquatic products, meat and eggs and the excessive intake of pure energy food and solid fat suggests that the dietary structure of tuberculosis patients was unreasonable. This study provides an idea of the diet structure of tuberculosis patients.

Therapeutic Drug Monitoring-Based Efficacy and Safety of Bedaquiline in Chinese Multidrug-Resistant Tuberculosis

Background: Bedaquiline was approved by the US Food and Drug Administration (FDA) for the treatment of drug-resistant tuberculosis in 2012, and significantly improved multidrug-resistant tuberculosis (MDR-TB) patients treatment outcomes. However, data of the efficacy, safety of bedaquiline for the Chinese tuberculosis patients were still lacked, and the plasma concentration of bedaquiline during the treatment and its elimination after treatment discontinuation also had not yet be elucidated. In this study, we demonstrated the efficacy and safety of bedaquiline for the treatment of MDR-TB or XDR-TB patients based on the therapeutic drug monitoring. Methods: 35 patients who started on bedaquiline for drug-resistant tuberculosis were identified. We extracted the patient's medical record information based on their informed consent, and established a standardized monitoring system to track outcomes of patients started on bedaquiline for MDR-TB. The plasma concentration of bedaquiline were determined by ultra-performance liquid chromatography combined with tandem mass spectrometry. Findings: After the 24 weeks bedaquiline treatment, 80% of these patients’ sputum culture conversed negative, and the median time to culture conversion was 75.5 (IQR 52-126) days. 21 (21/26, 80.8%) patients were eventually cured, 2 (2/26, 7.7%) patients failed. The most frequently adverse events during the treatment included QTc prolongation (16/35, 45.7%), peripheral neuropathy (9/35, 25.7%), and gastrointestinal disturbances (8/35, 22.9%). During treatment, the median plasma bedaquiline were fluctuated around 0.6 µg/ml, and gradually decreased after bedaquiline discontinued, about 0.2 µg/ml of bedaquiline was still undegraded after bedaquiline withdrawal 13 months. Moreover, combination with clofazimine increased the possibility of QTc prolongation during the treatment of MDR-TB with bedaquiline, and the decreased serum potassium concentration was also a reason for the prolonged QTc induction with bedaquiline. Interpretation: This study highlighted the efficacy and safety of bedaquiline based on the plasma concentration monitoring, analyzed the reasons of bedaquiline induced QTc prolongation, which had not yet be elucidated before. Funding: This work was supported by the Hospital Pharmacy Special Project of Zhejiang Pharmaceutical Society (2018ZYY31, 2019ZYY27, 2020ZYY08), Zhejiang Medical and Health Science and Technology Plan (2015PYA008, 2020KY741) and Zhejiang Provincial Natural Science Foundation of China under Grant (LYY18H300001), Medical promising youngster of Hangzhou. Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: This study was approved by the Ethic Committee of Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine.

Drug exposure of first-line anti-tuberculosis drugs in China: A prospective pharmacological cohort study.

Exploring the need for optimization of drug exposure to improve tuberculosis (TB) treatment outcome is of great importance. We aimed to describe drug exposure at steady state as well as the population pharmacokinetics (PK) of rifampicin (RIF), isoniazid (INH) and pyrazinamide (PZA) in Chinese TB patients. A prospective multicentre PK study of RIF, INH and PZA was conducted in China between January 2015 and December 2017. Six blood samples were collected from each subject for drug concentration measurement. Nonlinear mixed effect analyses were used to develop population PK models. In total, 217 patients were included. Positive correlations between body weight, clearance and volume of distribution were identified for RIF and PZA, whereas body weight only influenced clearance for INH. In addition, males had higher RIF clearance and thus lower RIF exposure than women. Acetylator status was significantly associated with INH clearance as INH exposure in intermediate and fast acetylators was significantly lower than in slow acetylators, especially in low-weight bands. Simulations also showed significantly lower drug exposures in low-weight bands for all three drugs. Patients weighing <38 kg were respectively exposed to 30.4%, 45.9% and 18.0% lower area under the concentration-time curve of RIF, INH and PZA than those weighing ≥70 kg. Higher doses by addition of one fixed-dose combination tablet or 150 mg INH were simulated and found to be effective in improving INH drug exposures, especially in low-weight bands. PK variability of first-line anti-TB drugs is common in Chinese TB patients. The developed population PK models can be used to optimize drug exposures in Chinese patients. Moreover, standard dosing needs to be adjusted to increase target attainment.

Clinical relevance of the lnc-HNF1B-3:1 genetic polymorphisms in Western Chinese tuberculosis patients.

BackgroundTuberculosis remains a global public health problem. Genetic polymorphisms may affect the susceptibility, clinical characteristics, and adverse drug reactions of patients with TB. The present study aimed to examine the association of single nucleotide polymorphisms of lncRNA‐HNF1B‐3:1 with the clinical manifestation of TB in a Western Chinese population.MethodA total of 526 tuberculosis patients and 561 healthy subjects were recruited in Western China. The correlation between lnc‐HNF1B‐3:1 polymorphism and tuberculosis susceptibility was investigated. Moreover, the influence on adverse drug reactions following treatment was explored. A total of 7 SNPs within the lnc‐HNF1B‐3:1 locus was genotyped by the improved multiplex ligation detection reaction method.ResultsNo significant associations were noted between TB susceptibility and the presence of all 7 SNPs of the lnc‐HNF1B‐3:1 as determined by single‐locus analysis (All P > .05). The AA genotype of rs12939622 (in the dominant model) and the AA genotype of rs4262994 (in the recessive model) caused increased susceptibility of the subjects to fever (P < .001 and P = .008, respectively). The Rs2542670 G allele was associated with increased risk of thrombocytopenia, leukopenia, and chronic kidney damage following drug administration (P = .007, .029, .003, respectively).ConclusionThe present study reported for the first time that the rs12939622, rs4262994 and rs2542670 genotypes in lnc‐HNF1B‐3:1 locus may influence the clinical manifestations of tuberculosis.

Clinical significance of LNC-AC145676.2.1–6 and LNC-TGS1–1 and their variants in Western Chinese tuberculosis patients

Clinical significance of LNC-AC145676.2.1–6 and LNC-TGS1–1 and their variants in Western Chinese tuberculosis patients

Clinical significance of lnc-AC145676.2.1-6 and lnc-TGS1-1 and their variants in western Chinese tuberculosis patients

ObjectivesTuberculosis (TB) remains a global public health problem. Recent studies have implicated long non-coding RNAs and their variants as possibly playing important roles in TB. The aim of this study was to assess the clinical relevance of lnc-AC145676.2.1-6 and lnc-TGS1-1 and their variants in a western Chinese population. MethodsThis case–control study included 467 TB patients and 473 healthy controls from West China Hospital. The expression levels of lnc-AC145676.2.1-6 and lnc-TGS1-1 were analyzed by reverse transcriptase quantitative real-time PCR. Single-nucleotide polymorphism genotyping was performed using a custom-designed 2 × 48-Plex SNPscan kit. ResultsIt was observed that lnc-AC145676.2.1-6 and lnc-TGS1-1 expression levels were both obviously down-regulated in TB patients. In addition, a lower expression level of lnc-TGS1-1 was associated with the presence of thrombocytopenia in TB patients during anti-TB treatment, and the homozygous CC genotype of rs4737420 correlated with a decreased risk of leukopenia, compared with individuals with the T allele (TT/CT genotype), in the dominant mode. ConclusionsFor the first time, potential TB-associated promoting effects were identified for the decreased expression levels of lnc-AC145676.2.1-6 and lnc-TGS-1, while lnc-TGS1-1 and its variant rs4737420 may be predictive indicators of anti-TB drug-induced adverse drug reactions. Larger validation studies on different populations are warranted to confirm these findings.

Prevalence of Depressive Symptoms and Related Risk Factors among Patients with Tuberculosis in China: A Multistage Cross-Sectional Study.

Poor mental health among tuberculosis (TB) patients affects not only their compliance with treatments but also their daily lives. Few studies in China have evaluated depressive symptoms among TB patients. The present study aimed to determine the prevalence of depressive symptoms and its associated risk factors among Chinese TB patients. A total of 1,342 TB patients were recruited using a multistage sampling method and interviewed using a structured questionnaire. Depressive symptoms were measured using the Center for Epidemiologic Studies Depression Scale. Multinomial logistic regression analysis was performed to identify risk factors of depressive symptoms. Of the 1,342 participants included in this study, 48.0% had depressive symptoms. Of these, 34.8% and 13.2% had mild and moderate-to-severe depressive symptoms, respectively. Factors associated with depressive symptoms included family dysfunction, TB-related stigma, poor doctor-patient communication, and lack of knowledge about TB. Depressive symptoms are common among TB patients in China. Efforts of government and stakeholders in the development of relevant policy documents to prevent stigma and create social support for TB patients are necessary. This would not only promote their mental health but also improve their compliance with treatments.

T Cell Profile was Altered in Pulmonary Tuberculosis Patients with Type 2 Diabetes.

BackgroundStudies have suggested that type 2 diabetes (T2D) increases the risk of active pulmonary tuberculosis (TB) infection. T2D might exacerbate TB severity and adversely impact the treatment of TB patients by suppressing the immune response of TB. However, how the immune cell profiles are changed in Chinese TB patients with coincident of T2D compared with TB patients without T2D is still unclear.Material/MethodsTo explore the immune cell profile alteration in TB patients with T2D, we collected blood samples from 46 TB patients with or without T2D and measured the profiles of T cell subsets.ResultsWe found TB patients with coincident of T2D had higher percentages of Th2 and Th17 cells after TB antigens stimulation, while they had unchanged Th1 cells and decreased CD8+ cytotoxic T cells compared to TB patients without T2D. However, no significant difference in baseline percentages of these T cells subsets was observed.ConclusionsT2D has important impacts on regulating anti-TB immunity by increasing Th2 and Th17 cell differentiation, but reducing the activity of CD8+ T cells. Our study supports the need to perform longitudinal studies to evaluate the roles of immunological interaction between T2D and TB in TB development.

Clinical relevance of LINC00152 and its variants in western Chinese tuberculosis patients.

Recent studies indicate that the long intergenic non-coding RNA LINC00152 plays crucial roles in various human diseases. Here, we investigated whether levels of LINC00152 or its genetic variants correlate with the clinical features of tuberculosis (TB) in western Chinese patients. We genotyped the single nucleotide polymorphism LINC00152 rs80292941 in 476 TB patients and 475 healthy subjects using a custom-by-design 48-Plex SNPscan Kit, and measured relative levels of LINC00152 using RT-qPCR. We observed that LINC00152 levels were lower in TB patients than controls. Moreover, rs80292941 TT genotype carriers had the lowest LINC00152 levels among TB patients, and rs80292941 AA genotype carriers are more likely to suffer from hepatotoxicity induced by antituberculosis therapy [OR = 3.97, 95% = 1.53-10.13, p = 0.002]. Our findings strongly suggest that LINC00152 may promote TB progression and highlight rs80292941 single nucleotide polymorphism as a novel predisposition marker for antituberculosis drug-induced hepatotoxicity.

Association of CYP2B6 gene polymorphisms and anti-tuberculosis drug-induced hepatotoxicity in a Chinese population

ObjectivesAntituberculosis drug-induced hepatotoxicity (ATDH) remains a common and severe challenge in tuberculosis (TB) chemotherapy. A growing number of studies have revealed that genetic polymorphisms affect an individual's susceptibility to ATDH. The aim of this study was to explore the role of cytochrome P450 family 2 subfamily B member 6 (CYP2B6) gene polymorphisms in the development of ATDH in Chinese TB patients. MethodsCYP2B6*6 genotypes were determined in TB patients with and without ATDH. Association between polymorphisms and risk of ATDH was estimated by multiple logistic regression analysis. ResultsA total of 343 eligible TB patients (166 with ATDH; 177 without ATDH) were included in this study. Analysis of all subjects revealed no statistical differences in genotype distribution between the two groups. However, the CYP2B6 *6/*6 genotype was significantly associated with decreased risk of ATDH in the male subgroup (P=0.039, OR=0.097, 95% CI: 0.011–0.885). Furthermore, in male patients, the presence of the CYP2B6*6 allele was significantly higher in the non-ATDH group compared with the ATDH group (26.2% vs. 15.5%, P=0.020, OR=0.522, 95% CI: 0.301–0.903). ConclusionsThis study is the first to demonstrate an association between CYP2B6 polymorphisms and the risk of ATDH in the Chinese population. We have shown that males who have the CYP2B6 *6/*6 genotype may be less susceptible to the development of ATDH. Further studies are required to confirm this genetic association result.

Long-term exposure to ambient air pollution and mortality in a Chinese tuberculosis cohort.

Evidence for the relationship between exposure to ambient air pollution and the mortality of tuberculosis (TB) patients is limited. We analyzed the association between long-term exposure to particulate matter <2.5μm in diameter (PM2.5) and cause-specific mortality in a Chinese TB patients cohort from 2003 to 2013. Data from the Global Burden of Disease 2013 estimate were used to assess yearly average concentrations of PM2.5 and ozone at the household addresses of participants. Cox regression was used to calculate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for cause-specific mortality, controlling for demographic and other TB-related factors. There were 4444 eligible subjects, including 891 deaths, over a median follow-up of 2464days. Per an interquartile range increase (2.06μg/m3), multivariable analysis indicated that exposure to PM2.5 was significantly associated with overall mortality (aHR=1.30, 95% CI: 1.19, 1.42), mortality from TB (aHR=1.46, 95% CI: 1.15, 1.85), respiratory cancers (aHR=1.72, 95% CI: 1.36, 2.19), other respiratory diseases (aHR=1.19, 95% CI: 1.02, 1.38), and other cancers (aHR=1.76, 95% CI: 1.33, 2.32). Long-term exposure to PM2.5 increases the risk of death from TB and other diseases among TB patients. It suggests that the control of ambient air pollution may help decreasing the mortality caused by TB.

Correlation of CpG Island Methylation of the Cytochrome P450 2E1/2D6 Genes with Liver Injury Induced by Anti-Tuberculosis Drugs: A Nested Case-Control Study.

This study investigated the role of CpG island methylation of the CYP2E1 and CYP2D6 genes in liver injury induced by anti-TB drugs from an epigenetic perspective in a Chinese cohort. A 1:1 matched nested case-control study design was applied. Pulmonary tuberculosis (TB) patients, who underwent standard anti-TB therapy and developed liver injury were defined as cases, while those who did not develop liver injury were defined as control. The two groups were matched in terms of sex, treatment regimen, and age. In 114 pairs of cases, CpG island methylation levels of the CYP2E1 and CYP2D6 genes in plasma cell-free DNA were found to be significantly correlated with the occurrence of anti-TB drug-induced liver injury (ADLI), with odds ratio (OR) values of 2.429 and 3.500, respectively (p < 0.01). Moreover, through multivariate logistic regression analysis, CpG island methylation of the CYP2E1 and CYP2D6 genes in plasma cell-free DNA were found to be significantly correlated with the occurrence of ADLI, with adjusted OR values of 4.390 (95% confidence interval (CI): 1.982–9.724) and 9.193 (95% CI: 3.624–25.888), respectively (p < 0.001). These results suggest that aberrantly elevated methylation of CpG islands of the CYP2E1 and CYP2D6 genes in plasma cell-free DNA may increase the risk of ADLI in Chinese TB patients.

Prevalence and Predictors of HIV among Chinese Tuberculosis Patients by Provider-Initiated HIV Testing and Counselling (PITC): A Multisite Study in South Central of China

BackgroundTuberculosis (TB) and HIV are two worldwide public health concerns. Co-infection of these two diseases has been considered to be a major obstacle for the global efforts in reaching the goals for the prevention of HIV and TB.MethodA comprehensive cross-sectional study was conducted to recruit TB patients in three provinces (Guangxi, Henan and Sichuan) of China between April 1 and September 30, 2010.ResultsA total of 1,032 consenting TB patients attended this survey during the study period. Among the participants, 3.30% were HIV positive; about one quarter had opportunistic infections. Nearly half of the participants were 50 years or older, the majority were male and about one third were from minority ethnic groups. After adjusting for site, gender and areas of residence (using the partial/selective Model 1), former commercial plasma donors (adjusted OR [aOR] = 33.71) and injecting drug users(aOR = 15.86) were found to have significantly higher risk of being HIV-positivity. In addition, having extramarital sexual relationship (aOR = 307.16), being engaged in commercial sex (aOR = 252.37), suffering from opportunistic infections in the past six months (aOR = 2.79), losing 10% or more of the body weight in the past six months (aOR = 5.90) and having abnormal chest X-ray findings (aOR = 20.40) were all significantly associated with HIV seropositivity (each p<0.05).ConclusionsHIV prevalence among TB patients was high in the study areas of China. To control the dual epidemic, intervention strategies targeting socio-demographic and behavioral factors associated with higher risk of TB-HIV co-infection are urgently called for.

Factors associated with patient, and diagnostic delays in Chinese TB patients: a systematic review and meta-analysis

BackgroundDelay in seeking care is a major impediment to effective management of tuberculosis (TB) in China. To elucidate factors that underpin patient and diagnostic delays in TB management, we conducted a systematic review and meta-analysis of factors that are associated with delays in TB care-seeking and diagnosis in the country.MethodsThis review was prepared following standard procedures of the Cochrane Collaboration and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement and checklist. Relevant studies published up to November 2012 were identified from three major international and Chinese literature databases: Medline/PubMed, EMBASE and CNKI (China National Knowledge Infrastructure).ResultsWe included 29 studies involving 38,947 patients from 17 provinces in China. Qualitative analysis showed that key individual level determinants of delays included socio-demographic and economic factors, mostly poverty, rural residence, lack of health insurance, lower educational attainment, stigma and poor knowledge of TB. Health facility determinants included limited availability of resources to perform prompt diagnosis, lack of qualified health workers and geographical barriers.Quantitative meta-analysis indicated that living in rural areas was a risk factor for patient delays (pooled odds ratio (OR) (95% confidence interval (CI)): 1.79 (1.62, 1.98)) and diagnostic delays (pooled OR (95% CI): 1.40 (1.23, 1.59)). Female patients had higher risk of patient delay (pooled OR (95% CI): 1.94 (1.13, 3.33)). Low educational attainment (primary school and below) was also a risk factor for patient delay (pooled OR (95% CI): 2.14 (1.03, 4.47)). The practice of seeking care first from Traditional Chinese Medicine (TMC) providers was also identified as a risk factor for diagnostic delay (pooled OR (95% CI): 5.75 (3.03, 10.94)).ConclusionPatient and diagnostic delays in TB care are mediated by individual and health facility factors. Population-based interventions that seek to reduce TB stigma and raise awareness about the benefits of early diagnosis and prompt treatment are needed. Policies that remove patients’ financial barriers in access to TB care, and integration of the informal care sector into TB control in urban and rural settings are central factors in TB control.

Adverse Reactions Due to Directly Observed Treatment Strategy Therapy in Chinese Tuberculosis Patients: A Prospective Study

BackgroundMore than 1 million tuberculosis (TB) patients are receiving directly observed treatment strategy (DOTS) therapy in China every year. As to the profile of adverse drug reactions (ADRs) due to DOTS therapy, no consensus has been reached. There is no report regarding ADRs due to DOTS therapy with a large Chinese TB population. This study aimed to determine the incidence and prognosis of ADRs due to DOTS therapy, and to evaluate their impact on anti-TB treatment in China.MethodsA prospective population-based cohort study was performed during 2007–2008. Sputum smear positive pulmonary TB patients who received DOTS therapy were included and followed up for six to nine months in 52 counties of four regions in China. The suspected ADRs were recorded and reviewed by Chinese State Food and Drug Administration.ResultsA total of 4304 TB patients were included in this study. 649 patients (15.08%) showed at least one ADR and 766 cases in total were detected. The incidence (count) of ADR based on affected organ was: liver dysfunction 6.34% (273), gastrointestinal disorders 3.74% (161), arthralgia 2.51% (108), allergic reactions 2.35% (101), neurological system disorders 2.04% (88), renal impairment 0.07% (3) and others 0.05% (2). Most cases of ADRs (95%) had a good clinical outcome, while two with hepatotoxicity and one with renal impairment died. Compared with patients without ADRs, patients with ADRs were more likely to have positive smear test results at the end of the intensive phase (adjusted OR, 2.00; 95%CI, 1.44–2.78) and unsuccessful anti-TB outcomes (adjusted OR, 2.58; 95%CI, 1.43–4.68).ConclusionsThe incidence of ADRs due to DOTS therapy was 15.08%. Those ADRs had a substantial impact on TB control in China. This highlighted the importance of developing strategies to ameliorate ADRs both to improve the quality of patient care and to control TB safely.

Association of TIRAP (MAL) gene polymorhisms with susceptibility to tuberculosis in a Chinese population

Toll-interleukin 1 receptor (TIR) domain containing adaptor protein (TIRAP; also known as MAL) is an essential adaptor molecule in Toll-like receptor signaling, involved in activating the innate immune response during infection. Genetic variations in the TIRAP gene may influence human susceptibility to infectious disease. To date, in the Chinese population, a possible predisposition of TIRAP gene variants to tuberculosis has not been reported. We investigated whether TIRAP gene polymorphisms are associated with the development of tuberculosis in a Chinese population. We investigated all the single-nucleotide polymorphisms (SNPs) within the TIRAP exon 5 in a case-control study of 212 patients with tuberculosis and 215 controls in a Chinese population. Genotyping was performed to identify the polymorphisms of TIRAP gene by PCR-DNA sequencing method. Haplotypes for the TIRAP gene variants were constructed using Haplo view version 4.2. Six polymorphisms of the SNPs listed in the National Center for Biotechnology Information database were detected in these Chinese tuberculosis patients. It was found that both the frequency of the 286A allele (odds ratio (OR) = 13.37; 95% confidence interval (CI) = 0.75-238.3; P < 0.01) and the frequency of 286AG genotype (OR = 13.57; 95%CI = 0.76-242.5; P < 0.01) were significantly higher in patients than in healthy controls. However, two other SNPs, C539T and C558T, reported to be associated with tuberculosis in other populations, were found not to be associated with tuberculosis in this Chinese population. We conclude that TIRAP G286A (D96N) polymorphism is associated with susceptibility to tuberculosis and may be a new risk factor for the development of tuberculosis in China.