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Clinical Infectious Diseases : An... Jul 2024Interferon-gamma release assays (IGRA) are widely used for diagnosis of latent tuberculosis infection. However, with repeat testing, IGRA transformation (conversion or...
BACKGROUND
Interferon-gamma release assays (IGRA) are widely used for diagnosis of latent tuberculosis infection. However, with repeat testing, IGRA transformation (conversion or reversion) may be detected and is challenging to interpret. We reviewed the frequency of and risk factors for IGRA transformation.
METHODS
We screened public databases for studies of human participants that reported the frequency of IGRA transformation. We extracted study and subject characteristics, details of IGRA testing and results. We calculated the pooled frequency of IGRA transformation (and transient transformation) and examined associated risk factors.
RESULTS
The pooled frequency of IGRA conversion or reversion from 244 studies was estimated at 7.3% (95% CI 6.1-8.5%) or 22.8% (20.1-25.7%), respectively. Transient conversion or reversion were estimated at 46.0% (35.7-56.4%) or 19.6% (9.2-31.7%) of conversion or reversion events respectively. Indeterminate results seldom reverted to positive (1.2% [0.1-3.5%]). IGRA results in the borderline positive or negative range were associated with increased risk of conversion or reversion (pooled OR: conversion, 4.15 [3.00-5.30]; reversion, 4.06 [3.07-5.06]). BCG vaccination was associated with decreased risk of conversion (0.70, 0.56-0.84), cigarette smoking with decreased risk of reversion (0.44, 0.06-0.82), and female sex with decreased risk of either conversion or reversion (conversion, 0.66 [0.58-0.75]; reversion, 0.46 [0.31-0.61]).
CONCLUSIONS
IGRA conversion is less common than reversion, and frequently transient. Research is needed to determine whether individuals with reversion would benefit from tuberculosis preventive treatment. Re-testing of people with indeterminate results is probably not indicated, since indeterminate results seldom revert to positive.
PubMed: 38954503
DOI: 10.1093/cid/ciae357 -
Organic Letters Jul 2024We herein report for the first time the inter- and intramolecular orthogonal cleavage of two -nitrobenzyl (NB) analogues. It is shown that the nitroveratryl (NV) group...
We herein report for the first time the inter- and intramolecular orthogonal cleavage of two -nitrobenzyl (NB) analogues. It is shown that the nitroveratryl (NV) group can be photolyzed with high priority when NV and -nitrobenzyl carbonate (NBC) are used together as the protecting groups of glycans. Notably, the photolytic products could be used directly in the subsequent glycosylation without further purification. With the above-mentioned orthogonal photolabile protecting group strategy in hand, a tetrasaccharide and a derivative of glucosyl glycerol were rapidly prepared.
PubMed: 38953872
DOI: 10.1021/acs.orglett.4c01906 -
Cureus May 2024Introduction Pulmonary tuberculosis (TB) remains a global health concern, exacerbated by the emergence of extensively drug-resistant (XDR) strains of . This study...
Introduction Pulmonary tuberculosis (TB) remains a global health concern, exacerbated by the emergence of extensively drug-resistant (XDR) strains of . This study employs advanced molecular techniques, specifically polymerase chain reaction (PCR) profiling, to comprehensively characterize the genetic landscape of XDR pathogenic bacteria in patients diagnosed with pulmonary TB. The objective of the study is to elucidate the genes that are associated with drug resistance in pulmonary TB strains through the application of PCR and analyze specific genetic loci that contribute to the development of resistance against multiple drugs. Materials and methods A total of 116 clinical samples suspected of TB were collected from the tertiary healthcare setting of Saveetha Medical College and Hospitals for the identification of MTB, which includes sputum (n = 35), nasal swabs (n = 17), blood (n = 44), and bronchoalveolar lavage (BAL) (n = 20). The collected specimens were processed and subjected to DNA extraction. As per the protocol, reconstitution of the DNA pellet was carried out. The reconstituted DNA was stored at -20 °C for the PCR assay. From the obtained positive sample specimens, XDR pulmonary TB specimens were focused on the targeted genes, specifically the gene for rifampicin resistance, , and gene for thepromoter region for isoniazid resistance. Results Out of a total of 116 samples obtained, 53 tested positive for pulmonary TB, indicative of a mycobacterial infection. Among these positive cases, 43 patients underwent treatment at a tertiary healthcare facility. Subsequently, a PCR assay was performed with the extracted DNA for the target genes , , and . Specifically, 22 sputum samples exhibited gene expression for , , and , while nine nasal swabs showed expression of the and genes. Additionally, gene expression was detected in seven blood specimens, and both and genes were expressed in five BAL samples. Conclusion The swift diagnosis and efficient treatment of XDR-TB can be facilitated by employing advanced and rapid molecular tests and oral medication regimens. Utilizing both newly developed and repurposed anti-TB drugs like pretomanid, bedaquiline, linezolid, and ethionamide. Adhering to these current recommendations holds promise for managing XDR-TB effectively. Nevertheless, it is significant to conduct well-designed clinical trials and studies to further evaluate the efficacy of new agents and shorter treatment regimens, thus ensuring continuous improvement in the management of this challenging condition.
PubMed: 38953074
DOI: 10.7759/cureus.61424 -
Cureus May 2024Tuberculosis is a disease with presentations both in the lungs and at other extrapulmonary sites. While pulmonary tuberculosis constitutes a significant proportion of...
Tuberculosis of the Cervical Vertebrae With Retropharyngeal and Parapharyngeal Abscesses Due to Staphylococcus aureus and Mycobacterium tuberculosis in an Adult: A Report of a Rare Case.
Tuberculosis is a disease with presentations both in the lungs and at other extrapulmonary sites. While pulmonary tuberculosis constitutes a significant proportion of total tuberculosis cases, extrapulmonary cases with infections at rare sites are also documented. Herein, an exceedingly rare case of tuberculosis of the cervical vertebrae with retropharyngeal and parapharyngeal abscesses due to and in a young Indian male is presented. The rarity of the locations of the lesions with coinfections with two bacteria made the diagnosis challenging. Besides, the potential for a retropharyngeal abscess to compress the airway is an emergency situation. However, the ultimate diagnosis was achieved with the help of a radiograph of the neck, contrast-enhanced computed tomography of the neck, fine-needle aspiration cytology, and a cartridge-based nucleic acid amplification test. He was initiated on appropriate antibiotics and antituberculous chemotherapy per his weight.
PubMed: 38953070
DOI: 10.7759/cureus.61412 -
Frontiers in Microbiology 2024The unique dormancy of plays a significant role in the major clinical treatment challenge of tuberculosis, such as its long treatment cycle, antibiotic resistance,...
INTRODUCTION
The unique dormancy of plays a significant role in the major clinical treatment challenge of tuberculosis, such as its long treatment cycle, antibiotic resistance, immune escape, and high latent infection rate.
METHODS
To determine the function of MtrA, the only essential response regulator, one strategy was developed to establish its regulatory network according to high-quality genome-wide binding sites.
RESULTS AND DISCUSSION
The complex modulation mechanisms were implied by the strong bias distribution of MtrA binding sites in the noncoding regions, and 32.7% of the binding sites were located inside the target genes. The functions of 288 potential MtrA target genes predicted according to 294 confirmed binding sites were highly diverse, and DNA replication and damage repair, lipid metabolism, cell wall component biosynthesis, cell wall assembly, and cell division were the predominant pathways. Among the 53 pathways shared between dormancy/resuscitation and persistence, which accounted for 81.5% and 93.0% of the total number of pathways, respectively, MtrA regulatory genes were identified not only in 73.6% of their mutual pathways, but also in 75.4% of the pathways related to dormancy/resuscitation and persistence respectively. These results suggested the pivotal roles of MtrA in regulating dormancy/resuscitation and the apparent relationship between dormancy/resuscitation and persistence. Furthermore, the finding that 32.6% of the MtrA regulons were essential and/or for provided new insight into its indispensability. The findings mentioned above indicated that MtrA is a novel promising therapeutic target for tuberculosis treatment since the crucial function of MtrA may be a point of weakness for .
PubMed: 38952446
DOI: 10.3389/fmicb.2024.1415554 -
Zhongguo Xue Xi Chong Bing Fang Zhi Za... Jun 2024To evaluate the auxiliary diagnostic value of T cells spot test of infection (T-SPOT.TB) for pulmonary and extra-pulmonary tuberculosis among the elderly.
OBJECTIVE
To evaluate the auxiliary diagnostic value of T cells spot test of infection (T-SPOT.TB) for pulmonary and extra-pulmonary tuberculosis among the elderly.
METHODS
A total of 173 elderly patients at ages of 60 years and older and with suspected tuberculosis that were admitted to People's Hospital of Xinjiang Uygur Autonomous Region during the period from October 2022 through February 2024 were enrolled, and all patients underwent T-SPOT.TB, acid fast staining and GeneXpert MTB/RIF tests. The etiological tests of MTB served as a gold standard, and the diagnostic values of T-SPOT.TB, acid fast staining and GeneXpert MTB/RIF tests for pulmonary and extra-pulmonary tuberculosis were compared among the elderly patients.
RESULTS
Of the 173 elderly patients suspected of tuberculosis, there were 44 patients definitely diagnosed with pulmonary tuberculosis, 30 cases with extra-pulmonary tuberculosis, and 99 cases without tuberculosis. The sensitivities of T-SPOT.TB, acid fast staining and GeneXpert MTB/RIF tests were 86.5%, 27.0% and 54.1% for diagnosis of tuberculosis. The sensitivities of T-SPOT.TB were 86.4% and 86.7% for diagnosis of pulmonary tuberculosis and extra-pulmonary tuberculosis, with an 80.8% specificity for diagnosis of tuberculosis. The sensitivities of GeneXpert MTB/RIF were 56.8% and 50.0% for diagnosis of pulmonary tuberculosis and extra-pulmonary tuberculosis, with a 100.0% specificity each, and the sensitivities of acid fast staining were 31.8% and 20.0% for diagnosis of pulmonary tuberculosis and extra-pulmonary tuberculosis, with a 100.0% specificity each. In addition, the areas under the receiver operating characteristic curve were 0.836, 0.635 and 0.770 for diagnosis of tuberculosis with T-SPOT.TB, acid fast staining and GeneXpert MTB/RIF tests among the elderly patients, respectively.
CONCLUSIONS
T-SPOT.TB has a high auxiliary diagnostic value for both pulmonary and extra-pulmonary tuberculosis among elderly patients.
Topics: Humans; Aged; Mycobacterium tuberculosis; Male; Female; Tuberculosis, Pulmonary; Middle Aged; Tuberculosis; Aged, 80 and over; T-Lymphocytes; Sensitivity and Specificity; Tuberculosis, Extrapulmonary
PubMed: 38952319
DOI: 10.16250/j.32.1374.2024121 -
Scientific Reports Jun 2024Bovine alveolar macrophages (AMs) defend the lungs against pathogens such as Mycobacterium bovis (M. bovis), the causative agent of bovine tuberculosis. However, little...
Bovine alveolar macrophages (AMs) defend the lungs against pathogens such as Mycobacterium bovis (M. bovis), the causative agent of bovine tuberculosis. However, little is known about the surface molecules expressed by bovine AMs and whether there is heterogeneity within the population. The purpose of this study was to characterise the bovine AM cell surface phenotype using flow cytometry. Bronchoalveolar lavage samples from four different calves were stained with a combination of antibodies against immune cell molecules prior to flow cytometric analysis. To assess the degree of expression, we considered the distribution and relative intensities of stained and unstained cells. We demonstrated that bovine AMs have high expression of CD172a, ADGRE1, CD206, and CD14, moderate expression of CD80, MHC II, CD1b, and CD40, low expression of CX3CR1 and CD86, and little or no expression of CD16 and CD26. Two distinct subsets of bovine AMs were identified based on CD163 expression. Subsequent analysis showed that the CD163 subset had greater expression of other typical macrophage molecules compared to the CD163 subset, suggesting that these cells may perform different roles during infection. The characterisation of the uninfected bovine AM phenotype will provide a foundation for the examination of M. bovis-infected AMs.
Topics: Animals; Cattle; Macrophages, Alveolar; Antigens, Differentiation, Myelomonocytic; Antigens, CD; Receptors, Cell Surface; Phenotype; Mycobacterium bovis; Flow Cytometry; Tuberculosis, Bovine; Immunophenotyping; Bronchoalveolar Lavage Fluid
PubMed: 38951667
DOI: 10.1038/s41598-024-65868-7 -
Methods in Molecular Biology (Clifton,... 2024Whole genome sequencing of Mycobacterium tuberculosis complex (MTBC) isolates has been shown to provide accurate predictions for resistance and susceptibility for many...
Whole genome sequencing of Mycobacterium tuberculosis complex (MTBC) isolates has been shown to provide accurate predictions for resistance and susceptibility for many first- and second-line anti-tuberculosis drugs. However, bioinformatic pipelines and mutation catalogs to predict antimicrobial resistances in MTBC isolates are often customized and detailed protocols are difficult to access. Here, we provide a step-by-step workflow for the processing and interpretation of short-read sequencing data and give an overview of available analysis pipelines.
Topics: Mycobacterium tuberculosis; Whole Genome Sequencing; Microbial Sensitivity Tests; Humans; Antitubercular Agents; Computational Biology; Genome, Bacterial; Drug Resistance, Bacterial; Mutation; Tuberculosis
PubMed: 38949712
DOI: 10.1007/978-1-0716-3981-8_18 -
Methods in Molecular Biology (Clifton,... 2024Whole genome sequencing (WGS) is becoming an important diagnostic tool for antimicrobial susceptibility testing of Mycobacterium tuberculosis complex (MTBC) isolates in...
Whole genome sequencing (WGS) is becoming an important diagnostic tool for antimicrobial susceptibility testing of Mycobacterium tuberculosis complex (MTBC) isolates in many countries. WGS protocols usually start with the preparation of a DNA-library: the critical first step in the process. A DNA-library represents the genomic content of a DNA sample and consists of unique short DNA fragments. Although available DNA-library protocols come with manufacturer instructions, details of the entire process, including quality controls, instrument parameters, and run evaluations, often need to be developed and customized by each laboratory to implement WGS technology effectively. Here, we provide a detailed workflow for a DNA-library preparation based on an adapted Illumina protocol optimized for the reduction of reagent costs.
Topics: Mycobacterium tuberculosis; Whole Genome Sequencing; Microbial Sensitivity Tests; Genome, Bacterial; Humans; Antitubercular Agents; Gene Library; DNA, Bacterial; Tuberculosis; High-Throughput Nucleotide Sequencing
PubMed: 38949711
DOI: 10.1007/978-1-0716-3981-8_17 -
Methods in Molecular Biology (Clifton,... 2024The diagnosis and monitoring of tuberculosis treatment is difficult as many patients are unable to produce sputum. This means that many patients are treated on the basis...
The diagnosis and monitoring of tuberculosis treatment is difficult as many patients are unable to produce sputum. This means that many patients are treated on the basis of clinical findings and consequently some will be exposed to anti-tuberculosis drugs unnecessarily. Moreover, for those appropriately on treatment and unable to produce a sputum sample, it will be impossible to monitor the response to treatment. We have shown that stool is a potential alternative sample type for diagnosis of tuberculosis. Currently, available protocols like the Xpert MTB/RIF use DNA as a target to detect Mycobacterium tuberculosis in stool but DNA survives long after the organism is dead so it is not certain whether a positive test is from an old or a partially treated infection. The TB MBLA only detects live organisms and thus, can be used to follow the response to treatment. In this chapter, we describe a protocol for TB-MBLA, an RNA-based assay, and apply it to quantify TB bacteria in stool.
Topics: Feces; Mycobacterium tuberculosis; Humans; Bacterial Load; Tuberculosis; Antitubercular Agents; DNA, Bacterial; Sputum
PubMed: 38949709
DOI: 10.1007/978-1-0716-3981-8_15