Search Results (72)

Indigenous people possess unique health literacy issues and challenges with preventing infectious diseases. This research assessed the baseline knowledge and misinformation in the Semai indigenous subgroup in Perak state, Malaysia, and the impact of a culturally adapted health education intervention. A single-group pre-test/post-test design was used with 156 participants ranging from 7 to 69 years old, predominantly children. The survey addressed key issues of head lice, intestinal parasites, tuberculosis (TB), handwashing, and germ transmission. An interactive, multi-station health education session in the local language produced a significant increase in overall knowledge (mean score increased from 3.17 to 3.83 out of 5, p < 0.0001), with the largest increase among the adult group aged 31–50 years. This was most notable for handwashing knowledge, which had the greatest increase, and misconceptions about intestinal worms and head lice remained. Differences in outcome by age suggest the need for targeted educational strategies, particularly for teenagers and elderly individuals who achieved less gain. The results support the effectiveness of culturally tailored, community-based health education in promoting the awareness of disease among indigenous communities. The drawbacks are convenience sampling, the child dominance of the sample, and the short-term follow-up. Future emphasis should be placed on long-term, community-based intervention using culturally tailored content and digital media. Full article

Studies have indicated that there was a disease interaction of pandemic influenza with respiratory tuberculosis (TB) in Malta, which could explain the heightened mortality recorded in young adults. We revisit the 1918/19 influenza and TB syndemic potential on the island of Malta. Borrowing from crisis studies that explore the harvesting effect, we used the method of assessing changes in pre-pandemic, pandemic, fallow, and post-pandemic mortality/life expectancy to reveal the syndemic experience. Pre-pandemic (1914–1917) life expectancy at birth was significantly higher, at 37.91 years, than during the pandemic (1918), when life expectancy dropped to 33.26 years (Z = 10.56, p < 0.0001). Post-pandemic (1919) life expectancy rose to 43.49 years, which was an even longer life expectancy than pre-pandemic (Z = 17.61, p < 0.0001). There were significant changes in TB mortality death rates during the four periods in those of reproductive age. Augmenting our framework for studies of syndemics involving short-term events, we proposed the identification of contributing, driving, and limiting factors. Underlying living conditions contributed to the syndemic. The exacerbation of housing conditions, the economy associated with the First World War, and meteorological measures—temperature, relative humidity, and rainfall—were driving factors. The early implementation of mitigation strategies, such as restrictions on mass gatherings, were limiting factors of the syndemic. Full article

Hearing loss (HL) is a major global health concern, with drug-induced ototoxicity contributing significantly, particularly in patients undergoing treatment for drug-resistant tuberculosis (DR-TB). In South Africa, where both TB and HIV are prevalent, the risk of treatment-related auditory damage is especially high. This study aimed to assess the prevalence and predictors of hearing impairment among DR-TB patients in rural Eastern Cape, South Africa. A retrospective analysis was conducted on 438 DR-TB patients treated between 2018 and 2020, using pure tone audiometry (PTA) to assess hearing status post-treatment. Demographic, clinical, and lifestyle data were extracted from patient records and analyzed using logistic regression. The overall prevalence of hearing loss was 37.2%. Risk was significantly associated with an older age, a male gender, DR-TB classification (MDR, pre-XDR, and XDR), unsuccessful treatment outcomes, and substance use. Prevalence of HL increased notably in patients aged 70 and older. Lifestyle factors, particularly combined use of tobacco, alcohol, and drugs, were linked to higher odds of HL. These findings underscore the need for routine audiometric screening and personalized treatment monitoring in DR-TB care, especially for high-risk populations. Early identification of ototoxicity risk factors can inform safer treatment regimens and improve patient outcomes in resource-limited settings. Full article

The COVID-19 pandemic disrupted tuberculosis (TB) control, increasing mortality and potentially worsening disparities. This study aimed to analyze the temporal trends of TB mortality in Brazil and to trace the COVID-19 pandemic’s effect using a Bayesian approach, focusing on nationwide data. An ecological study of TB deaths recorded in the Mortality Information System (SIM) from 2012 to 2022 was conducted. Trends and percentage changes in the mortality were estimated. A Bayesian Structural Time Series model combined with an Autoregressive Integrated Moving Average model was used to assess the pandemic’s effect on TB. A total of 51,809 TB deaths were identified, with a mortality rate of 2.27 per 100,000. Higher rates were found among the elderly (6.86), indigenous populations (5.58), and black individuals (4.21). The Bayesian model estimated a 9.9% (CI 8.8–11%) increase in TB mortality due to COVID-19. The Midwest region showed the highest increase (30%, 25–35%). Females experienced a greater post-pandemic monthly increase (2.80%) in mortality than males (0.72%). The Bayesian analysis revealed a significant rise in TB mortality during the COVID-19 pandemic, with notable disparities affecting females, the elderly, the indigenous, and the black populations. These findings highlight the pandemic’s long-term impact on TB and stress the need for equity-focused, data-driven public health responses in Brazil. Full article

Background: This case is unique in demonstrating the reactivation of latent tuberculosis (TB) following co-infection with SARS-CoV-2 and Epstein–Barr virus (EBV) in an otherwise healthy young adult. It highlights a rare clinical scenario in which viral immune dysregulation likely facilitated TB progression. To date, few reports have explored the complex interplay between COVID-19, EBV reactivation, and TB in a single patient, particularly with isolated extrapulmonary involvement. Case Presentation: A 24-year-old woman presented with persistent low-grade fever, fatigue, night sweats, unintentional weight loss, and progressive cervical and supraclavicular lymphadenopathy. These symptoms emerged shortly after a moderate COVID-19 infection. Laboratory studies revealed elevated inflammatory markers and pronounced lymphopenia. EBV reactivation was confirmed via serology and PCR. Despite antiviral therapy, symptoms persisted, and imaging revealed necrotic lymphadenopathy. Tuberculous lymphadenitis was diagnosed through fine-needle aspiration cytology and PCR detection of Mycobacterium tuberculosis. The patient was treated with a standard anti-tuberculosis regimen, resulting in clinical, radiological, and immunological improvement. Conclusions: This case underscores the importance of considering latent TB reactivation in patients with persistent lymphadenopathy and recent viral infections, particularly in regions with high TB prevalence. It also emphasizes the need for thorough immunological and microbiological assessment in complex post-viral syndromes. The main clinical takeaway is that COVID-19 and EBV co-infection may create a permissive environment for TB reactivation through immune system compromise. Full article

Background: Pulmonary tuberculosis (TB) frequently leads to long-term lung complications that contribute to increased mortality. Understanding the pathogenesis of post-TB lung impairments is crucial for improving long-term outcomes in TB patients; yet this area remains poorly researched. Methods: Our study assessed circulatory inflammatory markers in patients who completed TB treatment more than one year before enrolment (population 1) and patients receiving in-hospital treatment for active drug-sensitive TB (population 2). Results: IL-6 was seven times higher in both populations compared to the normal range. IL-8 was below the limit of detection (LOD) in population 1, while it was approximately 2.5 times higher in population 2 compared to the normal range. TNF-α was 21 times higher in population 1 and 19 times higher in population 2 compared to the normal range. CRP was almost 49 times higher in both populations, and IL-1Ra was below the LOD in population 1, while it was ~1.5 times higher in population 2 compared to the normal range. Conclusions: These inflammatory biomarkers correlated well with lung function in the post-TB state, and their high levels suggest a persistent pro-inflammatory state post-TB, which may contribute to post-TB lung disease. More research is warranted to better understand this phenomenon, but these findings may highlight a need to consider anti-inflammatory therapy for patients with post-TB lung disease, especially since these high levels of cytokines can directly contribute to lung damage. Full article

Background: Multiple endocrine neoplasia type 1 (MEN1)-related primary hyperparathyroidism (MPHPT) belongs to genetic PHPT that accounts for 10% of all PHPT cases, being considered the most frequent hereditary PHPT (less than 5% of all PHPT). Objective: We aimed to provide an updated clinical perspective with a double purpose: to highlight the clinical features in MPHPT, particularly, the bone health assessment, as well as the parathyroidectomy (PTx) impact. Methods: A comprehensive review of the latest 5-year, English-published, PubMed-accessed original studies. Results: The sample-based analysis (n = 17 studies) enrolled 2426 subjects (1720 with MPHPT). The study design was retrospective, except for one prospective and one case–control study. The maximum number of patients per study was of 517. Female predominance (an overall female-to-male ratio of 1.139) was confirmed (except for three studies). Age at MPHPT diagnosis (mean/median per study): 28.7 to 43.1 years; age at PTx: 32 to 43.5 years. Asymptomatic PHPT was reported in 38.3% to 67% of MPHPT. Mean total calcium varied between 1.31 and 2.88 mmol/L and highest PTH was of 317.2 pg/mL. Two studies reported similar PTH and calcaemic levels in MPHPT vs. sporadic PHPT, while another found higher values in MPHPT. Symptomatic vs. asymptomatic patients with MPHPT had similar PTH and serum calcium levels (n = 1). Osteoporosis (n = 8, N = 723 with MPHPT) was reported in 10% to 55.5% of cases, osteopenia in 5.88% to 43.9% (per study); overall fracture rate was 10% (of note, one study showed 0%). Lower bone mineral density (BMD) at DXA (n = 4) in MPHPT vs. sporadic PHPT/controls was found by some studies (n = 3, and only a single study provided third distal radius DXA-BMD assessment), but not all (n = 1). Post-PTx DXA (n = 3, N = 190 with MPHPT) showed a BMD increase (e.g., +8.5% for lumbar spine, +2.1% for total hip, +4.3% for femoral neck BMD); however, post-operatory, BMD remains lower than controls. Trabecular bone score (TBS) analysis (n = 2, N = 142 with MPHPT vs. 397 with sporadic PHPT) showed a higher prevalence of reduced TBS (n = 1) or similar (n = 1). PTx analysis in MPHPT (n = 14): rate of subtotal PTx of 39% to 66.7% (per study) or less than subtotal PTx of 46.9% (n = 1). Post-PTx complications: persistent PHPT (5.6% to 25%), recurrent PHPT (16.87% to 30%, with the highest re-operation rate of 71% in one cohort); hypoparathyroidism (12.4% to 41.7%). Genetic analysis pointed out a higher risk of post-PTx recurrence in exon 10 MEN1 pathogenic variant. Post-PTx histological exam showed a multi-glandular disease in 40% to 52.1% of MPHPT, and a parathyroid carcinoma prevalence of 1%. Conclusions: MPHPT remains a challenging ailment amid a multi-layered genetic syndrome. Current data showed a lower age at MPHPT diagnosis and surgery than found in general population, and a rate of female predominance that is lower than seen in sporadic PHPT cases, but higher than known, for instance, in MEN2. The bone involvement showed heterogeneous results, more consistent for a lower BMD, but not necessarily for a lower TBS vs. controls. PTx involves a rather high rate of recurrence, persistence and redo surgery. About one out of ten patients with MPHPT might have a prevalent fracture and PTx improves the overall bone health, but seems not to restore it to the general population level, despite the young age of the subjects. This suggests that non-parathyroid components and potentially menin protein displays negative bone effects in MEN1. Full article

There are limited studies on the community-based outcomes of tuberculosis (TB) preventive treatment (TPT) among children and adolescent contacts <15 years in Ethiopia. Our objective was to assess TPT uptake and completion rates among eligible under-15-year-old TB household contacts through an enhanced community-based model of interventions. The study was conducted between July 2021 and June 2022 in twenty primary health care units in the Sidama and Southern Nations, Nationalities, and Peoples’ Region (SNNPR) regions. A total of 4367 (99.2%) household contacts of 1069 bacteriologically confirmed PTB index cases were symptomatically screened for TB by trained health extension workers (HEWs) at the community level. A total of 696 (15.9%) symptomatic contacts were identified, of which 694 (99.7%) were evaluated for TB, resulting in 60 (8.6%) TB cases. A total of 1567 (95.3%) asymptomatic children and adolescent contacts <15 years of age were initiated on TPT (88.8%) at health posts in the community. After the interventions, there was a significant increase in contact screening coverage (95.6% vs. 99.2%, Odds Ratio (OR), 5.54; 95% Confidence interval (CI), 2.93–10.13) and TPT uptake (81.7% vs. 95.4%; OR, 4.67; 95% CI, 2.54–8.23). The TPT completion rate was also 98.1% (of 1567). The TPT completion rate at health posts in the community was higher than the rate at health centers (99.4% vs. 88.0%; OR, 20.95; 95% CI, 8.97–52.71). TPT uptake and completion in children and adolescent contacts could be improved remarkably with the implementation of an enhanced community-based model of intervention in high-TB-burden districts. Full article

Background/Objectives: Tuberculosis (TB), caused by Mycobacterium tuberculosis H37Rv (M. tuberculosis), primarily affects the lungs. The Bacillus Calmette–Guérin (BCG) vaccine is the only available TB vaccine. Guinea pigs serve as an excellent preclinical model due to the similarity to human Tuberculosis pathology. However, the lack of a standardized vaccination protocol in guinea pigs causes inconsistencies in efficacy assessments, limiting precise evaluation and its application in vaccine studies. This study aims to address this gap by establishing a consistent and reliable protocol for evaluating the immunological efficacy of BCG vaccination. Methods: Guinea pigs were divided into control, M. tuberculosis-infected, and BCG-vaccinated groups. Four weeks post-vaccination, the infected and vaccinated groups were challenged with M. tuberculosis. The bacterial burden in the lungs and spleen was measured, histopathological changes were analyzed using hematoxylin and eosin (H&E) staining, and the infection levels of M. tuberculosis, as well as the presence of interleukin-2 (IL-2), tumor necrosis factor-alpha (TNF-α), and interferon-gamma (IFN-γ) positive cells, were evaluated through immunohistochemical (IHC) staining. Results: BCG vaccination reduced the bacterial load to 3.60 × 10⁴ CFU/lung and 5.52 × 10³ CFU/spleen compared to 3.78 × 10⁵ CFU/lung and 1.54 × 10⁴ CFU/spleen in the infected group. The mean histopathological score for lungs was 1.67 compared to 2.67 in the infected group. Similarly, the mean histopathological score for the spleen was 1.33 compared to 2.33 in the infected group. IHC analysis showed a notable reduction in M. tuberculosis and inflammatory cytokine-positive cells in the vaccinated group. The TNF-α, IL-2, and IFN-γ staining intensity decreased by 9.3, 4.8, and 11, respectively, compared to the infected group. Conclusions: This protocol enhances consistency in vaccine assessments, providing a reliable benchmark for the development of safer, more effective, and accessible TB vaccines. Full article

This study presents an evaluation of the microtensile bond strength (µTBS) and microleakage (ML) of a bulk-fill (BF) composite, Ormocer, and Alkasite in comparison to the conventional composite bonded to caries-affected dentin (CAD) in deciduous dentition. Eighty-four human primary molars displaying carious lesions involving the middle third of dentin were included. CAD was exposed, and the teeth were randomly assigned to four groups based on the type of restorative material used: Group 1 (conventional composite), Group 2 (BF composite), Group 3 (Alkasite), and Group 4 (Ormocer). Sample storage and artificial aging were performed. Dye penetration, a universal testing machine, and a stereomicroscope were used for microleakage, µTBS, and failure mode assessment. The interface was evaluated by scanning electron microscopy (SEM). µTBS and ML results were analyzed using a one-way analysis of variance (ANOVA) and Tukey’s post hoc tests (p < 0.05). Group 1 (conventional composite) exhibited the highest microleakage and lowest bond strength. The minimum ML and maximum μTBS values were demonstrated by Group 4 (Ormocer). Ormocer and Alkasite proved to be better alternatives to conventional composites in terms of ML and bond strength in deciduous dentition. Full article

The widespread implementation of new CAD/CAM materials has led to the necessity of establishing an adequate luting protocol. The aim of this study was to evaluate the microtensile bond strength (μTBS) and the film thickness of different luting methods on CAD/CAM resin blocks. Five Brilliant Crios CAD/CAM blocks (Coltene/Whaledent) were sequentially sectioned into two halves, air abraded with 50 µm aluminum oxide, and luted according to five different cementation protocols: Brilliant EverGlow (BEG), Brilliant EverGlow with ultrasound application (BEG-US), preheated Brilliant EverGlow (BEG-H), Brilliant EverGlow Flow (BEGF), and Duo Cem^® Trans (DC). Subsequently, the blocks were sectioned to obtain rods, which were then submitted to a microtensile bond strength test (n = 20). The surfaces were examined with optical microscopy to determine the failure mode and the bonding interface was assessed with scanning electron microscope (SEM) analysis. Bond strength values were analyzed using one-way ANOVA and Tukey’s post hoc tests (α = 0.05). The bond strength values varied with the different cementation protocols (p < 0.001): BEG (45.48 ± 18.14 MPa), BEG-US (42.15 ± 14.90 MPa), BEG-H (41.23 ± 15.15 MPa), BEGF (58.38 ± 15.65 MPa), and DC (81.07 ± 8.75 MPa). Regarding bond strength, DC presented significantly higher values than all other experimental groups (p < 0.050), whereas all luting methods using BEG presented similar values (p = 0.894). Adhesive failures were the predominant type. On SEM evaluation, all the luting materials presented a tight and homogeneous cement–block interface with variable film thicknesses. In conclusion, among the cementation protocols, the resin cement (DC) rendered the highest bond strength values. SEM analysis revealed that the lowest film thickness was associated with the flowable composite (BEGF). Full article

Background/Objectives: Studies show that SNPs in ABCB1 rs2032582 and SLCO1B1 rs4149015 affect the PK profile of moxifloxacin, a key drug for MDR-TB. This study aimed to assess the genotype frequencies of ABCB1 rs2032582 and SLCO1B1 rs4149015; describe moxifloxacin AUC_0–24 and C_max; and evaluate the association between genotype variations and moxifloxacin AUC_0–24 and C_max, corrected for the effect of other determinants in MDR-TB patients in Indonesia. Methods: The genotypes were identified using DNA sequencing. Plasma samples for PK analysis were collected at either two or four timepoints post-dose, at steady state. AUC_0–24 values were assessed with a limited sampling formula. A multivariate linear regression analysis identified the determinants for moxifloxacin AUC_0–24 and C_max. Results: We recruited 204 MDR-TB patients for PG analysis, with 80 providing PK samples. The majority of the ABCB1 and SLCO1B1 genotypes were wildtype (GG), 41.7% and 93.6%, respectively. The geometric mean AUC_0–24 for moxifloxacin was 78.6 mg·h/L and that for C_max was 6.1 mg/L. No statistically significant difference in exposure to moxifloxacin could be shown between the genotypes. Sex, age, and dose in mg/kg/body weight were significant determinants of the AUC_0–24 of moxifloxacin. Conclusions: The major genotype of ABCB1 rs2032582 and SLCO1B1 rs4149015 was wildtype, and the exposure to moxifloxacin was high but not related to the studied genotype in an Indonesian population. Full article

Due to their intriguing emission profile, Terbium-161 (¹⁶¹Tb) radiopharmaceuticals seem to bring significant advancement in theranostic applications to cancer treatment. The combination of ¹⁶¹Tb with nanoscale brachytherapy as an approach for cancer treatment is particularly advantageous and promising. Herein, we propose the application of a hybrid nanosystem comprising gold decorated (Au@TADOTAGA) iron oxide nanoflowers as a form of injectable nanobrachytherapy for the local treatment of breast cancer. More specifically, Au@TADOTAGA and NFAu@TADOTAGA NPs were efficiently radiolabeled with ¹⁶¹Tb, and their in vitro stability was assessed up to 21 d post-radiolabeling. Furthermore, their cytotoxic profile against 4T1 breast cancer cells was evaluated, and their ex vivo biodistribution characteristics were revealed after intratumoral injection in the same animal model. The enhanced retention at the tumor site urged us to evaluate the therapeutic effect of the [¹⁶¹Tb]Tb-NFAu@TADOTAGA nanosystem after intratumoral administration to 4T1-tumor-bearing mice, over a period of 24 days. Three different therapeutic protocols were performed in order to identify which therapeutic approach would offer the optimum results and identify the proposed nanosystem as a promising nanoscale brachytherapy agent. Full article

Boron (B) neutron capture therapy (BNCT) is a novel non-invasive targeted cancer therapy based on the nuclear capture reaction ¹⁰B (n, alpha) ⁷Li that enables the death of cancer cells without damaging neighboring normal cells. However, the development of clinically approved boron drugs remains challenging. We have previously reported on self-forming nanoparticles for drug delivery consisting of a biodegradable polymer, namely, “AB-type” Lactosome^® nanoparticles (AB-Lac particles)- highly loaded with hydrophobic B compounds, namely o-Carborane (Carb) or 1,2-dihexyl-o-Carborane (diC6-Carb), and the latter (diC6-Carb) especially showed the “molecular glue” effect. Here we present in vivo and ex vivo studies with human pancreatic cancer (AsPC-1) cells to find therapeutically optimal formulas and the appropriate treatment conditions for these particles. The biodistribution of the particles was assessed by the tumor/normal tissue ratio (T/N) in terms of tumor/muscle (T/M) and tumor/blood (T/B) ratios using near-infrared fluorescence (NIRF) imaging with indocyanine green (ICG). The in vivo and ex vivo accumulation of B delivered by the injected AB-Lac particles in tumor lesions reached a maximum by 12 h post-injection. Irradiation studies conducted both in vitro and in vivo showed that AB-Lac particles-loaded with either ¹⁰B-Carb or ¹⁰B-diC6-Carb significantly inhibited the growth of AsPC-1 cancer cells or strongly inhibited their growth, with the latter method being significantly more effective. Surprisingly, a similar in vitro and in vivo irradiation study showed that ICG-labeled AB-Lac particles alone, i.e., without any ¹⁰B compounds, also revealed a significant inhibition. Therefore, we expect that our ICG-labeled AB-Lac particles-loaded with ¹⁰B compound(s) may be a novel and promising candidate for providing not only NIRF imaging for a practical diagnosis but also the dual therapeutic effects of induced cancer cell death, i.e., “theranostics”. Full article

The Eurasian wild boar (Sus scrofa) is a key wildlife host for tuberculosis (TB) in central and southwestern Spain, posing a challenge to TB eradication in livestock. New strategies, including the use of beneficial microbes, are being explored to mitigate wildlife diseases. This study evaluated the effect of oral supplementation with postbiotic antimycobacterial metabolites produced using Ingulados’ lactic acid bacteria (LAB) collection on TB development in wild boar. A total of 20 game estates in mid-western Spain were divided into two groups: one fed with standard feed containing the postbiotic product and a control group fed without postbiotics. Data were collected from wild boar during hunting events pre- and post-supplementation. The presence of TB-like lesions (TBLLs), lesion severity and seropositivity against Mycobacterium bovis were assessed. Postbiotic supplementation led to a 36.87% reduction in TBLLs and a 35.94% decrease in seropositivity. Notably, young wild boar showed a 64.72% reduction in TBLLs and an 81.80% drop in seropositivity, suggesting reduced transmission. These findings support the potential of postbiotics as a safe, feasible and sustainable tool to control TB in wild boar, offering a promising addition to broader TB eradication efforts. Full article