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Sujet(s)
Tuberculose miliaire , Humains , Enfant , Adolescent , Tuberculose miliaire/diagnostic , Tuberculose miliaire/traitement médicamenteux , Test tuberculinique , Enfant d'âge préscolaire , Antituberculeux/administration et posologie , Vaccin BCG/administration et posologieRÉSUMÉ
Skin scar formation following Bacille Calmette-Guérin (BCG) or smallpox (Vaccinia) vaccination is an established marker of successful vaccination and 'vaccine take'. Potent pathogen-specific (tuberculosis; smallpox) and pathogen-agnostic (protection from diseases unrelated to the intentionally targeted pathogen) effects of BCG and smallpox vaccines hold significant translational potential. Yet despite their use for centuries, how scar formation occurs and how local skin-based events relate to systemic effects that allow these two vaccines to deliver powerful health promoting effects has not yet been determined. We review here what is known about the events occurring in the skin and place this knowledge in the context of the overall impact of these two vaccines on human health with a particular focus on maternal-child health.
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Vaccin BCG , Cicatrice , Peau , Vaccin antivariolique , Vaccination , Animaux , Humains , Vaccin BCG/administration et posologie , Vaccin BCG/immunologie , Cicatrice/étiologie , Cicatrice/anatomopathologie , Cicatrice/immunologie , Peau/anatomopathologie , Peau/immunologie , Variole/prévention et contrôle , Variole/immunologie , Vaccin antivariolique/administration et posologie , Vaccin antivariolique/immunologieRÉSUMÉ
Bacillus Calmette-Guerin (BCG) vaccination and tuberculosis (TB) incidence in children under 1 year of age are critical public health indicators in Brazil. The coronavirus disease 2019 pandemic disrupted vaccination coverage (VC), potentially impacting TB incidence. Understanding regional disparities in VC and TB incidence can inform targeted interventions. We conducted an observational and ecological study using BCG vaccination data (2019-21) and TB incidence (2020-22) for all births in Brazil. Data were collected from public health databases, stratified by state, and analyzed using descriptive and analytical statistics to explore VC and TB incidence. Between 2019 and 2021, average BCG VC was 79.59%, with significant variation among states (P < .001). Only four states achieved minimum recommended coverage (>90%). TB incidence varied significantly among states (P = .003). There was a notable decline in VC from 2019 (90.72%) to 2021 (78.67%) (P < .001). This study highlights regional disparities in BCG VC and TB incidence among Brazilian states. Lower VC post-pandemic may increase TB incidence, requiring targeted interventions in states with inadequate coverage. The findings underscore the importance of sustaining vaccination programs amidst public health crises and implementing strategies to enhance access and uptake.
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Vaccin BCG , COVID-19 , Tuberculose , Couverture vaccinale , Humains , Brésil/épidémiologie , Vaccin BCG/administration et posologie , Couverture vaccinale/statistiques et données numériques , Incidence , Nourrisson , Tuberculose/épidémiologie , Tuberculose/prévention et contrôle , COVID-19/prévention et contrôle , COVID-19/épidémiologie , Femelle , Programmes de vaccination , Mâle , Vaccination/statistiques et données numériques , SARS-CoV-2 , Disparités d'accès aux soins , Nouveau-néRÉSUMÉ
The aim of this study was to investigate the prognostic role of blood-based nutritional biomarkers, including red blood cell (RBC count), hemoglobin (Hb), total protein (TP), albumin, the serum albumin to globulin ratio (AGR) and the prognostic nutritional index (PNI) in patients who underwent intravesical treatment for non-muscle invasive bladder cancer (NMIBC). A total of 501 NMIBC patients who received intravesical Bacillus Calmette-Guerin (BCG) treatment following transurethral resection of bladder tumor (TURBT) were included. The optimal cutoff values for these nutrition-based indicators were determined using receiver operating characteristic curve analysis. We observed a significantly higher recurrence-free survival (RFS) rate in patients with elevated levels of RBC count, Hb, TP, and albumin. Cox univariate and multivariate Cox regression analyses demonstrated that serum albumin (P = 0.002, HR = 0.51, 95%CI: 0.33-0.78), RBC count (P = 0.002, HR = 0.50, 95%CI: 0.32-0.77), TP (P = 0.028, HR = 0.62, 95%CI: 0.41-0.95), Hb (P = 0.004, HR = 0.53, 95%CI: 0.33-0.84), AGR (P = 0.003, HR = 0.46, 95%CI: 0.27-0.76) and PNI (P = 0.019, HR = 0.56, 95%CI: 0.35-0.91) were significant independent factors predicting RFS. These cost-effective and convenient blood-based nutritional biomarkers have the potential to serve as valuable prognostic indicators for predicting recurrence in NMIBC patients undergoing BCG-immunotherapy.
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Adjuvants immunologiques , Vaccin BCG , Invasion tumorale , Évaluation de l'état nutritionnel , Tumeurs de la vessie urinaire , Humains , Tumeurs de la vessie urinaire/sang , Tumeurs de la vessie urinaire/anatomopathologie , Tumeurs de la vessie urinaire/traitement médicamenteux , Tumeurs de la vessie urinaire/thérapie , Tumeurs de la vessie urinaire/chirurgie , Vaccin BCG/usage thérapeutique , Vaccin BCG/administration et posologie , Mâle , Femelle , Sujet âgé , Pronostic , Adulte d'âge moyen , Administration par voie vésicale , Adjuvants immunologiques/usage thérapeutique , Adjuvants immunologiques/administration et posologie , Études rétrospectives , Sérumalbumine/analyse , Hémoglobines/analyse , Hémoglobines/métabolisme , Marqueurs biologiques/sang , Période préopératoire , Numération des érythrocytes , État nutritionnel , Tumeurs de la vessie n'infiltrant pas le muscleRÉSUMÉ
BACKGROUND: The COVID-19 pandemic had a profound impact on healthcare systems and services, including routine immunization (RI). To date, there is limited information on the effects of the COVID-19 pandemic on RI in West African countries such as Sierra Leone, which had already experienced public health emergencies that disrupted its healthcare system. Here, we describe the impact of the COVID-19 pandemic on the RI of key antigens in Sierra Leone. METHODS: We used vaccination data from the District Health Information System for BCG, measles-rubella 1 and 2, and pentavalent 1 and 3 antigens. We compared 2019, 2020, 2021, and 2022 annual coverage rates for the selected antigens at the national and district levels. We used the Pearson chi-square test to assess the difference between annual coverage rates between 2019 and 2020, 2020-2021, and 2021-2022. RESULTS: National coverage rates for all antigens declined in 2019-2020, notably measles-rubella 1 and pentavalent 3 (-5.4% and - 4.9%). Between 2020 and 2021, there was an overall increase in coverage (+ 0.2% to + 2.5%), except for measles-rubella 2 (-1.8%). Measles-rubella antigens rebounded in 2021-2022, while others decreased between - 0.5 and - 1.9% in coverage. Overall, all district-level coverage rates in 2022 were lower than those in 2019. Most districts decreased between 2019 and 2022, though a few had a continuous increase; some had an increase/recovery between 2020 and 2021; some districts had recovered 2019 levels by 2022. CONCLUSION: The COVID-19 pandemic impacted Sierra Leone's national BCG, measles-rubella, and pentavalent antigen immunization, which were not fully restored in 2022. Most districts experienced notable coverage declines during the pandemic, though a few reached or surpassed 2019 rates in 2022. Examining pandemic impact can benefit from a focus beyond the national level to identify vulnerable regions. Sierra Leone's post-pandemic RI reestablishment needs targeted strategies and continual investments for equitable access and coverage, as well as to prevent vaccine-preventable diseases.
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COVID-19 , Couverture vaccinale , Sierra Leone/épidémiologie , Humains , COVID-19/prévention et contrôle , COVID-19/épidémiologie , Couverture vaccinale/statistiques et données numériques , Programmes de vaccination/statistiques et données numériques , Vaccin BCG/administration et posologie , Vaccin BCG/usage thérapeutiqueRÉSUMÉ
BACKGROUND: Bacillus Calmette-Guérin (BCG) vaccination, primarily administered to prevent tuberculosis, exhibits nonspecific immune effects and could play a role in inflammatory bowel disease prevention. We investigated the associations of BCG with Crohn's disease and ulcerative colitis, and assessed sex-differences. METHODS: This two-stage study included 365,206 Canadians from the Quebec Birth Cohort on Immunity and Health (1970-2014; stage 1). Vaccination status was registry-based and inflammatory bowel disease cases were identified from health services with validated algorithms. We documented additional factors among 2644 participants in a nested case-control study in 2021 (stage 2). A two-stage logistic regression analysis was applied to estimate the odds ratios (OR), corrected for sampling fractions and adjusted for confounding factors. We used interaction terms to assess sex-differences on the multiplicative scale. RESULTS: In the stage 1 sample, 2419 cases of Crohn's disease and 1079 of ulcerative colitis were included. Forty-six percent of non-cases received the BCG vaccine as compared to 47% for Crohn's disease and 49% for ulcerative colitis. Associations differed by sex. BCG vaccination was not associated with Crohn's disease among men (OR = 0.91; 95% CI: 0.79-1.04) but was related to an increased risk among women (OR = 1.13; 95% CI: 1.00-1.28, P interaction: 0.001). For ulcerative colitis, there was a tendency toward a slightly elevated risk among men (OR = 1.09; 95%CI: 0.90-1.32), whereas the risk was more substantial for women (OR = 1.17; 95% CI:0.99-1.39, P interaction: <0.001). CONCLUSION: BCG vaccination does not play a preventive role in inflammatory bowel disease. Our results point to distinct associations between men and women.
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Vaccin BCG , Humains , Vaccin BCG/administration et posologie , Mâle , Femelle , Québec , Études cas-témoins , Adulte , Vaccination , Rectocolite hémorragique/immunologie , Études de cohortes , Maladie de Crohn , Maladies inflammatoires intestinales/immunologie , Adulte d'âge moyen , Facteurs sexuels , Tuberculose/prévention et contrôleRÉSUMÉ
Background and Objectives: Mycobacterium bovis Bacillus Calmette-Guérin (BCG) vaccine administration has been suggested to prevent glucose metabolism abnormalities and fatty liver in genetically obese ob/ob mice; however, it is not clear whether the beneficial effects of BCG are also observed in the progression of glucose intolerance induced by a high-fat diet (HFD). Therefore, the effects of BCG vaccination on changes in glucose tolerance and insulin response were investigated in HFD-fed C57BL/6 mice. Materials and Methods: We used the BCG Tokyo 172 strain to determine effects on abnormalities in glucose metabolism. For vaccination, five-week-old male mice were injected intraperitoneally with BCG and maintained on a HFD for three weeks. The mice were regularly subjected to intraperitoneal glucose tolerance and insulin tolerance tests (IGTTs and ITTs). These tests were also performed in mice transplanted with bone marrow cells from BCG-vaccinated donor mice. Results: Significant effects of BCG vaccination on blood glucose levels in the IGTTs and ITTs were observed from week 12 of the experiment. BCG vaccination significantly improved changes in fasting glucose and insulin levels, insulin resistance indexes, and glucagon-to-insulin ratios in conjunction with the HFD at the end of the experiment. Significant inhibitory effects in the IGTTs and ITTs on glucose intolerance were also observed with transplantation with bone marrow cells derived from BCG-vaccinated donor mice. Conclusions: BCG vaccination significantly delayed glucose intolerance progression, suggesting a beneficial effect of BCG on the pathogenesis of type 2 diabetes. It has also been suggested that the effects of BCG vaccination may be at least partially due to an immune memory (trained immunity) for hematopoietic stem and progenitor cells of the bone marrow.
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Vaccin BCG , Alimentation riche en graisse , Intolérance au glucose , Souris de lignée C57BL , Animaux , Alimentation riche en graisse/effets indésirables , Vaccin BCG/administration et posologie , Souris , Mâle , Glycémie/analyse , Insulinorésistance , Évolution de la maladie , Hyperglycémie provoquée , Insuline/sang , Modèles animaux de maladie humaine , Vaccination/méthodesRÉSUMÉ
A Mycobacterium ulcerans human challenge model has the potential to fundamentally advance our understanding of early human immune responses to infection, while rapidly evaluating vaccines and other therapeutic interventions. Here, using a murine tail infection model, we tested a very well-characterized working cell bank of the proposed challenge isolate M. ulcerans JKD8049 in naïve and Mycobacterium bovis bacille Calmette-Guérin (BCG)-vaccinated BALB/c mice. All 10 naïve mice were successfully infected with 20 colony-forming units (CFU) of M. ulcerans [95% confidence interval (CI) 17-22 CFU] with a mean time to visible lesion of 86 days (95% CI 79-92 days). In the 10 vaccinated mice, there was a significant delay in the mean time to lesion compared to the naïve controls of 24 days (P = 0.0003), but all mice eventually developed ulcerative lesions. This study informs a future human infection model by demonstrating the successful application of the challenge agent in this in vivo model and highlights both the promise and the problems with trying to induce protective immunity against M. ulcerans. IMPORTANCE: In preparation for its proposed use in a controlled human infection model (CHIM), this study reports the successful infection of BALB/c mice using a carefully characterized, low-dose inoculum of Mycobacterium ulcerans JKD8049 (our proposed CHIM strain). We also demonstrate that Mycobacterium bovis bacille Calmette-Guérin delays the onset of disease but cannot alter the course of illness once a lesion becomes apparent. We also validate the findings of previous low-dose challenges that used less accurate methods to determine the inoculum, but our presented methodology is practical, accurate, and anticipated to be reproducible.
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Vaccins antibactériens , Ulcère de Buruli , Modèles animaux de maladie humaine , Souris de lignée BALB C , Mycobacterium ulcerans , Animaux , Souris , Mycobacterium ulcerans/immunologie , Projets pilotes , Femelle , Humains , Ulcère de Buruli/immunologie , Ulcère de Buruli/prévention et contrôle , Ulcère de Buruli/microbiologie , Vaccins antibactériens/immunologie , Vaccins antibactériens/administration et posologie , Mycobacterium bovis/immunologie , Vaccination , Vaccin BCG/immunologie , Vaccin BCG/administration et posologieRÉSUMÉ
BACKGROUND: A BCG booster vaccination administered via the respiratory mucosa may establish protective immune responses at the primary site of Mycobacterium tuberculosis infection. The primary objective of this trial was to compare the safety and immunogenicity of inhaled versus intramuscular administered ChAdOx1-85A. METHODS: We conducted a single-centre, randomised, double-blind, controlled phase 1 study (Swiss National Clinical Trials Portal number SNCTP000002920). After a dose-escalation vaccination in nine BCG-vaccinated healthy adults, a dose of 1 × 1010 vp of ChAdOx1-85A was administered to twenty BCG-vaccinated adults that were randomly allocated (1:1) into two groups: aerosol ChAdOx1-85A with intramuscular saline placebo or intramuscular ChAdOx1-85A with aerosol saline placebo, using block randomisation. A control group of ten BCG-naïve adults received aerosol ChAdOx1-85A at the same dose. Primary outcomes were solicited and unsolicited adverse events (AEs) up to day 16 post-vaccination and Serious AEs (SAEs) up to 24 weeks; secondary outcomes were cell-mediated and humoral immune responses in blood and bronchoalveolar lavage (BAL) samples. FINDINGS: Both vaccination routes were well tolerated with no SAEs. Intramuscular ChAdOx1-85A was associated with more local AEs (mostly pain at the injection site) than aerosol ChAdOx1-85A. Systemic AEs occurred in all groups, mainly fatigue and headaches, without differences between groups. Respiratory AEs were not different between BCG-vaccinated groups. Aerosol ChAdOx1-85A vaccination induced Ag85A BAL and systemic cellular immune responses with compartmentalisation of the immune responses: aerosol ChAdOx1-85A induced stronger BAL cellular responses, particularly IFNγ/IL17+CD4+ T cells; intramuscular ChAdOx1-85A induced stronger systemic cellular and humoral responses. INTERPRETATION: Inhaled ChAdOx1-85A was well-tolerated and induced lung mucosal and systemic Ag85A-specific T-cell responses. These data support further evaluation of aerosol ChAdOx1-85A and other viral vectors as a BCG-booster vaccination strategy.
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Vaccins antituberculeux , Humains , Mâle , Injections musculaires , Adulte , Femelle , Vaccins antituberculeux/administration et posologie , Vaccins antituberculeux/immunologie , Vaccins antituberculeux/effets indésirables , Méthode en double aveugle , Administration par inhalation , Jeune adulte , Aérosols , Vaccin ChAdOx1 nCoV-19/administration et posologie , Vaccination/méthodes , Mycobacterium tuberculosis/immunologie , Tuberculose/prévention et contrôle , Tuberculose/immunologie , Adulte d'âge moyen , Rappel de vaccin/méthodes , Vaccin BCG/administration et posologie , Vaccin BCG/immunologie , Vaccin BCG/effets indésirables , Immunité cellulaire , Immunité humorale , Anticorps antibactériens/sang , Immunogénicité des vaccinsRÉSUMÉ
BackgroundDenmark possesses an exceptional historical data collection on tuberculosis (TB) from 1876 to the present, providing a unique opportunity to assess TB epidemiology over 147 years in Denmark.AimOur aim was to describe the TB disease burden in Denmark in relation to historical events, living conditions and health interventions during the past 147 years.MethodsWe performed a nationwide register-based ecological study including all persons with TB in Denmark from 1876 through 2022, correlating the TB incidence to social, economic and health indicators.ResultsIn Denmark, the overall TB incidence and mortality declined markedly over the past 147 years, only marginally influenced by specific TB interventions such as sanatoria, Bacillus Calmette-Guèrin (BCG) vaccination, mass screenings and antibiotics. Parallel to this decline, the country experienced improved living conditions, as illustrated by decreased infant mortality and increased life expectancy and wealth. In 1978, Denmark became a low-incidence country for TB with risk groups predominantly affected, and with a continuous change in demographics towards fewer Danish-born cases and relatively more migrant cases.ConclusionsThe decline over time in TB incidence and mortality in Denmark preceded specific TB interventions and can, first of all, be attributed to improved living conditions. TB has now become a rare disease in Denmark, predominantly occurring in particular risk groups. Future elimination of TB will require a combination of specific health interventions in these risk groups combined with a continued focus on improving socioeconomic status and living conditions.
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Enregistrements , Tuberculose , Humains , Danemark/épidémiologie , Incidence , Tuberculose/épidémiologie , Tuberculose/prévention et contrôle , Femelle , Mâle , Histoire du 20ème siècle , Histoire du 19ème siècle , Histoire du 21ème siècle , Adulte , Adulte d'âge moyen , Nourrisson , Facteurs socioéconomiques , Dépistage de masse , Sujet âgé , Espérance de vie , Adolescent , Vaccin BCG/administration et posologie , Facteurs de risque , Enfant d'âge préscolaire , Jeune adulte , Enfant , Surveillance de la populationRÉSUMÉ
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Vaccin BCG , Tuberculose , Humains , Vaccin BCG/administration et posologie , Nourrisson , Enfant , Enfant d'âge préscolaire , Tuberculose/épidémiologie , Tuberculose/prévention et contrôle , Adolescent , Nouveau-né , Vaccination/statistiques et données numériques , Politique de santéRÉSUMÉ
The short-lived nature and heterogeneity of Natural Killer (NK) cells limit the development of NK cell-based therapies, despite their proven safety and efficacy against cancer. Here, we describe the biological basis, detailed phenotype and function of long-lived anti-tumour human NK cells (CD56highCD16+), obtained without cell sorting or feeder cells, after priming of peripheral blood cells with Bacillus Calmette-Guérin (BCG). Further, we demonstrate that survival doses of a cytokine combination, excluding IL18, administered just weekly to BCG-primed NK cells avoids innate lymphocyte exhaustion and leads to specific long-term proliferation of innate cells that exert potent cytotoxic function against a broad range of solid tumours, mainly through NKG2D. Strikingly, a NKG2C+CD57-FcεRIγ+ NK cell population expands after BCG and cytokine stimulation, independently of HCMV serology. This strategy was exploited to rescue anti-tumour NK cells even from the suppressor environment of cancer patients' bone marrow, demonstrating that BCG confers durable anti-tumour features to NK cells.
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Prolifération cellulaire , Cellules tueuses naturelles , Cellules tueuses naturelles/immunologie , Cellules tueuses naturelles/effets des médicaments et des substances chimiques , Humains , Prolifération cellulaire/effets des médicaments et des substances chimiques , Tumeurs/immunologie , Tumeurs/traitement médicamenteux , Vaccin BCG/immunologie , Vaccin BCG/administration et posologie , Mycobacterium bovis/immunologie , Activation des lymphocytes/effets des médicaments et des substances chimiques , Sous-famille K des récepteurs de cellules NK de type lectine/métabolisme , Interleukines/métabolisme , Antigènes CD56/métabolisme , Sous-famille C des récepteurs de cellules NK de type lectine/métabolismeRÉSUMÉ
The Montreal Cognitive Assessment (MoCA) is a valuable assessment of the patient's awareness of time and place. We show that bacille Calmette-Guerin (BCG) significantly affects MoCA testing when administered by the intravesical route. MoCA scores were lower with increasing age and higher in more formally educated individuals. Patients receiving BCG tended to maintain their MoCA scores, whereas almost half the control cases tended to show reduced scores. This benefit is supported by reduced pre-amyloid biomarkers in BCG-injected healthy volunteers and a favorable effect on neuronal dendritic development in animal models. Our results suggest that BCG has a beneficial impact on the cognitive status of older individuals.
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Vaccin BCG , Humains , Vaccin BCG/administration et posologie , Mâle , Femelle , Sujet âgé , Animaux , Administration par voie vésicale , Tests de l'état mental et de la démence , Adulte d'âge moyen , Cognition/effets des médicaments et des substances chimiques , Sujet âgé de 80 ans ou plusRÉSUMÉ
PURPOSE: Nonmuscle-invasive bladder cancer (NMIBC) has high recurrence rates and is often treated with mitomycin C (MMC) and bacillus Calmette-Guérin (BCG). Their efficacy relies on phase 2 enzyme metabolism and immune response activation, respectively. Dietary isothiocyanates, phytochemicals in cruciferous vegetables, are phase 2 enzyme inducers and immunomodulators, and may impact treatment outcomes. We investigated the modifying effects of cruciferous vegetable and isothiocyanate intake on recurrence risk following MMC or BCG treatment. MATERIALS AND METHODS: Self-reported cruciferous vegetable intake, estimated isothiocyanate intake, and urinary isothiocyanate metabolites were collected from 1158 patients with incident NMIBC in the prospective Be-Well Study. Hazard ratios (HRs) and 95% CIs were calculated from Cox proportional hazards regression models for risk of first recurrences, and random effects Cox shared frailty models for multiple recurrences. RESULTS: Over median follow-up of 23 months, 343 (30%) recurrences occurred. Receipt of MMC and BCG was associated with decreased risks of first recurrence (MMC: HR = 0.58; 95% CI: 0.46-0.73; BCG: HR = 0.66; 95% CI: 0.49-0.88) and multiple recurrences (MMC: HR = 0.55; 95% CI: 0.44-0.68; BCG: HR = 0.72; 95% CI: 0.55-0.95). Patients receiving BCG and having high intake (>2.4 servings/mo), but not low intake, of raw cruciferous vegetables had reduced risk of recurrence (HR: 0.56; 95% CI: 0.36-0.86; P for interaction = .02) and multiple recurrences (HR: 0.51; 95% CI: 0.34-0.77; P for interaction < .001). The inverse association between MMC receipt and recurrence risk was not modified. CONCLUSIONS: For NMIBC patients who receive induction BCG, increasing consumption of raw cruciferous vegetables could be a promising strategy to attenuate recurrence risk.
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Vaccin BCG , Isothiocyanates , Mitomycine , Récidive tumorale locale , Tumeurs de la vessie urinaire , Humains , Tumeurs de la vessie urinaire/anatomopathologie , Tumeurs de la vessie urinaire/traitement médicamenteux , Mitomycine/usage thérapeutique , Vaccin BCG/usage thérapeutique , Vaccin BCG/administration et posologie , Mâle , Femelle , Isothiocyanates/usage thérapeutique , Isothiocyanates/pharmacologie , Études prospectives , Sujet âgé , Adulte d'âge moyen , Récidive tumorale locale/prévention et contrôle , Récidive tumorale locale/épidémiologie , Résultat thérapeutique , Antibiotiques antinéoplasiques/usage thérapeutique , Adjuvants immunologiques/usage thérapeutique , Régime alimentaire , Invasion tumorale , Études de suiviRÉSUMÉ
BACKGROUND: Although photodynamic-diagnosed transurethral resection of bladder cancer (PDD-TURBT) and Bacillus Calmette-Guérin (BCG) intravesical instillation are the two representative therapies for non-muscle invasive bladder cancer (NMIBC), no studies directly compare their efficacy. We evaluated the outcome of PDD-TURBT alone compared with white light TURBT with intravesical BCG therapy and analyzed the efficacy of both therapies depending on the characteristics of the tumors. METHODS: We retrospectively analyzed intermediate- and high-risk NMIBC patients treated with PDD-TURBT alone (the PDD group) or white light TURBT with BCG therapy (the white light group) using propensity score matched analysis. RESULTS: In the propensity score matched cohort, the 1-, 2-, and 3-year recurrence-free survival rates for the PDD group were 77.6 %, 64.1 %, and 48.1 %, respectively, compared to 84.6 %, 75.1 %, and 75.1 % for the white light group (p = 0.44, 0.27, 0.17, respectively). The difference in recurrence rates between the two groups tended to become more pronounced over time, although there was no significant difference. In the univariate and multivariate analysis, recurrence, multiplicity, and tumor grade were the significant prognostic factors of recurrence in the PDD group (p = 0.010, 0.047, 0.048, respectively). Long-term RFS was similar in the PDD and white light groups when the population was limited to the primary and single tumors, suggesting that PDD-TURBT alone may be sufficient in this spectrum of patients. CONCLUSIONS: PDD-TURBT alone is insufficient to control the long-term recurrence of bladder cancer but can be effective in selected cases such as primary and single tumors.
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Vaccin BCG , Score de propension , Tumeurs de la vessie urinaire , Humains , Tumeurs de la vessie urinaire/traitement médicamenteux , Tumeurs de la vessie urinaire/thérapie , Mâle , Vaccin BCG/usage thérapeutique , Vaccin BCG/administration et posologie , Femelle , Études rétrospectives , Administration par voie vésicale , Sujet âgé , Adulte d'âge moyen , Photothérapie dynamique/méthodes , Récidive tumorale locale , Photosensibilisants/usage thérapeutique , Association thérapeutique , Sujet âgé de 80 ans ou plus , Adjuvants immunologiques/usage thérapeutique , Adjuvants immunologiques/administration et posologieRÉSUMÉ
Cretostimogene grenadenorepvec is a serotype-5 oncolytic adenovirus designed to selectively replicate in cancer cells with retinoblastoma pathway alterations, previously tested as monotherapy in bacillus Calmette-Guérin (BCG)-experienced non-muscle-invasive bladder cancer. In this phase 2 study, we assessed the potential synergistic efficacy between intravesical cretostimogene and systemic pembrolizumab in patients with BCG-unresponsive non-muscle-invasive bladder cancer with carcinoma in situ (CIS). Thirty-five patients were treated with intravesical cretostimogene with systemic pembrolizumab. Induction cretostimogene was administered weekly for 6 weeks followed by three weekly maintenance infusions at months 3, 6, 9, 12 and 18 in patients maintaining complete response (CR). Patients with persistent CIS/high-grade Ta at the 3-month assessment were eligible for re-induction. Pembrolizumab was administered for up to 24 months. The primary endpoint was CR at 12 months as assessed by cystoscopy, urine cytology, cross-sectional imaging and mandatory bladder mapping biopsies. Secondary endpoints included CR at any time, duration of response, progression-free survival and safety. The CR rate in the intention-to-treat population at 12 months was 57.1% (20 out of 35, 95% confidence interval (CI) 40.7-73.5%), meeting the primary endpoint. A total of 29 out of 35 patients (82.9%, 95% CI 70.4-95.3%) derived a CR at 3 months. With a median follow-up of 26.5 months, the median duration of response has not been reached (95% CI 15.7 to not reached). The CR rate at 24 months was 51.4% (18 out of 35) (95% CI 34.9-68.0%). No patient progressed to muscle-invasive bladder cancer in this trial. Adverse events attributed to cretostimogene were low grade, self-limiting and predominantly limited to bladder-related symptoms. A total of 5 out of 35 patients (14.3%) developed grade 3 treatment-related adverse effects. There was no evidence of overlapping or synergistic toxicities. Combination intravesical cretostimogene and systemic pembrolizumab demonstrated enduring efficacy. With a toxicity profile similar to its monotherapy components, this combination may shift the benefit-to-risk ratio for patients with BCG-unresponsive CIS. ClinicalTrials.gov Identifier: NCT04387461 .
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Adenoviridae , Anticorps monoclonaux humanisés , Vaccin BCG , Thérapie virale de cancers , Tumeurs de la vessie urinaire , Humains , Tumeurs de la vessie urinaire/thérapie , Tumeurs de la vessie urinaire/anatomopathologie , Tumeurs de la vessie urinaire/traitement médicamenteux , Anticorps monoclonaux humanisés/usage thérapeutique , Femelle , Mâle , Sujet âgé , Thérapie virale de cancers/méthodes , Adulte d'âge moyen , Vaccin BCG/usage thérapeutique , Vaccin BCG/administration et posologie , Vaccin BCG/effets indésirables , Adenoviridae/génétique , Association thérapeutique , Sujet âgé de 80 ans ou plus , Virus oncolytiques/génétique , Antinéoplasiques immunologiques/usage thérapeutique , Épithélioma in situ/thérapie , Épithélioma in situ/anatomopathologie , Épithélioma in situ/traitement médicamenteux , Tumeurs de la vessie n'infiltrant pas le muscleRÉSUMÉ
BACKGROUND: The aim of this study was to evaluate whether the sequential use of Mitomycin C (MMC) and Bacillus Calmette-Guérin (BCG) is superior to BCG alone in reducing the risk of disease recurrence in patients with non-muscle invasive bladder cancer (NMIBC) with high risk of progression. METHODS: Prospective randomized trial was conducted from March 2021 to March 2023 and included 72 patients with high risk NMIBC. Trial registration number: NCT03790384; EUDRACT Number: 2017-004540-37. Thirty-one patients underwent to BCG alone and forty-one to MMC plus BCG during the induction course. The BCG schedule comprised six weekly instillation of 81 mg Connaught strain BCG as the induction course, followed by a further three-monthly instillation at three, six and twelve months, as the maintenance course. Forty mg of MMC were administered the day prior to each weekly BCG instillation in BCG plus MMC arm. A planned interim analysis was carried out in June 2023, at the end of the 12mo follow-up period. RESULTS: Six out of thirteen 6/31(19.3%) and 10/41 (24.4%) patients experienced recurrence in BCG and BCG plus MMC group (P=0.611), respectively. BCG plus MMC did not improve Disease Free Interval (HR: 1.23 95% CI:0.46-3.50; P=0.640). Patients receiving sequential treatment experienced similar AEs (P>0.05) and more urinary symptoms (P<0.05). CONCLUSIONS: This interim pre-planned analysis suggested absence of clinical advantages in terms of disease recurrence rate when MMC is administered one day prior to BCG during induction course.
Sujet(s)
Vaccin BCG , Mitomycine , Invasion tumorale , Tumeurs de la vessie urinaire , Humains , Tumeurs de la vessie urinaire/traitement médicamenteux , Tumeurs de la vessie urinaire/anatomopathologie , Mitomycine/administration et posologie , Mitomycine/usage thérapeutique , Mitomycine/effets indésirables , Vaccin BCG/usage thérapeutique , Vaccin BCG/administration et posologie , Mâle , Femelle , Études prospectives , Sujet âgé , Adulte d'âge moyen , Adjuvants immunologiques/usage thérapeutique , Adjuvants immunologiques/administration et posologie , Traitement médicamenteux adjuvant , Antibiotiques antinéoplasiques/usage thérapeutique , Antibiotiques antinéoplasiques/administration et posologie , Association de médicaments , Récidive tumorale locale/prévention et contrôle , Récidive tumorale locale/anatomopathologie , Résultat thérapeutique , Administration par voie vésicaleRÉSUMÉ
In the wake of the COVID-19 pandemic caused by SARS-CoV-2, questions emerged about the potential effects of Bacillus Calmette-Guérin (BCG) vaccine on the immune response to SARS-CoV-2 infection, including the neurodegenerative diseases it may contribute to. To explore this, an experimental study was carried out in BCG-stimulated and non-stimulated k18-hACE2 mice challenged with SARS-CoV-2. Viral loads in tissues determined by RT-qPCR, histopathology in brain and lungs, immunohistochemical study in brain (IHC) as well as mortality rates, clinical signs and plasma inflammatory and coagulation biomarkers were assessed. Our results showed BCG-SARS-CoV-2 challenged mice presented higher viral loads in the brain and an increased frequency of neuroinvasion, with the greatest differences observed between groups at 3-4 days post-infection (dpi). Histopathological examination showed a higher severity of brain lesions in BCG-SARS-CoV-2 challenged mice, mainly consisting of neuroinflammation, increased glial cell population and neuronal degeneration, from 5 dpi onwards. This group also presented higher interstitial pneumonia and vascular thrombosis in lungs (3-4 dpi), BCG-SARS-CoV-2 mice showed higher values for TNF-α and D-dimer values, while iNOS values were higher in SARS-CoV-2 mice at 3-4 dpi. Results presented in this study indicate that BCG stimulation could have intensified the inflammatory and neurodegenerative lesions promoting virus neuroinvasion and dissemination in this experimental model. Although k18-hACE2 mice show higher hACE2 expression and neurodissemination, this study suggests that, although the benefits of BCG on enhancing heterologous protection against pathogens and tumour cells have been broadly demonstrated, potential adverse outcomes due to the non-specific effects of BCG should be considered.
Sujet(s)
Vaccin BCG , Encéphale , COVID-19 , SARS-CoV-2 , Animaux , Souris , Vaccin BCG/administration et posologie , COVID-19/immunologie , COVID-19/virologie , SARS-CoV-2/physiologie , Encéphale/anatomopathologie , Encéphale/virologie , Charge virale , Poumon/anatomopathologie , Poumon/virologie , Poumon/immunologie , Angiotensin-converting enzyme 2/métabolisme , Souris transgéniques , FemelleRÉSUMÉ
Although BCG use as an anticancer drug was nearly abandoned due to the poor results in most tumors, in 1976 Morales reported a relevant reduction in recurrence with intravesical BCG in few patients affected by NMIBC. Since then BCG was globally accepted as an empirical and effective therapy in treating Tis and preventing recurrence of intermediate and high risk NMIBC. Forty-eight years after Morales' report, although some open questions remain object of debate, we have been able to find answers to many doubts improving BCG activity and toxicity. We better select patients undergoing BCG and many trials have indicated the best dosage and schedule. Moreover, we are able to better identify the patient unresponsive to BCG who might benefit of a timely radical cystectomy. We are also aware of the difficulties and toxicities that can be encountered with BCG use in every-day clinical practice. Research is ongoing to obtain genetically modified BCG to increase its efficacy and reduce toxicity. Moreover, the combination of BCG with other immunotherapeutic drugs given intravesically or systemically, first immune checkpoint inhibitors, is under study to obtain a response in patients unresponsive or intolerant to BCG. Almost 50 years after Morales publication, intravesical BCG remains an inalienable tool against NMIBC.
Sujet(s)
Adjuvants immunologiques , Vaccin BCG , Tumeurs de la vessie urinaire , Tumeurs de la vessie urinaire/thérapie , Tumeurs de la vessie urinaire/traitement médicamenteux , Humains , Vaccin BCG/administration et posologie , Vaccin BCG/usage thérapeutique , Adjuvants immunologiques/usage thérapeutique , Adjuvants immunologiques/administration et posologie , Facteurs temps , Administration par voie vésicaleRÉSUMÉ
The effect of the Bacille Calmette-Guérin (BCG) vaccine on the immunogenicity of separately administered serogroup C meningococcal vaccine and other vaccinations was examined in 28 infants randomized to receive BCG at age ≤7 days, at 3 months or after study completion. Immunogenicity of the serogroup C meningococcal vaccine and other routine vaccines might be improved when BCG is administered in early infancy.