The World Health Organization (WHO) “Global Tuberculosis Report 2024” underscores the ongoing challenges and progress in the global fight against tuberculosis (TB). Despite a slowdown in the annual increase in TB cases and a decline in TB-related deaths, the disease remains a significant public health threat with 10.8 million new cases reported in 2023. The report reveals a persistently high burden of TB, especially in low- and middle-income countries, and highlights the escalating issue of drug-resistant TB. The report also emphasizes the critical need for increased funding, improved diagnostics, and more effective TB treatment regimens. The impact of the COVID-19 pandemic on TB control has been substantial, disrupting healthcare services and exacerbating existing challenges. This paper provides an in-depth interpretation of the report, analyzes global TB trends, updates the status of drug-resistant TB, discusses the intersection between TB and HIV, and summarizes the implications of the pandemic on TB control efforts. The report concludes with a call for intensified global action, including increased investment in research and innovation, to achieve the United Nations’ Sustainable Development Goals related to TB control. The stakes are high, but with concerted efforts, the goal of ending the TB epidemic is within reach.

Background: To determine the diagnostic accuracy of a nanopore sequencing assay of PCR products from a M. tuberculosis complex-specific region for testing of bronchoalveolar lavage fluid (BALF) samples or sputum samples from suspected pulmonary tuberculosis (PTB) patients and compare the results to results obtained for MGIT and Xpert assays. Methods: Cases with suspected PTB (n = 55) were diagnosed from January 2019 to December 2021 based on results of nanopore sequencing, MGIT culture, and Xpert MTB/RIF testing of BALF and sputum samples collected during hospitalization. Diagnostic accuracies of assays were compared. Results: Ultimately, data from 29 PTB patients and 26 non-PTB cases were analyzed. PTB diagnostic sensitivities of MGIT, Xpert MTB/RIF, and nanopore sequencing assays were 48.28%, 41.38%, and 75.86%, respectively, thus demonstrating that nanopore sequencing provided greater sensitivity than was provided by MGIT culture and Xpert assays (P < 0.05). PTB diagnostic specificities of the respective assays were 65.38%, 100%, and 80.77%, which corresponded with kappa coefficient (κ) values of 0.14, 0.40, and 0.56, respectively. These results indicate that nanopore sequencing provided superior overall performance as compared to Xpert and MGIT culture assays and provided significantly greater PTB diagnostic accuracy than Xpert and sensitivity comparable to that of the MGIT culture assay. Conclusion: Our findings suggest that improved detection of PTB in suspected cases was achieved using nanopore sequencing-based testing of BALF or sputum samples than was achieved using Xpert and MGIT culture-based assays, and nanopore sequencing results alone cannot be used to rule out PTB.

Non-tuberculous mycobacteria (NTM) are opportunistic pathogens that can infect all body tissues and organs. In particular, the lungs are the most commonly involved organ, with NTM pulmonary diseases causing serious health issues in patients with underlying lung disease. Moreover, NTM infections have been steadily increasing worldwide in recent years. NTM are also naturally resistant to many antibiotics, specifically anti-tuberculosis (anti-TB) drugs. The lack of drugs targeting NTM infections and the increasing drug resistance of NTM have further made treating these mycobacterial diseases extremely difficult. The currently recommended NTM treatments rely on the extended indications of existing drugs, which underlines the difficulties of new antibiotic discovery against NTM. Another challenge is determining which drug combinations are most effective against NTM infection. To a certain extent, anti-NTM drug development depends on using already available antibiotics and compounds. Here, we aimed to review new antibiotics or compounds with good antibacterial activity against NTM, focusing on their mechanisms of action,in vitroandin vivoantibacterial activities.

Purpose of this paper is to analyze different species’ proportion of nontuberculosis mycobacteria (NTM) and susceptibility to clarithromycin of different species. 278 clinical NTM isolates were identified into species by using 16S rRNA,rpoBandhsp65. Then clarithromycin susceptibility testing against different species was done separately, using microplate Alamar Blue assay. Finally, resistance isolates’erm(41)ofM. abscessuswere sequenced in order to analyze mechanisms for clarithromycin resistant. In this test, 131 isolates (47%) belonged toM. aviumcomplex (MAC), and 70 isolates (25%) belonged toM. abscessus. Nearly all theM. abscessussubsp.abscessusresistant to clarithromycin had T28 inerm(41). However, all theM. abscessussubsp.abscessussusceptible to clarithromycin had C28 inerm(41). In this study, we find that MAC was the most common pathogens of NTM, and the second one wasM. abscessus. However,M. chelonei, M. fuerth, andM. gordonwere rare. Clarithromycin had a good inhibition activity against all the NTM species exceptM. abscessussubsp.abscessus. Theerm(41)genotype is of high relevance to clarithromycin resistance.

The objective of the study is to determine the accuracy of metagenomic next-generation sequencing (mNGS) in diagnosing osteoarticular tuberculosis (TB) infection and to compare it with mycobacteria growth indicator tube (MGIT) and Xpert assays. We retrospectively analyzed 162 patients admitted with suspected osteoarticular TB. Osteoarticular tissue (66.67%) and abscess specimens (33.33%) from patients were tested for MGIT, GeneXpert/RIF, and mNGS. mNGS assay detected 76 cases (46.9%) with bacterial, 63 cases (38.9%) with mycobacterial, 22 cases (13.6%) with fungal, and 1 case (0.6%) with actinomycetal organisms. These 162 pathogens were classified into 21 species. The most frequent species detected was Mycobacterium tuberculosis complex (29.0%), followed by Staphylococcus aureus (20.4%), Mycobacterium abscessus (5.6%), and Candida albicans (5.6%). Taking the “gold standard” TB diagnosis as the standard, the positive predictive values of mNGS, Xpert, and MGIT culture were both 100.00%. The negative predictive values of mNGS, Xpert, and MGIT culture and assays were 94.26%, 98.29%, and 88.46%, respectively. The sensitivity of mNGS detection (85.11%) was similar to that of Xpert (95.74%) and higher than that of MGIT culture (68.08%). The specificities of mNGS detection, Xpert, and MGIT culture were both 100.00%. The area under the curve value of the mNGS assay was 0.895 (95% CI: 0.830, 0.960), which was greater than that of the MGIT culture-based assay of 0.840 (95% CI: 0.757, 0.924), which was similar to 0.979 (95% CI: 0.945, 1.000) for Xpert assay. The pathogen detection rate of mNGS in diagnosing suspected osteoarticular TB exceeded that of conventional methods. IMPORTANCE: In the detection of unknown infectious disease pathogens, the overall efficacy of traditional detection methods, such as culture, is low, and traditional PCR testing is also limited to the gene sequences of known pathogenic microorganisms. Metagenomic next-generation sequencing (mNGS) performs DNA sequencing by studying the entire microbial community genome in a given sample, without the need for isolation and culture. Previous studies have shown that mNGS performs better on pulmonary and extrapulmonary samples when compared with Xpert, traditional pathogenetic tests, and even parallel diagnostics. However, it should be emphasized that only a few studies have explored the performance of mNGS in detecting Mycobacterium tuberculosis in clinical samples associated with bone and joint infections. We conducted this retrospective study to provide additional data to support the use of mNGS in the clinical setting to identify pathogens within abscesses or tissue samples associated with bone and joint infections.

Purpose: In this prospective study, the diagnosis accuracy of nanopore sequencing-based Mycobacterium tuberculosis (MTB) detection was determined through examining bronchoalveolar lavage fluid (BALF) samples from pulmonary tuberculosis (PTB) -suspected patients. Compared the diagnostic performance of nanopore sequencing, mycobacterial growth indicator tube (MGIT) culture and Xpert MTB/rifampin resistance (MTB/RIF) assays. Methods: Specimens collected from suspected PTB cases across China from September 2021 to April 2022 were tested then assay diagnostic accuracy rates were compared. Results: Among the 111 suspected PTB cases that were ultimately diagnosed as PTB, the diagnostic rate of nanopore sequencing was statistically significant different from other assays (P < 0.05). Fleiss’ kappa values of 0.219 and 0.303 indicated fair consistency levels between MTB detection results obtained using nanopore sequencing versus other assays, respectively. Respective PTB diagnostic sensitivity rates of MGIT culture, Xpert MTB/RIF and nanopore sequencing of 36.11%, 40.28% and 83.33% indicated superior sensitivity of nanopore sequencing. Analysis of area under the curve (AUC), Youden’s index and accuracy values and the negative predictive value (NPV) indicated superior MTB detection performance for nanopore sequencing (with Xpert MTB/RIF ranking second), while the PTB diagnostic accuracy rate of nanopore sequencing exceeded corresponding rates of the other methods. Conclusions: In comparison with MGIT culture and Xpert MTB/RIF assays, BALF’s nanopore sequencing provided superior MTB detection sensitivity and thus is suitable for testing of sputum-scarce suspected PTB cases. However, negative results obtained using these assays should be confirmed based on additional evidence before ruling out a PTB diagnosis.