RESUMO
BACKGROUND: Intravesical bacillus Calmette-Guerin (IVBCG) is considered the most optimal follow-up therapy for high-risk urothelial cancers. Although side effects such as cystitis, hematuria, and low-grade fever are common, they are generally mild. Severe reactions involving the kidneys are extremely rare. Here, we present the case of a 64-year-old male who developed acute renal failure due to acute tubulointerstitial nephritis (ATIN) following the first IVBCG administration. We have also conducted a literature review concerning IVBCG-induced nephritis. CASE REPORT: A 64-year-old male presented to the Nephrology Department with acute kidney injury indicators and hematuria. The patient was suffering from high-grade papillary urothelial carcinoma. Transurethral resection of the bladder tumor was performed twice and followed by one IVBCG administration - two days before the symptoms occurred. The latest follow-up cystoscopy excluded the recurrence of the cancer. Laboratory tests displayed hyperkalemia, decreased glomerular filtration rate (GFR = 4 ml/min/1.73 m2), elevated C-reactive protein, and acute metabolic acidosis. Urinalysis showed proteinuria (900 mg/24 h), leukocyturia, and erythrocyturia (20,402.7 per microliter). Renal ultrasound demonstrated slight bilateral renal enlargement. The patient was identified with acute tubulointerstitial nephritis (ATIN). The treatment involved intravenous methylprednisolone (250 mg three times every two days and then 125 mg four times every two days), fol-lowed by oral methylprednisolone (24 mg and 12 mg daily alternately for a week). Piperacillin and tazobactam, probiotics, and proton pump inhibitors were also administered. Hemodialysis was conducted three times. Two weeks after the admission, a significant improvement was observed: creatinine decreased to 2.04 mg/dl, and GFR increased to 33 ml/min/1.73 m2. The patient was discharged with a recommendation to reduce the dose of glucocorticosteroids and continued in the outpatient clinic. CONCLUSIONS: IVBCG may lead to acute kidney injury due to ATIN. Symptoms may occur as early as after the first IVBCG, contrary to previous reports. Patients should be regularly assessed for potential complications, including creatine level measurement, after each IVBCG treatment.
Assuntos
Injúria Renal Aguda , Vacina BCG , Nefrite Intersticial , Humanos , Masculino , Nefrite Intersticial/induzido quimicamente , Nefrite Intersticial/diagnóstico , Pessoa de Meia-Idade , Vacina BCG/efeitos adversos , Vacina BCG/administração & dosagem , Injúria Renal Aguda/induzido quimicamente , Neoplasias da Bexiga Urinária/tratamento farmacológico , Administração IntravesicalRESUMO
BACKGROUND: The BCG vaccine has been traditionally administered to prevent TB. It has been additionally used in bladder cancer patients as a therapy with success. Some observational studies found that bladder cancer patients receiving BCG may have reduced dementia risk, however, the evidence is not conclusive. OBJECTIVE: To investigate the impact of BCG vaccine on dementia risk in bladder cancer patients. METHODS: Six databases were searched from inception to January 13, 2024, for published and unpublished studies that examine the association between BCG and dementia risk in bladder cancer patients. We conducted meta-analyses using a random-effects model. RESULTS: Eight retrospective cohort studies were included in the systematic review and seven in the meta-analyses. Because there were studies with overlapping populations, two separate main analyses were performed reassuring the avoidance of overlap. The first analysis showed that compared to controls, BCG did not reduce dementia risk [5 studies pooled, n=88,852, HR = 0.65, 95% CI (0.40, 1.06), I2 = 85%] whereas there was a marginally significant risk reduction in the second analysis [6 studies pooled, n=70,025, HR = 0.63, 95% CI (0.40, 0.97), I2 = 83%]. Sensitivity analysis excluding the unpublished studies did not affect the outcome importantly. Additional meta-analysis showed that BCG did not reduce the risk of Alzheimer's disease. CONCLUSION: This meta-analysis of observational studies found that BCG administration in bladder cancer patients has likely a minimally positive impact on dementia risk if any. To better understand the effect of BCG on dementia, randomized controlled trials are needed.
Assuntos
Vacina BCG , Demência , Neoplasias da Bexiga Urinária , Neoplasias da Bexiga Urinária/prevenção & controle , Humanos , Vacina BCG/administração & dosagem , Demência/prevenção & controleRESUMO
OBJECTIVES: Current data suggests that Bacille Calmette-Guerin (BCG) vaccination contributes to nonspecific enhancement of resistance to various infections. Thus, BCG vaccination induces both specific immunity against mycobacteria and non-specific "trained immunity" against various pathogens. To understand the fundamental mechanisms of "trained" immunity, studies of transcriptome changes occurring during BCG vaccination in innate immunity cells, as well as in their precursors, are necessary. Furthermore, this data possesses important significance for practical applications associated with the development of recombinant BCG strains aimed to enhance innate immunity against diverse infectious agents. DATA DESCRIPTION: We performed RNA sequencing of innate immune cells derived from murine bone marrow and spleen three days after subcutaneous BCG vaccination. Using fluorescence-activated cell sorting we obtained three cell populations for each mouse from both control and BCG vaccinated groups: bone marrow monocytes and neutrophils and splenic NK-cells. Then double-indexed cDNA libraries for Illumina sequencing from the collected samples were prepared, the resulting cDNA library mix was subjected to NovaSeq 6000 sequencing. This paper describes the collection of 24 RNA sequencing samples comprising 4 sets of immune cell populations obtained from subcutaneously BCG-vaccinated and control mice.
Assuntos
Vacina BCG , Imunidade Inata , Baço , Transcriptoma , Animais , Vacina BCG/imunologia , Vacina BCG/administração & dosagem , Camundongos , Transcriptoma/genética , Baço/imunologia , Vacinação/métodos , Células Matadoras Naturais/imunologia , Camundongos Endogâmicos C57BL , Injeções Subcutâneas , Monócitos/imunologia , Feminino , Neutrófilos/imunologia , Análise de Sequência de RNA/métodos , Células da Medula Óssea/imunologiaRESUMO
BACKGROUND: Bladder cancer continues to be a significant health issue, leading to ongoing research into novel biomarkers and treatment strategies. This study aims to evaluate the potential of serum fibronectin levels and fibronectin gene polymorphisms as biomarkers for predicting the recurrence and treatment response in patients with NMIBC undergoing intravesical BCG therapy. METHODS: Between June 2022 and December 2022, data of 73 patients who applied to the Mersin University Urology Clinic due to NMIBC and were followed and treated in our clinic, receiving intravesical BCG treatment, when necessary, as well as 56 individuals without any malignancy, were prospectively examined. Serum fibronectin levels were measured using the enzyme-linked immunosorbent assay method. PCR testing was applied for the fibronectin gene RS10202709 and RS 35,343,655 gene polymorphisms by using Real-Time PCR. RESULTS: The mean serum fibronectin level in the patient group was 76.794 ± 66.998ng/ml. Simultaneously, it was 50.486 ± 25.156ng/ml in the control group, and these differences in serum fibronectin levels were statistically significant(p = 0.003). Out of the 73 patients included in the study, recurrence of bladder cancer was observed in 53 of them. They were divided into two groups based on the recurrence times: early recurrence and late recurrence. The mean fibronectin level in the early recurrence group was 102 ± 86.1 ng/ml, while it was 44.7 ± 11.8 ng/ml in the late recurrence group. Emphasize the significance of the higher fibronectin levels in the early recurrence group by stating, patients with early recurrence exhibited significantly higher serum fibronectin levels compared to those with late recurrence (p < 0.001), suggesting a potential role for fibronectin as a prognostic biomarker. CONCLUSIONS: The statistically higher concentrations of serum fibronectin levels in patients with bladder cancer observed in our study are a noteworthy finding. These findings suggest that serum fibronectin levels could serve as a valuable prognostic biomarker for early recurrence in NMIBC patients, although their predictive value for BCG treatment response remains limited.
Assuntos
Adjuvantes Imunológicos , Vacina BCG , Fibronectinas , Invasividade Neoplásica , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/sangue , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética , Fibronectinas/sangue , Vacina BCG/uso terapêutico , Vacina BCG/administração & dosagem , Masculino , Feminino , Administração Intravesical , Pessoa de Meia-Idade , Idoso , Prognóstico , Adjuvantes Imunológicos/uso terapêutico , Adjuvantes Imunológicos/administração & dosagem , Polimorfismo Genético , Estudos Prospectivos , Recidiva Local de Neoplasia/sangue , Biomarcadores Tumorais/sangue , Neoplasias não Músculo Invasivas da BexigaRESUMO
Bacille Calmette-Guérin (BCG) vaccine has been used increasingly in immunotherapy, including treatment of non-muscle-invasive bladder cancer, as an adjuvant therapy in metastatic prostate cancer and metastatic melanoma. However, systemic infection from inadvertent intravenous (instead of intravesical) injection is uncommon and can have systemic ramifications. We encountered 3 patients with disseminated Mycobacterium bovis infection that ensued after intravenous BCG injection.
Assuntos
Vacina BCG , Mycobacterium bovis , Humanos , Vacina BCG/efeitos adversos , Vacina BCG/administração & dosagem , Masculino , Mycobacterium bovis/isolamento & purificação , Mycobacterium bovis/imunologia , Pessoa de Meia-Idade , Injeções Intravenosas , Tuberculose/tratamento farmacológico , Idoso , Neoplasias da Bexiga Urinária/tratamento farmacológicoRESUMO
Background: As part of the Immunisation Agenda 2030, the World Health Organization set a goal to reduce the number of children who did not receive any routine vaccine by 50% by 2030. We aimed to describe the patterns of vaccines received for children with zero, one, and up to full vaccination, while considering newly deployed vaccines (pneumococcal conjugate vaccine (PCV) and rotavirus (ROTA) vaccine) alongside longstanding ones such as the Bacille Calmete-Guérin (BCG), diphtheria, tetanus, and pertussis (DPT), and poliomyelitis vaccines, and measles-containing vaccines (MCVs). Methods: We used data from national household surveys (Demographic and Health Surveys and Multiple Indicator Cluster Surveys) carried out in 43 low- and middle-income countries since 2014. We calculated the immunisation cascade as a score ranging from zero to six, considering BCG, polio, DPT, and ROTA vaccines, and the MCV and PCV. We also described the most prevalent combination of vaccines. The analyses were pooled across countries and stratified by household wealth quintiles. Results: In the pooled analyses with all countries combined, 9.0% of children failed to receive any vaccines, 58.6% received at least one dose of each of the six vaccines, and 47.2% were fully vaccinated with all doses. Among the few children receiving 1-5 vaccines, the most frequent were BCG vaccines, polio vaccines, DPT vaccines, PCV, ROTA vaccines, and MCV. Conclusions: Targeting children with their initial vaccine is crucial, as those who receive a first vaccine are more likely to undergo subsequent vaccinations. Finding zero-dose children and starting their immunisation is essential to leaving no one behind during the era of Sustainable Development Goals.
Assuntos
Programas de Imunização , Humanos , Lactente , Pré-Escolar , Vacina contra Difteria, Tétano e Coqueluche/administração & dosagem , Esquemas de Imunização , Vacinas contra Rotavirus/administração & dosagem , Vacina contra Sarampo/administração & dosagem , Cobertura Vacinal/estatística & dados numéricos , Vacina BCG/administração & dosagem , Vacinas Pneumocócicas/administração & dosagem , Feminino , Masculino , Vacinação/estatística & dados numéricos , Países em DesenvolvimentoRESUMO
BackgroundsË The objective of this study was to assess the efficacy of gemcitabine as a treatment option for patients diagnosed with non-muscle invasive bladder cancer (NMIBC) who had previously experienced failure with Bacillus Calmette-Guerin (BCG) therapy in the last year. METHODS: We prospectively enrolled 28 patients with recurrent NMIBC after previous intravesical treatment in the last year who declined or were unsuitable for cystectomy between 2021 and 2023. Gemcitabine at 2,000 mg/100 mL was instilled weekly for 6 weeks. Patients were assessed for response after 8 weeks, with subsequent evaluations scheduled every three months to one year. RESULTS: The findings demonstrated that out of the 28 patients, 20 (71.4%) exhibited a complete response to intravesical gemcitabine treatment, and 8 (28.6%) had no complete response. The average age of the participants was 60.25 years. The study identified significant differences in treatment response based on age but without significant differences based on gender. Furthermore, there was no noteworthy association between tumor stage and grade and treatment response. Moreover, among patients with low-grade tumors, 66.7% achieved a complete response, while 72.7% reached a complete response among those with high-grade tumors. Of the patients who reached a complete response, 28.6% experienced no recurrence during one year of follow-up, and 42.9% developed recurrent disease within one year of treatment initiation. Ten months following treatment, a patient developed muscle-invasive bladder cancer and went on to cystectomy. CONCLUSION: In conclusion, the results suggest that intravesical gemcitabine could represent a feasible choice for NMIBC patients unresponsive to BCG therapy and ineligible for or unwilling to undergo cystectomy.
Assuntos
Antimetabólitos Antineoplásicos , Vacina BCG , Desoxicitidina , Gencitabina , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Desoxicitidina/análogos & derivados , Desoxicitidina/administração & dosagem , Desoxicitidina/uso terapêutico , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Prospectivos , Administração Intravesical , Vacina BCG/administração & dosagem , Vacina BCG/uso terapêutico , Idoso , Antimetabólitos Antineoplásicos/uso terapêutico , Antimetabólitos Antineoplásicos/administração & dosagem , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Seguimentos , Falha de Tratamento , Adjuvantes Imunológicos/administração & dosagem , Invasividade Neoplásica , Prognóstico , Adulto , Neoplasias não Músculo Invasivas da BexigaAssuntos
Vacina BCG , Neoplasias da Bexiga Urinária , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Humanos , Vacina BCG/administração & dosagem , Vacina BCG/uso terapêutico , Administração Intravesical , Seguimentos , Invasividade Neoplásica , Adjuvantes Imunológicos/administração & dosagem , Adjuvantes Imunológicos/uso terapêutico , Resultado do TratamentoRESUMO
SARS-CoV-2 is the causative virus of COVID-19, which has been responsible for millions of deaths worldwide since its discovery. After its emergence, several variants have been identified that challenge the efficacy of the available vaccines. Previously, we generated and evaluated a vaccine based on a recombinant Bacillus Calmette-Guérin (rBCG) expressing the nucleoprotein (N) of SARS-CoV-2 (rBCG-N-SARS-CoV-2). This protein is a highly immunogenic antigen and well conserved among variants. Here, we tested the administration of this vaccine with recombinant N and viral Spike proteins (S), or Receptor Binding Domain (RBD-Omicron variant), plus a booster with the recombinant proteins only, as a novel and effective strategy to protect against SARS-CoV-2 variants. METHODS: BALB/c mice were immunized with rBCG-N-SARS-CoV-2 and recombinant SARS-CoV-2 proteins in Alum adjuvant, followed by a booster with recombinant proteins to assess the safety and virus-specific cellular and humoral immune responses against SARS-CoV-2 antigens. RESULTS: Immunization with rBCG-N-SARS-CoV-2 + recombinant proteins as a vaccine was safe and promoted the activation of CD4+ and CD8+ T cells that recognize SARS-CoV-2 N, S, and RBD antigens. These cells were able to secrete cytokines with an antiviral profile. This immunization strategy also induced robust titers of specific antibodies against N, S, and RBD and neutralizing antibodies of SARS-CoV-2. CONCLUSIONS: Co-administration of the rBCG-N-SARS-CoV-2 vaccine with recombinant SARS-CoV-2 proteins could be an effective alternative to control particular SARS-CoV-2 variants. Due to its safety and capacity to induce virus-specific immune responses, we believe the rBCG-N-SARS-CoV-2 + Proteins vaccine could be an attractive candidate to protect against this virus, especially in newborns.
Assuntos
Anticorpos Antivirais , Vacina BCG , Vacinas contra COVID-19 , COVID-19 , Camundongos Endogâmicos BALB C , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Animais , Camundongos , SARS-CoV-2/imunologia , SARS-CoV-2/genética , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/genética , COVID-19/prevenção & controle , COVID-19/imunologia , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Vacina BCG/imunologia , Vacina BCG/administração & dosagem , Vacina BCG/genética , Feminino , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Imunização Secundária , Vacinas Sintéticas/imunologia , Vacinas Sintéticas/administração & dosagem , Imunidade Humoral , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/genética , Proteínas do Nucleocapsídeo de Coronavírus/imunologia , Proteínas do Nucleocapsídeo de Coronavírus/genética , Linfócitos T CD8-Positivos/imunologia , Fosfoproteínas/imunologia , Fosfoproteínas/genética , Adjuvantes Imunológicos/administração & dosagem , Imunidade CelularRESUMO
OBJECTIVES: Bacille Calmette-Guérin (BCG) vaccine has immunomodulatory effects that may provide protection against unrelated infectious diseases. We aimed to determine whether BCG vaccination protects adults against COVID-19. DESIGN: Phase III double-blind randomised controlled trial. SETTING: Healthcare centres in Australia, Brazil, the Netherlands, Spain, and the United Kingdom during the COVID-19 pandemic. PARTICIPANTS: 3988 healthcare workers with no prior COVID-19 and no contraindication to BCG. INTERVENTION: Randomised 1:1 using a web-based procedure to receive a single 0.1 mL intradermal dose of BCG-Denmark (BCG group, n = 1999) or saline (placebo group, n = 1989). MAIN OUTCOME MEASURES: Difference in incidence of (i) symptomatic and (ii) severe COVID-19 during the 12 months following randomisation in the modified intention to treat (mITT) population (confirmed SARS-CoV-2 naïve at inclusion). RESULTS: Of the 3988 participants randomised, 3386 had a negative baseline SARS-CoV-2 test and were included in the mITT population. The 12-month adjusted estimated risk of symptomatic COVID-19 was higher in the BCG group (22.6%; 95% confidence interval [CI] 20.6 to 24.5%) compared with the placebo group (19.6%; 95% CI 17.6 to 21.5%); adjusted difference +3.0% points (95% CI 0.2 to 5.8%; p = 0.04). The 12-month adjusted estimated risk of severe COVID-19 (mainly comprising those reporting being unable to work for ≥3 consecutive days) was 11.0% in the BCG group (95% CI 9.5 to 12.4%) compared with 9.6% in the placebo group (95% CI 8.3 to 11.1%); adjusted difference +1.3% points (95% CI -0.7 to 3.3%, p = 0.2). Breakthrough COVID-19 (post COVID-19 vaccination) and asymptomatic SARS-CoV-2 infections were similar in the two groups. There were 18 hospitalisations due to COVID-19 (11 in BCG group, 7 in placebo group; adjusted hazard ratio 1.56, 95% CI 0.60 to 4.02, p = 0.4) and two deaths due to COVID-19, both in the placebo group. CONCLUSIONS: Compared to placebo, vaccination with BCG-Denmark increased the risk of symptomatic COVID-19 over 12 months among healthcare workers and did not decrease the risk of severe COVID-19 or post-vaccination breakthrough COVID-19. TRIAL REGISTRATION: ClinicalTrials.gov NCT04327206.
Assuntos
Vacina BCG , COVID-19 , Pessoal de Saúde , SARS-CoV-2 , Humanos , Vacina BCG/administração & dosagem , Vacina BCG/imunologia , COVID-19/prevenção & controle , COVID-19/epidemiologia , Masculino , Feminino , Adulto , Método Duplo-Cego , Pessoa de Meia-Idade , SARS-CoV-2/imunologia , Vacinação , Austrália/epidemiologia , Brasil/epidemiologia , Reino Unido/epidemiologia , Espanha/epidemiologiaRESUMO
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.
Assuntos
Vacina BCG , Cicatriz , Pele , Vacina Antivariólica , Vacinação , Animais , Humanos , Vacina BCG/administração & dosagem , Vacina BCG/imunologia , Cicatriz/etiologia , Cicatriz/patologia , Cicatriz/imunologia , Pele/patologia , Pele/imunologia , Varíola/prevenção & controle , Varíola/imunologia , Vacina Antivariólica/administração & dosagem , Vacina Antivariólica/imunologiaAssuntos
Artrite Reativa , Vacina BCG , Interleucina-17 , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/cirurgia , Vacina BCG/efeitos adversos , Vacina BCG/administração & dosagem , Interleucina-17/antagonistas & inibidores , Artrite Reativa/tratamento farmacológico , Administração Intravesical , Masculino , Idoso , Pessoa de Meia-IdadeRESUMO
X-linked severe combined immunodeficiency (X-SCID), caused by mutations in the gamma-chain gene of the interleukin-2 receptor (IL2RG), is a prevalent form of SCID characterized by recurrent and fatal opportunistic infections that occur early in life. The incidence of disseminated bacillus Calmette-Guérin (BCG) disease among children with SCID is much higher than in the general population. Here, we report the case of a 4-month-old male infant who presented with subcutaneous induration, fever, an unhealed BCG vaccination site, and hepatosplenomegaly. Metagenomic next-generation sequencing in blood, and the detection of gastric juice and skin nodule pus all confirmed the infection of Mycobacterium tuberculosis. Lymphocyte subset analysis confirmed the presence of T-B+NK immunodeficiency. Whole-exome and Sanger sequencing revealed a novel microdeletion insertion mutation (c.316_318delinsGTGAT p.Leu106ValfsTer42) in the IL2RG gene, resulting in a rare shift in the amino acid sequence of the coding protein. Consequently, the child was diagnosed with X-SCID caused by a novel mutation in IL2RG, complicated by systemic disseminated BCG disease. Despite receiving systemic anti-infection treatment and four days of hospitalization, the patient died three days after discharge. To the best of our knowledge, this specific IL2RG mutation has not been previously reported. In our systemic review, we outline the efficacy of systemic anti-tuberculosis therapy, hematopoietic stem cell transplantation, and gene therapy in children with SCID and BCG diseases caused by IL2RG gene mutation.
Assuntos
Subunidade gama Comum de Receptores de Interleucina , Tuberculose , Doenças por Imunodeficiência Combinada Ligada ao Cromossomo X , Humanos , Lactente , Masculino , Vacina BCG/administração & dosagem , Vacina BCG/efeitos adversos , Vacina BCG/imunologia , Éxons , Subunidade gama Comum de Receptores de Interleucina/genética , Mutação , Mycobacterium bovis/imunologia , Mycobacterium bovis/patogenicidade , Tuberculose/imunologia , Tuberculose/prevenção & controle , Doenças por Imunodeficiência Combinada Ligada ao Cromossomo X/complicações , Doenças por Imunodeficiência Combinada Ligada ao Cromossomo X/diagnóstico , Doenças por Imunodeficiência Combinada Ligada ao Cromossomo X/genética , Doenças por Imunodeficiência Combinada Ligada ao Cromossomo X/imunologiaRESUMO
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.
Assuntos
Vacina BCG , COVID-19 , Tuberculose , Cobertura Vacinal , Humanos , Brasil/epidemiologia , Vacina BCG/administração & dosagem , Cobertura Vacinal/estatística & dados numéricos , Incidência , Lactente , Tuberculose/epidemiologia , Tuberculose/prevenção & controle , COVID-19/prevenção & controle , COVID-19/epidemiologia , Feminino , Programas de Imunização , Masculino , Vacinação/estatística & dados numéricos , SARS-CoV-2 , Disparidades em Assistência à Saúde , Recém-NascidoRESUMO
While more than four decades have elapsed since intravesical Bacillus Calmette-Guérin (BCG) was first used to manage non-muscle invasive bladder cancer (NMIBC), its precise mechanism of anti-tumor action remains incompletely understood. Besides the classic theory that BCG induces local (within the bladder) innate and adaptive immunity through interaction with multiple immune cells, three new concepts have emerged in the past few years that help explain the variable response to BCG therapy between patients. First, BCG has been found to directly interact and become internalized within cancer cells, inducing them to act as antigen-presenting cells (APCs) for T-cells while releasing multiple cytokines. Second, BCG has a direct cytotoxic effect on cancer cells by inducing apoptosis through caspase-dependent pathways, causing cell cycle arrest, releasing proteases from mitochondria, and inducing reactive oxygen species-mediated cell injury. Third, BCG can increase the expression of programmed death ligand 1 (PD-L1) on both cancer and infiltrating inflammatory cells to impair the cell-mediated immune response. Current data has shown that high-grade recurrence after BCG therapy is related to CD8+ T-cell anergy or 'exhaustion'. High-field cancerization and subsequently higher neoantigen presentation to T-cells are also associated with this anergy. This may explain why BCG therapy stops working after a certain time in many patients. This review summarizes the detailed immunologic reactions associated with BCG therapy and the role of immune cell subsets in this process. Moreover, this improved mechanistic understanding suggests new strategies for enhancing the anti-tumor efficacy of BCG for future clinical benefit.
Assuntos
Vacina BCG , Neoplasias da Bexiga Urinária , Neoplasias da Bexiga Urinária/imunologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/terapia , Neoplasias da Bexiga Urinária/patologia , Humanos , Vacina BCG/imunologia , Vacina BCG/uso terapêutico , Vacina BCG/administração & dosagem , Administração Intravesical , Antígeno B7-H1/imunologia , Antígeno B7-H1/metabolismo , Neoplasias não Músculo Invasivas da BexigaRESUMO
The study aimed to examine the impact of diabetes mellitus type 2 (DMII) on the oncological outcomes of non-muscle invasive bladder cancer (NMIBC) treated with Bacillus Calmette-Guérin (BCG) using comprehensive real-world data. We performed an analysis of data on NMIBC patients treated with BCG from the United States (US) National Phase II BCG/Interferon (IFN) trial database (125 centers) and pooled databases from three tertiary care institutions: France (FR), Lebanon (LB) (2000-2021), and the US (University of Iowa) (2011-2021). There were 867 patients from the Phase II trial, 1232 from the FR/LB cohort, and 233 from the US (Iowa) cohort (n = 2332). DM II was reported in 13% of the Phase II trial cohort, 14.4% of the FR/LB cohort, and 33.5% of the US (Iowa) cohort. The median follow-up was 24 months in the Phase II trial cohort, 25 months in the FR/LB cohort, and 48 months in the US (Iowa) cohort. In multivariable Cox regression analyses, DMII was not significantly associated with recurrence or progression of the tumor in any of the cohorts included in this study. DMII may not be a clinical prognostic factor for NMIBC patients treated with BCG. Prospective evaluation is needed.
Assuntos
Vacina BCG , Diabetes Mellitus Tipo 2 , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Vacina BCG/uso terapêutico , Vacina BCG/administração & dosagem , Feminino , Masculino , Idoso , Prognóstico , Pessoa de Meia-Idade , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Estados Unidos , Idoso de 80 Anos ou mais , Líbano , França , Neoplasias não Músculo Invasivas da BexigaRESUMO
BACKGROUND: The beneficial off-target effects of Bacille Calmette-Guérin (BCG) vaccination potentially include protection against allergy. OBJECTIVE: In the MIS BAIR trial, we aimed to determine whether neonatal BCG vaccination reduces atopic sensitisation and clinical food allergy in infants. METHODS: In this randomised controlled trial, 1272 neonates were allocated to BCG-Denmark vaccine (0.05 mL intradermal dose) or no BCG at birth. Randomisation was stratified by recruitment site, mode of delivery and plurality of birth. The primary outcome was the incidence of atopic sensitisation determined by skin prick test at 1 year of age. Food allergy was determined by 3-monthly online questionnaires and oral food challenges. Data were analysed by intention-to-treat using binary regression. CLINICALTRIALS: gov (NCT01906853). RESULTS: Atopic sensitisation during the first year of life was 22.9% among infants in the BCG group and 18.9% in the control group (adjusted risk difference (aRD) 3.8% (95% CI -1.5 to 9.1) after multiple imputation). Clinical food allergy was similar between infants in the BCG and control groups (9.8% vs. 9.6%; aRD 0.2, 95% CI -3.4 to 3.8). An interaction was observed between the primary outcome and maternal history of BCG vaccination. No interaction was observed for the additional prespecified potential effect modifiers tested (sex, delivery mode, family history of any allergy, season of birth, hepatitis B vaccination at randomisation, BCG scar and age at BCG administration). CONCLUSIONS AND CLINICAL RELEVANCE: Neonatal BCG-Denmark vaccination does not protect against atopic sensitisation or clinical food allergy in the first year of life.
Assuntos
Vacina BCG , Vacinação , Humanos , Vacina BCG/administração & dosagem , Vacina BCG/imunologia , Masculino , Feminino , Recém-Nascido , Lactente , Hipersensibilidade Alimentar/prevenção & controle , Hipersensibilidade Alimentar/imunologia , Testes Cutâneos , Hipersensibilidade/prevenção & controle , Hipersensibilidade/imunologiaRESUMO
The Bacille Calmette-Guerin (BCG) vaccine is a well-established inducer of innate immune memory (also termed trained immunity), causing increased cytokine production upon heterologous secondary stimulation. Innate immune responses are known to be influenced by season, but whether seasons impact induction of trained immunity is not known. To explore the influence of season on innate immune memory induced by the BCG vaccine, we vaccinated healthy volunteers with BCG either during winter or spring. Three months later, we measured the ex vivo cytokine responses against heterologous stimuli, analyzed gene expressions and epigenetic signatures of the immune cells, and compared these with the baseline before vaccination. BCG vaccination during winter induced a stronger increase in the production of pro-inflammatory cytokines by peripheral blood mononuclear cells (PBMCs) upon stimulation with different bacterial and fungal stimuli, compared to BCG vaccination in spring. In contrast, winter BCG vaccination resulted in lower IFNγ release in PBMCs compared to spring BCG vaccination. Furthermore, NK cells of the winter-vaccinated people had a greater pro-inflammatory cytokine and IFNγ production capacity upon heterologous stimulation. BCG had only minor effects on the transcriptome of monocytes 3 months later. In contrast, we identified season-dependent epigenetic changes in monocytes and NK cells induced by vaccination, partly explaining the higher immune cell reactivity in the winter BCG vaccination group. These results suggest that BCG vaccination during winter is more prone to induce a robust trained immunity response by activating and reprogramming the immune cells, especially NK cells. (Dutch clinical trial registry no. NL58219.091.16).
Assuntos
Vacina BCG , Citocinas , Imunidade Inata , Memória Imunológica , Leucócitos Mononucleares , Estações do Ano , Humanos , Vacina BCG/imunologia , Vacina BCG/administração & dosagem , Adulto , Masculino , Citocinas/imunologia , Citocinas/metabolismo , Leucócitos Mononucleares/imunologia , Feminino , Adulto Jovem , Células Matadoras Naturais/imunologia , Vacinação , Voluntários Saudáveis , Interferon gama/imunologia , Interferon gama/metabolismo , Imunidade TreinadaRESUMO
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.