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American Journal of Infection Control Jul 2024Laboratory algorithms using Acid Fast Bacilli (AFB) staining and Mycobacterium tuberculosis (Mtb) polymerase chain reaction (PCR) are often used to remove isolation...
Laboratory algorithms using Acid Fast Bacilli (AFB) staining and Mycobacterium tuberculosis (Mtb) polymerase chain reaction (PCR) are often used to remove isolation precautions. A retrospective case review of 52 patients with culture confirmed pulmonary Mtb revealed 4 subjects with negative sputum AFB smears and negative Mtb PCRs. All had significant risk factors for Mtb and had a positive interferon gamma release assay. A negative PCR test result does not exclude an Mtb diagnosis.
PubMed: 38964661
DOI: 10.1016/j.ajic.2024.06.023 -
The Lancet. Microbe Jul 2024Tuberculosis is a leading cause of death from an infectious agent globally. Infectious subclinical tuberculosis accounts for almost half of all tuberculosis cases in... (Review)
Review
Tuberculosis is a leading cause of death from an infectious agent globally. Infectious subclinical tuberculosis accounts for almost half of all tuberculosis cases in national tuberculosis prevalence surveys, and possibly contributes to transmission and might be associated with morbidity. Modelling studies suggest that new tuberculosis vaccines could have substantial health and economic effects, partly based on the assumptions made regarding subclinical tuberculosis. Evaluating the efficacy of prevention of disease tuberculosis vaccines intended for preventing both clinical and subclinical tuberculosis is a priority. Incorporation of subclinical tuberculosis as a composite endpoint in tuberculosis vaccine trials can help to reduce the sample size and duration of follow-up and to evaluate the efficacy of tuberculosis vaccines in preventing clinical and subclinical tuberculosis. Several design options with various benefits, limitations, and ethical considerations are possible in this regard, which would allow for the generation of the evidence needed to estimate the positive global effects of tuberculosis vaccine trials, in addition to informing policy and vaccination strategies.
PubMed: 38964359
DOI: 10.1016/S2666-5247(24)00127-7 -
Molecular Medicine Reports Sep 2024As sequencing technology transitions from research to clinical settings, due to technological maturity and cost reductions, metagenomic next‑generation sequencing... (Review)
Review
As sequencing technology transitions from research to clinical settings, due to technological maturity and cost reductions, metagenomic next‑generation sequencing (mNGS) is increasingly used. This shift underscores the growing need for more cost‑effective and universally accessible sequencing assays to improve patient care and public health. Therefore, targeted NGS (tNGS) is gaining prominence. tNGS involves enrichment of target pathogens in patient samples based on multiplex PCR amplification or probe capture with excellent sensitivity. It is increasingly used in clinical diagnostics due to its practicality and efficiency. The present review compares the principles of different enrichment methods. The high positivity rate of tNGS in the detection of pathogens was found in respiratory samples with specific instances. tNGS maintains high sensitivity (70.8‑95.0%) in samples with low pathogen loads, including blood and cerebrospinal fluid. Furthermore, tNGS is effective in detecting drug‑resistant strains of , allowing identification of resistance genes and guiding clinical treatment decisions, which is difficult to achieve with mNGS. In the present review, the application of tNGS in clinical settings and its current limitations are assessed. The continued development of tNGS has the potential to refine diagnostic accuracy and treatment efficacy and improving infectious disease management. However, further research to overcome technical challenges such as workflow time and cost is required.
Topics: Humans; High-Throughput Nucleotide Sequencing; Communicable Diseases; Metagenomics; Molecular Diagnostic Techniques
PubMed: 38963022
DOI: 10.3892/mmr.2024.13277 -
Frontiers in Public Health 2024Non-tuberculous mycobacteria (NTM) infections pose a significant public health challenge worldwide, affecting individuals across a wide spectrum of immune statuses.... (Review)
Review
Non-tuberculous mycobacteria (NTM) infections pose a significant public health challenge worldwide, affecting individuals across a wide spectrum of immune statuses. Recent epidemiological studies indicate rising incidence rates in both immunocompromised and immunocompetent populations, underscoring the need for enhanced diagnostic and therapeutic approaches. NTM infections often present with symptoms similar to those of tuberculosis, yet with less specificity, increasing the risk of misdiagnosis and potentially adverse outcomes for patients. Consequently, rapid and accurate identification of the pathogen is crucial for precise diagnosis and treatment. Traditional detection methods, notably microbiological culture, are hampered by lengthy incubation periods and a limited capacity to differentiate closely related NTM subtypes, thereby delaying diagnosis and the initiation of targeted therapies. Emerging diagnostic technologies offer new possibilities for the swift detection and accurate identification of NTM infections, playing a critical role in early diagnosis and providing more accurate and comprehensive information. This review delineates the current molecular methodologies for NTM species and subspecies identification. We critically assess the limitations and challenges inherent in these technologies for diagnosing NTM and explore potential future directions for their advancement. It aims to provide valuable insights into advancing the application of molecular diagnostic techniques in NTM infection identification.
Topics: Humans; Nontuberculous Mycobacteria; Mycobacterium Infections, Nontuberculous; Molecular Diagnostic Techniques
PubMed: 38962772
DOI: 10.3389/fpubh.2024.1410672 -
Nagoya Journal of Medical Science May 2024We describe a case of erythema induratum of Bazin (EIB) that presented recurrently on the extremities during treatment with anti-tuberculosis medications. The...
We describe a case of erythema induratum of Bazin (EIB) that presented recurrently on the extremities during treatment with anti-tuberculosis medications. The anti-tuberculosis medications were effective, so they were continued despite the occurrence of the EIB lesions, and those lesions disappeared 5 months after first appearing. EIB is currently considered a multifactorial disorder with many different causes, with tuberculosis being an example, and it is thought to be a hypersensitive immune response to . The clinical manifestations may fluctuate depending on the immune response of the host. Our patient was affected with myelodysplastic syndrome, and we believe that this was a major factor that interfered with a normal immune response. This case illustrates the importance of providing intensive anti-tuberculosis treatment from the start, and in cases where EIB co-presents, to continue this treatment until the end, in order to prevent relapse.
Topics: Humans; Myelodysplastic Syndromes; Erythema Induratum; Antitubercular Agents; Recurrence; Male; Aged; Female
PubMed: 38962409
DOI: 10.18999/nagjms.86.2.341 -
The International Journal of... Jul 2024
Topics: Humans; Tuberculosis, Multidrug-Resistant; Antitubercular Agents; Tuberculosis; Mycobacterium tuberculosis
PubMed: 38961549
DOI: 10.5588/ijtld.23.0548 -
Nature Jul 2024Bedaquiline (BDQ), a first-in-class diarylquinoline anti-tuberculosis drug, and its analogue, TBAJ-587, prevent the growth and proliferation of Mycobacterium...
Bedaquiline (BDQ), a first-in-class diarylquinoline anti-tuberculosis drug, and its analogue, TBAJ-587, prevent the growth and proliferation of Mycobacterium tuberculosis by inhibiting ATP synthase. However, BDQ also inhibits human ATP synthase. At present, how these compounds interact with either M. tuberculosis ATP synthase or human ATP synthase is unclear. Here we present cryogenic electron microscopy structures of M. tuberculosis ATP synthase with and without BDQ and TBAJ-587 bound, and human ATP synthase bound to BDQ. The two inhibitors interact with subunit a and the c-ring at the leading site, c-only sites and lagging site in M. tuberculosis ATP synthase, showing that BDQ and TBAJ-587 have similar modes of action. The quinolinyl and dimethylamino units of the compounds make extensive contacts with the protein. The structure of human ATP synthase in complex with BDQ reveals that the BDQ-binding site is similar to that observed for the leading site in M. tuberculosis ATP synthase, and that the quinolinyl unit also interacts extensively with the human enzyme. This study will improve researchers' understanding of the similarities and differences between human ATP synthase and M. tuberculosis ATP synthase in terms of the mode of BDQ binding, and will allow the rational design of novel diarylquinolines as anti-tuberculosis drugs.
PubMed: 38961288
DOI: 10.1038/s41586-024-07605-8 -
Scientific Reports Jul 2024Nontuberculous mycobacteria (NTM) infection diagnosis remains a challenge due to its overlapping clinical symptoms with tuberculosis (TB), leading to inappropriate...
Nontuberculous mycobacteria (NTM) infection diagnosis remains a challenge due to its overlapping clinical symptoms with tuberculosis (TB), leading to inappropriate treatment. Herein, we employed noninvasive metabolic phenotyping coupled with comprehensive statistical modeling to discover potential biomarkers for the differential diagnosis of NTM infection versus TB. Urine samples from 19 NTM and 35 TB patients were collected, and untargeted metabolomics was performed using rapid liquid chromatography-mass spectrometry. The urine metabolome was analyzed using a combination of univariate and multivariate statistical approaches, incorporating machine learning. Univariate analysis revealed significant alterations in amino acids, especially tryptophan metabolism, in NTM infection compared to TB. Specifically, NTM infection was associated with upregulated levels of methionine but downregulated levels of glutarate, valine, 3-hydroxyanthranilate, and tryptophan. Five machine learning models were used to classify NTM and TB. Notably, the random forest model demonstrated excellent performance [area under the receiver operating characteristic (ROC) curve greater than 0.8] in distinguishing NTM from TB. Six potential biomarkers for NTM infection diagnosis, including methionine, valine, glutarate, 3-hydroxyanthranilate, corticosterone, and indole-3-carboxyaldehyde, were revealed from univariate ROC analysis and machine learning models. Altogether, our study suggested new noninvasive biomarkers and laid a foundation for applying machine learning to NTM differential diagnosis.
Topics: Humans; Machine Learning; Metabolomics; Male; Biomarkers; Female; Middle Aged; Tuberculosis; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Aged; Adult; Metabolome; ROC Curve; Diagnosis, Differential
PubMed: 38961191
DOI: 10.1038/s41598-024-66113-x -
Bulletin of Experimental Biology and... Jul 2024The dynamics of lung microbiota in tuberculosis remains poorly understood. Sequencing of variable regions of the 16S rRNA gene from surgically excised tuberculosis foci...
The dynamics of lung microbiota in tuberculosis remains poorly understood. Sequencing of variable regions of the 16S rRNA gene from surgically excised tuberculosis foci and biopsy specimens of normal lung tissue allowed characterization of the diversity and predictive potential of bacterial communities. Taxonomic diversity indices attested to differences in the structure of microbial communities between "healthy" lungs and tuberculomas. The microbial composition of "healthy" lungs varied in taxonomic diversity and was presented by both gram-positive and gram-negative bacteria with sufficiently similar metabolic potential. The microbiota of the examined tuberculomas consisted of Mycobacterium tuberculosis in 99.9% of cases. A significant part of the metabolic pathways predicted by PICRUSt2 included cholesterol catabolism, sulfate assimilation, and various pathways for the biosynthesis of cell wall components.
PubMed: 38960962
DOI: 10.1007/s10517-024-06146-4 -
Internal Medicine (Tokyo, Japan) Jul 2024We report the case of a 42-year-old man with bronchiectasis who had a history of infertility treatment for obstructive azoospermia. Young's syndrome was suspected based...
Primary Ciliary Dyskinesia Due to Compound Heterozygous Variants in CFAP221 with Obstructive Azoospermia: Young's Syndrome May Be a Phenotype of Primary Ciliary Dyskinesia.
We report the case of a 42-year-old man with bronchiectasis who had a history of infertility treatment for obstructive azoospermia. Young's syndrome was suspected based on the triad of obstructive azoospermia, sinusitis, and bronchiectasis. He had normal electron microscopy findings, normal nasal nitric oxide levels (116 nL/min), and no situs inversus. However, we found compound heterozygous variants in CFAP221. This led to a diagnosis of primary ciliary dyskinesia (PCD). Distinguishing PCD from Young's syndrome in patients with the triad of obstructive azoospermia, sinusitis, and bronchiectasis is challenging. Young's syndrome may be a phenotype of PCD.
PubMed: 38960684
DOI: 10.2169/internalmedicine.3978-24