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Objectives: Silicosis people are at high risk of developing pulmonary tuberculosis. Whether silica exposure increases the likelihood of latent tuberculosis infection (LTBI) was not well understood, and potential factors involved in LTBI risk among silicosis people were not evaluated before. Thus, LTBI among silicosis people and potential risk factors for LTBI among silicosis people were evaluated in this study., Methods: A cross-sectional study was undertaken for 130 miner workers with silicosis. The QFT-GIT was performed for LTBI detection., Results: The LTBI was high to 31.6% (36/114) for silicosis participants, and 13.1% (13/99) had a history of tuberculosis. Drinking was associated with LTBI risk (OR = 6.92, 95%CI, 1.47-32.66, P = 0.015). Meanwhile, tunneling work was associated with an increased risk of LTBI compared with other mining occupations (OR = 3.91,95%CI,1.20-12.70, P = 0.024)., Conclusions: The LTBI rate of silicosis participants was high and more than 10% had a history of tuberculosis. Drinking alcohol and tunneling were independent risk factors for LTBI in silicosis participants., (© 2024. The Author(s).)

Objectives: Tuberculosis recurrence after an initial successful treatment episode can occur from either reinfection or relapse. In a population-based sample and whole genome sequencing in eastern China, we aimed to evaluate risk factors for tuberculosis recurrence and assess the proportion of recurrence because of either reinfection or relapse., Methods: Successfully treated pulmonary tuberculosis patients with sputum culture positive results were recruited from five cities in Jiangsu Province from 2013 to 2015 and followed for 2 years for tuberculosis recurrence. Among patients developing a second tuberculosis episode, whole genome sequencing was performed to distinguish relapse or reinfection through a distance threshold of 6-single-nucleotide polymorphisms. We analyzed risk factors for recurrence and epidemiological characteristics of different types of recurrent patients., Results: Of 1897 successfully treated tuberculosis patients, 7.4% (141/1879) developed recurrent tuberculosis. Compared with nonrecurrent tuberculosis, patients were at higher risk of recurrence in older age (adjusted odds ratio, 1.02 for each additional year; 95% CI, 1.01 to 1.03, p = 0.003), patients previously treated for tuberculosis (adjusted odds ratio = 2.22; 95% CI, 1.52 to 3.26, p < 0.001), or with bilateral cavities (adjusted odds ratio, 1.56; 95% CI, 1.05 to 2.32, p = 0.029). Among 27.0% (38/141) recurrent tuberculosis patients with successfully sequenced pairs, relapse was substantially more common than reinfection (71.1% vs 28.9%, p = 0.014)., Discussion: Endogenous relapse was significantly more common than exogenous reinfection in the first 2 years after treatment in eastern China. Prioritization of high-risk groups for recurrence, such as the elderly, with a previous tuberculosis diagnosis, or with bilateral cavities, may provide opportunities to reduce post-tuberculosis morbidity., (Copyright © 2022 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Purpose: Recurrent tuberculosis (TB) is defined by more than one TB episode per patient and is caused by re-infection with a new Mycobacterium tuberculosis (Mtb) strain or relapse with the previous strain. Recurrence of TB is one important obstacle for End TB strategy in the world and elucidating the triggers of recurrence is important for the current TB control strategy in China. This study aimed to analyze the sources of recurrent TB by the molecular genotyping method., Method: A population-based surveillance was undertaking on all culture-positive TB cases in Jiangsu province, China from 2013 to 2019. Phenotypic drug susceptibility test (DST) by proportion method and mycobacterial interspersed repetitive units-variable number of tandem repeat (MIRU-VNTR) were adopted for drug resistance and genotype detection., Results: A total of 1451 culture-positive TB patients were collected and 30 (2.06%, 30/1451) TB cases had recurrent TB episodes. Except 7 isolates were failed during subculture, 23 paired isolates were assessed. After genotyping by MIRU-VNTR, 12 (52.17%, 12/23) paired recurrence TB were demonstrated as relapse and 11 (47.83%,11/23) paired cases were identified as re-infection. The average interval time for recurrence was 24.04 (95%CI: 19.37-28.71) months, and there was no significant difference between relapse and re-infection. For the relapsed cases, two paired isolates exhibited drug resistance shifting, while four paired isolates revealed inconsistent drug resistance among the re-infection group including two multidrug-resistant tuberculosis (MDR-TB) at the second episode., Conclusion: Relapse and re-infection contributed equally to the current situation of recurrence TB in Jiangsu, China. Besides, more efficient treatment assessment, specific and vigorous interventions are urgently needed for MDR-TB patients, considering obvious performance among re-infection cases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Shao, Song, Li, Li, Li, Zhu, Lu and Chen.)

Background: ASAP1 (also known as AMAP1 or DDEF1) encodes an Arf GTPase-activating protein (Arf GAP), a multifunctional scaffold protein that induces hydrolysis of GTP bound to the ADP-ribosylation factor (Arf) family GTP-binding proteins. Reduction of ASAP1 expression in vitro was related to suppression of cell migration and invasiveness. The genetic variant rs4733781 of the ASAP1 gene was revealed as a significant locus for tuberculosis (TB) susceptibility, but the results still need to be validated., Methods: Blood samples from a total of 1914 active TB and healthy controls (HC) were collected to evaluate rs4733781 and the risk of TB. Meanwhile, a total of 48 noninfected HC, latent TB-infected (LTBI) controls, and active TB were collected to assay ASAP1 expression difference among the three groups. The QuantiFERON-TB Gold In-Tube was adopted to identify noninfected HC and LTBI., Results: The genetic variant of rs4733781 was found to be significantly associated with TB, and the A allele of rs4733781 (C>A) was 0.38 and 0.43 among TB cases and HC, respectively ( P = 0.0035). Meanwhile, the peripheral blood monocyte RNA fold changes for the ASAP1 gene among the 16 HC, 16 LTBI, and 16 active TB were 1.088 ± 0.4919, 2.237 ± 0.6505, and 10.12 ± 10.98 ( F = 9.559, P = 0.0003), respectively, and the expression of ASAP1 was increased by 2.06-fold ( P < 0.0001) and 9.30-fold ( P < 0.0052) for LTBI and active TB, when compared to the HC., Conclusions: Our data indicated that the A allele of rs4733781 for the ASAP1 gene was in association with a decreased risk of TB. But not only that, the overexpression of the ASAP1 gene among LTBI and TB was related to the progression of TB, which further implies that the expression of ASAP1 would be a potential biomarker for LTBI and TB diagnoses.

Background: The genotypes of Mycobacterium tuberculosis (MTB) have been found to be related to the risk of transmission and the development of drug resistance of this pathogen. Thus, exploring the molecular characteristics of MTB is helpful for understanding and controlling the spread of strains in areas with a high incidence of tuberculosis., Methods: We recruited 512 sputum smear-positive tuberculosis patients from 30 counties from 1 April to 30 June 2010; 503 MTB strains were isolated and 497 were successfully genotyped. We genotyped the strains based on a new 15-locus mycobacterial interspersed repetitive unit-variable number of tandem repeats (MIRU-VNTR) method in combination with spacer-oligonucleotide typing (spoligotyping) technology., Results: Based on spoligotyping, 487 strains displayed known patterns, and 10 were absent from the current global spoligotyping database (SpolDB4). The predominant spoligotypes belonged to the Beijing or Beijing-like family (81.1%). When we used the new 15-locus (MIRU-15) set for the MIRU-VNTR analysis, 388 different patterns were identified, including 46 clusters and 342 unique patterns. The combination of spoligotyping and MIRU-15 demonstrated a high discriminatory power. The proportion of clusters varied significantly between the Beijing and non-Beijing family strains, but no significant association was observed between multidrug resistance and Beijing family strains., Conclusions: The present study demonstrated that the Beijing family strains are the most prevalent in rural China. Spoligotyping in combination with the new MIRU-15 technique is useful for the epidemiological analysis of MTB transmission and could be used as a first-line method for the large-scale genotyping of MTB.

Background: Globally, China is the second place with high burden of tuberculosis (TB). To explore the characteristics of the pathogens of Mycobacterium tuberculosis (MTB) circulating in this area is helpful for understanding and controlling the spread of the strains. Recent developments in molecular biology have allowed prompt identification and tracking specific strains of MTB spreading through the population., Methods: Spacer-oligonucleotide typing (spoligotyping) and mycobacterial interspersed repetitive units variable number tandem repeat (MIRU-VNTR) were performed in combination to yield specific genetic profiles of 260 MTB strains isolated from 30 counties of Jiangsu province in China between June and July 2010. The spoligotyping results were in comparison to the world Spoligotyping Database of Institute Pasteur de Guadeloupe (SpolDB4). Drug susceptibility test (DST) was performed on all strains by proportion method on Lowenstein-Jensen (LJ) culture media., Results: Based on the spoligotyping method, 246 strains displayed known patterns and 14 were absent in the database. Predominant spoligotypes belonged to the Beijing family (80.4%). By using the 24-loci VNTR typing scheme, 224 different patterns were identified, including 20 clusters and 204 unique patterns. The largest clade comprised 195 strains belonging to the Beijing family. The combination of spoligotyping and 24-loci MIRU-VNTR demonstrated maximal discriminatory power. Furthermore, we observed a significant association between Beijing family strains and drug-resistant phenotypes. The Beijing family strains presented increased risks for developing multi-drug resistant TB, with the OR (95% CI) of 11.07(1.45-84.50)., Conclusions: The present study demonstrated that Beijing family isolates were the most prevalent strains circulating in Jiangsu province of China. The utility of spoligotyping in combination with 24-loci MIRU-VNTR might be a useful tool for epidemiological analysis of MTB transmission.

Purified protein derivative (PPD) skin tests often yield poor specificity, so that to develop new serological antigens for distinguishing between Mycobacterium tuberculosis infection and Bacille Calmette-Guerin (BCG) vaccination is a priority, especially for developing countries like China. We predicted the antigenicity for selected open reading frames (ORFs) based on the genome sequences of M. tuberculosis H37Rv and M. bovis BCG, as well as their functions and differences of expression under different stimulus. The candidate ORFs were cloned from H37Rv sequences and expressed as recombinant proteins in Escherichia coli. We studied the serodiagnostic potential of 11 purified recombinants by using enzyme-linked immunosorbent assay (ELISA) and involving a cohort composed of 58 TB patients (34 males and 24 females), 8 healthy volunteers and 50 PPD-negative individuals before and after BCG vaccination. For all the 11 antigens, the median OD values for the sera from TB patients were statistically significantly higher than those for PPD-negative individuals before or after BCG vaccination (P<0.01). They had at least 92% specificity in healthy controls and six seroantigens (Rv0251c, Rvl973, Rv2376c, Rv2537c, Rv2785c and Rv3873A) were never reported with seroantigenicities previously. Thus the approach combining comparative genomics, bioinformatics and ELISA techniques can be employed to identify new seroantigens distinguishing M. tuberculosis infection from BCG vaccination.

Background: Isoniazid-resistant, rifampicin-susceptible tuberculosis (Hr-TB) is the most frequent drug-resistant tuberculosis (DR-TB) in the world, and unfavorable outcomes of Hr-TB are more common compared to drug-susceptible TB. Considering there is no optimal regimen accepted worldwide, we undertook a retrospective cohort study in eastern China to estimate incidence trends and risk factors associated with unfavorable outcomes of Hr-TB. Methods: Between January 2012 and December 2022, all Hr-TB patients' information was extracted from the Tuberculosis Information Management System (TIMS), which is a national electronic information platform, to record TB patients' clinical information in this study. The incidence of Hr-TB was determined by the mid-year population according to census data published by the government. We categorized treatment regimens depending on fluoroquinolone (FQ) use, and potential risk factors were analyzed using multivariable logistic regression. Results: A total of 3116 Hr-TB patients fulfilled the inclusion criteria and were enrolled in this study. The average annual rate of Hr-TB in the 11 years under investigation was 0.34 per 100,000 and increased to 0.53 per 100,000 until 2019. In total, six different treatment regimens were utilized in the study sites, and less than 1% of regimens adopted FQ. There was no difference in the unfavorable outcomes between the FQ-included and FQ-excluded groups (p = 0.22). The average treatment duration was 7.06 months, and the longest treatment was 26 months. Approximately 20% (637/3116) of Hr-TB patients had unfavorable outcomes, and 60.13% (383/637) of them proceeded to multidrug-resistant tuberculosis (MDR-TB). Treatment duration and a positive smear at the end of the 5th month were significantly associated with unfavorable outcomes (p < 0.001). Conclusion: The unfavorable treatment outcomes of Hr-TB are still high in eastern China, and the efficacy of FQ-containing regimens needs to be validated for Hr-TB treatment. [ABSTRACT FROM AUTHOR]

The association between smoking exposure and latent tuberculosis infection (LTBI) has been investigated in a few studies; however, further investigation is needed. In this study, the 2011–2012 NHANES population was used to evaluate smoking exposure and LTBI risk. A total of 7042 participants with available LTBI results and without active tuberculosis were included for analysis. Smoking was defined as participants who smoked at least 100 cigarettes in their life. Both univariable and multivariable analysis were adopted to evaluate smoking exposure, as well as related factors on the risk of LTBI. LTBI rates among current smokers (12.1%) and former smokers (9.9%) were higher than non-smokers (5.9%). However, current smokers and former smokers were not significantly associated with LTBI risk when compared to non-smokers after adjusting by age and sex in the multivariable analysis. Meanwhile, we found that passive smoking was not associated with LTBI (adjusted odds ratio (AOR), 0.85; 95%CI, 0.66–1.09). In multivariable analysis, current smoking was associated with LTBI (OR, 1.67; 95%CI, 1.28–2.19), while former smokers had an increased OR of LTBI, but the OR did not reach statistical significance (OR, 1.15; 95%CI, 0.90–1.48). Household tuberculosis (TB) contact was also related to LTBI (OR, 1.93; 95%CI, 1.25–2.99). However, BMI and diabetes were not found to be associated with LTBI. Smoking, especially current smoking, was significantly associated with LTBI. LTBI screening should be recommended for active smokers. Former smoking and passive smoking exposure were not found to have a significant relationship with LTBI risk. However, the high LTBI rate among quitters indicated we should pay more attention to former smokers with LTBI. [ABSTRACT FROM AUTHOR]