Search Results (190)

The article analyzes the effects of psychosocial interventions on adherence to tuberculosis (TB) treatment among vulnerable populations in Romania. The study includes 4104 patients from disadvantaged groups (rural, injecting drug users, homeless), beneficiaries of a national multidisciplinary support program. Multivariate analyses conducted on drug-susceptible TB (DS-TB) patients within this cohort identified some predictors of therapeutic success, such as extrapulmonary diagnosis, peer-to-peer educational support, and a higher level of education. At the same time, men, occupationally inactive people and those in the initial phase of treatment at project entry showed lower adherence. The results support the integration of psychosocial interventions in TB management. Full article

Background/Objectives: Tuberculosis (TB) remains a major public health challenge in Davao City, Philippines, with persistent issues in both disease burden and treatment outcomes. Understanding the risk factors for TB and its unsuccessful treatment is essential for guiding effective interventions. This study aimed to evaluate the association of sociodemographic and clinical factors with TB occurrence and to identify predictors of unsuccessful TB treatment outcomes among patients in Davao City. Methods: A retrospective cohort study was conducted using data from 521 patients diagnosed with drug-susceptible TB at Davao Chest Center between January 2021 and May 2024. The sociodemographic and clinical profiles of the patients were described using descriptive statistics. Chi-square tests were used to assess the associations between sociodemographic and clinical variables with TB risk and treatment outcomes. Results: The patient cohort was predominantly aged 31–50 years (n = 201, 38.58%), male (n = 284, 54.51%), and married (n = 285, 54.70%), with most residing in Districts I and II (n = 98, 38% each), and had no previous TB treatment (n = 344, 66.03%). Among the 456 patients assessed for comorbidities, 56.14% (n = 256) had at least one comorbidity. Evaluation of the risk factors for TB occurrence among the study population revealed that comorbidity status was not significantly associated with an increased risk of TB diagnosis (p = 0.682). However, among patients diagnosed with TB, the presence of comorbidities was significantly associated with unsuccessful treatment outcomes (p = 0.003). Conclusions: Although sociodemographic factors did not significantly influence TB risk or treatment outcomes, the presence of comorbidities was a significant predictor of unsuccessful TB treatment. These findings highlight the importance of integrating comorbidity management with TB care to improve treatment success in high-burden urban settings. Full article

Background: Accurate and rapid diagnosis of drug-resistant tuberculosis is essential for initiating appropriate treatment and preventing the transmission of these strains. This study compares phenotypic and genotypic methods of drug susceptibility testing for Mycobacterium tuberculosis (M. tuberculosis). Methods: Resistance to first-line drugs, as well as resistance to second-line drugs (fluoroquinolones and aminoglycosides), was assessed using the Löwenstein–Jensen medium phenotypic method and the GenoType MTBDRplus genotypic method and analyzed. Results: The phenotypic resistance rate was 84.85% for INH (n = 56), 46.97% for RIF (n = 31), 48.48% for STR (n = 32), and 30.30% for EMB (n = 20). Of the MDR-TB isolates (n = 29), 41.37% were resistant to fluoroquinolones (n = 12) and 31.03% were resistant to both fluoroquinolones and injectable aminoglycosides, being classified as XDR-TB (n = 9). In addition, 22.73% of the MDR-TB isolates were resistant to all four first-line drugs (n = 15). The overall concordance between the line probe assay method and phenotypic testing was 94.74% for RIF and 95.16% for INH. Discordances were identified in three cases for RIF and two cases for INH, where isolates were reported as susceptible by GenoType MTBDRplus, but phenotypically resistant. Conclusions: Genotypic testing using GenoType MTBDRplus provides rapid and accurate results, but some cases of phenotypic resistance are not detected by this method. The results highlight the importance of using combined phenotypic and genotypic methods for accurate diagnosis of MDR-TB, as well as the need to integrate genomic sequencing to improve diagnostic accuracy. Full article

Tuberculosis (TB) and undernutrition are intricately linked, significantly impacting health outcomes. However, nutritional support for TB patients is not systematically implemented in Lao People’s Democratic Republic (Lao PDR). This study evaluated the effects of nutritional counselling and support on nutritional recovery and TB treatment outcomes. A longitudinal study involved 297 individuals with drug-susceptible TB, 39.4% of whom had a body mass index (BMI) below 18.5 kg/m². Participants were divided into an observation group and an intervention group, the latter receiving nutritional support. Nutritional support included ready-to-use therapeutic food and therapeutic milk products, tailored to patients’ nutritional status. Data collection was conducted at four intervals during treatment. By the end of treatment, 84.3% of participants improved their nutritional status to a BMI of 18.5 kg/m² or higher. The intervention group showed early nutritional recovery, particularly during the intensive phase of TB treatment, although the p-value (p = 0.067) should be interpreted with caution. The overall treatment success rate was high at 90.6%, with no significant difference between groups. Factors associated with treatment success included age under 45, HIV-negative status, a BMI of 18.5 kg/m² or higher, and clinically diagnosed pulmonary TB. Further assessment is required for the operational feasibility to provide systematic nutritional assessment and counselling for people with TB in Lao PDR. Full article

Objectives: To investigate epidemiological/drug-resistance characteristics and identify potential factors related to drug-resistant and clustered tuberculosis in Sichuan. Methods: A total of 295 Mycobacterium tuberculosis (MTB) isolates were collected from surveillance sites in Sichuan from 2019 to 2021. The minimum inhibitory concentrations (MICs) of 12 anti-TB drugs were acquired using the broth microdilution method, followed by whole-genome sequencing (WGS) analysis. Results: Of 268 MTB isolates with both WGS and drug-susceptibility testing (DST) results, 159 (59.3%, 159/268) strains belonged to the Beijing lineage (L2). Isoniazid had the highest resistance rate (15.3%, 41/268), followed by rifampicin (9.3%, 25/268). The sensitivity of WGS to predict drug resistance varied from 75% to 97.6%, and the specificity was above 96.0% for all. rpoB Ser450Leu (41.7%, 10/24) and katG Ser315Thr (70%, 28/40) were the most frequent mutations in rifampicin and isoniazid resistance isolates, respectively. The clustering rate in Sichuan was 9.3% (25/268), and patients ≤ 24 years old (aOR = 11.697; 95% CI: 0.817–167.463) had a greater risk of clustering. Conclusions: Our findings prove that WGS is a promising tool for predicting drug resistance to isoniazid, rifampicin, ethambutol, moxifloxacin and levofloxacin in Sichuan. The higher resistance rate to isoniazid emphasizes the urgent need for susceptibility testing surveillance and application management. Improving the diagnosis, treatment and management of patients ≤ 24 years old may reduce the transmission of MTB in Sichuan. Full article

Tuberculosis (TB), primarily caused by Mycobacterium tuberculosis complex (MTBC), remains a global health challenge and can lead to severe pulmonary and extrapulmonary complications. Multidrug-resistant TB (MDR-TB) poses additional challenges, requiring advanced diagnostic and treatment strategies. This study evaluates the BD MAX MDR-TB molecular test for a rapid diagnosis of MDR-TB, detecting resistance to rifampicin (RIF) and isoniazid (INH). The BD MAX MDR-TB test, utilizing real-time PCR, was used to analyze specimens collected from TB-suspected patients, identifying MTB DNA and mutations associated with rifampicin and isoniazid resistance. Results were compared with traditional drug susceptibility testing, and 79 out of 638 samples tested were positive for MTB DNA, with 65 showing a sufficient amount of genetic material for resistance gene identification. The BD MAX test showed a 100% correlation with phenotypic rifampicin resistance, though discrepancies were noted for isoniazid resistance, with a 93% concordance. The BD MAX MDR-TB test is an effective tool for a rapid diagnosis of MDR-TB, especially for rifampicin resistance. However, it may not detect certain mutations related to isoniazid resistance. Complementary tests like Xpert MTB/XDR or whole-genome sequencing could improve diagnostic accuracy and support more effective TB control strategies. Full article

Background and Objectives: Tuberculosis (TB) is one of the most common infectious diseases in developing countries. The resistance of the causative agent, Mycobacterium tuberculosis, to two or more first-line anti-TB drugs results in multidrug-resistant (MDR) TB, posing a serious challenge to the control of TB worldwide. This study was designed to determine the changes in drug resistance over time in TB strains isolated from patients in all departments of Uludağ University Hospital in western Türkiye. Materials and Methods: We retrospectively analyzed 104,598 clinical samples sent to our laboratory for the investigation of the presence of TB between 1996 and 2023. BACTEC 460 TB, BACTEC MGIT 960 culture systems and Löwenstein–Jensen medium were used for the culture of these samples. The susceptibility of M. tuberculosis complex strains grown in culture to isoniazid (INH) (0.1 μg/mL), rifampicin (RIF) (1.0 μg/mL), ethambutol (ETB) (5.0 μg/mL) and streptomycin (SM) (1.0 μg/mL) antibiotics was studied according to the manufacturer’s recommendation. Results: Out of 104,598 patient samples, 2752 (2.6%) were culture-positive, and the susceptibility test results of 1869 of these were analyzed. Of the isolates, 358 (19.2%) were found to be resistant to at least one first-line drug, i.e., INH, RIF, ETB, or SM. In addition, 2.9% were resistant to two or more first-line drugs. Conclusions: Drug susceptibility testing is essential to ensure the optimal treatment and control of drug-resistant TB strains. This study highlights the value of ongoing efforts to control tuberculosis drug resistance in the fight against this disease. Full article

During 2022, AIDS claimed a life every minute and about 9.2 million HIV-infected people were not on treatment. In addition, a person living with HIV is estimated to be 20–30 times more susceptible to developing active tuberculosis. Every year, 130,000 infants are newly infected, with vertical transmission being the main cause of pediatric HIV infection. Thus, the development of an effective, safe, and accessible vaccine for neonates and/or adults is an urgent need to prevent or control HIV infection or progression to AIDS. An effective HIV vaccine should induce long-lasting mucosal immunity, broadly neutralizing antibodies, innate immunity, and robust stimulation of CD4+ and CD8+ T-cell responses. Recombinant BCG is a promising live-attenuated bacterial vaccine vector because of its capacity to stimulate T-cell immunity. As a slow-growing microorganism, it provides prolonged low-level antigenic exposure upon infecting macrophages and APCs, potentially stimulating both effector and memory T-cell responses. BCG is considered safe and is currently administered to 80% of infants in countries where it is part of the national immunization program. Additionally, BCG offers several benefits as a live vaccine vehicle since it is cost-effective, easy to mass-produce, and heat stable. It is also well-suited for newborns, as maternal antibodies do not interfere with its efficacy. Furthermore, BCG has a strong safety profile, having been administered to over three billion people as a TB vaccine. In this review, we provide an extensive summary of the literature relating to immunogenicity studies in animal models performed since 2011. Moreover, we provide a comprehensive analysis of the key factors influencing the design of recombinant BCG as a live vaccine vehicle: (i) expression vectors; (ii) selection of HIV immunogen; (iii) promoters to regulate gene expression; (iv) BCG strain and BCG codon optimization; (v) genetic plasmid stability; (vi) influence of preexisting immunity, route, and dose immunization; and (vii) safety profile. Full article

Tuberculosis remains a significant health issue in Mexico, which has one of the highest incidence rates in the Americas. This study aimed to analyze the circulating sublineages, spoligotypes, drug resistance, and transmission patterns of Mycobacterium tuberculosis in Mexico’s Central Western region using whole-genome sequencing. Seventy-seven Mycobacterium tuberculosis strains underwent phenotypic drug susceptibility testing via MGIT. Genotypic resistance was assessed with TB-Profiler and Mykrobe, while phylogenetic relationships were reconstructed using Snippy and RaxML. SpoTyping identified circulating SITs and families, with a 5-SNP threshold defining genomic transmission clusters. The predominant sublineages were 4.1.1.3 (X-type, n = 19) and 4.1.2.1 (LAM, n = 11), with rare sublineages (EAI5, EAI2-Manila, and Beijing) also observed. Resistance to at least one first-line drug was found in 63.3% of strains, with streptomycin mono-resistance (24.5%) being notable. Multidrug-resistant TB was identified in 16.3% (n = 8) of strains. Five genomic clusters, involving 18.7% of strains, were identified. This study highlights the sublineage diversity in Mexico, emphasizing its importance in global databases and resistance research. The findings, such as SIT47 in GC1, underscore the value of localized genomic studies for effective TB control. Full article

Background: Tuberculosis (TB) and diabetes mellitus (DM) comorbidity (TB-DM) presents a significant global health challenge, with diabetes increasing susceptibility to TB, worsening clinical outcomes, and impairing immune responses. Among these dysfunctions, macrophages—the primary immune cells responsible for pathogen recognition, phagocytosis, and bacterial clearance—exhibit profound alterations in TB-DM. However, the complex interplay between metabolic dysregulation, immune impairment, and macrophage dysfunction remains poorly defined. Objective: This scoping review systematically maps the literature on macrophage dysfunction in TB-DM, identifying key immunological impairments affecting phagocytosis, cytokine production, antigen presentation, macrophage polarisation, reactive oxygen species (ROS) and nitric oxide (NO) regulation, and chronic inflammation. Methods: A systematic search was conducted in PubMed, Web of Science, and Embase, covering studies from 2014 to 2024. Inclusion criteria focused on human studies investigating macrophage-specific mechanisms in TB-DM. Data extraction and synthesis were performed using Covidence, with findings grouped into key immunological themes. Results: A total of 44 studies were included, revealing significant impairments in macrophage function in TB-DM. Findings indicate reduced NO production, variable ROS dysregulation, altered M1/M2 polarisation, defective antigen presentation, and chronic inflammation. Elevated IL-10 and VEGF were associated with immune suppression and granuloma destabilisation, while eicosanoids (PGE2, LXA4) contributed to sustained inflammation. Conclusions: Macrophage dysfunction emerges as a central driver of immune failure in TB-DM, creating a self-perpetuating cycle of inflammation, immune exhaustion, and bacterial persistence. Understanding these mechanisms is essential for developing biomarker-driven diagnostics, host-directed therapies, targeted immunomodulation, and improving TB outcomes in diabetic populations. Future research should explore macrophage-targeted interventions to enhance immune function and mitigate TB-DM burden. Full article

Background: Extrapulmonary tuberculosis (TB) presents significant diagnostic challenges, particularly in the context of multidrug-resistant (MDR) strains. This study assessed the utility of the WHO-recommended rapid molecular assays, originally validated for pulmonary TB, in diagnosing extrapulmonary TB and detecting the MDR Mycobacterium tuberculosis complex (MTBC). Materials and Methods: A total of 6274 clinical samples, including 4891 pulmonary and 1383 extrapulmonary samples, were analyzed between 2019 and 2022 using the BD MAX™ MDR-TB assay (BD MAX), the Xpert^® MTB/RIF assay (Xpert MTB/RIF), the Xpert^® MTB/XDR assay (Xpert MTB/XDR), FluoroType MTB, and phenotypic drug susceptibility testing (DST). Results: MTBC was detected in 426 samples using BD MAX (376 pulmonary and 50 extrapulmonary), of which 277 were culture-confirmed. Phenotypic testing confirmed 299 positive cultures on Löwenstein–Jensen (LJ) medium and 347 in BD BACTEC™ MGIT™ (BACTEC MGIT) mycobacterial growth indicator tube (BBL) liquid culture. BD MAX showed high sensitivity and specificity for extrapulmonary TB detection (93.1% and 98.4%, respectively). Resistance to isoniazid or rifampicin was identified in 11% of MTBC-positive cases, whereas 3.69% were confirmed as MDR-TB. The molecular assays effectively detected resistance-associated mutations (katG, inhA, and rpoB), with high concordance to phenotypic tests (DST) (κ = 0.69–0.89). Conclusions: This study demonstrates that molecular assays, although validated for pulmonary TB, are also reliable for extrapulmonary TB detection and drug resistance profiling. Their rapid turnaround and robust accuracy support broader implementation in routine diagnostics, especially for challenging extrapulmonary specimens where early detection is critical for targeted therapy. Full article

Diabetes mellitus (DM) and tuberculosis (TB) are two global health challenges that significantly impact population health, with DM increasing susceptibility to TB infections. However, early risk prediction methods for DM patients complicated with TB (DM–TB) are lacking. This study mined transcriptome data of DM–TB patients from the GEO database (GSE181143 and GSE114192) and used differential analysis, weighted gene co-expression network analysis (WGCNA), intersecting immune databases, combined with ten machine learning algorithms, to identify immune biomarkers associated with DM–TB. An early alert model for DM–TB was constructed based on the identified core differentially expressed genes (DEGs) and validated through a prospective cohort study and reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) for gene expression levels. Furthermore, we performed a detailed immune status analysis of DM–TB patients using the CIBERSORT algorithm. We identified 1090 DEGs associated with DM–TB and further pinpointed CETP (cholesteryl ester transfer protein) (AUC = 0.804, CI: 0.744–0.864), TYROBP (TYRO protein tyrosine kinase binding protein) (AUC = 0.810, CI: 0.752–0.867), and SECTM1 (secreted and transmembrane protein 1) (AUC = 0.811, CI: 0.757–0.864) as immune-related biomarkers for DM–TB patients. An early alert model was developed based on these three genes (AUC = 0.86, CI: 0.813–0.907), with a sensitivity of 0.80829 and a specificity of 0.75758 at a Youden index of 0.56587. External validation using the GSE114192 dataset showed an AUC of 0.901 (CI: 0.847–0.955). Population cohort research and RT-qPCR verified the expression levels of these three genes, demonstrating consistency with trends seen in the training set. KEGG enrichment analysis revealed that NF-κB and MAPK signaling pathways play crucial roles in the DM–TB pathogenic mechanism, and immune infiltration analysis showed significant suppression of certain adaptive immune cells and activation of inflammatory cells in DM–TB patients. This study identified three potential immune-related biomarkers for DM–TB, and the constructed risk assessment model demonstrated significant predictive efficiency, providing an early screening strategy for DM–TB. Full article

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a significant global health challenge, affecting millions annually and leading to substantial mortality, particularly in developing countries. The pathogen’s ability to persist latently and evade host immunity, combined with the emergence of drug-resistant strains, underscores the need for innovative therapeutic strategies. This review highlights the crucial role of interleukin-12 (IL-12) in coordinating immune responses against TB, focusing on its potential as an immunotherapy target. IL-12, a key Th1 cytokine, enhances cellular immunity by promoting Th1 cell differentiation and IFN-γ production, vital for Mtb clearance. By stimulating cytotoxic T lymphocytes and establishing immune memory, IL-12 supports robust host defense mechanisms. However, the complexity of IL-12 biology, including its roles in pro-inflammatory and regulatory pathways, necessitates a nuanced understanding for effective therapeutic use. Recent studies have shown how IL-12 impacts T cell synapse formation, exosome-mediated bystander activation, and interactions with other cytokines in shaping T cell memory. Genetic defects in the IL-12/IFN-γ axis link to susceptibility to mycobacterial diseases, highlighting its importance in TB immunity. The review also addresses challenges like cytokine imbalances seen in TNF-α/IFN-γ synergy, which exacerbate inflammation, and the implications for IL-12-based interventions. Research into modulating IL-12, including its use as an adjuvant and in recombinant vaccines, promises improved TB treatment outcomes and vaccine efficacy. The review concludes by stressing the need for continued investigation into IL-12’s molecular mechanisms towards precision immunotherapies to combat TB and its complications. Full article

Hearing loss remains a significant but underexplored health challenge in individuals with HIV/AIDS, particularly those exposed to occupational noise. The ototoxic effects of antiretroviral therapy (ART) and comorbid conditions like tuberculosis (TB) further compound the risk. This narrative review examines the intersection of HIV/AIDS, ART, and occupational noise-induced hearing loss (ONIHL), emphasizing the South African and broader African contexts. The aim of the study was to map the existing literature on the association between HIV/AIDS, its treatments, and ONIHL, and to identify research gaps to inform policy and clinical practice. A narrative review approach was adopted, systematically searching databases including PubMed, Scopus, and Web of Science. Studies published between 2000 and 2024 were included, focusing on the effects of HIV/AIDS, ART, and occupational noise exposure on hearing health. Data extraction and thematic synthesis were performed to identify key findings and gaps. Twenty studies were included, covering diverse settings such as South Africa, Cameroon, Tanzania, and the USA. Three key themes emerged: (1) dual burden of HIV and occupational noise exposure: HIV-positive individuals in noise-intensive industries, such as mining, face amplified risks of hearing loss due to immunological compromise and ototoxic TB treatments; (2) ototoxicity of ART: older ART regimens, widely used in resource-limited settings, are associated with a higher prevalence of sensorineural hearing loss (SNHL); and (3) immunological susceptibility to ONIHL: HIV-related immune suppression exacerbates cochlear damage from noise and ototoxic agents, contributing to both peripheral and central auditory dysfunction. This review highlights the urgent need for integrated hearing health interventions in HIV care and occupational health frameworks, particularly in high-prevalence regions like South Africa. Routine audiological assessments, access to safer ART regimens, and enhanced workplace protections are essential to mitigate the dual burden of HIV/AIDS and ONIHL. Future research should prioritize longitudinal studies and innovative, low-cost solutions for resource-limited settings. Full article

Background/Objectives: Mitochondrial dysfunction has been implicated in the pathogenesis of tuberculosis (TB). Despite emerging evidence of the importance of mitochondrial gene regulation in the immune response, the specific role of mitochondrial-related genes in TB susceptibility remains to be fully elucidated. Methods: We employed a multi-omics approach integrating genetic, methylation, and protein-level data. Mendelian randomization (MR) and colocalization analyses were conducted to explore causal associations between mitochondrial gene features—expression quantitative trait loci (eQTL), methylation quantitative trait loci (mQTL), and protein quantitative trait loci (pQTL)—and TB susceptibility. Data were obtained from the FinnGen cohort and validated using independent datasets. Results: Our analyses identified several key mitochondrial genes (e.g., ACSF3, AK3, LYRM4, and PDHB) significantly associated with TB susceptibility. Random forest analysis and gene set enrichment analysis (GSEA) supported the predictive power of these genes. Furthermore, we observed significant correlations between mitochondrial gene expression and immune cell infiltration in TB patients, suggesting a role of these genes in modulating immune responses during infection. Receiver operating characteristic (ROC) analysis confirmed strong predictive accuracy for the identified feature genes, with area under the curve (AUC) values exceeding 0.7. Conclusions: This study demonstrates that mitochondrial-related gene regulation influences TB susceptibility across genetic, methylation, and protein levels. The integration of multi-omics data provides valuable insight into the molecular mechanisms underlying TB, highlighting the potential of mitochondrial genes as biomarkers and therapeutic targets. Full article