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International Journal of... Apr 2024Environmental mycobacteria are involved in several infections ranging from lung to skin infections. In Côte d'Ivoire, apart from Mycobacterium ulcerans and...
BACKGROUND
Environmental mycobacteria are involved in several infections ranging from lung to skin infections. In Côte d'Ivoire, apart from Mycobacterium ulcerans and Mycobacterium tuberculosis, little information exists on other species. The culture of these species, a real challenge, especially in developing countries like Cote d'Ivoire, limits their identification. However, there are reports in literature of infections caused by these mycobacteria, and few species have never been described in human or animal infections. These are difficult cases to treat because of their resistance to most antituberculosis antibiotics. The aim of our work was to study the diversity of potentially pathogenic mycobacterial species in wastewater drainage channels in different townships and in two hospital effluents in the city of Abidjan.
METHODS
Wastewater samples were cultured, followed by conventional polymerase chain reaction (PCR) targeting mycobacterial 16S ribonucleic acid (16S RNA) using PA/MSHA primers. 16 S RNA identified were sequenced by Sanger techniques. Sequences obtained were analyzed, and a phylogenic tree was built.
RESULTS
Fast-growing mycobacteria, including Mycobacterium fortuitum, Mycobacterium phocaicum, Mycobacterium sp., and others presence, were confirmed both by culture and molecular techniques. M. fortuitum strain was the same in effluents of the Treichville University Hospital and in the wastewater of the township of Koumassi. New species never isolated in Côte d'Ivoire, such as M. phocaicum, have been identified in wastewater of the township of Yopougon.
CONCLUSION
This study showed that the sewer network in the city of Abidjan is colonized by both potentially pathogenic mycobacteria and saprophytic environmental mycobacteria.
Topics: Cote d'Ivoire; Phylogeny; RNA, Ribosomal, 16S; Humans; Nontuberculous Mycobacteria; Wastewater; Polymerase Chain Reaction; DNA, Bacterial; Mycobacterium
PubMed: 38916386
DOI: 10.4103/ijmy.ijmy_96_24 -
International Journal of... Apr 2024GeneXpert Mycobacterium tuberculosis/rifampicin (MTB/RIF) is a conceptually helpful tool for establishing tuberculosis (TB) disease. Negative results from the GeneXpert...
OBJECTIVE
GeneXpert Mycobacterium tuberculosis/rifampicin (MTB/RIF) is a conceptually helpful tool for establishing tuberculosis (TB) disease. Negative results from the GeneXpert test do not exclude the possibility of diagnosing non-tuberculous mycobacteria lung disease (NTMLD) as a chronic pulmonary disease. When a patient is diagnosed on a clinical basis, and there is no bacteriological evidence of TB, it is necessary to consider NTM as one of the causes of disease with TB-like symptoms. The prevalence of non-tuberculous mycobacteria (NTM) disease is rising globally, but its diagnosis is still delayed and often misdiagnosed as multidrug-resistant TB (MDR-TB). This study highlights the implication of negative GeneXpert MTB/RIF results in suspected TB patients who conducted mycobacteria culture and detected the incidence of NTMLD.
METHODS
In this experimental study, the performance of GeneXpert MTB/RIF-negative results with those of mycobacteria cultures and lung abnormalities among suspected TB patients in a referral hospital in Indonesia were evaluated. From January to August 2022, 100 sputum samples from suspected chronic pulmonary TB patients with GeneXpert MTB/RIF assay-negative results were cultured in Lowenstein-Jensen medium, and the implication among negative GeneXpert result MTB/RIF assay.
RESULTS
7% were confirmed to have MTB and 1% had NTM by culture assay. Moreover, 34% were diagnosed with clinical TB and treated with anti-TB drugs.
CONCLUSION
For patients with negative assay results of GeneXpert MTB/RIF regarding clinically suspected chronic TB infection, further diagnostic tests to determine the causative agents of the lung abnormalities should be carried out.
Topics: Humans; Mycobacterium tuberculosis; Rifampin; Male; Sputum; Female; Adult; Middle Aged; Indonesia; Tuberculosis, Pulmonary; Mycobacterium Infections, Nontuberculous; Tuberculosis, Multidrug-Resistant; Nontuberculous Mycobacteria; Aged; Young Adult
PubMed: 38916385
DOI: 10.4103/ijmy.ijmy_100_24 -
International Journal of... Apr 2024Bedaquiline is one of the core drugs used to treat multidrug-resistant TB (MDR-TB). Delamanid is one of the companion drugs in group C which is used to complete the... (Observational Study)
Observational Study Comparative Study
Comparison of Individual Regimen Containing Bedaquiline with Delamanid and Bedaquiline without Delamanid on Efficacy and Safety in Multidrug-resistant Tuberculosis Patients: Implementation in Dr. Soetomo General Academic Hospital, Indonesia.
BACKGROUND
Bedaquiline is one of the core drugs used to treat multidrug-resistant TB (MDR-TB). Delamanid is one of the companion drugs in group C which is used to complete the treatment regimen when drugs in groups A and B can not be used. This study was conducted to analyze the efficacy and safety between individual regimens containing bedaquiline with delamanid and bedaquiline without delamanid.
METHODS
This was an observational analytic study with a retrospective design in MDR-TB patients treated with individual regimens containing bedaquiline with delamanid (bedaquiline-delamanid group) and bedaquiline without delamanid (bedaquiline group). Efficacy was measured according to the time to Acid Fast Bacilli (AFB) conversion and Mycobacterium tuberculosis culture conversion, while safety was measured specifically on QTc interval prolongation.
RESULTS
The median (range) time to AFB conversion in bedaquiline-delamanid group was faster than bedaquiline group, although there was no significant difference (1.5 (1-4) months vs. 1 (1-6) months, P=0.429), the median time to culture conversion in bedaquiline-delamanid group also faster than bedaquiline group, although there was no significant difference (1 (1-6) months vs. 2 (1-6) months, P=0.089). The incidence of QTc interval prolongation in bedaquiline-delamanid group was less than bedaquiline group, although there was no significant difference (26.9% vs. 40.3%, P=0.223).
CONCLUSIONS
Individual regimens containing bedaquiline with delamanid was proven to provide similar efficacy and safety profiles with individual regimens containing bedaquiline without delamanid. Delamanid should be preferred when selecting drugs to complete the treatment regimen when drugs in groups A and B can not be used.
Topics: Humans; Nitroimidazoles; Diarylquinolines; Oxazoles; Tuberculosis, Multidrug-Resistant; Antitubercular Agents; Retrospective Studies; Female; Adult; Male; Middle Aged; Indonesia; Treatment Outcome; Young Adult; Drug Therapy, Combination; Mycobacterium tuberculosis; Adolescent; Aged
PubMed: 38916383
DOI: 10.4103/ijmy.ijmy_88_24 -
International Journal of... Apr 2024Microbiological diagnosis of mycobacteriosis is often difficult, as it is necessary to differentiate between transient colonization and active infection.
Construction of Composite Correlation Index Matrix and Analysis of Cultural Properties of Representatives of Mycobacterium abscessus Complex Isolated from Patients with Cystic Fibrosis.
BACKGROUND
Microbiological diagnosis of mycobacteriosis is often difficult, as it is necessary to differentiate between transient colonization and active infection.
METHODS
We studied the cultural properties of Mycobacterium abscessus complex (MABSc) strains obtained from cystic fibrosis patients, and also analyzed composite correlation index (CCI) values in patients with repeated MABSc inoculation and their correlation with the presence of clinical and radiological manifestations of mycobacteriosis.
RESULTS
As a result, MABSc more often grew in S-form colonies in patients without clinical manifestations of chronic infection, while R-form colonies were characteristic of patients with chronic infection and clinical symptoms. At the same time, in patients examined once, no growth of colonies in the R-form was recorded, and all strains produced growth in the form of either S-colonies or in the S- and R-forms simultaneously. Statistically significant results were obtained for the relationship of the CCI with the clinical and radiological picture. In addition, a heterogeneous MABSc population with low CCI score values correlated with the development of mycobacteriosis in patients. In patients with high CCI score values (homogeneity of isolated strains), on the contrary, there were no radiological or clinical signs of the disease.
CONCLUSION
These data make it possible to build a strategy for monitoring patients depending on changes in CCI score values. The use of CCI matrix to evaluate microorganisms' identification results is a potentially new method that expands the use of matrix-assisted laser desorption ionization time-of-flight mass spectrometry.
Topics: Humans; Cystic Fibrosis; Mycobacterium abscessus; Mycobacterium Infections, Nontuberculous; Female; Male
PubMed: 38916382
DOI: 10.4103/ijmy.ijmy_70_24 -
BMC Research Notes Jun 2024Recent spoligotyping results in the island nation of Indonesia had revealed the existence of Mycobacterium tuberculosis complex lineage 3 (MTBC L3) or Central Asian...
OBJECTIVE
Recent spoligotyping results in the island nation of Indonesia had revealed the existence of Mycobacterium tuberculosis complex lineage 3 (MTBC L3) or Central Asian (CAS) strains. In this work, whole-genome sequencing (WGS) - based methods were used to search for the presence of MTBC L3.
RESULTS
Two unrelated Indonesian L3 strains discovered by WGS-based SNP phylogenomics are presented here for the first time. Assemblies of their genomes yielded 96.95% (MTBC strain Mtb_S6970) and 98.35% (Mtb_S19106) of the known reference strain H37Rv. Their respective constructed genome coverages are 45.38 ± 12.95x and 63.13 ± 21.10x. The two L3 genomes have 4062 and 4121 genes, respectively, which are well within the number of genes predicted in MTBC strains. Instead of having three rRNA genes usually, Mtb_S6970 possesses four. These L3 isolates exhibit cross-class antibiotic susceptibility. FadD26, fadE24, fbpA, lprO, and panC, which are thought to be important in the pathophysiology of MTBC, were discovered to have 3-7 times more loci in L3 than L2 or L4. The penetration of L3 in the nation, despite its antibiotic sensitivity, is a concerning indicator of borderless global spread that may eventually be overcome by the phenotypes of acquired drug resistance.
Topics: Indonesia; Mycobacterium tuberculosis; Whole Genome Sequencing; Genome, Bacterial; Phylogeny; Humans; Polymorphism, Single Nucleotide; Tuberculosis
PubMed: 38915046
DOI: 10.1186/s13104-024-06825-5 -
Scientific Reports Jun 2024Accurate tuberculosis (TB) diagnosis remains challenging, especially in resource-limited settings. This study aims to assess the diagnostic performance of the QIAreach... (Meta-Analysis)
Meta-Analysis Comparative Study
Accurate tuberculosis (TB) diagnosis remains challenging, especially in resource-limited settings. This study aims to assess the diagnostic performance of the QIAreach QuantiFERON-TB (QFT) assay, with a specific focus on comparing its diagnostic performance with the QuantiFERON-TB Gold Plus (QFT-Plus). We systematically reviewed relevant individual studies on PubMed, Scopus, and Web of Science up to January 20, 2024. The focus was on evaluating the diagnostic parameters of the QIAreach QFT assay for TB infection, which included sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and concordance with the QFT-Plus assay. QIAreach QFT demonstrated strong diagnostic performance with a pooled sensitivity of 99% (95% CI 95-100%) and specificity of 94% (95% CI 85-97%). Additionally, it showed a PLR of 15.6 (95% CI 6.5-37.5) and NLR of 0.01 (95% CI 0-0.03). The pooled PPV and NPV were 88% (95% CI 70-98%) and 100% (95% CI 99-100%), respectively. Concordance analysis with QFT-Plus revealed a pooled positive percent agreement of 98% (95% CI 88-100%) and pooled negative percent agreement of 91% (95% CI 81-97%), with a pooled overall percent agreement of 92% (95% CI 83-98). In conclusion, QIAreach QFT has shown promising diagnostic performance, with a strong concordance with QFT-Plus. However, further studies are needed to comprehensively evaluate its diagnostic performance in the context of TB infection.
Topics: Humans; Tuberculosis; Sensitivity and Specificity; Interferon-gamma Release Tests; Mycobacterium tuberculosis
PubMed: 38914731
DOI: 10.1038/s41598-024-65663-4 -
BMC Infectious Diseases Jun 2024Spinal tuberculosis (STB) is a local manifestation of systemic infection caused by Mycobacterium tuberculosis, accounting for a significant proportion of joint...
BACKGROUND
Spinal tuberculosis (STB) is a local manifestation of systemic infection caused by Mycobacterium tuberculosis, accounting for a significant proportion of joint tuberculosis cases. This study aimed to explore the diagnostic value of MRI combined with mannose-binding lectin (MBL) for STB.
METHODS
124 patients suspected of having STB were collected and divided into STB and non-STB groups according to their pathological diagnosis. Serum MBL levels were measured using ELISA and a Pearson analysis was constructed to determine the correlation between MBL and STB. ROC was plotted to analyze their diagnostic value for STB. All the subjects included in the study underwent an MRI.
RESULTS
The sensitivity of MRI for the diagnosis of STB was 84.38% and specificity was 86.67%. The serum MBL levels of the patients in the STB group were significantly lower than the levels in the non-STB group. ROC analysis results indicated that serum MBL's area under the curve (AUC) for diagnosis of STB was 0.836, with a sensitivity of 82.3% and a specificity was 77.4%. The sensitivity of MRI combined with MBL diagnosis was 96.61%, and the specificity was 92.31%, indicating that combining the two diagnostic methods was more effective than using either one alone.
CONCLUSIONS
Both MRI and MBL had certain diagnostic values for STB, but their combined use resulted in a diagnostic accuracy than either one alone.
Topics: Humans; Male; Female; Magnetic Resonance Imaging; Mannose-Binding Lectin; Adult; Middle Aged; Tuberculosis, Spinal; Sensitivity and Specificity; ROC Curve; Aged; Young Adult; Mycobacterium tuberculosis; Clinical Relevance
PubMed: 38907240
DOI: 10.1186/s12879-024-09462-2 -
Scientific Reports Jun 2024Bovine tuberculosis (bTB) is endemic and has a substantial impact on the livestock sector in Ethiopia and other low and middle-income countries (LMICs). With a national...
Bovine tuberculosis (bTB) is endemic and has a substantial impact on the livestock sector in Ethiopia and other low and middle-income countries (LMICs). With a national emphasis on dairy farm intensification to boost milk production and spur economic growth, the incidence of bTB is anticipated to rise. However, Ethiopia, like other LMICs, lacks a comprehensive national bTB control strategy due to the economic and social infeasibility of traditional test-and-cull (TC) approaches. To inform the development of such a strategy, we evaluated the effectiveness and feasibility of TC and test-and-segregation (TSg) strategies for bTB control on Ethiopian dairy farms. A TC approach was used at Farm A [N = 62; comparative cervical test (CCT) > 4 mm, starting prevalence 11.3%] while TSg was implemented at Farm B (N = 45; CCT > 4 mm, prevalence 22.2%), with testing intervals of 2-4 months. Both strategies achieved a reduction in bTB prevalence to 0%, requiring seven rounds of TC over 18 months at Farm A, and five rounds of TSg over 12 months at Farm B's negative herd. The results show that adopting more sensitive thresholds [CCT > 0 mm or single cervical test (SCT) > 2 mm] during later rounds was pivotal in identifying and managing previously undetected infections, emphasizing the critical need for optimized diagnostic thresholds. Cost analysis revealed that TC was approximately twice as expensive as TSg, primarily due to testing, labor, and cow losses in TC, versus construction of new facilities and additional labor for TSg. This underscores the economic and logistical challenges of bTB management in resource-limited settings. Taken together, our study highlights an urgent need for the exploration of alternative approaches including TSg and or vaccination to mitigate within herd transmission and enable implementation of bTB control in regions where TC is not feasible.
Topics: Cattle; Animals; Tuberculosis, Bovine; Ethiopia; Dairying; Prevalence; Feasibility Studies; Farms; Female; Mycobacterium bovis
PubMed: 38906922
DOI: 10.1038/s41598-024-64884-x -
BMC Infectious Diseases Jun 2024Blood-based transcriptional gene signatures for tuberculosis (TB) have been developed with potential use to diagnose disease. However, an unresolved issue is whether... (Comparative Study)
Comparative Study
BACKGROUND
Blood-based transcriptional gene signatures for tuberculosis (TB) have been developed with potential use to diagnose disease. However, an unresolved issue is whether gene set enrichment analysis of the signature transcripts alone is sufficient for prediction and differentiation or whether it is necessary to use the original model created when the signature was derived. Intra-method comparison is complicated by the unavailability of original training data and missing details about the original trained model. To facilitate the utilization of these signatures in TB research, comparisons between gene set scoring methods cross-data validation of original model implementations are needed.
METHODS
We compared the performance of 19 TB gene signatures across 24 transcriptomic datasets using both rrebuilt original models and gene set scoring methods. Existing gene set scoring methods, including ssGSEA, GSVA, PLAGE, Singscore, and Zscore, were used as alternative approaches to obtain the profile scores. The area under the ROC curve (AUC) value was computed to measure performance. Correlation analysis and Wilcoxon paired tests were used to compare the performance of enrichment methods with the original models.
RESULTS
For many signatures, the predictions from gene set scoring methods were highly correlated and statistically equivalent to the results given by the original models. In some cases, PLAGE outperformed the original models when considering signatures' weighted mean AUC values and the AUC results within individual studies.
CONCLUSION
Gene set enrichment scoring of existing gene sets can distinguish patients with active TB disease from other clinical conditions with equivalent or improved accuracy compared to the original methods and models. These data justify using gene set scoring methods of published TB gene signatures for predicting TB risk and treatment outcomes, especially when original models are difficult to apply or implement.
Topics: Humans; Tuberculosis; Gene Expression Profiling; Mycobacterium tuberculosis; Transcriptome; ROC Curve; Reproducibility of Results
PubMed: 38902649
DOI: 10.1186/s12879-024-09457-z -
Nature Communications Jun 2024Aerobic life is powered by membrane-bound redox enzymes that shuttle electrons to oxygen and transfer protons across a biological membrane. Structural studies suggest...
Aerobic life is powered by membrane-bound redox enzymes that shuttle electrons to oxygen and transfer protons across a biological membrane. Structural studies suggest that these energy-transducing enzymes operate as higher-order supercomplexes, but their functional role remains poorly understood and highly debated. Here we resolve the functional dynamics of the 0.7 MDa IIIIV obligate supercomplex from Mycobacterium smegmatis, a close relative of M. tuberculosis, the causative agent of tuberculosis. By combining computational, biochemical, and high-resolution (2.3 Å) cryo-electron microscopy experiments, we show how the mycobacterial supercomplex catalyses long-range charge transport from its menaquinol oxidation site to the binuclear active site for oxygen reduction. Our data reveal proton and electron pathways responsible for the charge transfer reactions, mechanistic principles of the quinone catalysis, and how unique molecular adaptations, water molecules, and lipid interactions enable the proton-coupled electron transfer (PCET) reactions. Our combined findings provide a mechanistic blueprint of mycobacterial supercomplexes and a basis for developing drugs against pathogenic bacteria.
Topics: Mycobacterium smegmatis; Electron Transport; Cryoelectron Microscopy; Oxidation-Reduction; Bacterial Proteins; Protons; Electron Transport Complex III; Oxygen; Electron Transport Complex IV; Catalytic Domain; Models, Molecular
PubMed: 38902248
DOI: 10.1038/s41467-024-49628-9