Background: Bedaquiline (BDQ) has been designated as a Group A drug by the World Health Organization (WHO) for the management of multi-drug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB). This systematic review and meta-analysis aim to evaluate the efficacy and safety of BDQ-containing regimens for the treatment of patients with pulmonary TB. Methods: PubMed (MEDLINE), Elton B. Stephens Company (EBSCO) database, the Cochrane Register of Controlled Trials, and the China National Knowledge Infrastructure (CNKI) database were initially searched on 15 June 2022 and again on 20 March 2023. We included randomized controlled trials (RCTs) and non-randomized studies (NRSs) that administered BDQ to TB patients. The outcomes of interest were as follows: (1) efficacy, including the rate of sputum culture conversion at 8 weeks, 24 weeks, and during follow-up, as well as the rates of completion cure, death, treatment failure, and loss at follow-up and at the end of the treatment; and (2) safety, which encompassed the incidences of cardiotoxicity, hepatotoxicity, and grade 3–5 adverse events during the treatment period. Results: A total of 29 articles were included in this meta-analysis, representing 23,358 individuals. Patients who were treated with BDQ were compared with patients who were not exposed to BDQ. The use of BDQ-containing regimens demonstrated improved rates of sputum conversion in RCTs at 24 weeks (RR = 1.27, 95% CI: 1.10 to 1.46) and during follow-up (RR = 1.33, 95% CI: 1.06 to 1.66). Additionally, BDQ-containing regimens showed increased cure rates (RR = 1.60, 95% CI: 1.13 to 2.26) and decreased failure rates (RR = 0.56, 95% CI: 0.56 to 0.88). In NRSs, BDQ-containing regimens improved the sputum culture conversion rate during follow-up (RR = 1.53, 95% CI: 1.07 to 2.20), increased the rate of cure (RR = 1.86, 95% CI: 1.23 to 2.83), reduced deaths from all causes (RR = 0.68, 95% CI: 0.48 to 0.97), and reduced failure rates (RR = 0.57, 95% CI: 0.46 to 0.71). However, the use of BDQ-containing regimens was associated with increased incidences of cardiotoxicity (RR = 4.54, 95% CI: 1.74 to 11.87) and grade 3–5 adverse events (RR = 1.42, 95% CI: 1.17 to 1.73) in RCTs. NRSs also showed an association between BDQ-containing regimens and cardiotoxicity (RR = 6.00, 95% CI: 1.32 to 27.19). No significant differences were observed between intervention groups and control groups with respect to other outcomes. Conclusions: Data from both RCTs and NRSs support the efficacy of BDQ for the treatment of pulmonary tuberculosis. However, the use of BDQ is associated with a higher incidence of cardiotoxicity and serious adverse events. Comparative data on efficacy and safety are limited, and further confirmation is required, due to potential bias and discrepancies in the available studies.

Pulmonary tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (MTB). Whole-genome sequencing (WGS) holds great promise as an advanced technology for accurately predicting anti-TB drug resistance. The development of a reliable method for detecting drug resistance is crucial in order to standardize anti-TB treatments, enhance patient prognosis, and effectively reduce the risk of transmission. In this study, our primary objective was to explore and determine the potential of WGS for assessing drug resistance based on genetic variants recommended by the World Health Organization (WHO). A total of 1105 MTB strains were selected from samples collected from 2014–2018 in Zhejiang Province, China. Phenotypic drug sensitivity tests (DST) of the anti-TB drugs were conducted for isoniazid (INH), rifampicin (RFP), streptomycin, ethambutol, fluoroquinolones (levofloxacin and moxifloxacin), amikacin, kanamycin, and capreomycin, and the drug-resistance rates were calculated. The clean WGS data of the 1105 strains were acquired and analyzed. The predictive performance of WGS was evaluated by the comparison between genotypic and phenotypic DST results. For all anti-TB drugs, WGS achieved good specificity values (>90%). The sensitivity values for INH and RFP were 91.78% and 82.26%, respectively; however, they were ≤60% for other drugs. The positive predictive values for anti-TB drugs were >80%, except for ethambutol and moxifloxacin, and the negative predictive values were >90% for all drugs. In light of the findings from our study, we draw the conclusion that WGS is a valuable tool for identifying genome-wide variants. Leveraging the genetic variants recommended by the WHO, WGS proves to be effective in detecting resistance to RFP and INH, enabling the identification of multi-drug resistant TB patients. However, it is evident that the genetic variants recommended for predicting resistance to other anti-TB drugs require further optimization and improvement.

Tuberculosis (TB) is a common infectious disease, and the present study aims to explore the associations of single nucleotide polymorphisms (SNPs) at rs1135216 and rs1057141 of transporter-associated antigen processing (TAP1) and rs2228396 of TAP2 with pulmonary tuberculosis (PTB) risk. A case-control study including 168 smear-positive PTB cases and 251 controls was conducted. Genotyping of the SNPs at rs1135216, rs1057141 and rs2228396 was performed, and their associations with PTB risk were analysed with SPSS software version 19.0. After conducting stratification for age, a significant association was detected for rs1057141 with increased PTB risk (OR = 0.17, 95% CI 0.04-0.79) among those aged >= 60 years. For those aged = 60 years, while rs1135216 might be a potential genetic predictor for those aged <60 years. Haplotype AT at rs1135216 and rs2228396, as well as AAT at rs1057141, rs1135216 and rs2228396, is a genetic marker that may predict PTB risk.

Tuberculosis (TB) is the leading cause of death caused by single pathogenic microorganism, Mycobacterium tuberculosis (MTB). The study aims to explore the associations of microRNA (miRNA) single-nucleotide polymorphisms (SNPs) with pulmonary TB (PTB) risk. A population-based case−control study was conducted, and 168 newly diagnosed smear-positive PTB cases and 251 non-TB controls were recruited. SNPs located within miR-27a (rs895819), miR-423 (rs6505162), miR-196a-2 (rs11614913), miR-146a (rs2910164), miR-618 (rs2682818) were selected and MassARRAY^® MALDI-TOF System was employed for genotyping. SPSS19.0 was adopted for statistical analysis, non-conditional logistic regression was performed. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were computed to estimate the associations. Associations of haplotypes with PTB risk were performed with online tool. Rs895819 CT/CC genotype was associated with reduced PTB risk among female population (OR = 0.45, 95% CI: 0.23–0.98), P = 0.045. Haplotypes (combined with rs895819, rs2682818, rs2910164, rs6505162 and rs11614913) TCCCT, TAGCC, CCCCC, CCGCT and TCGAT were associated with reduced PTB risk and the ORs were 0.67 (95% CI: 0.45–0.99), 0.49 (0.25–0.94), 0.34 (95% CI: 0.14–0.81), 0.22 (95% CI: 0.06–0.84) and 0.24 (95% CI: 0.07–0.79), respectively; while the haplotypes of TAGCT, CCCCT, CACCT and TCCAT were associated with increased PTB risk, and the ORs were 3.63 (95% CI: 1.54–8.55), 2.20 (95% CI: 1.00–4.86), 3.90 (95% CI: 1.47–10.36) and 2.95 (95% CI: 1.09–7.99), respectively. Rs895819 CT/CC genotype was associated with reduced female PTB risk and haplotype TCCCT, TAGCC, CCCCC, CCGCT and TCGAT were associated with reduced PTB risk, while TAGCT, CCCCT, CACCT and TCCAT were associated with increased risk.

Background: Pulmonary tuberculosis (PTB) is a common infectious disease caused by mycobacterium tuberculosis (MTB) and the present study aims to explore the associations of genetic variants within tyrosine kinases 2 (TYK2) with PTB incidence.Methods: A population‐based case control study including 168 smear‐positive PTB cases and 251 controls was conducted. Five single nucleotide polymorphisms (SNPs) including rs280520, rs91755, rs2304256, rs12720270, rs280519 located within TYK2 gene were selected and MassARRAY® MALDI‐TOF system was employed for genotyping. SPSS 19.0 was adopted for statistical analysis, non‐conditional logistic regression was conducted. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were computed to estimate their contributions to PTB incidence.Results: In the overall study population, rs91755 TT and rs280519 AA genotypes were found to be associated with reduced PTB risk (OR = 0.34, 95% CI: 0.16–0.72; OR = 0.38, 95% CI: 0.18–0.79, respectively). After stratification for sex, we found that among the male population, rs91755TG/TT, rs12720270AG/GG and rs280519AG/AA genotypes were associated with reduced PTB risk (OR = 0.41, 95% CI: 0.21–0.80; OR = 0.44, 95% CI: 0.21–0.94; OR = 0.42, 95% CI: 0.21–0.82, respectively). After stratification for age, we found that among those aged <60 years, rs91755TT and rs280519AA genotype were associated with reduced PTB risk (OR = 0.29, 95% CI: 0.09–0.90; OR = 0.34, 95% CI: 0.11–1.08, respectively); while rs2304256AC/AA genotype was associated with increased PTB risk (OR = 2.68, 95% CI: 1.05–6.85). Haplotype analysis revealed that AGAAG and ATCGA (Combined with rs280520, rs91755, rs2304256, rs12720270 and rs280519) were associated with increased (OR = 1.54, 95% CI: 1.01–2.37) and decreased PTB risk (OR = 0.70, 95% CI: 0.52–0.94), respectively.Conclusions: The genetic variants located within TYK2 including rs91755, rs12720270 and rs280519 were found to be associated with modified PTB risk and the SNPs had potential to be the biomarkers to predict PTB incidence risk.

Background. The Mycobacterium tuberculosis H37Rv reference genome (Lineage 4), sequenced in 1998, may be incomplete and inaccurate due to earlier technology. Moreover, its use is problematic in regions like East Asia where the dominant Beijing lineage (Lineage 2) is prevalent, as it may introduce biases due to lineage-specific genetic differences. Methods. We performed hybrid sequencing to generate high-quality assemblies of a clinically isolated Beijing family strain (A2018772) and a Chinese laboratory-adapted H37Rv strain (H37Rv_CN). Comparative genomic analysis was conducted against the standard H37Rv reference. The impact of reference genome choice on transmission clustering was evaluated using a dataset of 3,359 M. tuberculosis Lineage 2 strains from China. Results. Comprehensive genomic analysis revealed substantial differences between both studied strains and H37Rv_ref. The Chinese laboratory-adapted H37Rv_CN strain differed by 145 SNPs, 49 InDels and 14 structural variants from the reference genome. The Beijing family clinical isolated strain A2018772 showed even greater divergence with 2,277 SNPs, 373 InDels and 219 structural variants compared to H37Rv_ref, with particular enrichment in PE/PPE genes and metabolic pathways. Among these variations, a 9.2 kb deletion was prevalent in 89.7% of 78 publicly available Lineage 2 genomes. When applied to transmission analysis of 3,359 Chinese Lineage 2 strains, the A2018772 as a reference genome demonstrated superior performance with higher mapping rates (99.52% vs. 98.72%) and coverage (99.73% vs. 98.50%) compared to H37Rv_ref. This improved resolution resulted in fewer transmission clusters (273 vs. 285) at the 5-SNP threshold, indicating that H37Rv_ref consistently overestimates transmission events in Lineage 2-dominated populations. Conclusion. Our study demonstrates the incompleteness of the H37Rv reference genome and also finds that using a lineage-specific reference genome could significantly improve transmission inference accuracy for Lineage 2 strains, highlighting the need for region-specific genomic references to enhance tuberculosis control strategies in high-burden areas.