Search Results (298)

The P1104A variant in the TYK2 gene is recognized as the first common monogenic cause of tuberculosis, and recent studies also suggest a potential role in COVID-19 severity. However, its frequency and impact in admixed Latin American populations remain underexplored. Therefore, we investigated the P1104A/TYK2 variant in a cohort comprising 1826 RT-PCR-confirmed COVID-19 patients from Southern Brazil. Cases were stratified by severity into non-severe (n = 1190) and severe (n = 636). Three homozygous individuals were identified—one non-severe and two severe cases—although no statistically significant association with disease severity was observed. The frequency of the C allele in the COVID-19 cohort (2.85%) was significantly higher than in Brazilian population databases, including “DNA do Brasil” (1.81%, p < 0.001) and ABraOM (2.34%, p = 0.03), but lower than in the multi-ancestry gnomAD database (3.71%, p = 0.01), possibly reflecting ancestry bias. We also observed associations between COVID-19 severity and sex (p = 0.003), age (p < 0.001), obesity (p < 0.001), diabetes (p < 0.001), and hypertension (p < 0.001). Future studies in larger and more diverse cohorts are needed to characterize the prevalence of the variant in admixed populations and assess its contribution to COVID-19 susceptibility. Full article

Background: Disease-modifying drugs (DMDs) for multiple sclerosis (MS) slightly increase the risk of tuberculosis (TB) disease. The QuantiFERON-TB-Plus (QFT-Plus) test is approved for TB infection (TBI) screening. Currently, there are no data available regarding the characterization of QFT-Plus response in patients with MS. Objectives: This study aimed to compare the magnitude of QFT-Plus responses between patients with MS and TBI (MS-TBI) and TBI subjects without MS (NON-MS-TBI). Additionally, discordant responses to TB1/TB2 stimulation were documented. Results were evaluated considering demographic and clinical data, particularly the impact of DMDs and the type of TB exposure. Methods: Patients with MS (N = 810) were screened for TBI (2018–2023). Thirty (3.7%) had an MS-TBI diagnosis, and 20 were recruited for the study. As a control group, we enrolled 106 NON-MS-TBI. Results: MS-TBI showed significantly lower IFN-γ production in response to TB1 (p = 0.01) and TB2 stimulation (p = 0.02) compared to NON-MS-TBI. The 30% of TB2 results of MS-TBI fell into the QFT-Plus grey zone (0.2–0.7 IU/mL). Only 7% of NON-MS-TBI showed this profile (p = 0.002). Conclusions: MS-TBI had a lower QFT-Plus response and more borderline results compared to NON-MS-TBI. Future studies should clarify the significance of the borderline results in this vulnerable population to improve QFT-Plus accuracy regarding sensitivity, specificity, and TB prediction. Full article

Background/Objectives: Mucosal vaccines, delivered intranasally or via inhalation, are being studied for respiratory infectious diseases like COVID-19 and influenza. These vaccines aim to provide non-invasive administration and strong immune responses at infection sites, making them a promising area of research. This systematic review and meta-analysis assessed their immunogenicity, safety, and protective efficacy. Methods: The study design was a systematic review and meta-analysis, searching PubMed and Cochrane databases up to 30 May 2025. Inclusion criteria followed the PICOS framework, focusing on mucosal vaccines for COVID-19, influenza, RSV, pertussis, and tuberculosis. Results: A total of 65 studies with 229,614 participants were included in the final analysis. Mucosal COVID-19 vaccines elicited higher neutralizing antibodies compared to intramuscular vaccines (SMD = 2.48, 95% CI: 2.17–2.78 for wild-type; SMD = 1.95, 95% CI: 1.32–2.58 for Omicron), with varying efficacy by route (inhaled VE = 47%, 95% CI: 22–74%; intranasal vaccine VE = 17%, 95% CI: 0–31%). Mucosal influenza vaccines protected children well (VE = 62%, 95% CI: 30–46%, I² = 17.1%), but seroconversion rates were lower than those of intramuscular vaccines. RSV and pertussis vaccines had high seroconversion rates (73% and 52%, respectively). Tuberculosis vaccines were reviewed systemically, exhibiting robust cellular immunogenicity. Safety was comparable to intramuscular vaccines or placebo, with no publication bias detected. Conclusions: Current evidence suggests mucosal vaccines are immunogenic, safe, and protective, particularly for respiratory diseases. This review provides insights for future research and vaccination strategies, though limitations include varying efficacy by route and study heterogeneity. Full article

This review addresses the urgent need for alternative strategies to combat drug-resistant mycobacterial infections, including multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis, as well as non-tuberculous mycobacterial (NTM) diseases. Traditional antibiotics are increasingly limited by resistance, toxicity, and poor efficacy, particularly in immunocompromised patients. A comprehensive literature search was conducted using PubMed, Scopus, and Google Scholar, covering publications primarily from 2000 to 2025. Only articles published in English were included to ensure consistency in data interpretation. Search terms included “mycobacteriophages,” “phage therapy,” “drug-resistant mycobacteria, “diagnostic phages,” and “phage engineering.” The review examines the therapeutic and diagnostic potential of mycobacteriophages—viruses that specifically infect mycobacteria—focusing on their molecular biology, engineering advances, delivery systems, and clinical applications. Evidence suggests that mycobacteriophages offer high specificity, potent bactericidal activity, and adaptability, positioning them as promising candidates for targeted therapy. Although significant obstacles remain—including immune interactions, limited host range, and regulatory challenges—rapid progress in synthetic biology and delivery platforms continues to expand their clinical potential. As research advances and clinical frameworks evolve, mycobacteriophages are poised to become a valuable asset in the fight against drug-resistant mycobacterial diseases, offering new precision-based solutions where conventional therapies fail. Full article

Background: Development Assistance for Health (DAH) plays a vital role in health financing across Sub-Saharan Africa, particularly in tackling communicable diseases such as HIV/AIDS, malaria, and tuberculosis. Despite its importance, the efficiency and equity of DAH allocation remain contested. Objectives: The study aims to evaluate the cost-effectiveness of DAH in Sub-Saharan Africa from 1995 to 2018, as well as to explore differences in efficiency across diseases and country contexts. Methods: Data were drawn from the Institute for Health Metrics and Evaluation and applied Generalized Cost-Effectiveness Analysis in conjunction with the Gross Domestic Product-based thresholds. Averted Disability-Adjusted Life Years were analyzed across countries and diseases, and countries were categorized by the Human Development Index (HDI) level to assess differential DAH performance. Results: DAH cost-effectiveness showed similar patterns across HDI groups, with roughly equal proportions of cost-effective and dominated outcomes in both low- and middle-HDI countries. Thirteen countries were identified as very cost-effective, nine as cost-effective, and two as non-cost-effective. Twenty-one countries were dominated, reflecting persistent inefficiencies in aid impact that transcends the various levels of development. Conclusions: Tailoring DAH allocation to specific disease burdens and development levels enhances its impact. The study underscores the need for targeted investment and a strategic shift toward integrated health system strengthening. Additionally, microinsurance is highlighted as a key mechanism for improving healthcare access and financial protection in low-income settings. Full article

Background: In the medical field, various deep learning (DL) algorithms have been effectively used to extract valuable information from unstructured clinical text data, potentially leading to more effective outcomes. This study utilized clinical text data to classify clinical case reports into tuberculosis (TB) and non-tuberculosis (non-TB) groups using natural language processing (NLP), a pre-processing technique, and DL models. Methods: This study used 1743 open-source respiratory disease clinical text data, labeled via fuzzy matching with ICD-10 codes to create a labeled dataset. Two tokenization methods preprocessed the clinical text data, and three models were evaluated: the existing Text-CNN, the proposed Text-CNN with t-test, and Bio_ClinicalBERT. Performance was assessed using multiple metrics and validated on 228 baseline screening clinical case text data collected from ICMR–NIRT to demonstrate effective TB classification. Results: The proposed model achieved the best results in both the test and validation datasets. On the test dataset, it attained a precision of 88.19%, a recall of 90.71%, an F1-score of 89.44%, and an AUC of 0.91. Similarly, on the validation dataset, it achieved 100% precision, 98.85% recall, 99.42% F1-score, and an AUC of 0.982, demonstrating its effectiveness in TB classification. Conclusions: This study highlights the effectiveness of DL models in classifying TB cases from clinical notes. The proposed model outperformed the other two models. The TF-IDF and t-test showed statistically significant feature selection and enhanced model interpretability and efficiency, demonstrating the potential of NLP and DL in automating TB diagnosis in clinical decision settings. Full article

Mushroom production, mushroom knowledge and mushroom cultivation have aroused the interest of many researchers, scientists, institutions, cultural and mushroom-loving associations, and ordinary mushroom pickers as well. The contribution of wild mushrooms to the economic, cultural and touristic development and social cohesion of the Greek rural population is considered very important. In addition to their therapeutic and dietary value, they are also valuable for their diverse chemical and medicinal properties. The PubMed—Medline, Web of Science and Cochrane Library databases were searched for relevant articles published up to January, 2025. Even today, some macromycetes are still used in medicine due to their remarkable healing properties. In the form of powders or solutions, they were formerly used as a remedy for epilepsy, tuberculosis, nervous diseases and various severe inflammations. This review documents the benefits of mushroom consumption suggested by health experts for pathological conditions and health improvement and highlights their superiority as non-animal protein sources according to their nutrients. Full article

We primarily focus on the formulation, theoretical, and numerical analyses of a non-autonomous model for tuberculosis (TB) prevention and control programs in a population where individuals suffering from the double trouble of tuberculosis and diabetes are present. The model incorporates four time-dependent control functions, saturated treatment of non-infectious individuals harboring tuberculosis, and saturated incidence rate. Furthermore, the basic reproduction number of the autonomous form of the proposed optimal control mathematical model is calculated. Sensitivity indexes regarding the constant control parameters reveal that the proposed control and preventive measures will reduce the tuberculosis burden in the population. This study establishes that the combination of campaigns that teach people how the development of tuberculosis and diabetes can be prevented, a treatment strategy that provides saturated treatment to non-infectious individuals exposed to tuberculosis infections, and prompt effective treatment of individuals infected with tuberculosis disease is the optimal strategy to achieve zero TB by 2035. Full article

The Iberian lynx (Lynx pardinus) population has been increasing in recent years thanks to the collaboration of several associations within the framework of the Life Lynxconnect project, which promotes captive breeding for the subsequent release of specimens into the environment. It is therefore important to know their population status, the diseases to which these animals are exposed, and how they affect their repopulation. In this sense, this study aims to study how the presence of mycobacteria affects the lynx population in Extremadura (southwest of Spain). To this end, blood samples, tracheal swabs, and tracheobronchial washings from live-captured lynxes, as well as mediastinal and mesenteric lymph nodes from roadkill animals, were collected. The association between the presence of mycobacteria and various factors—including body condition, age, sex, and blood parameters—was subsequently evaluated. Up to date, our findings show the absence of tuberculosis (TB) in all lynxes tested, while they seem to be reservoirs of non-tuberculous mycobacteria (NTM), mainly M. lentiflavum, the most isolated species. Nonetheless, these mycobacteria appear to have no significant effect on the health condition of the animals. Full article

Background: Bovine tuberculosis (bTB) is an infectious disease which causes significant damage to the farming industry and remains a disease of global significance. Although control strategies have focused on a test and cull approach primarily based around specific cell-mediated immune responses, serological assays are increasingly being used as a supplementary test alongside skin testing and interferon-gamma release (IGRA) assays. The UK is moving towards the use of the Bacillus Calmette–Guérin (BCG) vaccination of cattle as an additional targeted control tool against bTB. However, there are concerns over its potential impact on the outcomes of bTB diagnostic tests and other non-TB assays, such as serological tests for Mycobacterium avium subsp. paratuberculosis (MAP). Methods: We investigated the performance of commercially available serology tests designed to detect bTB and MAP using serum samples from BCG-vaccinated animals which were subsequently infected with Mycobacterium bovis (M. bovis). Results: BCG vaccination per se did not significantly impact the specificity of serological diagnostic tests for bTB or Johne’s disease. However, increased numbers of false-positive responses in bTB serology tests were seen in BCG-vaccinated animals 3 weeks following a tuberculin skin test, where up to 23% and 54% of animals gave a positive result in IDEXX and Enferplex tests, respectively. Furthermore, M. bovis infection gave rise to false-positive test results for Johne’s disease, irrespective of the animals’ prior BCG vaccination status. Conclusions: Caution should be taken when assessing results from serology tests for bTB if tuberculin skin testing has occurred shortly before collection of blood from BCG-vaccinated cattle. Furthermore, these results highlight the potential for misdiagnosis of MAP infection when using serology tests in bTB-infected cattle. Full article

(1) Background: Extrapulmonary tuberculosis (EPTB) of the head and neck is a rare but difficult diagnosis due to mostly absent pulmonary involvement and high clinical resemblance to neoplastic or chronic inflammatory conditions. This diagnosis still poses a challenge for otorhinolaryngologists, due to non-specific symptoms and the low index of suspicion in non-endemic regions. (2) Methods: This study presents a retrospective review of nine cases of head and neck EPTB diagnosed at two regional hospitals in southern Romania. Patients presented with pharyngeal, laryngeal, or cervical lymph node involvement. All cases underwent surgical biopsies for histopathological and microbiological confirmation, followed by standard anti-tubercular therapy. (3) Results: In all nine cases, surgical biopsies were essential for the accurate diagnosis and excluded malignancy or other granulomatous diseases. Diagnostic delays were observed due to atypical clinical presentations. Integration of biopsy findings with anti-tubercular treatment resulted in favorable disease control and clinical recovery. (4) Conclusions: Head and neck EPTB requires a high index of suspicion and clinical discernment. Surgical biopsy remains a critical diagnostic tool in practice and should be considered early in the diagnostic process when encountering atypical lesions. A timely use improves diagnostic accuracy, may eliminate delays, ensures patient safety, and improves therapeutic outcomes. Full article

HIV/AIDS and Mycobacterial tuberculosis (Mtb) are the leading cause of deaths worldwide. Thus, better medicaments are required to manage these diseases. Quinolines have shown great potential due to their broad spectrum of biological activity. Thus, quinoline–1,2,3-triazole–aniline hybrids were synthesised in moderate to good yields. Compounds 11g (IC₅₀ = 0.388 µM), 11h (IC₅₀ = 0.01032 µM) and 11i (IC₅₀ = 0.167 µM) exhibited the most promising in vitro activities against the wild-type HIV-1 subtype B, with 11h being 9-fold more active than AZT (IC₅₀ = 0.0909 µM), the reference drug. Furthermore, compound 11h displayed moderate activity, with a MIC₉₀ of 88μM against Mtb’s H37Rv strain. Cytotoxicity studies on TZM-bl cell lines revealed that most of the tested compounds were generally non-cytotoxic; the selectivity index (SI) for 11h, the front runner, is >2472. Molecular docking studies revealed that 11h interacted with Phe112, Tyr108, Glu283 and Trp86 amino acid residues in the active site of HIV-1. DFT studies revealed that 11h has the ability to donate and accept electrons to and from available orbitals. The predicted ADMET studies showed that these compounds possess drug-likeness, and 11h has the potential for further optimisation as an anti-HIV-1 agent. Full article

In recent decades, the world has observed the emergence and re-emergence of a multitude of previously non-existent or re-emerging infectious diseases, for which there is a paucity of timely and effective preventative measures. The WHO has published a catalogue of priority pathogens that are likely to trigger future epidemics, with the objective of designing effective prophylactic and therapeutic interventions. The rationale behind these interventions is rooted in a comprehensive understanding of the aetiology, epidemiology, and pathogenesis of the target diseases. While it is imperative to acknowledge the pivotal role that evolutionary changes in pathogens play, it is equally important to recognise the influence of a multifaceted interplay of factors on the emergence and re-emergence of infectious diseases. These include changes in human populations, the vectors and reservoirs of exposure, and environmental changes. This review summarises the aetiology, epidemiology, and pathogenesis of the ten WHO priority diseases, as well as those with high epidemic potential that are already the focus of specific control programme initiatives, such as HIV/AIDS, tuberculosis, and malaria diseases. Furthermore, this review concentrated on the means of addressing these infections through public health surveillance and response systems. Such systems must be designed to rapidly detect unusual and unexpected disease patterns, track and share information in real time, and rapidly mobilise global responses, which are the most important ways to effectively contain transmission. Full article

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a global health challenge. The human-adapted TB-causing bacteria are distributed into ten lineages with distinct global distributions and clinical outcomes. Mtb lineages 4 (L4) and L6 are good prototypes of these differences, because L4 is globally prevalent, whereas L6 is geographically restricted to West Africa and associated with slower disease progression. Given the fundamental role of T cells for the control of TB, we questioned whether Mtb L4 or L6 antigens and HLA interactions would be disrupted in West African hosts. Here, we selected variable and validated antigens and demonstrate their expression during in vivo Mtb L4 or L6 infections. We then compared the predicted number of IFN-γ-inducing and HLA high-binding-affinity peptides in Mtb ancestral, L4, or L6 proteins, considering HLA alleles of high or low frequency in West Africa. Our immunoinformatics approach predicts that non-synonymous substitutions of high variance in Mtb L6 strains diminish binding affinities to HLA alleles prevalent in West African populations, suggesting specific adaptations of these strains to their preferred hosts. Future functional studies will advance our knowledge on lineage-specific evolution and inform strategies to enhance TB control in endemic regions. Full article

Sarcoidosis is a rare multisystem inflammatory disease characterized by non-necrotizing granulomas, typically affecting the lungs, lymph nodes, skin, and bones. Due to its extreme clinical heterogeneity, diagnosis remains challenging. Within the skeletal system, the thoracic spine, ankles, and knees are the most commonly involved joints. We report a rare case of non-articular osseous sarcoidosis with progressive pulmonary lesions and persistently normal inflammatory biomarkers (ACE, CRP, ESR, IL-2, and TNF-α) that required differentiation from metastatic bone tumors and tuberculosis. Prior to presentation at our hospital, the patient did not respond to six months of anti-tuberculosis treatment and one month of systemic glucocorticoid therapy in three other hospitals. Based on lung and bone biopsies, she was finally diagnosed as having active sarcoidosis in our hospital. Despite 3 months of prednisone, pulmonary consolidation and bone lesions persisted until methotrexate was added. This case highlights the preference of combined glucocorticoid and methotrexate therapy for sarcoidosis with atypical osseous involvement and normal biomarkers, underscoring the urgent need for novel diagnostic tools to mitigate misdiagnosis. Full article