anti-TB Drug Treatment Research Articles

Adjunctive administration of parabiotic Lactobacillus sakei CVL-001 ameliorates drug-induced toxicity and pulmonary inflammation during antibiotic treatment for tuberculosis

Tuberculosis (TB) treatment requires a long therapeutic duration and induces adverse effects such as hepatotoxicity, causing discontinuation of treatment. Reduced adherence to TB medications elevates the risk of recurrence and the development of drug resistance. Additionally, severe cavitary TB with a high burden of Mycobacterium tuberculosis (Mtb) and inflammation-mediated tissue damage may need an extended treatment duration, resulting in a higher tendency of drug-induced toxicity. We previously reported that the administration of Lactobacillus sakei CVL-001 (L. sakei CVL-001) regulates inflammation and improves mucosal barrier function in a murine colitis model. Since accumulating evidence has reported the functional roles of probiotics in drug-induced liver injury and pulmonary inflammation, we employed a parabiotic form of the L. sakei CVL-001 to investigate whether this supplement may provide beneficial effects on the reduction in drug-induced liver damage and pulmonary inflammation during chemotherapy. Intriguingly, L. sakei CVL-001 administration slightly reduced Mtb burden without affecting lung inflammation and weight loss in both Mtb-resistant and -susceptible mice. Moreover, L. sakei CVL-001 decreased T cell-mediated inflammatory responses and increased regulatory T cells along with an elevated antigen-specific IL-10 production, suggesting that this parabiotic may restrain excessive inflammation during antibiotic treatment. Furthermore, the parabiotic intervention significantly reduced levels of alanine aminotransferase, an indicator of hepatotoxicity, and cell death in liver tissues. Collectively, our data suggest that L. sakei CVL-001 administration has the potential to be an adjunctive therapy by reducing pulmonary inflammation and liver damage during anti-TB drug treatment and may benefit adherence to TB medication in lengthy treatment.

Case report on anti-tuberculosis drug-induced hepatitis and pancreatitis

Tuberculosis (TB) is a widespread infectious disease primarily impacting the lungs but with potential effects on various organs, such as bones, kidneys, and intestines. This case underscores a rare yet serious complication associated with anti-TB drug (ATD) treatment-the development of drug-induced acute pancreatitis. In this instance, a 65-year-old male undergoing ATD therapy exhibited symptoms including fever, vomiting, and fatigue. Despite receiving medical intervention, including intravenous antibiotics and hepatoprotective drugs, the patient's condition progressively worsened, ultimately resulting in a fatal outcome. This case emphasizes the crucial significance of early identification and effective management of such complications, highlighting the necessity for vigilant monitoring and regular assessment of liver function tests throughout ATD treatment.

Differences in pulmonary nodular consolidation and pulmonary cavity among drug-sensitive, rifampicin-resistant and multi-drug resistant tuberculosis patients: the Guangzhou computerized tomography study.

Pulmonary nodular consolidation (PN) and pulmonary cavity (PC) may represent the two most promising imaging signs in differentiating multidrug-resistant (MDR)-pulmonary tuberculosis (PTB) from drug-sensitive (DS)-PTB. However, there have been concerns that literature described radiological feature differences between DS-PTB and MDR-PTB were confounded by that MDR-PTB cases tend to have a longer history. This study seeks to further clarify this point. All cases were from the Guangzhou Chest Hospital, Guangzhou, China. We retrieved data of consecutive new MDR cases [n=46, inclusive of rifampicin-resistant (RR) cases] treated during the period of July 2020 and December 2021, and according to the electronic case archiving system records, the main PTB-related symptoms/signs history was ≤3 months till the first computed tomography (CT) scan in Guangzhou Chest Hospital was taken. To pair the MDR-PTB cases with assumed equal disease history length, we additionally retrieved data of 46 cases of DS-PTB patients. Twenty-two of the DS patients and 30 of the MDR patients were from rural communities. The first CT in Guangzhou Chest Hospital was analysed in this study. When the CT was taken, most cases had anti-TB drug treatment for less than 2 weeks, and none had been treated for more than 3 weeks. Apparent CT signs associated with chronicity were noted in 10 cases in the DS group (10/46) and 9 cases in the MDR group (10/46). Thus, the overall disease history would have been longer than the assumed <3 months. Still, the history length difference between DS patients and MDR patients in the current study might not be substantial. The lung volume involvement was 11.3%±8.3% for DS cases and 8.4%±6.6% for MDR cases (P=0.022). There was no statistical difference between DS cases and MDR cases both in PN prevalence and in PC prevalence. For positive cases, MDR cases had more PN number (mean of positive cases: 2.63 vs. 2.28, P=0.38) and PC number (mean of positive cases: 2.14 vs. 1.38, P=0.001) than DS cases. Receiver operating characteristic curve analysis shows, PN ≥4 and PC ≥3 had a specificity of 86% (sensitivity 25%) and 93% (sensitivity 36%), respectively, in suggesting the patient being a MDR cases. A combination of PN and PC features allows statistical separation of DS and MDR cases.

Multi-drug-resistant tuberculosis and its associated factors among pulmonary tuberculosis patients linked to first-line anti-tuberculosis drugs in north-west Ethiopia

Introduction. Multi-drug-resistant tuberculosis (MDR-TB) is an emerging global challenge. Ethiopia is one of the 20 top countries with the highest estimated numbers of incidents of MDR-TB. Recently, the World Health Organization warned that drug-resistant TB is escalating and called for concerted action to reduce the spread of drug resistance. Hypothesis. The current study investigated MDR-TB in patients receiving first-line anti-TB drug treatment and associated factors. Aim. The study aimed to determine the prevalence of MDR-TB and its associated factors among smear-positive pulmonary TB patients receiving first-line anti-TB drug treatment. Methodology. An institution-based cross-sectional study was employed. All data were collected from laboratory result log books and information via a questionnaire. Samples from 205 smear-positive pulmonary TB patients were selected among first-line drug treatment by a systematic sampling method. Specimens were transported to Felege Hiwot referral hospital laboratory for GeneXpert testing. Factors associated with an outcome variable in binary multi-variable logistic regression analysis at P&lt;0.05 were considered statistically significant variables. An ethical approval letter was taken to the respective health facility and written consent was obtained from each participant. Results. The overall prevalence of MDR-TB was 9.3 % (95 % CI, 5.4 13.7 %). Sign and symptom experience of anti-TB drug side effects [adjusted odds ratio (AOR)=0.18, 95 % CI=0.03–0.99, P=0.049] and co-morbidity (AOR=0.03, 95 % CI=0.01–0.55, P=0.02) were statistically associated with the development of MDR-TB infection Conclusion. The prevalence of MDR-TB was high (9.3 %) and contributed highly to new cases (8.3 %). Factors associated with MDR-TB were previous treatment, co-morbidity and laboratory diagnosis method prior to TB treatment. Therefore, this finding aims to maximize early detection and treatment, strengthening TB infection control, and proper implementation of directly observed therapy short course recommendations to reduce the burden of MDR-TB.

Pediatric and adult meningeal, parenchymal, and spinal tuberculosis: A neuroimaging review.

Neurotuberculosis is defined as a tuberculous infection of the meninges, brain parenchyma, vessels, cranial and spinal nerves, spinal cord, skull, and spine that can occur either in a localized or in a diffuse form. It is a heterogeneous disease characterized by many imaging appearances and it has been defined as "the great mimicker" due to similarities with many other conditions. The diagnosis of central nervous system (CNS)tuberculosis (TB) is based on clinical presentation, neuroimaging findings, laboratory and microbiological findings, and comprehensive evaluation of the response to anti-TB drug treatment. However, the absence of specific symptoms, the wide spectrum of neurological manifestations, the myriad of imaging findings, possible inconclusive laboratory results, and the paradoxical reaction to treatment make the diagnosis often challenging and difficult, potentially delaying adequate treatment with possible devastating short-term and long-term neurologic sequelae. Familiarity with the imaging characteristics helps in accurate diagnosis and may prevent or limit significantly morbidity and mortality. The goal of this review is to provide a comprehensive up-to-date overview of the conventional and advanced imaging features of CNS TB for radiologists, neuroradiologists, and pediatric radiologists. We discuss the most typical neurotuberculosis imaging findings and their differential diagnosis in children and adults with the goal to provide a global overview of this entity.

Mortality Rates Of Adult Pulmonary Tuberculosis With Malnutrition: A Case Report And Comprehensive Literature Review

Tuberculosis (TB) and malnutrition are still major public health problems in the world. These two clinical conditions can occur simultaneously and create a vicious cycle that worsens TB infection or nutritional status. This case report aims to examine the relationship between low nutritional status (malnutrition) of patients and death due to pulmonary TB. A 31 year old woman came to the pulmonary clinic of a tertiary hospital in Jakarta for her third month of drug-sensitive anti-TB drug (OAT) treatment control. Three months earlier, the patient underwent a rapid diagnostic test (RDT) to determine OAT resistance. The conclusion of her anthropometric examination was body mass index (BMI) of 15.6 kg/m2. Before being diagnosed with pulmonary TB, she always had difficulty gaining weight. During the course of disease, her weight decreased by 5 kg per month. After undergoing treatment for 6 months, the patient was declared complete after 6 months of therapy, without any improvement in nutritional status. At 1 year follow-up, the patient experienced a relapse of pulmonary TB with a BMI of 13.2 kg/m2. She died 2 months after diagnosis of relapse TB. Improvement in clinical complaints and conversion to bacteriological examination are indications of successful therapy, including improvement in nutritional status. To analyze the relationship between malnutrition and pulmonary TB and death, the authors conducted a comprehensive literature search in the journal databases PubMed, Cochrane, and Scopus, followed by analysis according to the PRISMA 2020 flowchart, for a prognostic cohort study of cases of death in pulmonary TB patients with malnutrition. There is a relationship between BMI and the risk of death in TB patients. Anthropometric measurements, especially BMI, need to be carried out during every physical examination of pulmonary TB cases.&#x0D; Keywords: Body mass index; Malnutrition; Mortality; Tuberculosis

Adverse Drug Reaction Patterns of First-line Anti-tubercular Drugs among Saharia Tuberculosis Patients: An Observational Study in Particularly Vulnerable Tribal Group of Madhya Pradesh, India.

The Saharia tribe of Madhya Pradesh has a very high tuberculosis (TB) burden. However, there is no report of adverse drug reaction (ADR) available in patients receiving anti-TB chemotherapy in the community. Reporting and monitoring of ADRs among TB patients is still rare in marginalized communities. An observational prospective study was performed from November 2019 to June 2020 to assess the patterns of ADRs in 250 Saharia TB patients, who were prescribed Category-I daily DOTS (HRZE) by the physician. Both male and female participants equally experienced ADR during the treatment, but relatively more females (92.6%) than males (88.6%) reported ADR during Phase I. Out of 250 patients, 224 patients (89.6%) experienced one or more ADRs in Phase I. The central nervous system-related (75.6%) ADR was mostly reported followed by any gastrointestinal (74.4%), cardiovascular (49.2%) and any dermatological related (44.4%) ADRs. It is paramount to timely monitor and proactively manages ADRs pertaining to anti-TB drug treatment with minimal alteration in the treatment course.

A rare case of endobronchial tuberculosis with left main bronchial stenosis in a patient with pulmonary tuberculosis

Endobronchial tuberculosis (EBTB) is a condition that occurs as a result of pulmonary tuberculosis (TB), where the infection spreads to the inner walls of the bronchial tubes or the trachea. This causes the inner lining and the layer underneath to become inflamed, swollen, ulcerated, or to develop granulated tissue or scar. We discuss a 19-year-old lady with active pulmonary TB who was receiving anti-TB drug treatment. Despite being on anti-TB medications, she had persistent cough, loss of weight and increasing dyspnea. She was diagnosed with EBTB with left main bronchus (LMB) stenosis, based upon a strong clinical suspicion, followed by using a variety of techniques, including lung function testing, a chest and neck CT scan, and a bronchoscopy. Given that EBTB is a rare consequence of TB, it is crucial for clinicians to take it into account when patients present with symptoms that are comparable. This will enable prompt and effective treatment.

Effects of second-line anti-tuberculosis drugs on the intestinal microbiota of patients with rifampicin-resistant tuberculosis.

To determine the effects of second-line anti-tuberculosis (TB) drugs on the composition and functions of intestinal microbiota in patients with rifampicin-resistant TB (RR-TB). In this cross-sectional study, stool samples and relevant clinical information were collected from patients with RR-TB admitted to the Drug-resistant Specialty Department at Hunan Chest Hospital (Hunan Institute For Tuberculosis Control). The composition and functions of intestinal microbiota were analyzed using metagenomic sequencing and bioinformatics methods. Altered structural composition of the intestinal microbiota was found when patients from the control, intensive phase treatment, and continuation phase treatment groups were compared (P<0.05). Second-line anti-TB treatment resulted in a decrease in the relative abundance of species, such as Prevotella copri, compared with control treatment. However, the relative abundance of Escherichia coli, Salmonella enterica, and 11 other conditionally pathogenic species increased significantly in the intensive phase treatment group. Based on differential functional analysis, some metabolism-related functions, such as the biosynthesises of phenylalanine, tyrosine, and tryptophan, were significantly inhibited during second-line anti-TB drug treatment, while other functions, such as phenylalanine metabolism, were significantly promoted during the intensive phase of treatment. Second-line anti-TB drug treatment caused changes in the structural composition of the intestinal microbiota in patients with RR-TB. In particular, this treatment induced a significant increase in the relative abundance of 11 conditionally pathogenic species, including Escherichia coli. Functional analysis revealed significantly decreased biosynthesises of phenylalanine, tyrosine, and tryptophan and significantly increased phenylalanine metabolism.

Gut microbiota characteristics of Mongolian and Han populations in anti-tuberculosis drug-induced liver injury: a population-based case–control study

BackgroundThe pathogenesis of anti-tuberculosis (TB) drug-induced liver injury (ADLI) is complicated and remains unclear. We aimed to analyse the relationship between the characteristics of gut microbiota and ADLI in Mongolian and Han patients with pulmonary TB and identify the most notable bacteria related to the occurrence of liver injury in those populations.MethodsPatients with concurrent liver injury (LI) and no liver injury (ULI) before receiving first-line anti-TB drug treatment (T1) from the Han population in Tangshan and the Mongolian population in Inner Mongolia were selected as research subjects. At the time of liver injury (T2), stool samples were measured by bacterial 16S rRNA gene high-throughput sequencing to analyse and compare the differences in the gut microbiota of the LI and ULI Mongolian and Han patients at T1 and T2 and identify the differences between those patients.ResultsA total of 45 Mongolian and 37 Han patients were enrolled in our study. A dynamic comparison from T1 to T2 showed that the microbiota of the LI and ULI groups changed significantly from T1 to T2 in both the Mongolian and Han populations. However, there were commonalities and personality changes in the microbiota of the two ethnic groups.ConclusionDifferences in gut microbes in ADLI were found among the Han and Mongolian patients in our study. Ekmania and Stenotrophomonas were related to the occurrence of ADLI in Mongolian patients, while Ekmania and Ruminococcus__gnavus_group were related to the occurrence of ADLI in the Han population.

Hepatocyte ferroptosis contributes to anti-tuberculosis drug-induced liver injury: Involvement of the HIF-1α/SLC7A11/GPx4 axis

Anti-tuberculosis drug-induced liver injury (ATB-DILI) is a common serious adverse event observed during the clinical treatment of tuberculosis. However, the molecular mechanisms underlying ATB-DILI remain unclear. A recent study has indicated that ferroptosis and lipid peroxidation may be involved in liver injury. Therefore, this study aimed to investigate the role of ferroptosis in the molecular mechanisms underlying ATB-DILI. Our results showed that anti-TB drugs induced hepatocyte damage in vivo and in vitro and inhibited BRL-3A cell activity in a dose-dependent manner, accompanied by increased lipid peroxidation and reduced antioxidant levels. Moreover, ACSL4 expression and Fe2+ concentration significantly increased following anti-TB drug treatment. Interestingly, anti-TB drug-induced hepatocyte damage was reversed by ferrostatin-1 (Fer-1, a specific ferroptosis inhibitor). In contrast, treatment with erastin (a ferroptosis inducer) resulted in further elevation of ferroptosis indicators. Additionally, we also found that anti-TB drug treatment inhibited HIF-1α/SLC7A11/GPx4 signaling in vivo and in vitro. Notably, HIF-1α knockdown significantly enhanced anti-TB drug-induced ferroptotic events and the subsequent exacerbation of hepatocyte damage. In conclusion, our findings indicated that ferroptosis plays a crucial role in the development of ATB-DILI. Furthermore, anti-TB drug-induced hepatocyte ferroptosis was shown to be regulated by HIF-1α/SLC7A11/GPx4 signaling. These findings shed new light on the mechanisms underlying ATB-DILI and suggest novel therapeutic strategies for this disease.

Clinical Manifestation, Imaging Features and Treatment Follow-up of 29 Cases with Hepatic Tubercolosis.

To understand the clinical and imaging manifestations and the treatment and follow-up of hepatic tuberculosis (HTB), we retrospectively analysed the clinical and imaging data of 29 patients with HTB who had been diagnosed clinically or by biopsy, and the clinical and imaging data had been summarised. Patient characteristics were followed up after anti-TB drug treatment. The median age of the 29 patients with HTB was 37 years, and most were male (58.6%). The patient’s symptoms included fever (48.2%), respiratory symptoms (27.5%), abdominal pain (24.1%), and abdominal distension (10.3%). Elevated erythrocyte sedimentation rate (79.3%), elevated serum C-reactive protein (75.8%) and hypoalbuminemia (62.0%) were common features. Three patients were serologically positive for acquired human immunodeficiency syndrome, and two were serologically positive for hepatitis B surface antigen with normal tumour markers. The 29 patients with HTB included 17 with serous HTB, 9 with parenchymal HTB (8 with parenchymal nodular HTB and 1 with parenchymal miliary HTB), 1 with intrahepatic abscess type HTB, and 2 with hilar HTB. Approximately 86% of the patients also had pulmonary TB. Most of the serous HTB patients also had tuberculous peritonitis. Enhanced computerized tomography scans of the serous and parenchymal HTB cases showed the progressive development of lesions. Abnormal blood perfusion was observed in the hepatic artery, and the clearest evidence of TB was observed in the hepatic portal vein. Magnetic resonance imaging indicated that the lesions returned a high signal in the diffusion-weighted imaging sequence. However, the lesions’ apparent diffusion coefficient values reflected high signals. The Xpert MTB/RIF test detected Mycobacterium TB complex in the liver biopsy fluid from 10 patients.Regarding histopathology, one patient showed granulomatous inflammation, and one patient’s acid-fast bacillus (AFB) stain was positive. The treatment of two patients was stopped due to their adverse reactions to the drugs and the risk of creating drug-resistant TB. The remaining patients received anti-TB treatment, but one subsequently died, and two were unavailable for follow-up. The clinical symptoms of HTB are difficult to detect, and it has diverse manifestations by imaging, with no obvious specificity in terms of pathological results. Therefore, follow-up of liver lesions for checking anti-TB therapy is another method for diagnosing HTB. In addition, early active anti-TB treatment can achieve good curative results.

Nonadherence Predictors to Tuberculosis Medications among TB Patients in Gambella Region of Ethiopia.

Background Global tuberculosis (TB) disease deaths rise comparable to the one seen in 2015 (by 200,000) or even in 2012 (by 400,000) as a result of the potential impact of the COVID-19 pandemic. Ethiopia's Gambella region is leading for years in terms of TB cases and its comorbidities. The TB control program effectiveness depends on in large on the patients completing the appropriate treatment regimen. Hence, the objective of this study was to determine the determinants of nonadherence to anti-TB drug treatment among patients in Gambella regional state of Ethiopia. Methods A case-control study was conducted on cohorts of TB patients sampled from four public health facilities in Gambella Region from January 2019 to 2020, followed by 18 months of follow-up. The total sample size was 296 patients (74 cases and 222 controls) with a response rate of 97.3% (288 : 72 nonadhered cases and 216 controls). Cases (nonadhered) were TB patients who missed 10% of the doses while controls were patients, who completed 90% or more doses. Results TB patients, who perceived stigma [AOR = 2.7 at 95% CI (1.1–6.6) with P value <0.05], failed to receive any counseling during the treatment course [AOR = 65.24 at 95% CI (11.69–363.95) with P value <0.01], patients who used to smoking during treatment [AOR = 15.4 at 95% CI (7.7–30) with P value <0.01], taking TB medications regularly has no benefits [AOR = 6.8 at 95% CI (1.8–24.9) with P value <0.05], and patients believing TB disease as not severe [AOR = 8.38 at 95% CI (2.0–34.6) with P value <0.05] were significantly or highly significantly associated with nonadherence to anti-TB drugs medications. Conclusion The determinants of nonadherence to anti-TB treatment among TB patients in the Gambella region during the study period were the absence of counselling services, and patients' behavior (smoking habits, undermining the severity of TB disease, lack of trust in the outcomes of regular medications, and perceived stigmatization). Accordingly, capacitating healthcare providers and workers at all TB clinics for effective counseling , preventing perceived stigma by protecting the patient's secrecy, and routine health education has paramount importance for effective TB control in Gambella.

Concentrated specimen smear microscopy utilising a polymer membrane sandwich filtration vessel for the detection of acid-fast bacilli in health facilities in Sabah, East Malaysia

A simple, ready-to-use concentrated specimen smear microscopy method employing a nanometer silicon polyvinylidene fluoride (PVDF) polymer membrane sandwich filtration vessel to concentrate acid-fast bacilli (AFB) in samples (SFV-CSSM, Hunan-Tech New Medical System Co. Ltd. China) was compared with direct sputum smear microscopy (DSSM) to determine its performance using culture on modified Ogawa agar as reference. The results for 4114 clinical samples collected from health facilities in Sabah were interpreted with reference to culture results, sample collection-transportation conditions and clinical data including responses to anti-TB drug treatment. The SFV-CSSM showed higher sensitivity than DSSM (79.4% versus 60.5%) and less background interference. Its ability to detect low levels of AFB at an affordable cost makes it an excellent tool for the screening of pauci-bacillary samples as well as for active case finding in TB control programs.

Gallic acid attenuates isoniazid and rifampicin-induced liver injury by improving hepatic redox homeostasis through influence on Nrf2 and NF-κB signalling cascades in Wistar Rats.

Anti-TB drugs-isoniazid and rifampicin induced hepatotoxicity present a significant clinical problem. We aimed to evaluate the beneficial effect of gallic acid in anti-TB drug-induced liver injury in vivo and for the mechanism of action, we explored the influence of gallic acid on Nrf2 and NF-κB pathways. We assessed serum liver function tests and histopathological analysis for the preventive effect of gallic acid on liver injury. For exploring the beneficial mechanism, we studied Nrf2 and NF-κB signalling pathways using molecular assays. Subsequently, we conducted in vitro cytotoxicity assays with Nrf2(ML385) and NF-κB(BAY 11-7085) antagonists. Gallic acid co-administration attenuated the elevation of liver function enzymes, hepatic necrosis and inflammation compared to the anti-TB drug treatment alone. Mechanistic investigations reveal that gallic acid increased Nrf2 activation and induction of its downstream targets, preventing cytotoxicity by isoniazid and rifampicin. The protective effect of gallic acid diminished in the presence of Nrf2 antagonists in vitro. Furthermore, we found that gallic acid treatment inhibited NF-κB/TLR-4 axis upregulated by the anti-TB drugs. Gallic acid is effective in preventing isoniazid and rifampicin induced hepatotoxicity in vivo by improving the redox homeostasis by activating Nrf2 and inhibiting NF-κB signalling pathways.

Decreased Serum Cholinesterase Activity- A Reliable Diagnostic Aid for Tuberculosis

Introduction: Siderophore, the low molecular weight ferric iron chelator, is secreted extracellularly by Mycobacterium tuberculosis, an obligate aerobe. The pathogenic mycobacteria need iron as co-factor for the extracellularly secreted enzyme Superoxide Dismutase (SOD) for its pathogenicity as well as it requires iron for its metabolic functions like reduction of oxygen for synthesis of Adenosine Triphosphate (ATP), etc. The termination of impulse conduction is endorsed by the rapid hydrolysis of Acetylcholine (ACh) by Acetylcholinesterase (AChE) in the central as well as peripheral nervous system (cholinergic pathway). The inhibitors to Cholinesterase (ChE) might lead to accumulation of ACh, hyper stimulation of nicotinic and muscarinic receptors and also disruption of neurotransmission. Possibility of an inhibitor substance for AChE in Tuberculosis (TB) patients interestingly correlates with the symptom of night sweating in those subjects. Aim: To assay the level of serum ChE in normal control, lung disease control and tubercular subjects;circumvent the serum ChE level as a diagnostic potential in TB at an early stage. Materials and Methods: The study was conducted on total 124 subjects, and were divided into three groups: Group 1: normal control (n=31), Group 2: lung disease control (n=31) and Group 3: patients suffering from TB {3A: pulmonary TB (n=31) and 3B: extrapulmonary TB (n=31)}. Serum ChE activity for all the subjects were measured according to the method of Hestrin S. Serum ChE level was assayed for group 3 subjects after additional one month’s anti-TB drug treatment and also for group 2 subjects after one month with usual treatment. The level of significance was assessed using Student’s t-test. Results: There was a significant inhibition of serum ChE activity in both pulmonary and extrapulmonary TB patients in comparison to that of in normal control as well as lung disease control subjects (p&lt;0.01). With the anti-tubercular drug therapy for one month, there was significant recovery in the serum ChE activity in pulmonary as well as extrapulmonary tubercular subjects (p&lt;0.01). Conclusion: It appears that the high level of hydroxamate type of siderophores (secreted by Mycobacterium tuberculosis for acquiring iron) might form ACh ferric hydroxamate complex binding more strongly with serum ChE resulting in inhibition of serum ChE activity in tubercular subjects. With anti-tubercular drug therapy, there was decrease in serum ACh ferric hydroxamate complex level resulting in recovery of serum ChE activity.

Alzheimer's Disease: Protective Effects of Mycobacterium vaccae, a Soil-Derived Mycobacterium with Anti-Inflammatory and Anti-Tubercular Properties, on the Proteomic Profiles of Plasma and Cerebrospinal Fluid in Rats.

Alzheimer's disease (AD) is an inflammatory neurodegenerative disease that may be associated with prior bacterial infections. Microbial "old friends" can suppress exaggerated inflammation in response to disease-causing infections or increase clearance of pathogens such as Mycobacterium tuberculosis, which causes tuberculosis (TB). One such "old friend" is Mycobacterium vaccae NCTC 11659, a soil-derived bacterium that has been proposed either as a vaccine for prevention of TB, or as immunotherapy for the treatment of TB when used alongside first line anti-TB drug treatment. The goal of this study was to use a hypothesis generating approach to explore the effects of M. vaccae on physiological changes in the plasma and cerebrospinal fluid (CSF). Liquid chromatography-tandem mass spectrometry-based proteomics were performed in plasma and CSF of adult male rats after immunization with a heat-killed preparation of M. vaccae NCTC 11659 or borate-buffered saline vehicle. Gene enrichment analysis and analysis of protein-protein interactions were performed to integrate physiological network changes in plasma and CSF. We used RT-qPCR to assess immune and metabolic gene expression changes in the hippocampus. In both plasma and CSF, immunization with M. vaccae increased proteins associated with immune activation and downregulated proteins corresponding to lipid (including phospholipid and cholesterol) metabolism. Immunization with M. vaccae also increased hippocampal expression of interleukin-4 (IL-4) mRNA, implicating anti-inflammatory effects in the central nervous system. M. vaccae alters host immune activity and lipid metabolism. These data are consistent with the hypothesis that microbe-host interactions may protect against possible infection-induced, inflammation-related cognitive impairments.

Efficacy and safety of oncoplastic surgery plus drug therapy for chronic tuberculous granulomatous mastitis.

BACKGROUND: Chronic tuberculous granulomatous mastitis (CTGM) is a rare form of tuberculosis (TB) treated primarily with anti-TB drugs. Oncoplastic surgery (OS) has been proposed as adjuvant therapy for CTGM.METHOD: We followed for 1 year every CTGM patients and assessed the efficacy (defined as non-recurrence and no need for corticosteroids) and safety attributable to the standard anti-TB drugs therapy with and without OS.RESULTS: We analysed 128 CTGM cases, including 78 (61%) treated with OS plus anti-TB drugs and 50 (39%) with anti-TB drugs only. We observed a significantly higher efficacy among those exposed vs. unexposed to OS (100% vs. 92%; prevalence ratio [PR] 1.09, 95% CI 1.00-1.18), with no difference in the number of complications (21% vs. 8%; PR 2.56, 95% CI 0.91-7.26). We also observed that the incidence of post-operative complications decreased by 50% when OS was postponed from after Month 1 to after completing Month 2 of anti-TB drugs treatment (19% to 8%; PR 0.46, 95% CI 0.13-1.62).CONCLUSION: OS appears to represent an efficacious and safe adjuvant therapy when combined with anti-TB drugs in the treatment of CTGM patients, but clinical trials are needed to prove this observation.

Proteomic analysis of infected primary human leucocytes revealed PSTK as potential treatment-monitoring marker for active and latent tuberculosis.

Markers for monitoring clearance of Mycobacterium tuberculosis (Mtb) infection during anti-TB drug treatment could facilitate management of tuberculosis (TB) treatment, but are lacking. We aimed to screen for Mtb clearance markers from in-vitro-infected leucocytes and to evaluate these markers in followed-up active TB (ATB) patients and latent TB (LTBI) cases after anti-TB drug treatment. Extracellular proteins from primary leucocytes infected with each of the Mtb lineages (East-Asian, Indo-Oceanic, Euro-American and the laboratory strain H37Rv) were screened as possible clearance markers. Leucocytes infected with Staphylococcus aureus acted as controls. The proteomic analysis was performed using GeLC-MS/MS. Several quantitative and qualitative candidate clearance markers were found. These proteins were suppressed during the infection stage of all Mtb lineages and re-expressed after bacillary clearance. PSTK, FKBP8 and MGMT were common clearance markers among the four Mtb lineages in our model. Only PSTK was a potential clearance marker based on western blot validation analysis from culture supernatants. The PSTK marker was further validated with western blot analysis using serum samples (n = 6) from ATB patients and LTBI cases during anti-TB drug treatment, and from healthy controls (n = 3). Time-dependent increase of PSTK was found both in ATB and LTBI patients during the course of anti-TB drug treatment, but not in healthy controls. We have demonstrated that PSTK is a potential treatment-monitoring marker for active and latent TB.

Oxidative stress biomarkers in pulmonary tuberculosis patients in Gombe, North-eastern Nigeria

Background: Oxidative stress may play an important role in the pathogenesis of pulmonary tuberculosis (PTB). To our knowledge there is paucity of data on the status of oxidative stress biomarkers among PTB patients in Gombe, North-eastern Nigeria. Our study was designed to evaluate the oxidative stress biomarkers in pulmonary tuberculosis patients in Gombe, North-eastern Nigeria.&#x0D; Aims and Objectives: To determine the serum levels of oxidative stress biomarkers among patients with pulmonary tuberculosis in Gombe metropolis, North-eastern Nigeria and to assess the correlation between the oxidative stress biomarkers in pulmonary tuberculosis patients.&#x0D; Materials and Methods: A cross sectional comparative study was conducted in a tertiary health care facility with 40 pulmonary tuberculosis (PTB) patients on anti-TB drugs treatment (ATT), 40 newly diagnosed PTB patients not yet on anti-TB drugs treatment (ATT-naïve) and 40 age- and sex-marched apparently healthy subjects (controls). Serum total antioxidant status (TAS), total oxidant status (TOS), malondialdehyde (MDA), nitric oxide (NO) and oxidative stress index (OSI) determined using standard techniques. Data was analysed using INSTAT® (Graph Pad Software Inc., La Jolla, CA, USA).&#x0D; Results: Serum levels of TOS, OSI, MDA and NO were significantly (p ˂ 0.001) increased in PTB patients (ATT and ATT-naïve) when compared with healthy individuals. Serum TAS and body mass index (BMI) were significantly (p ˂ 0.001) decreased in PTB patients when compared with healthy individuals. Serum TOS significantly correlated with serum OSI, MDA and NO in ATT-naïve PTB patients.&#x0D; Conclusion: This study observed an increased oxidative stress biomarkers and decreased total antioxidant status in newly diagnosed pulmonary tuberculosis patients and those on treatment. Our findings suggest that antioxidants supplementation and improved nutrition in the management of pulmonary tuberculosis patients may go a long way in preventing the oxidative onslaught and further complications in PTB patients.