In Silico Approach: Anti-Tuberculosis Activity of Caespitate in the H37Rv Strain.

Tuberculosis is a highly lethal bacterial disease worldwide caused by Mycobacterium tuberculosis (Mtb). Caespitate is a phytochemical isolated from Helichrysum caespititium, a plant used in African traditional medicine that shows anti-tubercular activity, but its mode of action remains unknown. It is suggested that there are four potential targets in Mtb, specifically in the H37Rv strain: InhA, MabA, and UGM, enzymes involved in the formation of Mtb's cell wall, and PanK, which plays a role in cell growth. Two caespitate conformational structures from DFT conformational analysis in the gas phase (GC) and in solution with DMSO (CS) were selected. Molecular docking calculations, MM/GBSA analysis, and ADME parameter evaluations were performed. The docking results suggest that CS is the preferred caespitate conformation when interacting with PanK and UGM. In both cases, the two intramolecular hydrogen bonds characteristic of caespitate's molecular structure were maintained to achieve the most stable complexes. The MM/GBSA study confirmed that PanK/caespitate and UGM/caespitate were the most stable complexes. Caespitate showed favorable pharmacokinetic characteristics, suggesting rapid absorption, permeability, and high bioavailability. Additionally, it is proposed that caespitate may exhibit antibacterial and antimonial activity. This research lays the foundation for the design of anti-tuberculosis drugs from natural sources, especially by identifying potential drug targets in Mtb.

Design and Synthesis of Isatin-Tagged Isoniazid Conjugates with Cogent Antituberculosis and Radical Quenching Competence: In-vitro and In-silico Evaluations.

In pursuit of potential chemotherapeutic alternates to combat severe tuberculosis infections, novel heterocyclic templates derived from clinically approved anti-TB drug isoniazid and isatin have been synthesized that demonstrate potent inhibitory action against Mycobacterium tuberculosis, and compound 4i with nitrophenyl motif exhibited the highest anti-TB efficacy with a MIC value of 2.54 µM/ml. Notably, the same nitro analog 4i shows the best antioxidant efficacy among all the synthesized compounds with an IC50 value of 37.37 µg/ml, suggesting a synergistic influence of antioxidant proficiency on the anti-TB action. The titled compounds exhibit explicit binding affinity with the InhA receptor. The befitting biochemical reactivity and near-appropriate pharmacokinetic proficiency of the isoniazid conjugates is reflected in the density functional theory (DFT) studies and ADMET screening. The remarkable anti-TB action of the isoniazid cognates with marked radical quenching ability may serve as a base for developing multi-target medications to confront drug-resistant TB pathogens. Keywords Isoniazid . Isatin . H37Rv . Antituberculosis . Antioxidant . Molecular Docking.

Thyroid tuberculosis mimicking multinodular goiter: a case report.

BACKGROUND: Mycobacterium tuberculosis is the second most common infectious cause of death in adults worldwide. The ability of this organism to efficiently establish latent infection has enabled it to spread to nearly one-third of individuals worldwide. Approximately 8 million new cases of active tuberculosis disease occur each year, leading to about 1.7 million deaths. The disease incidence is magnified by the concurrent epidemic of human immunodeficiency virus infection. A total of 1.3 million people died from tuberculosis in 2022. In 2022, an estimated 10.6 million people fell ill with tuberculosis worldwide, including 5.8 million men, 3.5 million women, and 1.3 million children. We report a case of thyroid tuberculosis presenting as multinodular goiter. Neck ultrasound was done and revealed abscess collection on the background of multinodular colloid goiter. The diagnosis of thyroid tuberculosis was confirmed by a positive GeneXpert of the pus sample and the presence of extensive caseous necrosis on cytopathology examination. Furthermore, anterior neck swelling may provide a diagnostic challenge by clinically mimicking multinodular goiter or thyroid neoplasms. Owing to its rarity and its tendency to pose a clinical diagnostic challenge, we decided to report it. CASE PRESENTATION: A 60-year-old retired female Ethiopian high-school teacher presented to University of Gondar Hospital, Gondar, Ethiopia with firm, nontender multinodular anterior neck swelling measuring at largest 2 × 3 cm that moves with swallowing. GeneXpert of the pus sample and cytopathology examination confirmed the diagnosis of thyroid tuberculosis, and the patient was started on 2 rifampicin-ethambutol-isoniazid-pyrazinamide/4 rifampicin-isoniazid 3 tablets by mouth/day, which is defined as the preferred first-line anti-tuberculosis regimen in Ethiopia, and pyridoxine 50 mg by mouth per day for 6 months. Since then, she has been followed with regular liver function tests. The patient has shown a smooth course with no significant adverse effects encountered. Currently, the patient has completed her anti-tuberculosis treatment and is doing well. CONCLUSION: In the clinical evaluation of a patient with anterior neck swelling, tuberculosis must be considered as a differential diagnosis in subjects from endemic areas for early diagnostic workup and management.

Exploring the potential of Lactocaseibacillus rhamnosus PMC203 in inducing autophagy to reduce the burden of Mycobacterium tuberculosis.

Mycobacterium tuberculosis, a lethal pathogen in human history, causes millions of deaths annually, which demands the development of new concepts of drugs. Considering this fact, earlier research has explored the anti-tuberculosis potential of a probiotic strain, Lactocaseibacillus rhamnosus PMC203, leading to a subsequent focus on the molecular mechanism involved in its effect, particularly on autophagy. In this current study, immunoblotting-based assay exhibited a remarkable expression of autophagy marker LC3-II in the PMC203 treated group compared to an untreated group. A remarkable degradation of p62 was also noticed within treated cells compared to control. Furthermore, the immunofluorescence-based assay showed significant fold change in fluorescence intensity for alexa-647-LC3 and alexa-488-LC3, whereas p62 was degraded noticeably. Moreover, lysosomal biogenesis generation was elevated significantly in terms of LAMP1 and acidic vesicular organelles. As a result, PMC203-induced autophagy played a vital role in reducing M. tuberculosis burden within the macrophages in treated groups compared to untreated group. A colony -forming unit assay also revealed a significant reduction in M. tuberculosis in the treated cells over time. Additionally, the candidate strain significantly upregulated the expression of autophagy induction and lysosomal biogenesis genes. Together, these results could enrich our current knowledge of probiotics-mediated autophagy in tuberculosis and suggest its implications for innovatively managing tuberculosis.

Serum Ceruloplasmin-to-Albumin Ratio as a Biochemical Marker in Pulmonary Tuberculosis Before and After Treatment.

BACKGROUND: The study compares the serum ceruloplasmin-to-albumin ratio of tuberculosis (TB) patients before and after anti-tuberculosis treatment (ATT) to assess its diagnostic and prognostic value. Despite the pandemic's impact on TB notifications, global TB cases rose by 16% in 2022. METHODS: The study was conducted at Meenakshi Medical College Hospital and Research Institute, Kanchipuram, from November 2022 to November 2023, with participants aged 15 and above diagnosed with pulmonary TB. The analysis of clinical, radiographic, microbiological, and biochemical data revealed a gender distribution of 58% male and 42% female individuals, with an average age of 49. Significant reductions in ceruloplasmin levels and increases in albumin levels were found following therapy, as well as a decrease in the ceruloplasmin-to-albumin ratio, showing that ceruloplasmin may serve as a severity measure and treatment indicator. RESULTS: Male patients accounted for 58% of the study population, while females accounted for 42%. Patients aged 36-45 made up the largest group (26%). Following treatment, serum ceruloplasmin levels decreased significantly (from 66.28 mg/dL to 35.56 mg/dL), but albumin levels increased (from 2.96 g/dL to 4.19 g/dL). The ceruloplasmin-to-albumin ratio dropped from 0.022 to 0.008, showing treatment efficacy. CONCLUSIONS: The study highlights the potential of serum biomarkers for diagnosing and monitoring TB. The serum ceruloplasmin-to-albumin ratio is a promising biochemical diagnostic. Further research is needed to validate these findings and investigate their clinical significance in TB management.

Unlocking the biological potential of transition metal complexes with Thiosemicarbazone ligands: Insights from computational studies.

In the previous study, the synthesis and characterization of 4-(3-fluorophenyl)-3-thiosemicarbazide and benzaldehyde derivatives based thiosemicarbazone ligands and their Co(II), Ni(II), Cu(II), Zn(II) complexes were carried out to evaluate their malarial and oxidant and inflammatory inhibition abilities, demonstrating that these compounds have robust efficacy for these ailments. In the present research, to find out a combating agent against breast cancer, tuberculosis, bacterial and fungal ailments, the compounds were tested through MTT, microplate alamar blue and serial dilution protocols. ADMET and DFT investigation were analyzed against highly bioactive compounds (2, 7-10) to give a new insight about compound's reactivity, stability and drug likeness properties. Furthermore, activity results shows that the ligand (2) and its complexes demonstrate greater efficacy compared to ligand (1) and its complexes. The Cu(II) (9) and Zn(II) (10) complexes were observed as highly efficient for breast cancer (MCF-7 cell line), TB (H37Rv strain), bacterial and fungal ailments in comparison of standard drugs with 0.029 ± 0.001 µM IC50 value for (9) in anticancer activity and 0.0034 ± 0.0017 µmol/mL MIC value for (10) in anti-tuberculosis activity. In the molecular docking investigation, the various kind of binding interactions and lowest binding affinity of (9) (against 4RJ3 (-10.0 kcal/mol), 2VCJ (-7.9 kcal/mol)) and (10) (-7.8 and -8.3 kcal/mol for 5V3Y and 3PTY protein) support their bioactivity. This research highlights the pharmaceutical importance of transition metal complexes having thiosemicarbazones, presenting a significant approach for the discovery of potent anti-infectious agent.

Can Ultrasound Evaluation of Lymph Node Size and Necrosis Rate Predict Chemotherapy Response in Cervical Tuberculous Lymphadenitis?

Purpose: To explore the relationship between the initial size and the necrotic rate of lymph nodes evaluated by ultrasound in patients with cervical tuberculous lymphadenitis (CTL) and therapeutic response. Methods: Overall, 55 patients were included in this study. Conventional ultrasound and contrast-enhanced ultrasound examination were performed before anti-tuberculosis chemotherapy. Based on the different therapeutic outcomes, they were divided into responder groups (n = 39) and non-responder groups (n = 16). The relationship between the initial size (maximum area, length diameter, short diameter), rate of necrosis, and therapeutic response were compared and analyzed between two groups. Results: There was a significant difference in maximum area, short diameter and rate of necrosis of lymph nodes between the responder groups and the non-responder groups (P < 0.05). The receiver-operating-characteristic (ROC) curve analysis was used to differentiate the two groups, it showed that the area under the curve was 0.746 for maximum area and 0.721 for short diameter, respectively. The cut-off value for the lymph node maximum area and short diameter based on ROC curve analysis was determined as 3.94cm2 (sensitivity 76.9%, specificity 68.7%) and 1.15cm (sensitivity 59.0%, specificity 93.7%), respectively. A negative correlation was observed between maximum area, short diameter, and therapeutic response. Conclusion: The initial maximum area and short diameter of lymph nodes were found to have a negative correlation with chemotherapy response in patients with CTL. The treatment outcomes are typically unsatisfactory for lymph nodes exhibiting an initial necrosis rate of 50% or higher. These findings may be helpful for evaluating therapeutic response.

In this study, we evaluated the relationship between the initial size and the necrotic rate by ultrasound with cervical tuberculous lymphadenitis (CTL) and therapeutic response. We found that the initial maximum area and short diameter of lymph nodes have a negative correlation with chemotherapy response in patients with CTL. The treatment outcomes are typically unsatisfactory for lymph nodes exhibiting an initial necrosis rate of 50% or higher. These findings may be helpful for evaluating therapeutic response in the early stages.

Synthesis of indole-functionalized isoniazid conjugates with potent antimycobacterial and antioxidant efficacy.

Aim: Developing potent medicinal alternates for tuberculosis (TB) is highly desirable due to the advent of drug-resistant lethal TB strains. Methods & results: Novel indole-isoniazid integrates have been synthesized with promising antimycobacterial action against the H37Rv strain, and the nitro analogs 4e and 4j show the highest efficacy with a minimum inhibitory concentration of 1.25 µg/ml. The molecular docking studies against InhA support the experimental findings. Indole conjugates display remarkable radical quenching efficiency, and compounds 4e and 4j demonstrate maximum IC50 values of 50.19 and 52.45 µg/ml, respectively. Pharmacokinetic analysis anticipated appreciable druggability for the title compounds. Conclusion: The notable bioaction of the indole-isoniazid templates projects them as potential lead in developing anti-TB medications with synergetic antioxidant action.

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Acute Large Pericardial Effusion With Haemodynamic Compromise Secondary to Undiagnosed Tuberculosis.

Tuberculous pericardial effusion is uncommon in the developed countries. However, it remains one of the main causes of presentation with a pericardial presentation with pericardial effusion in the developing world. We present the case of a 24-year-old male patient who presented with a weekly history of diarrhoea, vomiting, shortness of breath and feeling hot. Chest computed tomography revealed a large pericardial effusion with significant haemodynamic compromise. The patient underwent emergency pericardiocentesis, and the pericardial fluid interferon-gamma assay result was positive for tuberculosis. He was unable to tolerate endobronchial biopsy under ultrasound despite heavy sedation and was commenced on anti-tuberculous therapy following a discussion in a multidisciplinary team meeting. He was started on four standard anti-tuberculosis medications, including rifampicin, isoniazid, pyrazinamide, ethambutol and prednisolone. The patient had re-accumulation of pericardial fluid on repeat echocardiography in the first few weeks, which eventually resolved with anti-tuberculous therapy.

Mycobacterial biofilms: A therapeutic target against bacterial persistence and generation of antibiotic resistance.

Mycobacterium tuberculosis (M. tb) is the causative agent of Tuberculosis, one of the deadliest infectious diseases. According to the WHO Report 2023, in 2022, approximately 10.6 million people got infected with TB, and 1.6 million died. It has multiple antibiotics for treatment, but the major drawback of anti-tuberculosis therapy (ATT) is, its prolonged treatment duration. The major contributors to the lengthy treatment period are mycobacterial persistence and drug tolerance. Persistent M. tb is phenotypically drug tolerant and metabolically slow down which makes it difficult to be eliminated during ATT. These persisting bacteria are a huge reservoir of impending disease, waiting to get reactivated upon the onset of an immune compromising state. Directly Observed Treatment Short-course, although effective against replicating bacteria; fails to eliminate the drug-tolerant persisters making TB still the second-highest killer globally. There are different mechanisms for the development of drug-tolerant mycobacterial populations being investigated. Recently, the role of biofilms in the survival and host-evasion mechanism of persisters has come to light. Therefore, it is crucial to understand the mechanism of adaptation, survival and attainment of drug tolerance by persisting M. tb-populations, in order to design better immune responses and therapeutics for the effective elimination of these bacteria by reducing the duration of treatment and also circumvent the generation of drug-resistance to achieve the goal of global eradication of TB. This review summarizes the drug-tolerance mechanism and biofilms' role in providing a niche to dormant-M.tb. We also discuss methods of targeting biofilms to achieve sterile eradication of the mycobacteria and prevent its reactivation by achieving adequate immune responses.

Incidence of side effects of antituberculosis drugs and their related factors in northern Iran: a retrospective cohort study.

Background: Antituberculosis drugs may cause mild, moderate or severe adverse drug reactions (ADR) leading to poor compliance. Description of the pattern of ADR and their related factors can help tuberculosis (TB) control program as part of the WHO programs. This study aims to investigate the incidence of ADR and associated factors among TB patients in northern Iran. Methods: This is a retrospective cohort study. The required information, including year of diagnosis, age, gender, residence area, nationality, HIV co-morbidity, history of anti TB treatment and ADR, was obtained from the Deputy of Health, Mazandaran University of Medical Sciences, Iran. All data were analyzed using SPSS version 21 software. Results: Out of 3903 TB patients, 136 (3.5%) experienced major ADR. The incidence of ADR for men and women as well as for those with and without previous treatment history were 3.9% vs. 3.3% and 5.3% vs. 3.4%, respectively (p>0.05). Multiple logistic regression models showed a higher chance of ADR among those aged over 59 compared with those aged under 29 (OR=2.63, 95% confidence interval: 1.54-4.49). Conclusions: Age over 59 can be considered a risk factor for ADR with anti-TB drug administration.

Polymorphism of CYP3A4*18 is associated with anti-tuberculosis drug-induced hepatotoxicity.

Aim: The association between cytochrome P450 (CYP) gene polymorphisms and anti-tuberculosis drug-induced hepatotoxicity (ATDH) was investigated in patients with or without pre-existing liver diseases (PLD). Materials & methods: We followed 164 tuberculosis subjects, 58 with PLD and 106 without PLD. Polymorphisms in CYP2D6, CYP2C9, CYP2C19, CYP3A4 and CYP3A5 were analyzed using the TaqMan® SNP genotyping assay. Results: The CYP3A4*18 heterozygous genotype was associated with ATDH (OR: 3.24, 95% CI: 1.06-9.86) regardless of PLD presence. Among subjects without PLD, CYP3A4*18 heterozygotes had significantly higher ATDH risk (OR: 9.10, 95% CI: 1.56-53.16). Conversely, in the PLD group, CYP3A4*18 heterozygotes had lower ATDH risk (OR: 0.21, 95% CI: 0.05-0.98). Conclusion: CYP3A4*18 genotype is linked to ATDH in tuberculosis patients, with differential effects based on PLD presence.

[Box: see text].

DRESS syndrome due to anti-TB drugs: A complex case with successful re-desensitization of group A drugs.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare, life-threatening adverse reaction caused by certain medications. Clinical findings usually include rash, fever, lymphadenopathy, and eosinophilia, and in some cases, they may affect major organs. This reaction caused by antituberculosis (TB) medication poses a public health risk due to treatment discontinuation, adherence, or success in cure. We present a 23-year-old female patient who developed DRESS syndrome as a result of group A anti-TB drugs (ATDs), an exceedingly rare occurrence. The patient's medication was successfully retrieved using a re-desensitization protocol.

First-line anti-tuberculosis drug challenge reactions in DRESS in an HIV endemic setting.

BACKGROUND: In high HIV prevalence settings, first line anti-tuberculosis drug (FLTD)-associated DRESS poses therapeutic challenges. Sequential and additive drug challenge (SADC) of FLTDs best identifies offending drug(s), avoids unnecessary exclusions, and optimises re-initiation of non-offending drugs. However, SADC-associated reaction complexities limit its utility. OBJECTIVE: We aimed to describe characteristics of FLTD-associated DRESS patients, their treatment-limiting SADC reactions and related outcomes. METHODS: Patients hospitalized with FLTD-associated DRESS from 2013-2023 in a South African tertiary hospital and enrolled (retrospectively or prospectively) in an existing registry were eligible. RESULTS: SADC was undertaken in 41 patients. Overall, 47 classifiable reactions occurred, 34/47(72%) in 29/41(71%) patients, were treatment-limiting and 12/41(29%) reinitiated FLTDs uneventfully. Fifteen single and eight multiple drug-reactors were identified. Rifampicin, in 13/23(57%) reactors was the commonest individual offender. Ethambutol was most frequently involved in multiple drug-reactors. Median(IQR) time to a detectable reaction was 24(12-120) hours, 6/34(18%) being immediate (<6hours). Itch (65%), eosinophilia (56%), fever (41%), atypical lymphocytosis (41%), rash (38%), transaminitis (32%) and facial oedema (18%), singly or in combination were commonest features. Three reactions, one epidermal necrolysis and two liver derangements, were CTCAE grade 4 (life-threatening) events. No predictors of multiple drug-reactivity were identified, but multiple reactors were hospitalised significantly longer, 125(100-134) versus 60(45-80) days. CONCLUSIONS: SADC optimises FLTD reinitiation. However, timing, clinical presentation and severity of SADC-associated reactions following FLTD-associated DRESS is markedly heterogenous. Additionally, multiple drug-reactors are a complex group requiring longer hospitalisation, and without routine biomarkers to differentiate true multiple drug hypersensitivity from non-specific flare-ups and guide long-term drug avoidance strategies.

Recent Biochemical Advances in Antitubercular Drugs: Challenges and Future.

Tuberculosis (TB) is one of the leading causes of death world-wide after AIDS. It infects around one-third of global population and approximately two million people die annually from this disease because it is a very contagious disease spread by Mycobacterium tuberculosis. The increasing number of drug-resistant strains and the failure of conventional treatments against this strain are the challenges of the coming decades. New therapeutic techniques aim to confirm cure without deterioration, to reduce deaths, contagions and the formation of drug-resistant strains. A plethora of new diagnostic tests are available to diagnose the active tuberculosis, screen latent M. tuberculosis infection, and to identify drug-resistant strains of M. tuberculosis. When effective prevention strategies do not prevail, high rates of early case detection and successive cures to control TB emergence would not be possible. In this review, we discussed the structural features of M. tuberculosis, Multi drug resistance tuberculosis (MDR-TB), extremely drug-resistant tuberculosis (XDR-TB), the mechanism of M. tuberculosis infection, the mode of action of first and second-line antitubercular drugs, the mechanism of resistance to the existing drugs, compounds in preclinical and clinical trial and drugs presently available for the treatment of tuberculosis. Moreover, the new diagnostic techniques to detect M. Tuberculosis are also discussed in this review.

Drug-Resistant Tuberculosis Case-Finding Strategies: Scoping Review.

BACKGROUND: Finding individuals with drug-resistant tuberculosis (DR-TB) is important to control the pandemic and improve patient clinical outcomes. To our knowledge, systematic reviews assessing the effectiveness, cost-effectiveness, acceptability, and feasibility of different DR-TB case-finding strategies to inform research, policy, and practice, have not been conducted and the scope of primary research is unknown. OBJECTIVE: We therefore assessed the available literature on DR-TB case-finding strategies. METHODS: We looked at systematic reviews, trials, qualitative studies, diagnostic test accuracy studies, and other primary research that sought to improve DR-TB case detection specifically. We excluded studies that included patients seeking care for tuberculosis (TB) symptoms, patients already diagnosed with TB, or were laboratory-based. We searched the academic databases of MEDLINE, Embase, The Cochrane Library, Africa-Wide Information, CINAHL (Cumulated Index to Nursing and Allied Health Literature), Epistemonikos, and PROSPERO (The International Prospective Register of Systematic Reviews) using no language or date restrictions. We screened titles, abstracts, and full-text articles in duplicate. Data extraction and analyses were carried out in Excel (Microsoft Corp). RESULTS: We screened 3646 titles and abstracts and 236 full-text articles. We identified 6 systematic reviews and 61 primary studies. Five reviews described the yield of contact investigation and focused on household contacts, airline contacts, comparison between drug-susceptible tuberculosis and DR-TB contacts, and concordance of DR-TB profiles between index cases and contacts. One review compared universal versus selective drug resistance testing. Primary studies described (1) 34 contact investigations, (2) 17 outbreak investigations, (3) 3 airline contact investigations, (4) 5 epidemiological analyses, (5) 1 public-private partnership program, and (6) an e-registry program. Primary studies were all descriptive and included cross-sectional and retrospective reviews of program data. No trials were identified. Data extraction from contact investigations was difficult due to incomplete reporting of relevant information. CONCLUSIONS: Existing descriptive reviews can be updated, but there is a dearth of knowledge on the effectiveness, cost-effectiveness, acceptability, and feasibility of DR-TB case-finding strategies to inform policy and practice. There is also a need for standardization of terminology, design, and reporting of DR-TB case-finding studies.

Synthesis, Biological and Molecular Docking Studies of Thiazole-Thiadiazole derivatives as potential Anti-Tuberculosis Agents.

Tuberculosis remains a global health threat, with increasing infection rates and mortality despite existing anti-TB drugs. The present work focuses on the research findings regarding the development and evaluation of thiadiazole-linked thiazole derivatives as potential anti-tuberculosis agents. We present the synthesis data and confirm the compound structures using spectroscopic techniques. The current study reports twelve thiazole-thiadiazole compounds (5 a-5 l) for their anti-tuberculosis and related bioactivities. This paper emphasizes compounds 5 g, 5 i, and 5 l, which exhibited promising MIC values, leading to further in silico and interaction analysis. Pharmacophore mapping data included in the present analysis identified tubercular ThyX as potential drug targets. The compounds were evaluated for anti-tubercular activity using standard methods, revealing significant MIC values, particularly compound 5 l, with the best MIC value of 7.1285 µg/ml. Compounds 5 g and 5 i also demonstrated moderate to good MIC values against M. tuberculosis (H37Ra). Structural inspection of the docked poses revealed interactions such as hydrogen bonds, halogen bonds, and interactions containing Pi electron cloud, shedding light on conserved interactions with residues like Arg 95, Cys 43, His 69, and Arg 87 from the tubercular ThyX enzyme.

Immunoglobulin A Vasculitis After Initiation of Treatment for Tuberculous Pleurisy: A Case Report and Literature Review.

Immunoglobulin A vasculitis (IgAV), also known as Henoch-Schönlein purpura (HSP), is a disease that causes inflammation and bleeding in small blood vessels in the skin, joints, intestines, and kidneys. Although various infections and chemicals are known to be triggers, the underlying cause of IgAV remains unknown. Here, we describe a case of an 86-year-old male patient with IgAV that developed after anti-tuberculosis treatment for tuberculous pleurisy. There have been several case reports implicating Mycobacterium tuberculosis and other acid-fast bacterium in the development of IgAV, but only a few case reports implicating anti-tuberculous drugs. This case highlights the importance of recognizing that IgAV can be caused by anti-tuberculous drugs.

Unraveling the potential of graphene quantum dots against Mycobacterium tuberculosis infection.

Introduction: The emergence of drug-resistant Mycobacterium tuberculosis (Mtb) strains has underscored the urgent need for novel therapeutic approaches. Carbon-based nanomaterials, such as graphene oxide (GO), have shown potential in anti-TB activities but suffer from significant toxicity issues. Methods: This study explores the anti-TB potential of differently functionalized graphene quantum dots (GQDs) - non-functionalized, L-GQDs, aminated (NH2-GQDs), and carboxylated (COOH-GQDs) - alone and in combination with standard TB drugs (isoniazid, amikacin, and linezolid). Their effects were assessed in both axenic cultures and in vitro infection models. Results: GQDs alone did not demonstrate direct mycobactericidal effects nor trapping activity. However, the combination of NH2-GQDs with amikacin significantly reduced CFUs in in vitro models. NH2-GQDs and COOH-GQDs also enhanced the antimicrobial activity of amikacin in infected macrophages, although L-GQDs and COOH-GQDs alone showed no significant activity. Discussion: The results suggest that specific types of GQDs, particularly NH2-GQDs, can enhance the efficacy of existing anti-TB drugs. These nanoparticles might serve as effective adjuvants in anti-TB therapy by boosting drug performance and reducing bacterial counts in host cells, highlighting their potential as part of advanced drug delivery systems in tuberculosis treatment. Further investigations are needed to better understand their mechanisms and optimize their use in clinical settings.

The effect of statins on the risk of anti-tuberculosis drug-induced liver injury among patients with active tuberculosis: A cohort study.

BACKGROUND: Tuberculosis (TB) remains prevalent worldwide, and anti-TB drugs are associated with drug-induced liver injury (DILI). Statins have pleiotropic effects which may decrease inflammation and achieve immunomodulation. However, few studies have investigated the pleiotropic effects of statins on the risk of DILI. The purpose of this study was to investigate whether statins prevent anti-tuberculosis DILI among active TB patients on standard anti-TB drug therapy. METHODS: We conducted a hospital-based retrospective cohort study using claims data from the Integrated Medical Database of National Taiwan University Hospital (NTUH-iMD). Patients with a positive TB culture were included. The use of statins was defined as a daily equivalent dose >0.5 mg of pitavastatin. Deterioration in liver function was evaluated according to elevated liver enzyme levels. The primary and secondary endpoints were the DILI and the severe DILI. The prognostic value of statins was evaluated by Kaplan-Meier analysis, and Cox proportional hazards models. RESULTS: A total of 1312 patients with a diagnosis of TB and receiving anti-TB treatment were included. During the study period, 193 patients had the DILI and 140 patients had the severe DILI. Kaplan-Meier analysis showed a significant difference between the usual statin users and controls in the DILI. In multivariable Cox proportional hazards analysis, statins showed a protective effect against the primary and secondary endpoints. In addition, the protective effect of statins showed a dose-response relationship against the DILI. CONCLUSION: Statin treatment had a protective effect against the risk of anti-TB DILI with a positive dose-response relationship.