Tuberculosis Therapy Research Articles

Solid dispersions of bedaquiline fumarate to improve its pharmaceutical attributes: A comparative study between PEG and PVP

ObjectivesThe therapeutic delivery of hydrophobic drugs via solid dispersion is an appealing methodology to enhance the dissolution rate and ultimately the in vivo bioavailability. The objective of current investigation was to enhance the solubility of anti-tubercular drug bedaquiline fumarate (BQF) via solid dispersion strategy, where the influence of polyethylene glycol and polyvinylpyrrolidone on the performance of solid dispersions was determined. MethodsBQF-solid dispersions with polyethylene glycol and polyvinylpyrrolidone were fabricated via solvent evaporation technique and evaluated for solubility, in vitro dissolution studies, cytotoxicity, cellular uptake, intestinal permeability, and pharmacokinetics. ResultsSolubility of BQF was improved by 6.4-fold and 13.44-fold with polyethylene glycol and polyvinylpyrrolidone-based ternary solid dispersions, respectively. The in vitro dissolution studies revealed significant enhancement in dissolution rate of BQF. The in vivo pharmacokinetic results demonstrated that solid dispersions significantly improved the pharmacokinetic parameters of BQF. The relative bioavailability of BQF with polyvinylpyrrolidone-based ternary solid dispersion was found to be enhanced by 173% and 154%, under fasted and fed state, respectively, when compared to BQF suspension. ConclusionsOur study reaffirms the applicability of solid dispersions as an alternative formulation strategy to improve the biopharmaceutical attributes of BQF in tuberculosis therapy.

Relationship between metformin use and mortality in tuberculosis patients with diabetes: a nationwide cohort study.

To determine whether metformin, which is considered a host-directed therapy for tuberculosis (TB), is effective in improving the prognosis of patients with TB and diabetes mellitus (DM), who have higher mortality than those without DM. This cohort study included patients who were registered as having TB in the National Tuberculosis Surveillance System. The medical and death records of matched patients were obtained from the National Health Information Database and Statistics Korea, respectively, and data from 2011 to 2017 were collected retrospectively. We classified patients according to metformin use among participants who used diabetes drugs for more than 28 days. The primary outcome was all-cause mortality during TB treatment. Double propensity score adjustment was applied to reduce the effects of confounding and multivariable Cox proportional hazard models were used to estimate adjusted hazard ratio (aHR) with 95% confidence interval (CI). The all-cause mortality rate during TB treatment was lower (9.5% vs. 12.4%, p < 0.01) in the metformin user group. The hazard of death due to all causes after double propensity score adjustment was also lower in the metformin user group (aHR 0.76, 95% CI 0.67-0.86, p < 0.01). There was no significant difference in mortality between metformin users and non-users for TB-related deaths (p = 0.22); however, there was a significant difference in the non-TB-related deaths (p < 0.01). Metformin use in patients with TB-DM co-prevalence is associated with reduced all-cause mortality, suggesting the potential for metformin adjuvant therapy in these patients.

A high-throughput target-based screening approach for the identification and assessment of Mycobacterium tuberculosis mycothione reductase inhibitors.

The growing anti-microbial resistance poses a global public health threat, impeding progress toward eradicating tuberculosis. Despite decades of active research, there is still a dire need for the discovery of drugs with novel modes of action and exploration of combination drug regimens. Within the European RespiriTB consortium, we explore Mycobacterium tuberculosis energy metabolism to identify new drug candidates that synergize with bedaquiline, with the aim of discovering more efficient combination drug regimens. In this study, we present the development of a high-throughput screening pipeline that led to the identification of M. tuberculosis mycothione reductase inhibitors.

A modern approach to surgical tactics in patients with residual post-tuberculosis changes of lungs

In patients with residual changes after the treatment of destructive forms of tuberculosis (TB), the risk of recurrence of the disease increases significantly. The study of the surgical material of patients with pulmonary TB as a result of the progression of residual post-tuberculosis changes a year or more after the completion of anti-tuberculosis therapy makes it possible to justify the need for surgery in this category of patients. Objective. To substantiate surgical tactics in patients with residual post-tuberculosis lung changes. Materials and methods. The analysis of 1121 adult patients who underwent surgery from 2015 to 2021 for etiologically verified pulmonary TB and completed anti-tuberculosis therapy more than a year before the operation. Of these, 176 patients were divided into two comparable groups: the main group included 37 patients in whom non-tuberculosis mycobacteria (NTMB) DNA was found in the surgical material, the comparison group included 139 patients in whom NTMB was not found in the surgical material. All patients underwent a comprehensive microbiological and morphological examination of the surgical material. Results. In the comparison group, in the majority of operated patients with microbiological screening of surgical material, the etiological diagnosis was positive: the most informative method for both destructive forms of pulmonary TB and forms without destruction was the real-time PCR method: in 82.0% and 87.2% of positive results, respectively, and luminescent microscopy, which allowed to identify acid-resistant Mycobacteria in 67.2% of cases with destructive forms of TB and in 73.1% – without lung destruction In the comparison group, in 19 (13.2%) patients, no evidence of TB was obtained by any screening method, but morphologic examination of surgical material showed the presence of TB inflammation with high activity in 11 (58.0%) and moderate activity in 8 (42.0%) patients. In the main group species identification of NTMB in the surgical material was obtained in the majority of cases, both in forms without destruction of lung tissue and in destructive forms – in 72.2 and 63.3% of patients, respectively, slow-growing NTMB prevailing. Fast-growing NTMB were detected in isolated cases. Morphological examination of the surgical material in a group of patients with NTMB revealed structural changes in the lungs that affected the air parenchyma and/or small airways in areas of the lungs free from TB foci, which should be taken into account when planning surgical intervention. Conclusion. Surgical treatment immediately after completion of the course of anti-tuberculosis therapy in case of formation of residual post-tuberculosis changes is the method of choice in the complex treatment of this category of patients.

Kidney transplantation in patients on anti-tubercular therapy: A single centre observational study.

Tuberculosis (TB) is a common infection in chronic kidney disease. The prolonged therapy of TB can delay kidney transplantation in patients on antitubercular therapy (ATT). This was a retrospective single-center study to analyze the safety of kidney transplantation and its outcomes in patients undergoing transplantation while on the continuation phase of ATT. Between 2013 and 2022, 30 patients underwent kidney transplantation while on ATT. Median age was 38 years and 70% were males. Majority of the patients (86.7%) had extrapulmonary tuberculosis, most common site of involvement being tubercular lymphadenitis. 14/30 patients had microbiological/histopathological diagnosis of TB and the rest were diagnosedby ancillary tests. Patients were treated with 4 drug ATT (isoniazid, rifampicin, pyrazinamide, ethambutol) before transplantation for aminimum of 2 months. Post-transplantation fluoroquinolone-based non-rifamycin ATT was used (median duration 11 months). All patients completed therapy. At 2 years, there was 100% patient survival and 96.7% graft survival. Median eGFR at 6, 12, and 24 months post-transplantation was 71.9, 64.7, and 67mL/min/1.73m2, respectively. The percentage of patients suffering a biopsy proven acute rejection at 6, 12, and 24 months was 3.3%, 6.7%, and 6.7%. Kidney transplantation can be done in patients with TB who have a satisfactory response to the intensive phase of the ATT. The decision for transplantation while on the continuation phase ofATT should be individualized. In our experience, there is excellent patient and graft survival in these patients with a low risk of failure of ATT or relapse of TB.

Hubungan Karakteristik Sosiodemografi dengan Hasil Terapi Tuberkulosis Paru di RSUD Banyumas

Pulmonary tuberculosis (TB) is one of the infectious diseases caused by Mycobacterium tuberculosis and is one of the highest causes of morbidity and mortality rates with a low level of treatment outcome. Indonesia is the second country in the world with the largest tuberculosis burden. This study aims to determine the relationship of sociodemographic characteristics with the results of pulmonary tuberculosis therapy at Banyumas Regional Public Hospital for the period 2019-2021. This study used a case-control method. The inclusion criteria in this study were new pulmonary tuberculosis patients at the Banyumas Regional Public Hospital and patients aged ≥18 years, both male and female. Multi-drug resistance (MDR) TB patients and patients with incomplete medical record data were excluded. There were 166 patients enrolled in this study. Data analysis was performed by univariate analysis and bivariate analysis by chi-square test. The results showed that the sociodemographic characteristics were dominated by male patients (57,2%), patients aged &lt;65 years (66,3%), patients weighing &lt;55 kg (53%), not graduating from college (94%), currently working (64,5%), married (68,7%), have health insurance (94%), and close distance (&lt;10 km) to the hospital (53%). The conclusion is that gender ((P=0,028; OR 2,112; 95%Cl(1,129 – 3,951)), age (P=0,014; OR 2,413; 95% Cl (1,242 – 4,689)), body weight (P=0,000; OR 3,306; 95%Cl (1,748 – 6,252)), and distance from the patient's house to the hospital (P=0,020; OR 2,190; 95% CI (1,176 – 4,077)) have a significant relationship with the outcome of pulmonary TB therapy at Banyumas Regional Public Hospital.

Prediction Models for Adverse Drug Reactions During Tuberculosis Treatment in Brazil.

Tuberculosis (TB) treatment-related adverse drug reactions (TB-ADRs) can negatively affect adherence and treatment success rates. We developed prediction models for TB-ADRs, considering participants with drug-susceptible pulmonary TB who initiated standard TB therapy. TB-ADRs were determined by the physician attending the participant, assessing causality to TB drugs, the affected organ system, and grade. Potential baseline predictors of TB-ADR included concomitant medication (CM) use, human immunodeficiency virus (HIV) status, glycated hemoglobin (HbA1c), age, body mass index (BMI), sex, substance use, and TB drug metabolism variables (NAT2 acetylator profiles). The models were developed through bootstrapped backward selection. Cox regression was used to evaluate TB-ADR risk. There were 156 TB-ADRs among 102 of the 945 (11%) participants included. Most TB-ADRs were hepatic (n = 82 [53%]), of moderate severity (grade 2; n = 121 [78%]), and occurred in NAT2 slow acetylators (n = 62 [61%]). The main prediction model included CM use, HbA1c, alcohol use, HIV seropositivity, BMI, and age, with robust performance (c-statistic = 0.79 [95% confidence interval {CI}, .74-.83) and fit (optimism-corrected slope and intercept of -0.09 and 0.94, respectively). An alternative model replacing BMI with NAT2 had similar performance. HIV seropositivity (hazard ratio [HR], 2.68 [95% CI, 1.75-4.09]) and CM use (HR, 5.26 [95% CI, 2.63-10.52]) increased TB-ADR risk. The models, with clinical variables and with NAT2, were highly predictive of TB-ADRs.

The uncharted territory of host-pathogen interaction in tuberculosis.

Mycobacterium tuberculosis (M.tb) effectively manipulates the host processes to establish the deadly respiratory disease, Tuberculosis (TB). M.tb has developed key mechanisms to disrupt the host cell health to combat immune responses and replicate efficaciously. M.tb antigens such as ESAT-6, 19kDa lipoprotein, Hip1, and Hsp70 destroy the integrity of cell organelles (Mitochondria, Endoplasmic Reticulum, Nucleus, Phagosomes) or delay innate/adaptive cell responses. This is followed by the induction of cellular stress responses in the host. Such cells can either undergo various cell death processes such as apoptosis or necrosis, or mount effective immune responses to clear the invading pathogen. Further, to combat the infection progression, the host secretes extracellular vesicles such as exosomes to initiate immune signaling. The exosomes can contain M.tb as well as host cell-derived peptides that can act as a double-edged sword in the immune signaling event. The host-symbiont microbiota produces various metabolites that are beneficial for maintaining healthy tissue microenvironment. In juxtaposition to the above-mentioned mechanisms, M.tb dysregulates the gut and respiratory microbiome to support its replication and dissemination process. The above-mentioned interconnected host cellular processes of Immunometabolism, Cellular stress, Host Microbiome, and Extracellular vesicles are less explored in the realm of exploration of novel Host-directed therapies for TB. Therefore, this review highlights the intertwined host cellular processes to control M.tb survival and showcases the important factors that can be targeted for designing efficacious therapy.

Shorter antitubercular therapy for extrapulmonary tuberculosis - a case report

IntroductionExtrapulmonary tuberculosis (EPTB) adds to India’s significant economic burden, with pericardial effusion being a potentially fatal complication. This case report highlights the need for early diagnosis and the feasibility of shorter-duration treatment for EPTB in developing countries.PresentationThis case report describes a 19-year-old male from Southeast Asia who had a history of bronchiectasis involving the left lower lobe and the right middle lobe, which was cystic in nature, as well as multiple episodes of non-tuberculous pneumonia. Currently, he presented with fever, hypotension, tachycardia, and acute kidney injury. Echocardiogram showed left ventricular dysfunction with a left ventricular ejection fraction (LVEF) of 45% and moderate pericardial effusion. Early signs of cardiac tamponade were noted, specifically the absence of respiratory variation in the right ventricle and left ventricle collapse. Emergent pericardiocentesis was performed, and hemorrhagic pericardial fluid was aspirated. Fluid analysis revealed high levels of LDH (5000 U/L), polymorphonuclear leukocytosis, and acid-fast bacilli that were visualized on microscopy, which led to the diagnosis of pericardial tuberculosis. A CT of the abdomen showed hepatosplenomegaly and polyserositis. Empirically, antitubercular therapy consisting of isoniazid, rifampin, pyrazinamide, and ethambutol was administered for 2 months and isoniazid along with rifampicin was given for the next 4 months. Serial echocardiograms in the following months showed an improvement in LVEF (55%) and decreased effusion. However, during this treatment period, due to frequent episodes of pneumonia, the evaluation of immunodeficiency disorders was performed and revealed low levels of IgG (4.741 g/L), IgA (0.238 g/L), and IgM (0.098 g/L). He was diagnosed with common variable immunodeficiency disease and received intravenous immunoglobulin therapy.ConclusionThis report emphasizes the timely identification of cardiac tamponade and the effective management of EPTB through a shorter-than-recommended course of antitubercular therapy, resulting in the alleviation of symptoms and better overall health outcomes.

The body mass index profiles in chronic pulmonary aspergillosis: trend and variability in post tuberculosis patients

Tuberculosis (TB) is the main risk factor for chronic pulmonary aspergillosis, especially in patients with residual cavitary lesions after completion of TB therapy. The body mass index (BMI) is one of the established markers in predicting the mortality of CPA. However, the data regarding BMI profiles of CPA patients in Indonesia is still limited. We evaluated the BMI profiles of CPA patients among post-TB patients. Patients diagnosed as CPA based on clinical, radiology and the Aspergillus IgG test. 50 patients were included with a mean age of 35 years; 13 patients met the criteria of CPA. The overall median of BMI in these patients was 21. The median BMI in the CPA group was 19,3. The lowest (19,8) median BMI value was observed in the positive Aspergillus IgG group (11,5 – 30 mg/L) with a minimum BMI of 14,7 and a maximum BMI of 29,2. The differences in median BMI across CPA and non CPA groups and Aspergillus IgG level were not statistically significant. However, there is a trend that lower BMI were distributed among patients with positive Aspergillus IgG. More than one third of CPA patients in this study were classified as underweight. Future study is necessary to better depict the BMI profiles in larger scale of populations of CPA in Indonesia in order to achieve better diagnosis and management of CPA.

Host-directed therapy against mycobacterium tuberculosis infections with diabetes mellitus.

Tuberculosis (TB) is caused by the bacterial pathogen Mycobacterium tuberculosis (MTB) and is one of the principal reasons for mortality and morbidity worldwide. Currently, recommended anti-tuberculosis drugs include isoniazid, rifampicin, ethambutol, and pyrazinamide. TB treatment is lengthy and inflicted with severe side-effects, including reduced patient compliance with treatment and promotion of drug-resistant strains. TB is also prone to other concomitant diseases such as diabetes and HIV. These drug-resistant and complex co-morbid characteristics increase the complexity of treating MTB. Host-directed therapy (HDT), which effectively eliminates MTB and minimizes inflammatory tissue damage, primarily by targeting the immune system, is currently an attractive complementary approach. The drugs used for HDT are repositioned drugs in actual clinical practice with relative safety and efficacy assurance. HDT is a potentially effective therapeutic intervention for the treatment of MTB and diabetic MTB, and can compensate for the shortcomings of current TB therapies, including the reduction of drug resistance and modulation of immune response. Here, we summarize the state-of-the-art roles and mechanisms of HDT in immune modulation and treatment of MTB, with a special focus on the role of HDT in diabetic MTB, to emphasize the potential of HDT in controlling MTB infection.

Towards pharmacogenomics-guided tuberculosis (TB) therapy: N-acetyltransferase-2 genotypes among TB-infected Kenyans of mixed ethnicity

BackgroundThough persons of African descent have one of the widest genetic variability, genetic polymorphisms of drug-metabolising enzymes such as N-Acetyltransferase-2 (NAT2) are understudied. This study aimed to identify prevalent NAT2 single nucleotide polymorphisms (SNPs) and infer their potential effects on enzyme function among Kenyan volunteers with tuberculosis (TB) infection. Genotypic distribution at each SNP and non-random association of alleles were evaluated by testing for Hardy-Weinberg Equilibrium (HWE) and Linkage Disequilibrium (LD).MethodsWe isolated genomic DNA from cryopreserved Peripheral Blood Mononuclear Cells of 79 volunteers. We amplified the protein-coding region of the NAT2 gene by polymerase chain reaction (PCR) and sequenced PCR products using the Sanger sequencing method. Sequencing reads were mapped and aligned to the NAT2 reference using the Geneious software (Auckland, New Zealand). Statistical analyses were performed using RStudio version 4.3.2 (2023.09.1 + 494).ResultsThe most frequent haplotype was the wild type NAT2*4 (37%). Five genetic variants: 282C > T (NAT2*13), 341 T > C (NAT2*5), 803A > G (NAT2*12), 590G > A (NAT2*6) and 481C > T (NAT2*11) were observed with allele frequencies of 29%, 18%, 6%, 6%, and 4% respectively. According to the bimodal distribution of acetylation activity, the predicted phenotype was 76% rapid (mainly consisting of the wildtype NAT2*4 and the NAT2*13A variant). A higher proportion of rapid acetylators were female, 72% vs 28% male (p = 0.022, odds ratio [OR] 3.48, 95% confidence interval [CI] 1.21 to 10.48). All variants were in HWE. NAT2 341 T > C was in strong complete LD with the 590G > A variant (D′ = 1.0, r2 = − 0.39) but not complete LD with the 282C > T variant (D′ = 0.94, r2 = − 0.54).ConclusionThe rapid acetylation haplotypes predominated. Despite the LD observed, none of the SNPs could be termed tag SNP. This study adds to the genetic characterisation data of African populations at NAT2, which may be useful for developing relevant pharmacogenomic tools for TB therapy. To support optimised, pharmacogenomics-guided TB therapy, we recommend genotype-phenotype studies, including studies designed to explore gender-associated differences.

Research on Services Requests and Utilisation Status and Satisfaction in a Family Health Center in Istanbul

Aim: In the family practice, the family doctor accompanied with the family health center employee renders integrated services to people registered in their department from physical, psychological and social points. The purpose of this research is to investigate the cognition, utilization, and satisfaction state of family practice services by the public of a family health center found at any district of Istanbul. Method: The research in question was done at the prefecture of Istanbul, at a family health center between the dates September 2013 and January 2014. We have applied the Cognition, Utilization and Satisfaction State of services survey (HBYMDA) developed by the researcher, we have collected data through the face-to-face method and applied the Patients Evaluate General/ Family Practice (EUROPEP) survey. The total points for HBYMDA was 24. Whereas the total point for EUROPEP was 115. Results: 302 (76%) of the persons who participated in the survey were women, and 98 (24%) men. The average age of the group was 37.17±14.10 years. The average age of women was 42±13.04 and 42.57±15.85 for men. The average of the total points for HBYMDA was calculated as 11.54±5.80. The average total point of EUROPEP was 93.87±21.32. The services that persons know the most, use the most and are satisfied the most are listed respectively, as following inspection, diagnosis and therapy, injection and medical dressing services, emergency services, free laboratory services. Whereas the services that participants know the less, use the less and are satisfied the less are listed respectively as following therapy of tuberculosis through direct observation, taking measures concerning contagious disease towards people and environment, military examination, and periodic examination. Conclusion: It is determined that the group of low social-economical-cultural uses more family practice services and that situation is related to the knowing, utilization and satisfaction state of the services.

Tuberculosis treatment monitoring tests during routine practice: study design guidance

ScopeThe current tools for tuberculosis (TB) treatment monitoring, smear microscopy and culture, cannot accurately predict poor treatment outcomes. Research into new TB treatment monitoring tools (TMTs) is growing, but data are unreliable. In this article, we aim to provide guidance for studies investigating and evaluating TB TMT for use during routine clinical care. Here, a TB TMT would guide treatment during the course of therapy, rather than testing for a cure at the regimen's end. This article does not cover the use of TB TMTs as surrogate endpoints in the clinical trial context. MethodsGuidelines were initially informed by experiences during a systematic review of TB TMTs. Subsequently, a small content expert group was consulted for feedback on initial recommendations. After revision, feedback from substantive experts across sectors was sought. Questions addressed by the guideline and RecommendationsThe proposed considerations and recommendations for studies evaluating TB TMTs for use during the treatment in routine clinical care fall into eight domains. We provide specific recommendations regarding study design and recruitment, outcome definitions, reference standards, participant follow-up, clinical setting, study population, treatment regimen reporting, and index tests and data presentation. Overall, TB TMTs should be evaluated in a manner similar to diagnostic tests, but TB TMT accuracy must be assessed at multiple timepoints throughout the treatment course, and TB TMTs should be evaluated in study populations who have already received a diagnosis of TB. Study design and outcome definitions must be aligned with the developmental phase of the TB TMT under evaluation. There is no reference standard for TB treatment response, so different reference standards and comparator tests have been proposed, the selection of which will vary depending on the developmental phase of the TMT under assessment. The use of comparator tests can assist in generating evidence. Clarity is required when reporting of timepoints, TMT read-outs, and analysis results.Implementing these recommendations will lead to higher quality TB TMT studies that will allow data to be meaningfully compared, thereby facilitating the development of novel tools to guide individual TB therapy and improve treatment outcomes.

Defining the end point of drug therapy in tuberculosis of spine: Analysis of 76 cases in a tertiary care centre

Abstract Background: The duration of chemotherapy for the tubercular spine is an unresolved issue. Various drug regimens have been used for various durations. Objectives: (1) To calculate the duration of antitubercular therapy (ATT) for achieving the healed status of the tubercular spine, (2) to report the behavior of kyphotic deformity, and (3) outcome of neurological deficit. Materials and Methods: This longitudinal descriptive study included 76 cases of tubercular spine diagnosed on clinico-imaging and/or on histopathology/molecular tests. They were treated as per the DOTS regime. Surgery was done for predetermined indications. ATT was stopped once healed status was demonstrated on CE-MRI/PET-CT. Kyphotic deformity was measured by modified Konstam’s method, and neurological grading was assessed by Tuli’s grading. Results: The mean duration of healing was 20.08 ± 8.09 months (range 9–48 months) in primary spinal TB with no recurrence after the mean follow-up of 15 months (range 3–108 months). Overall, 92.6% showed good neural outcomes at the final follow-up. Mean kyphotic deformity was found to be 16.75° ± 12.23°, 18.78° ± 12.62°, and 18.78° ± 12.53° at presentation, after stopping ATT and at the final follow-up. Conclusion: It is unscientific to stop ATT in spinal TB till healed status is demonstrated by contrast-enhanced MRI or PET-CT. Although the sample size is small, the data is enough to prove this point that if all patients were treated till healed status was achieved, there would be no recurrence.

Pathophysiological features of reparative processes in adjuvant therapy of renal tuberculosis with extracellular vesicles in an experiment

Currently, various studies are focusing on the potential of stem cells as adjuvant therapy for tuberculosis. In addi-tion, there is significant interest in the use of extracellular vesicles (EVs), since compared with whole-cell therapy, EVs derived from mesenchymal stromal cells (MSCs) have many advantages such as good tolerability, low immuno-genicity, no risk of malignancy, more stable membrane structure than MSCs, etc. These advantages open up broad prospects for the treatment of a large number of diseases. In the present study, we investigated the protein composition of extracellular vesicles and assessed their therapeutic potential in a rabbit model of renal tuber-culosis in combination with standard anti-TB treatment. Materials and methods. The study involved 20 rabbits with renal tuberculosis, which were intravenously injec-ted with extracellular vesicles isolated from mesenchymal stem cells. Therapeutic efficacy was assessed by analyzing changes in the level of anti- and pro-inflammatory cyto-kines, as well as by computed tomography of the kidneys with subsequent histological and morphometric examina-tion. The protein composition of extracellular vesicles was determined using liquid chromatography and mass spec-trometry. Results. The addition of extracellular vesicles to standard anti-tuberculosis treatment resulted in a statis-tically significant increase in anti-inflammatory cytokines and a decrease in pro-inflammatory cytokines, as well as a significant decrease in the area of specific inflammation compared to groups with standard treatment, which was largely due to the proteins included in the extracellular vesicles. Conclusion. The use of extracellular vesicles as a component of complex anti-tuberculosis therapy in-creases the effectiveness of renal tuberculosis treatment by accelerating reparative processes in the area of specific inflammation

LATENT TUBERCULOSIS IN PATIENTS WITH CROHN'S DISEASE IN A UNIVERSITY HOSPITAL IN NORTHEASTERN BRAZIL: A RETROSPECTIVE STUDY.

Among chronic condition problems, tuberculosis still represents a serious public health problem globally. To investigate latent tuberculosis infection in patients with Crohn's disease. Retrospective, descriptive cross-sectional study of quantitative analysis. The research was conducted on diagnosed cases of Crohn's disease at the University Hospital located in a city in Northeastern Brazil. All cases of patients with Crohn's disease undergoing isoniazid or rifampicin therapy for latent tuberculosis (LTBI) were included in the study. The data obtained were subsequently subjected to statistical analysis using the Statistical Package for the Social Sciences (SPSS) program. We analyzed 235 medical records, and it was observed that 56% were male, with a mean age of 42.7. Among these, 54% declared themselves as brown, 31% had completed high school, and 47% were residents of the city of Teresina. Regarding the clinical and epidemiological characteristics of the studied patients classified as having ILTB, 34% of the medical records were diagnosed by tuberculin test, 48.51% were investigated by x-ray examination, and the recent location affected the colon with 27%. Overall, the health profile of the participants in this study aligns with findings previously established in the literature, particularly studies conducted in other Brazilian states, as well as in other developing countries.

Completion rate of tuberculosis preventive therapy and incidence of tuberculosis among people living with the Human Immunodeficiency Virus on antiretroviral therapy in Ekurhuleni East subdistrict, Gauteng province.

the World Health Organization (WHO) has recommended the use of tuberculosis preventive therapy (TPT) as part of a comprehensive care package for the reduction of tuberculosis (TB) incidence among people who are living with human immunodeficiency virus (PLWHA). When used optimally, TPT efficacy ranges between 60% and 90% among adults and children who are living with HIV. Despite the wide adoption of this intervention in South Africa, the country remains heavily burdened with high rates of TB/HIV co-infections, reported to be 59% in 2018. Reported challenges include low uptake and completion rates. This study aimed to determine the TPT completion rate and investigate the incidence of TB among antiretroviral therapy (ART) patients who were initiated on TPT. this descriptive cross-sectional retrospective cohort study was conducted among HIV-positive patients who were on ART, 18 years old and above, and had been initiated on TPT between June 2019 and June 2021 at the selected PHC facilities in Ekurhuleni East sub-District. We conducted record reviews and face-to-face interviews to collect data. These were captured onto a Microsoft Excel spreadsheet, cleaned, and coded before importation onto the Epiinfo version 7 statistical software package for statistical analyses. the study found a majority of female participants, (60.5%). The median age of participants was 39.0 years (IQR=15), with most aged 50 years old and above, (21.3%). The treatment course of TPT was completed at the prescribed 12 months by 196 (30%) of the 395 participants. Only 12 (3%) of the participants were found to have TB, half 6 (50%) of which were breakthrough cases of TB. The reasons for non-completion of TPT included clinicians not offering it to patients, (46/276 (16.7%)). The barriers to TPT completion included not having a treatment supporter, (73.2%); p<0.001, while disclosure of positive HIV status was found to facilitate TPT completion (83.2%); p<0.001. the observed TPT completion rate of 30% needs to be addressed as it is far below the national threshold of 85%. The barriers and facilitators to TPT completion also require attention to help improve the TPT completion rate.

Assessment of Isoniazid Preventive Therapy and Incidence of Tuberculosis among People Living with Human Immunodeficiency Virus Seeking Care in an Anti-retroviral Therapy Center, Puducherry.

One in three deaths among people living with human immunodeficiency virus (PLHIV) is due to Tuberculosis. Isoniazid preventive therapy (IPT) was implemented in antiretroviral therapy (ART) center Puducherry in July 2017. We have determined the proportion of PLHIV who were eligible, initiated, completed IPT and also the incidence of tuberculosis before and after implementation of IPT. It was a facility based longitudinal descriptive study. All PLHIV, aged 10 years and above, seeking care in ART Centers was included. The number of PLHIV eligible, initiated and completed IPT was summarized as proportion with 95% CI. Among the registered PLHIV (999), the proportion of PLHIV those were found eligible for IPT was 93% [95% CI (91.24%-94.67%)] and initiated on IPT was 92% [95% CI (90.20%-93.95%)]. Completion rate of IPT was 96.3% [95% CI (94.59%-97.63%)]. Initiation of IPT was relatively less among newly registered PLHIV as compared to older cohort of PLHIV.

The advances in adjuvant therapy for tuberculosis with immunoregulatory compounds.

Tuberculosis (TB) is a chronic bacterial disease, as well as a complex immune disease. The occurrence, development, and prognosis of TB are not only related to the pathogenicity of Mycobacterium tuberculosis (Mtb), but also related to the patient's own immune state. The research and development of immunotherapy drugs can effectively regulate the body's anti-TB immune responses, inhibit or eliminate Mtb, alleviate pathological damage, and facilitate rehabilitation. This paper reviews the research progress of immunotherapeutic compounds for TB, including immunoregulatory compounds and repurposing drugs, and points out the existing problems and future research directions, which lays the foundation for studying new agents for host-directed therapies of TB.