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Metagenomic next-generation sequencing (mNGS) has greatly improved our understanding of pathogens in infectious diseases such as pulmonary tuberculosis (PTB). However, high human DNA background (> 95%) impedes the detection sensitivity of mNGS in identifying intracellular Mycobacterium tuberculosis (MTB), posing a pressing challenge for MTB diagnosis. Therefore, there is an urgent need to improve MTB diagnosis performance in PTB patients. In this study, we optimized mNGS method for diagnosis of PTB. This led to the development of the host DNA depletion assisted mNGS (HDA-mNGS) technique, which we compared with conventional mNGS and the host DNA depletion-assisted Nanopore sequencing (HDA-Nanopore) in diagnostic performance. We collected 105 bronchoalveolar lavage fluid (BALF) samples from suspected PTB patients across three medical centers to assess the clinical performance of these methods. The results of our study showed that HDA-mNGS had the highest sensitivity (72.0%) and accuracy (74.5%) in PTB detection. This was significantly higher compared to mNGS (51.2%, 58.2%) and HDA-Nanopore (58.5%, 62.2%). Furthermore, HDA-mNGS provided an increased coverage of the MTB genome by up to 16-fold. Antibiotic resistance gene analysis indicated that HDA-mNGS could provide increased depth to the detection of Antimicrobial resistance (AMR) locus more effectively. These findings indicate that HDA-mNGS can significantly improve the clinical performance of PTB diagnosis for BALF samples, offering great potential in managing antibiotic resistance in PTB patients. [ABSTRACT FROM AUTHOR]

Background: The coexistence of lung cancer and pulmonary tuberculosis (TB) makes differential diagnosis even more complicated. The purpose of the study is to explore superiority of [18F]-NOTA-FAPI-04 PET/CT in distinguishing TB from malignant lesions and accurately detecting inflammatory lymph nodes than [18F]-FDG PET/CT. Case summary: Herein, we described a case report of a patient with both lung cancer and tuberculosis underwent [18F]-FDG and Al[18F]-NOTA-FAPI-04 positron emission tomography/computed tomography (PET/CT) to determine staging. Additionally, a literature review was conducted to discuss the potential clinical applications of FAPI PET/CT. We reported a 70-year-old man with newly diagnosed lung squamous cell carcinoma underwent [18F]-FDG and Al[18F]-NOTA-FAPI-04 PET/CT to determine staging. The avid uptake of [18F]-FDG in old pulmonary TB and the right hilar inflammatory lymph nodes (<1 cm) were not found on Al [18F]-NOTA-FAPI-04 PET/CT. After 2 months of follow-up, the small lymph node was finally confirmed to be inflammatory. Conclusion: Al[18F]-NOTA-FAPI-04 PET/CT may perform better in distinguishing TB from malignancy and may offer greater specificity than [18F]-FDG PET/CT for the diagnosis inflammatory lymph nodes. [ABSTRACT FROM AUTHOR]

Introduction: The inadequate efficacy of the Bacillus Calmette–Guérin (BCG) vaccine against adult pulmonary tuberculosis (TB) necessitates the development of new and effective vaccines. Human adenovirus serotype 5 (Ad5), which induces T-cell response, is a widely used viral vector. In this study, we aimed to evaluate the efficacy of a multi-antigenic recombinant Ad5 vectored vaccine and determine the optimal immunization route for enhanced immune response against Mycobacterium tuberculosis. Methods: We constructed a multi-antigenic recombinant Ad5 vectored vaccine expressing four antigens (Ag85B-ESAT6-MPT64-Rv2660c) of M. tuberculosis (rAd-TB4), immunized with rAd-TB4 (5 × 107 infectious virus units/mouse) twice at an interval of 4 weeks starting at 10 weeks after BCG priming, and evaluated its boosting efficacy in a BCG-primed mouse model, and determined the optimal immunization route. Results: Compared with the BCG-only (2 × 105 colony forming units/mouse), subcutaneous injection of rAd-TB4 (1 × 107 infectious virus units/mL; two doses) elicited a T-cell response and cytokine production in lung lymphocytes and splenocytes. rAd-TB4 immunization significantly reduced bacterial loads and inflamed lung areas compared to BCG immunization (p < 0.01) and protected against the H37Rv challenge performed at 17 weeks of BCG priming. RNA sequencing of the whole blood of rAd-TB4-vaccinated mice collected pre- and, 1 and 4 weeks post-infection, identified differentially expressed genes associated with immune and inflammatory responses, especially those in the Wnt signaling pathway. Conclusion: Our results indicate that rAd-TB4 immunization enhances the immune response to the vaccine boosting antigens in BCG-primed mice, making it a potential adult pulmonary TB vaccine candidate. [ABSTRACT FROM AUTHOR]

Background: Early diagnosis of pulmonary tuberculosis can greatly reduce the harm caused by the disease. However, traditional diagnostic methods have various shortcomings in diagnosing pulmonary tuberculosis. Currently, with the increasing popularity, iteration, and decreasing costs of Next-generation sequencing (NGS) testing technology, NGS is being more widely applied in the diagnosis of pulmonary tuberculosis. Case presentation: A 29-year-old male presented with "fever accompanied by cough for more than 20 days." Multiple chest CT scans revealed progressive enlargement of the right hilar lymph nodes and thickening of the interlobular septa in the right upper lobe. Routine testing of bronchoalveolar lavage fluid, search for tuberculosis bacilli, bacterial and fungal cultures, X-pert MTB/RIF, and multiplex PCR-based targeted Next-generation sequencing (mp-tNGS) results were all inconclusive. Finally, bronchoalveolar lavage fluid was sent for hybrid capture-based targeted Next-generation sequencing (hc-tNGS) testing, and special staining of the enlarged lymph nodes confirmed the diagnosis of pulmonary tuberculosis. Conclusion: The hc-tNGS has significant value in diagnosing pulmonary tuberculosis, especially in cases that are difficult to detect with other methods. In the future, this could gradually become a routine diagnostic method for pulmonary tuberculosis, enhancing the accuracy of early diagnosis. [ABSTRACT FROM AUTHOR]

Background: Tubercular lymphadenitis (TBLN) is the most common extrapulmonary tuberculosis (EPTB) followed by tubercular pleural effusion (TPE). The bacteriological confirmation to diagnose EPTB is more difficult due to its paucibacillary nature often leading to delay or misdiagnosis. The role of the CBNAAT test for the diagnosis of EPTB is highly variable among different populations. Hence, the aim of the present study was to evaluate the role of CBNAAT in the diagnosis of EPTB in a tertiary care center in north India. Methods: This was a cross-sectional study conducted in the 100 stable patients of EPTB (55 TPE and 45 TBLN) who came to the Respiratory Medicine Department in MMMC&H, Solan, India. The total duration of the study was eighteen months from April 2021 to September 2022. Fine needle aspirate and pleural fluid samples were collected from all suspected TPE and TBLN patients respectively and were subjected to CBNAAT investigation. All other recommended investigations used for diagnosis of TBLN and TPE were also performed including ZN stain, FNAC, biochemical analysis of pleural fluid, Mantoux test, radiological imaging, and other routine investigations. The data analysis was done using SPSS version 20 software. Results: Out of 100 patients of EPTB, 55 were TPE, and 45 were TBLN patients. The positivity of CBNAAT was higher in TBLN patients (57.8%) as compared to TPE (23.7%) patients. The correlation between CBNAAT and ZN stain was statistically significant in both TBLN (p = 0.008) and TPE (p = 0.001) patients. The correlation of CBNAAT with FNAC, duration of illness, erythrocyte sedimentation rate (ESR), and Mantoux were all statistically significant (p < 0.05). Conclusion: Our study finding showed higher positivity of CBNAAT in the TBLN as compared to that in patients of TPE. The positivity of CBNAAT in the TBLN patients was higher in pus and cheesy FNAC samples, Mantoux-positive patients, and those with high ESR value. [ABSTRACT FROM AUTHOR]

Background: Pulmonary tuberculosis (PTB) is one of the most serious infectious diseases worldwide and poses a great threat to people's health. China has a vast territory with substantial regional disparities in the PTB disease burden. However, there have been no studies conducted to evaluate the PTB disease burden in Shenyang. The aim was to elucidate the magnitude, composition, and distribution of PTB disease burden in Shenyang. Methods: The disability-adjusted life years (DALYs) calculated based on Global Burden of Disease (GBD) framework was used to assess the disease burden of PTB in Shenyang in 2023, and descriptive epidemiological methods were employed to elucidate the magnitude, composition, and distribution characteristics of PTB disease burden in Shenyang. Results: In 2023, 4,169 PTB cases were reported in Shenyang, including 2,901 males and 1,268 females. The incidence of PTB was 45.50/105, of which 64.29/105 for males and 27.30/105 for females. The incidence among males was higher than that among females (X2 = 688.56, p<0.001). The highest incidence was 107.00/105 in the group of the population aged 80 and above (X2 = 1171.75, p<0.001). In 2023, 189 PTB deaths were reported in Shenyang, including 156 males and 33 females. The mortality of PTB was 2.06/105 of which 3.46/105 for males and 0.71/105 for females. The mortality among males was higher than that among females (X2 = 83.69, p<0.001). The highest mortality was 16.04/105 in the group of the population aged 80 and above (X2 = 285.61, p<0.001). The PTB DALYs rate was 58.25/105, of which 91.73/105 for males and 21.22/105 for females. The DALYs rate among males was higher than that among females (X2 = 44.04, p<0.001). The highest DALYs rate was 149.86/105 in the group of the population aged 80 and above (X2 = 305.35, p<0.001). Years of life lost (YLLs) due to PTB accounted for 71.38% of total DALYs, of which 74.33% for males and 52.89% for females. Conclusion: The PTB DALYs rate in Shenyang was 58.25/105, which was lower than that in China, equivalent to 80% of the national PTB disease burden rate. The disease burden showed a characteristic of increasing with age, and the PTB DALYs rate for males was higher than that for females, being equivalent to 4 times the female rate. The predominant disease burden of PTB was attributed to YLLs, accounting for as much as 71.38%, indicating that PTB primarily results in premature mortality rather than disability. Therefore, the focus should be shifted towards early intervention to reduce transmission, especially for the aged males. [ABSTRACT FROM AUTHOR]

Background: Genetic variations in endoplasmic reticulum aminopeptidase (ERAP1, ERAP2) genes are associated with the pathogenesis of multiple diseases, including infectious diseases. The objective of our study was to assess whether ERAP1, ERAP2 genes polymorphisms and methylation levels affect the risk of pulmonary tuberculosis (PTB). Methods: We genotyped ten single nucleotide polymorphisms (SNPs) in ERAP1, ERAP2 genes among 497 PTB patients and 502 controls by SNPscan technique. Additionally, we detected the ERAP1, ERAP2 genes methylation levels in 98 PTB patients and 97 controls through Illumina Hiseq platform. Results: Our results showed that the GG genotype, G allele frequencies of ERAP2 gene rs2549782 were significantly increased in PTB patients compared to controls, and rs2549782 polymorphism was related to the increased risk of PTB under recessive model. In addition, no significant relationship was found between ERAP1 gene rs13167972, rs17086651, rs469783, rs26618, rs3734016, ERAP2 gene rs17524572, rs1230358, rs2549794, rs117041256 and PTB susceptibility. Among PTB patients, the frequencies of rs17524572 TT genotype, T allele were significantly associated with drug-induced liver injury, and rs1230358, rs2549782, rs2549794 polymorphisms were linked to the occurrence of fever. Haplotype analysis of ERAP2 gene suggested that the frequency of CTGGT haplotype was higher, while the frequency of CTGTT haplotype was lower in PTB patients. When compared with controls, the ERAP1 methylation level was lower in PTB patients, while the ERAP2 methylation level was significantly increased. Moreover, rs1230358 polymorphism was found to affect the ERAP2 methylation level. Conclusion: The ERAP2 rs2549782 variant and altered methylation levels of ERAP1, ERAP2 genes were related to susceptibility to PTB. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), remains a global health crisis, especially in sub-Saharan Africa, where high human immune virus (HIV) prevalence exacerbates the problem. The co-infection of TB and HIV creates a deadly combination, increasing susceptibility and complicating disease progression and treatment. Ethiopia, classified as a high-burden country, faces significant challenges despite efforts to reduce co-infection rates. The rise of multidrug-resistant TB further complicates diagnosis and management, highlighting the urgent need for intensified efforts to combat this dual epidemic. Methods: Studies searched through the search engine of Cochrane Library, PubMed, Web of Science, Google Scholar. Data from included studies was extracted, organized in Excel, and then analyzed using STATA 17. The overall effect across all studies was calculated using a random-effect model. Potential publication bias and heterogeneity in the results between studies were assessed using Egger's test, forest plot, and I² statistic, respectively. Results: According to this systematic review and meta-analysis, the overall prevalence of pulmonary tuberculosis(PTB) among adults living with human immune virus /aquered immune deficieciency syndrome(HIV/AIDS) in Ethiopia was 15% (95% CI: 8-23%). Several factors were independently associated with pulmonary tuberculosis, including CD4 count below 200 cells/mm³ (OR = 4.491, 95% CI: 1.0001–8.132), WHO clinical stage III (OR = 4.487, 95% CI: 2.264–6.710)), WHO clinical stage IV (OR = 6.905, 95% CI: 5.239–8.571), smokers (AOR = 3.749, 95% CI: 2.626–5.271), ambulatory adults (AOR = 1.887, 95% CI: 1.439–2.335). Conclusion: This systematic review and meta-analysis found a significant 15% pooled prevalence of pulmonary tuberculosis (PTB) among adults living with HIV/AIDS in Ethiopia. The prevalence was notably higher in individuals with lower CD4 counts, advanced HIV stages (III and IV), and in smokers. These findings underscore the need for early detection, targeted interventions, and integrated TB control programs with HIV care to mitigate the burden of PTB in this population. [ABSTRACT FROM AUTHOR]

As one of the major public health security issues, pulmonary tuberculosis had a global death rate of 1.6 million in 2021 alone, ranking 13th in the world, posing a great threat to society and families. Analyzing the temporal and spatial distribution and evolution trend of tuberculosis, discussing the exposure factors and studying the environmental background that affects the incidence can provide the basis for accurate prevention and control and promote the healthy and stable development of society. Based on the county scale, this study determined the high-incidence areas through hot spot analysis and selected nine districts and counties covering meteorological stations and air monitoring stations. The explanatory power of each factor to the incidence of pulmonary tuberculosis was analyzed by geographical detector, and the main influencing factors were explored. The results show that the following: (1) The number and incidence of pulmonary tuberculosis in Gansu Province declined from 2020 to 2022. (2) The influence of meteorological conditions such as temperature, precipitation and air pressure on pulmonary tuberculosis in different regions shows significant regional differences. Although the meteorological influence in adjacent regions shows certain convergence, the change in wind speed has no significant influence on the risk of pulmonary tuberculosis. (3) PM10, altitude, temperature, population density and GDP per capita have strong explanatory power to the incidence of tuberculosis, and the interaction between any two factors exceeds the effect of a single factor in explanatory power, showing the characteristics of two-factor enhancement and nonlinear enhancement. [ABSTRACT FROM AUTHOR]

BACKGROUND: Tuberculosis (TB), primarily caused by Mycobacterium tuberculosis, remains a significant global health concern. Targeted Next-Generation Sequencing (tNGS) has emerged as a rapid and comprehensive diagnostic tool for tuberculosis, offering advantages over traditional methods and serving as an effective alternative for drug susceptibility testing and the detection of drug-resistant tuberculosis. OBJECTIVE: This study aimed to retrospectively analyze the clinical characteristics of pulmonary tuberculosis patients. After explore the application value of targeted next-generation sequencing technology in this patient population, providing valuable insights for clinical diagnosis and treatment. METHODS: In this retrospective study, we analyzed data from 65 patients with laboratory-confirmed tuberculosis admitted to Tianjin Baodi Hospital from November 14, 2020, to February 1, 2023. Patients underwent bronchoalveolar lavage fluid (BALF) testing, including acid-fast staining, culture, and tNGS. Biopsies and histopathological examinations were performed on some patients, along with comprehensive radiological assessments for all. RESULTS: Among the 65 pulmonary tuberculosis patients, targeted next-generation sequencing detected pathogens in bronchoalveolar lavage fluid with a positivity rate of 93.8%, significantly higher than traditional methods such as acid-fast staining, culture, and pathology. Compared to bronchoalveolar lavage fluid smear, targeted next-generation sequencing demonstrated significantly higher diagnostic sensitivity (98.46% vs. 26.15%) and accuracy (98.46% vs. 26.15%). CONCLUSION: Targeted next-generation sequencing, with its high sensitivity and specificity compared to traditional methods, provides unique advantages in detecting pathogens among these patients, highlighting its importance in disease management. [ABSTRACT FROM AUTHOR]

Background Respiratory isolation of people with pulmonary tuberculosis (TB), including after treatment initiation, is used to prevent community-based transmission; yet guidelines on duration are limited and implementation is heterogeneous. This systematic review synthesized evidence on respiratory isolation for TB to inform National TB Coalition of America guidelines. Methods After searching 6 databases, 8 reviewers screened and extracted data in duplicate on effects of respiratory isolation compared to no isolation or masking. Studies were stratified by outcomes: TB infection or disease in contacts, mortality, hospitalization duration, patient and health system costs, and impact on mental health or stigma. We used a convergent integrated approach to synthesize quantitative and qualitative findings and assess limitations. Results Seventeen studies were included. There were limited data directly comparing isolation to non-isolation interventions, including effects after treatment initiation. One randomized controlled trial suggested treatment in a sanatorium versus at home did not affect TB incidence in contacts. Modeling studies suggest isolation may reduce transmission but relied on various assumptions, and isolation was implemented alongside other interventions. Descriptive, mixed-methods, and qualitative studies described adverse impacts of isolation on employment, education, food/housing security, and mental health due to transmission fears, stigma, and social isolation. Impacts were compounded in marginalized groups including Indigenous and incarcerated persons. Conclusions Data to support current isolation practices, particularly after effective treatment initiation, to reduce TB transmission in communities are limited. Public health guidance should weigh the negative impacts on people with TB against decreased community transmission to make evidence-based decisions about respiratory isolation. [ABSTRACT FROM AUTHOR]

Background: Since the revolutionary introduction of the Gene Xpert Mycobacterium tuberculosis/resistance to rifampicin (MTB/RIF) assay into the field of diagnostic techniques for Tuberculosis (TB), it has been gaining increasing popularity as it offers of MTB detection together with RIF–Resistance in almost two hours with high accuracy, allowing physicians to customize appropriate and accurate treatment regimens without time delay. Objective: To assess the diagnostic utility of Gene Xpert in TB diagnosis and detection of RIF–Resistance in both pulmonary and extrapulmonary specimens. Methods: This is a prospective, cross-sectional study in which specimens from 77 suspected pulmonary and extrapulmonary TB cases were collected and examined via three techniques: Gene Xpert, direct smear microscopy for fast bacilli (AFB) along with culture on Löwenstein–Jensen medium (the reference standard method) and drug susceptibility testing for positive cultures. Results: The Xpert assay had the highest sensitivity and diagnostic accuracy in the detection of pulmonary TB (96.4%, 93.1%, respectively), with 90% specificity. Xpert assay showed much lower sensitivity and specificity in diagnosing extrapulmonary TB (71.4%, 83.3%, respectively). Moreover, Gene Xpert assay showed 100% specificity in the identification of RIF-Resistance with the highest sensitivity in pulmonary TB (90.9%). Conclusion: Gene Xpert MTB/RIF showed a comparable diagnostic yield to that of conventional culture with better performance among pulmonary specimens. In addition, the assay had 100% specificity in diagnosing RIF–Resistance in pulmonary and extrapulmonary specimens. [ABSTRACT FROM AUTHOR]

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To understand the current status and analyse the factors influencing frailty in older adults patients with pulmonary tuberculosis. Methods: This retrospective case-control study included 204 older adults patients with pulmonary tuberculosis. The enrolled patients were divided into a frailty group (n = 101) and a non-frailty group (n = 103). The study further collected and compared the data of various scores. Results: The total frailty score among the patients ranged from 0 to 15 points, with an average score of 5.23 ± 2.31 points. The total social support score ranged from 15 to 47 points, with an average of 33.43 ± 6.11 points. The physical function level scores ranged from 10 to 100 points, with an average of 84.58 ± 14.48 points. Additionally, univariate analysis showed significant differences between the groups in terms of age, body mass index (BMI), duration of disease, types of long-term medication and the number of complications and comorbidities (P < 0.05). Correlation analysis revealed negative correlations of social support (P < 0.001) and physical function (P < 0.001) with the overall frailty score and a positive correlation of depression levels (P < 0.001) with the overall frailty score. Further regression analysis indicated that being over 80 years old, having a low BMI, long-term polypharmacy and a high depression score were risk factors. High social support and physical function scores were protective factors against frailty in older adults patients with pulmonary tuberculosis. Conclusion: In older adults patients with pulmonary tuberculosis, the overall frailty score shows negative correlations with social support and physical function and a positive correlation with depression level. [ABSTRACT FROM AUTHOR]

In clinical practice, differentiating among pulmonary mucormycosis (PM), invasive pulmonary aspergillosis (IPA), and pulmonary tuberculosis (PTB) can be challenging. We aimed to evaluate the performance of chest CT-based artificial intelligence (AI) models in distinguishing among these three diseases. Patients with confirmed PM, IPA, or PTB were retrospectively recruited from three tertiary hospitals. Two models were developed: the unannotated supervised training (UST) model, trained with original CT images and the annotated supervised training (AST) model, trained with manually annotated lesion images. A network questionnaire with 20 cases was designed to assess the performance of clinicians. Sensitivity, specificity, and accuracy were calculated for both models and clinicians. A total of 61 PM cases, 136 IPA cases, and 155 PTB cases were included in the study. In the internal validation set, both models had an accuracy of 66.1%. The UST model had sensitivities of 27.3%, 73.9%, and 76.0% for PM, IPA, and PTB, while the AST model had sensitivities of 9.1%, 69.6%, and 88.0% for the same conditions. In the external validation set, both models had an accuracy of 57.6%. The UST model had sensitivities of 0, 85.7%, and 53.3% for PM, IPA, and PTB, respectively, while AST model had sensitivities of 0, 42.9% and 83.3%. A total of 112 clinicians had an accuracy of 42.9%, with sensitivities of 31.5%, 43.4%, and 48.0% for PM, IPA, and PTB. We demonstrated that two AI models showed comparable performance in diagnosing three diseases. Both models effectively detected IPA and PTB but struggled to identify PM. [ABSTRACT FROM AUTHOR]

A 73-year-old Japanese woman was admitted to our hospital with anorexia, weight loss, and fever. A few weeks prior to admission, she became aware of anorexia. She was leukopenic, complement-depleted, and positive for antinuclear antibodies and anti-double stranded DNA antibodies. She was also found to have chronic airway inflammation on computed tomography. At the time of admission, she had multiple erythematous plaques on face and neck. She had blood glucose 343 mg/dL, HbA1c 12.7%, serum C-peptide 0.74 ng/mL, urinary C-peptide 17 μg/day, and urinary ketone 3+; and was positive for anti-glutamic acid decarboxylase antibodies and anti-zinc transporter 8 antibodies. Her human leukocyte antigen type was DRB1* 09:01-DQB1* 03:03, which is a susceptibility haplotype for acute-onset type 1 diabetes (T1D). Therefore, she was diagnosed as having concomitant T1D and SLE. Initial treatment with insulin and prednisolone alleviated her symptoms. However, sputum culture revealed Mycobacterium tuberculosis 23 days later, and she was treated with a multidrug regimen. The timing of onset of the SLE and T1D was estimated to be 4–7 weeks prior to admission. No imaging findings were available prior to 3 weeks of admission, making it difficult to determine the timing of onset of pulmonary tuberculosis (TB). In summary, SLE and T1D are both autoimmune diseases, but rarely occur together. Environmental and genetic factors are involved in the development of T1D and SLE, but TB is rarely thought of as a causative environmental factor. In the present case, SLE, T1D, and TB may have interacted during their respective onsets. [ABSTRACT FROM AUTHOR]

Jun Ma,1,&ast; Li Wang,1,&ast; Xubin Zheng,2 Haiyan Cui,1 Wei Sha1– 3 1Department of Tuberculosis, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 2Clinic and Research Center of Tuberculosis, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 3Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haiyan Cui; Wei Sha, Department of Tuberculosis, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China, Tel +861861687019 ; +8613671758200, Email cuihaiyan23@163.com; shfksw@tongji.edu.cnPurpose: New economic, rapid, and efficient diagnostic methods are desirable for the control of tuberculosis. This study aimed to evaluate the performance of a dual-gene qPCR melting curve assay (DGPMC) in detecting tuberculosis among patients with suspected pulmonary tuberculosis.Patients and Methods: The DGPMC assay based on rpoB and IS6110 gene sequences has been established for detection of Mycobacterium tuberculosis. A prospective study was conducted among adult patients with suspected pulmonary tuberculosis from June 2021 to September 2023 at Shanghai Pulmonary Hospital, China. All patients received symptom assessment, high-resolution chest CT scan, and bronchoscopy. Bronchoalveolar lavage fluid was collected for mycobacterial culture and acid-fast staining, GeneXpert MTB/RIF, and DGPMC assay. The diagnostic performance of DGPMC assay was evaluated against the composite reference standard.Results: Overall, 240 patients were included in this trial, including 80 (33.3%) asymptomatic patients. Clinical diagnosis of tuberculosis was confirmed in 191 (79.6%) patients and 49 (20.4%) patients were confirmed without tuberculosis. The overall sensitivity of the DGPMC assay was 55.0% (95% CI: 47.6– 62.1%), and the corresponding specificity was 85.7% (95% CI: 72.1– 93.6%) in the diagnosis of tuberculosis. The sensitivity of DGPMC assay was higher than that of GeneXpert test (55.0% vs 47.1%, P = 0.038). The Youden index and weighted Youden index of the DGPMC assay were 40.7% and 28.4%, respectively. Subgroup analyses demonstrated that the sensitivity was 32.4% (95% CI: 22.3– 44.4%) in the individuals with negative results for both culture and GeneXpert test. The DGPMC assay performed significantly better than the melting curves based on rpoB gene or IS6110 gene alone (P = 0.0000; P = 0.0020).Conclusion: The DGPMC assay is an alternative tool favorable for the detection of tuberculosis in patients with suspected pulmonary tuberculosis, especially in the patients with low bacterial load.Keywords: pulmonary tuberculosis, polymerase chain reaction, melting curve, diagnostic performance

Abstract Metagenomic next-generation sequencing (mNGS) has greatly improved our understanding of pathogens in infectious diseases such as pulmonary tuberculosis (PTB). However, high human DNA background (> 95%) impedes the detection sensitivity of mNGS in identifying intracellular Mycobacterium tuberculosis (MTB), posing a pressing challenge for MTB diagnosis. Therefore, there is an urgent need to improve MTB diagnosis performance in PTB patients. In this study, we optimized mNGS method for diagnosis of PTB. This led to the development of the host DNA depletion assisted mNGS (HDA-mNGS) technique, which we compared with conventional mNGS and the host DNA depletion-assisted Nanopore sequencing (HDA-Nanopore) in diagnostic performance. We collected 105 bronchoalveolar lavage fluid (BALF) samples from suspected PTB patients across three medical centers to assess the clinical performance of these methods. The results of our study showed that HDA-mNGS had the highest sensitivity (72.0%) and accuracy (74.5%) in PTB detection. This was significantly higher compared to mNGS (51.2%, 58.2%) and HDA-Nanopore (58.5%, 62.2%). Furthermore, HDA-mNGS provided an increased coverage of the MTB genome by up to 16-fold. Antibiotic resistance gene analysis indicated that HDA-mNGS could provide increased depth to the detection of Antimicrobial resistance (AMR) locus more effectively. These findings indicate that HDA-mNGS can significantly improve the clinical performance of PTB diagnosis for BALF samples, offering great potential in managing antibiotic resistance in PTB patients.

Abstract Background Tuberculosis remains a major public health challenge worldwide. This study aimed to determine the long-term trends in the notification rate of tuberculosis in Zhejiang Province, and to assess the potential independent risks associated with age, time period, and birth cohort. Methods Data on all pulmonary tuberculosis (PTB) cases in Zhejiang Province from 2008 to 2022 were collected from the Tuberculosis Information Management System. Long-term trends in the notification rate and independent risks associated with quantitatively decomposed variables were determined using joinpoint regression model and age-period-cohort model. Results Between 2008 and 2022, a total of 323,745 PTB cases were notified in Zhejiang Province. Overall, the notification rate declined, with notable turning points in 2010 and 2019. Net drift analysis revealed an average annual decrease of 5.7% (95% CI: -6.8%, -4.6%; P

Abstract Background Early diagnosis of pulmonary tuberculosis can greatly reduce the harm caused by the disease. However, traditional diagnostic methods have various shortcomings in diagnosing pulmonary tuberculosis. Currently, with the increasing popularity, iteration, and decreasing costs of Next-generation sequencing (NGS) testing technology, NGS is being more widely applied in the diagnosis of pulmonary tuberculosis. Case presentation A 29-year-old male presented with “fever accompanied by cough for more than 20 days.” Multiple chest CT scans revealed progressive enlargement of the right hilar lymph nodes and thickening of the interlobular septa in the right upper lobe. Routine testing of bronchoalveolar lavage fluid, search for tuberculosis bacilli, bacterial and fungal cultures, X-pert MTB/RIF, and multiplex PCR-based targeted Next-generation sequencing (mp-tNGS) results were all inconclusive. Finally, bronchoalveolar lavage fluid was sent for hybrid capture-based targeted Next-generation sequencing (hc-tNGS) testing, and special staining of the enlarged lymph nodes confirmed the diagnosis of pulmonary tuberculosis. Conclusion The hc-tNGS has significant value in diagnosing pulmonary tuberculosis, especially in cases that are difficult to detect with other methods. In the future, this could gradually become a routine diagnostic method for pulmonary tuberculosis, enhancing the accuracy of early diagnosis.

Introduction: As one of the leading causes of death worldwide, pulmonary tuberculosis (PTB) is an infectious disease that continues to pose a serious threat to public health. The presence of cavities in radiological imaging of patients with PTB is associated with malnutrition, age, gender, and other comorbidities, including diabetes mellitus. This study aimed to find the association between nutritional status and lung cavity in PTB patients. Methods: This was an analytical observational study with a cross-sectional design that involved 134 adult patients who were diagnosed with PTB at Persahabatan National Respiratory Referral Hospital, Jakarta. All patients were interviewed using a questionnaire for sociodemographic and anthropometric data, the nutritional status was assessed using the subjective global assessment (SGA), and the lung cavity was determined using a chest X-ray interpreted by radiologists. The Chi-square test was performed using the Statistical Package for the Social Sciences (SPSS) version 25 for Windows. Results: Of 134 PTB patients, 61.9% were males, and 92.5% were from the 18-59 years old age group. Based on the SGA score, 77 (57.5%) were grouped as mild-moderate malnutrition/SGA B and 22 (16.4%) as severe malnutrition/SGA C. Lung cavity was found in 42 (31.3%) patients. The analysis showed that malnutrition was statistically significantly associated with lung cavity with OR=6.933 (95%CI 1.986-24.205; p=0.002) and the adjusted OR were 7.303 (95%CI 2.060-25.890; p=0.002) after controlling for age, sex, smoking, education, and comorbidities. Conclusion: This study found that malnutrition was associated with lung cavities in PTB patients. These findings might indicate how malnutrition impaired the immune function in PTB patients.

Objective:To investigate the urban and rural differences in adverse outcomes of pulmonary tuberculosis (PTB) in patients with pulmonary tuberculosis-diabetes mellitus comorbidity (PTB-DM), so as to provide insights into improving the prevention and treatment measures for PTB-DM. Methods:Patients with PTB-DM who were admitted and discharged from 14 designated tuberculosis hospitals in Hangzhou City from 2018 to 2022 were selected. Basic information, and history of diagnosis and treatment were collected through hospital information systems. The adverse outcomes of PTB were defined as endpoints, and the proportions of adverse outcomes of PTB in urban and rural patients with PTB-DM were analyzed. Factors affecting the adverse outcomes of PTB were identified using a multivariable Cox proportional hazards regression model. Results:A total of 823 patients with PTB-DM were enrolled, including 354 (43.01%) urban and 469 (56.99%) rural patients. There were 112 (13.61%) patients with adverse outcomes of PTB. The proportions of adverse outcomes of PTB in urban and rural patients were 14.41% and 13.01%, respectively, with no statistically significant difference (P>0.05). Multivariable Cox proportional hazards regression analysis identified first diagnosed in county-level hospitals or above (HR=2.107, 95%CI: 1.181-3.758) and drug resistance (HR=3.303, 95%CI: 1.653-6.600) as the risk factors for adverse outcomes of PTB in urban patients with PTB-DM, while the treatment/observed management throughout the process (HR=0.470, 95%CI: 0.274-0.803) and fixed-dose combinations throughout the process (HR=0.331, 95%CI: 0.151-0.729) as the protective factors for adverse outcomes in rural patients with PTB-DM. Conclusions:There are differences in influencing factors for adverse outcomes of PTB in urban and rural patients with PTB-DM. The adverse outcomes of PTB are associated with first diagnosed hospitals and drug resistance in urban patients, and are associated with the treatment/observed management and fixed-dose combinations throughout the process in rural patients.

Objective: To investigate the influencing factors for delay in healthcare-seeking, definitive diagnosis and identification in patients with pulmonary tuberculosis (PTB) in Minhang District, Shanghai Municipality, so as to provide the basis for effectively reducing delay in PTB patients. Methods: Data of PTB patients in Minhang District from 2017 to 2022 were collected from the Infectious Disease Reporting Information System of Chinese Disease Prevention and Control Information System. The prevalence rates of delay in healthcare-seeking, definitive diagnosis and identification were analyzed, and factors affecting delay in healthcare-seeking, definitive diagnosis and identification were identified using multivariable logistic regression models. Results: A total of 4 214 PTB patients were reported in Minhang District from 2017 to 2022, including 2 802 males and 1 412 females, with a male-to-female ratio of 1.98∶1. The majority of patients were aged 25 to

Objective: To analyze the spatio-temporal distribution of pulmonary tuberculosis (PTB) among students in Suzhou City, Jiangsu Province from 2015 to 2023, so as to provide the evidence for the prevention and control of PTB in schools. Methods: Data of PTB cases among students in Suzhou City from 2015 to 2023 were collected from Chinese Disease Prevention and Control Information System and Suzhou Report of Investigation and Disposal of Tuberculosis in Schools. The seasonal incidence of PTB among students was analyzed using seasonal index (SI). The spatio-temporal clustering characteristics of PTB among students were analyzed using spatial autocorrelation and retrospective spatio-temporal permutation scanning. Results: Totally 1 374 PTB cases among students were reported in Suzhou City from 2015 to 2023. PTB cases were reported in each month, and the SIs were 100.69%, 124.38%, 108.98%, 135.04%, 106.61% and 106.61% in April, May, July, September, October and November, respectively, indicating the prevalence of PTB among students. Spatial autocorrelation analysis showed there was a positive spatial correlation of PTB among students in 2019 and 2020 (Moran's I=0.053 and 0.089, both P

Abstract Background The common diagnostic methods for tuberculosis have been showing reduced sensitivity among chronic obstructive pulmonary disease patients. This study was conducted to evaluate and analyse the diagnostic value of an interferon-γ release assay in COPD patients complicated with pulmonary tuberculosis. Methods A nested case-control study was conducted on 123 COPD patients hospitalized at the Fifth Hospital of Shijiazhuang, Hebei Province, from January 2019 to June 2021. Thirty-one patients with active pulmonary tuberculosis complicated with COPD composed the observation group (Group A), 31 patients with nonactive pulmonary tuberculosis complicated with COPD composed the COPD control group (Group B), and 31 patients with active pulmonary tuberculosis not complicated with COPD composed the non-COPD control group (Group C). An interferon-γ release assay, a purified protein derivative of tuberculin (PPD) test, an anti-tuberculosis antibody test, a test of Mycobacterium tuberculosis by sputum smear microscopy and a test of Mycobacterium tuberculosis by PCR method were used to test patients in each group. The positive detection rates generated from the five test methods were compared and analysed. Results In COPD patients complicated with active pulmonary tuberculosis, the differences in the percentage of patients with positive interferon-γ release between the PPD test, anti-tuberculosis antibody test, Mycobacterium tuberculosis by sputum smear microscopy and PCR test results were statistically significant. Conclusion In patients with COPD complicated with active pulmonary tuberculosis, the percentage of patients who were positive according to the interferon-γ release assay was higher than that according to the sputum smear microscopy, PCR detection of Mycobacterium tuberculosis in sputum specimen, and detection of anti-tuberculosis antibodies. COPD-related complications did not affect the T-SPOT; the greater the T-SPOT value was, the greater the likelihood of active TB. For patients who are T-SPOT positive but clinically considered to have inactive tuberculosis, regular follow-ups should be performed to observe changes in the patient’s condition.

In this case report, a male patient in his 50′s presented with right-sided neck swelling for 2 months and an acute episode of hematochezia along with vague abdominal and systemic symptoms for 2-3 years. The clinical suspicion was gastric carcinoma.Fine needle aspiration cytology (FNAC) from the neck swelling was inconclusive, and upper gastrointestinal (GI) endoscopy was normal. However, contrast enhanced CT neck, chest, and abdomen revealed focal, heterogeneously enhancing wall thickening in the cardia of the stomach with periportal and perigastric nodes showing peripheral rim enhancement; ascites and peritoneal thickening; a cold abscess in the right axilla; cervical and mediastinal lymph nodes with central hypodensity; and tree-in-bud opacities with sub-segmental consolidation in the lower lobe of the left lung. A diagnosis of disseminated tuberculosis was made, and the patient was successfully treated with empirical antitubercular therapy.This case highlights an uncommon presentation of tuberculosis of gastric cardia and a need to have a high index of suspicion, even in the absence of positive microbiological confirmation of the disease.

This case study describes the case of a patient with lung cancer who developed pre-extensively drug-resistant pulmonary tuberculosis and venous thromboembolism. We discuss how lung cancer can predispose an individual to pulmonary tuberculosis and venous thromboembolism.

Abstract Background Pulmonary tuberculosis can spread by airborne transmission when an infected person coughs, sneezes and speaks via expectorates. Therefore, household contacts who are close to a tuberculosis patient are at the highest risk of contracting the disease. This analytical cross-sectional study aimed to determine the factors affecting prevention behaviors among household contacts in Phitsanulok Province, northern Thailand. Methods The study sample included 193 household contacts with pulmonary tuberculosis in Phitsanulok Province. They were randomly selected using a multistage sampling technique. Data were collected by a self-administered questionnaire consisting of 8 parts: (1) sociodemographic characteristics, (2) tuberculosis knowledge, (3) perceived susceptibility of tuberculosis infection, (4) perceived severity of tuberculosis, (5) perceived self-efficacy of tuberculosis prevention, (6) perceived outcome of tuberculosis prevention, (7) social support of tuberculosis prevention, and (8) tuberculosis prevention behaviors. Frequencies, percentages, means, standard deviations, and multiple regression analysis were explored for data analysis. Results Most participants (91.2%) had tuberculosis prevention behaviors at a high level (scores of 4.35). Factors that significantly affected tuberculosis prevention behaviors included perceived self-efficacy in tuberculosis prevention (β = 0.474), social support (β = 0.220), current smoker (β = -0.171), driving to the hospital (β = 0.150), unknown history of tuberculosis vaccination (BCG) (β = -0.122), and those who were older siblings, aunts, uncles, younger siblings, or nephews of participants (β = -0.116). These 6 factors explained 38.5% of tuberculosis prevention behaviors. Conclusion Household contacts to pulmonary tuberculosis should be educated about the perceived self-efficacy of tuberculosis prevention, and receive more social support to prevent the disease. The focus should be on current smokers, those who drive to the hospital, those who do not know the history of tuberculosis vaccination, and relatives of patients (older sibling, aunt, uncle, younger sibling, nephew) to reduce the risk of pulmonary tuberculosis in the future.