The re-engineered Xpert MTB/RIF Ultra (Xpert Ultra) assay was developed due to the poor sensitivity of the Xpert MTB/RIF assay for the detection of tuberculosis (TB) in some conditions. This new assay has been recommended by the World Health Organization since 2017. A systematic review and meta-analysis was performed to assess the accuracy of Xpert Ultra for the detection of TB and rifampicin (RIF) resistance. The Medline (via PubMed), Embase (via OvidSP), ISI Web of Science, Cochrane Central Register of Controlled Trials, and Scopus databases were screened for original articles. Summary sensitivity and specificity were calculated with a bivariate mixed-effects model. A Fagan nomogram was used to assess the clinical utility. The sources of heterogeneity were investigated by meta-regression and subgroup analyses. Sixteen studies were identified. The summary diagnostic accuracy of Xpert Ultra for the diagnosis of TB were as follows: sensitivity 87.2% (95% confidence interval (CI) 82.5-90.8%) and specificity 96.5% (95% CI 95.1-97.5%). For the detection of RIF resistance, sensitivity was 95.1% (95% CI 91.6-97.2%) and specificity was 98.9% (95% CI 97.6-99.5%). Meta-regression showed that the category of population, TB prevalence, reference standard, sample state, sample type, and study design attributed to the heterogeneity. Subgroup analyses found good performance of Xpert Ultra in settings with a low TB burden. As a rapid and highly sensitive test for the detection of TB and simultaneous detection of RIF resistance, Xpert Ultra exhibits a viable alternative in sensitivities in both pulmonary TB (PTB) and extrapulmonary TB (EPTB), which was proved to be higher than Xpert in the comparative analysis, and also shows a good performance in the detection of RIF resistance. Additional studies with comparative consistency tests are needed to precisely describe this finding for more forms of EPTB.

Toll-like receptor (TLR) single nucleotide polymorphisms (SNPs) have been associated with regulation of TLR expression and development of active tuberculosis (TB). The objectives of this study were to determine whether TLR8 and TLR9 SNPs were associated with the development of latent TB infection (LTBI) and the subsequent pulmonary TB (PTB) in a Chinese Han population. Two independent samples were enrolled. The first sample contained 584 TB cases and 608 controls; the second sample included 204 healthy controls, 201 LTBI subjects and 209 bacteria-confirmed active PTB patients. Three SNPs (rs3764880, rs187084 and rs5743836) were genotyped. The associations between the SNPs and risk of LTBI or PTB were investigated using unconditional logistic regression analysis. The A-allele of TLR8 rs3764880 SNP was protective against the development of TB in males (A vs G, OR = 0.58, 95%CI = 0.37–0.91). The AA genotype of rs3764880 SNP was found to increase the risk of PTB among females with an OR of 4.81 (1.11–20.85). The G allele of TLR9 SNP rs187084 was found to increase the risk of PTB (G vs A, P = 0.01, OR = 1.48, 95% CI = 1.10–2.00), the significance was also observed under dominant genetic models. The GA-genotype of TLR9 rs187084 SNP was found to increase the risk of PTB with an OR of 1.68 (1.07–2.65), but was found to decrease the risk of MTB infection with an OR = 0.64 (0.41–0.98). TLR9_rs5743836 SNP was excluded from the data analyses, because the minimum allele frequency was< 1%. Our findings in two independent samples indicated that SNPs in TLR8 and TLR9 were associated with the development of TB, and highlight that SNPs may have different effects on disease pathogenesis and progression.

Tuberculous meningitis (TBM) is the most severe form of infection caused by Mycobacterium tuberculosis (Mtb). Smurf1 represents a key component in anti-Mtb autophagic targeting in macrophages and in anti-TB host defense in vivo. We hypothesized that genetic variants in the Smurf1 gene region influence susceptibility to TBM. Using a case-control study design (235 TBM cases, 239 pulmonary TB cases and 478 healthy controls), we evaluated whether 8 haplotype-tagging single nucleotide polymorphisms (SNPs) in the Smurf1 gene are associated with the development of TBM. Even with the most conservative correction, the polymorphisms rs6956450 was associated with TBM under a dominant model (odds ratio [OR],1.653; 95% confidence interval [CI],1.192-2.294; P = 0.021), the CG haplotype consisting of rs3294 and rs6956450 was positively associated with TBM (P = 0.013) and another haplotype GC remained negatively associated with TBM in Tibetan subgroup (P < 0.001). No correlation between rs6956450 and TBM clinical characteristics as well as prognosis was found. These results firstly link the variants in Smurf1 gene region with TBM risk, indicating an important role for Smurf1 in the immunopathogenesis of TBM. Future studies will dissect the mechanism, which may help identify targets or genetic markers to guide diagnosis or host-directed therapy in patients with TBM.