Bacillus Calmette-Guérin Research Articles

Rationale of restaging transurethral resection of bladder tumor in patients with nonmuscle invasive bladder cancer in the current era.

We present retrospective data of patients with nonmuscle invasive bladder cancer (NMIBC) who underwent restaging transurethral resection of bladder tumor (Re-TURBT) at a tertiary care center. Records of all NMIBC patients undergoing Re-TURBT between March 2021 and September 2023 were retrospectively analyzed. Patients were risk stratified based on TURBT pathology. Re-TURBT was performed between 4 and 6 weeks. Adverse features such as number, size, and appearance were noted. Patients with persistent disease at Re-TURBT were counseled for early cystectomy with urinary diversion or intravesical Bacillus Calmette-Guerin (BCG). In case of disease upstaging, patients were counseled for radical cystectomy. Thirty-eight NMIBC patients (30 males and 8 females) underwent Re-TURBT. Six patients had residual/persistent disease at 6 weeks, all high risk and high grade (HG, P value not significant, P = 0.31). There was no association with number and appearance of tumors with residual/persistence at 6 weeks. The mean lesion size on imaging in cases with and without residual disease was 3.32 ± 0.86 versus 3.39 ± 0.92 cm, respectively, P value not significant (0.868). There was no residual disease in the low-grade (LG) pT1 group, but HG pTa and pT1 (n = 3) had residual disease. Four HG pT1 patients opted for early cystectomy. Two patients each had pT0 and two pT2. At 3 months of follow-up, urethral strictures were seen both in high risk and intermediate risk. Among four patients who had stricture, meatal stenosis was common (50%, n = 2). Two patients had long-segment stricture requiring perineal urethrostomy with stage I Johannsen repair. All HG pT1 lesion patients eventually underwent cystectomy (3 were under staged and two treated completely with TURBT, one with TURBT + BCG and one patient progressed to metastasis). Re-TURBT is essential for the management of HG pTa and HG pT1 lesions for accurate staging and treatment of residual disease. However, LG pT1 patients can safely be excluded from Re-TURBT.

Correlation Of BCG Vaccination And COVID-19 Disease Through Measurement Of Immunological Markers IFN-Γ And Anti-BCG Igg In Different Age Groups Running Title: Correlation Between BCG Vaccination And COVID-19 Disease

Introduction Coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in China in December 2019 and then became a pandemic. BCG vaccination has conferred non-specific (targeted-off) protective effects against unrelated pathogens including respiratory viral infections that have been hypothesized to it could reduce the severity of COVID-19 disease. Objective: Assess whether BCG vaccination has a role in the prevention of COVID-19. Methods: A cross-sectional study including 111 healthy people was carried out from October 2021 to December 2022. Specific anti-BGC-IgG and IFN-γ levels were estimated in blood samples after stimulation with BCG vaccine for 2 days. All participants were examined for BCG scar status and COVID-19 confirmation. Results: There was no significant difference in anti-BCG IgG levels or IFN-γ levels (p>0.05) in relation to COVID-19 infection. There was no statistically significant association between BCG scar diameter and COVID-19 infection (p>0.05). Furthermore, there was no statistically significant association between the BCG scar diameter and COVID-19 severity (p>0.05). There was no significant difference in anti-BCG IgG levels (p>0.05) in relation to COVID-19 severity. Likewise, there was no significant difference in between IFN γ levels and COVID-19 severity (p>0.05). Conclusion: There was no correlation between BCG vaccination and infection or severity of COVID-19.

Young age and adequate BCG are key factors for optimal BCG treatment efficacy in non-muscle-invasive bladder cancer

ObjectiveTo investigate the impact of ageing on survival outcomes in Bacillus Calmette–Guérin (BCG) treated non-muscle invasive bladder cancer (NMIBC) patients and its synergy with adequate BCG treatment.MethodPatients with NMIBC who received BCG treatment from 2001 to 2020 were divided into group 1 (< = 70 years) and group 2 (> 70 years). Overall Survival (OS), Cancer-Specific Survival (CSS), Recurrence-Free Survival (RFS), and Progression-Free Survival (PFS) were analyzed using the Kaplan–Meier method. Multivariable Cox regression analysis was used to adjust potential confounding factors and to estimate Hazard Ratio (HR) and 95% Confidence Interval (CI). Subgroup analysis was performed according to adequate versus inadequate BCG treatment.ResultsOverall, 2602 NMIBC patients were included: 1051 (40.4%) and 1551 (59.6%) in groups 1 and 2, respectively. At median follow-up of 11.0 years, group 1 (< = 70 years) was associated with better OS, CSS, and RFS, but not PFS as compared to group 2 (> 70 years). At subgroup analysis, patients in group 1 treated with adequate BCG showed better OS, CSS, RFS, and PFS as compared with inadequate BCG treatment in group 2, while patients in group 2 receiving adequate BCG treatment had 41% less progression than those treated with inadequate BCG from the same group.ConclusionsBeing younger (< = 70 years) was associated with better OS, CSS, and RFS, but not PFS. Older patients (> 70 years) who received adequate BCG treatment had similar PFS as those younger with adequate BCG treatment.

Real-word outcomes for high-risk non-muscle-invasive bladder cancer: screened patients for the BRAVO trial.

To report real-world outcomes for high-risk non-muscle-invasive bladder cancer (HRNMIBC), including bacillus Calmette-Guérin (BCG) and radical cystectomy (RC), as randomised comparisons of these have not been possible. We detail consecutive participants screened for the BRAVO randomised controlled trial comparing RC with BCG (International Standard Randomised Controlled Trial Number [ISRCTN]12509361). Patients were prospectively registered and case-note review used for outcomes. The primary outcome was overall survival. Secondary outcomes included recurrence, progression, metastasis, and bladder cancer-specific survival. A total of 193 patients were screened, including 106 (54.9%) who received BCG, 43 (22.3%) primary RC, 37 (19.2%) 'other' treatment and seven (3.6%) hyperthermic intravesical mitomycin C. All-cause death occurred in 55 (28.5%) patients at median (interquartile range [IQR]) of 29.0 (19.5-42.0) months. In multivariable analysis, overall mortality was more common in older patients (hazard ratio [HR] 2.63, 95% confidence interval [CI] 1.35-5.13; Cox P = 0.004 for age >70 years), those recruited from district hospitals (HR 0.53, 95% CI 0.3-0.95; P = 0.032) and those who did not undergo RC as their first treatment (HR 2.16, 95% CI 1.17-3.99; P = 0.014). In all, 17 (8.8%) patients died from bladder cancer (BC) at median (IQR) of 22.5 (19-36.25) months. In multivariable analysis, BC-specific mortality was more common in older patients (HR 4.87, 95% CI 1.1-21.6; P = 0.037) and those with Tis/T1 disease (HR 2.26, 95% CI 1.23-4.16; P = 0.008) but did not vary with initial treatment. Patients with HRNMIBC are at high-risk of mortality. Those choosing RC as their initial treatment have lower risks of mortality than others, although this may reflect fitness and selection.

Characterization of FGFR Alterations and Activation in Patients with High-Risk Non-Muscle-Invasive Bladder Cancer.

The Genomic Analysis of High-Risk Non-Muscle-Invasive Bladder Cancer (GARNER) study investigated FGFR alteration (ALT) frequency and the clinical outcome relationship with Bacillus Calmette-Guérin (BCG) treatment in high-risk non-muscle-invasive bladder cancer (HR-NMIBC). An FGFR predictive response signature (FGFR-PRS) was discovered that identifies patients with an activated FGFR pathway who could potentially benefit from FGFR-targeted therapy beyond those who are FGFR ALT (+). Pretreatment tumor samples and clinical data were analyzed from 582 BCG-treated patients with HR-NMIBC. FGFR-PRS was discovered using a separate bladder cancer dataset and applied to the GARNER and other bladder cancer cohorts. FGFR-PRS was also applied to in vitro data from urothelial cancer cell lines treated with FGFR-active agents. A total of 31% of pretreatment GARNER HR-NMIBC tumors were FGFR ALT (+), but this was not significantly associated with BCG response. For the subset of patients with paired pre- and post-BCG treatment samples, nearly one-third of pretreatment ALT (+) patients were ALT (-) posttreatment. FGFR-PRS identified patients with an activated FGFR pathway and identified approximately twofold additional patients compared with ALT status alone, and this increase was similar across tumor stage. A positive relationship between tumor growth inhibition and FGFR-PRS score was shown in bladder cancer in vitro models treated with FGFR-active agents. These data provide support for FGFR-targeted therapy use in FGFR ALT (+) HR-NMIBC and describe tumors with shared FGFR pathway-activated biology that is FGFR ALT (-) but FGFR-PRS (+). The latter suggests a broader potential patient population for FGFR-targeted therapy, which will require subsequent validation in patients treated with FGFR-targeted therapy.

The Impact of Vaccination Programs on the Prevention of Infectious Disease Tuberculosis: A Case Study with Gasabo District in Rwanda

Introduction Tuberculosis (TB) remained a significant public health challenge globally, including in Gasabo District, Rwanda. Vaccination programs, particularly Bacille Calmette-Guérin (BCG) vaccination, played a crucial role in TB prevention. This study aimed to assess the impact of vaccination programs on TB prevention in Gasabo District, Rwanda, by analyzing vaccination coverage, TB incidence rates, demographic characteristics, and healthcare system factors.  Methods A retrospective cohort study design was employed, utilizing secondary data sources from healthcare facilities in Gasabo District. Data on vaccination coverage, TB incidence rates, demographic characteristics, and healthcare system factors were collected and analyzed. Statistical methods, including regression analysis and descriptive statistics, were used to assess the association between vaccination programs and TB prevention outcomes.  Findings The study found a significant association between BCG vaccination coverage and lower TB incidence rates in Gasabo District. Higher vaccination coverage was associated with reduced TB incidence rates, particularly among children. However, challenges such as incomplete vaccination data, potential confounding factors, and socio-economic disparities were identified. Despite these challenges, vaccination programs were found to be effective in reducing TB transmission and protecting vulnerable populations from TB infection.  Conclusion The findings highlighted the importance of vaccination programs in TB prevention efforts in Gasabo District, Rwanda. Strengthening vaccination coverage, enhancing healthcare system capacity, addressing socio-economic determinants, fostering collaborations, promoting research and innovation, and strengthening surveillance and monitoring systems are essential for optimizing TB prevention efforts. By implementing these recommendations, we can accelerate progress towards ending the TB epidemic and improving public health outcomes in Gasabo District and beyond.

Intravenous Bacillus Calmette-Guérin (BCG) Induces a More Potent Airway and Lung Immune Response than Intradermal BCG in Simian Immunodeficiency Virus-infected Macaques.

Tuberculosis (TB), caused by Mycobacterium tuberculosis, is one of the leading causes of death due to an infectious agent. Coinfection with HIV exacerbates M. tuberculosis infection outcomes in people living with HIV. Bacillus Calmette-Guérin (BCG), the only approved TB vaccine, is effective in infants, but its efficacy in adolescents and adults is limited. In this study, we investigated the immune responses elicited by BCG administered via i.v. or intradermal (i.d.) routes in SIV-infected Mauritian cynomolgus macaques (MCM) without the confounding effects of M. tuberculosis challenge. We assessed the impact of vaccination on T cell responses in the airway, blood, and tissues (lung, thoracic lymph nodes, and spleen), as well as the expression of cytokines, cytotoxic effectors, and key transcription factors. Our results showed that i.v. BCG induces a robust and sustained immune response, including tissue-resident memory T cells in lungs, polyfunctional CD4+ and CD8αβ+ T cells expressing multiple cytokines, and CD8αβ+ T cells and NK cells expressing cytotoxic effectors in airways. We also detected higher levels of mycobacteria-specific IgG and IgM in the airways of i.v. BCG-vaccinated MCM. Although i.v. BCG vaccination resulted in an influx of tissue-resident memory T cells in lungs of MCM with controlled SIV replication, MCM with high plasma SIV RNA (>105 copies/ml) typically displayed reduced T cell responses, suggesting that uncontrolled SIV or HIV replication would have a detrimental effect on i.v. BCG-induced protection against M. tuberculosis.

Bacillus Calmette-Guérin Instillations May Mimic Prostate Cancer on Multiparametric Magnetic Resonance Imaging.

Granulomatous prostatitis (GP) is a rare and benign inflammatory condition of the prostate, often mimicking prostate cancer (PCa) in clinical and radiological evaluations. This study examines the characteristics and diagnostic challenges of GP in a cohort of 12 patients who received Bacillus Calmette-Guérin (BCG) therapy following treatment for non-muscle-invasive bladder urothelial carcinoma. In this case series, we analyze their clinical presentations, MRI findings, and histopathological results. Patients presented with elevated PSA levels and firm or nodular prostates on digital rectal examination, complicating the differentiation from PCa. Multiparametric MRI showed lesions with hypointensity on T2-weighted images, hypersignal on diffusion-weighted imaging and hyposignal on the apparent diffusion coefficient map, further mimicking malignancy. Histopathological examination remains the gold standard for diagnosing GP, distinguishing it from PCa through the identification of granulomas and associated inflammatory cells. This study underscores the importance of awareness and accurate diagnosis of GP to avoid unnecessary biopsies and treatments, highlighting the need for a multidisciplinary approach combining clinical, imaging, and pathological data.

Age and gender in drug resistance tuberculosis: A cross-sectional case study at a national tuberculosis reference hospital in Nigeria

ObjectivesDrug resistance in tuberculosis (TB) is a very important public health threat that should not be ignored. Understanding the gender, age, and characteristics of individuals affected by TB (without HIV, diabetes, or hepatitis B complications), particularly in terms of drug resistance or susceptibility, is crucial for effective prevention and management strategies, as most studies focus on TB/HIV co-infection. MethodsA cross-sectional case study of age and gender was carried out in 140 individuals grouped into drug-resistant tuberculosis (DR-TB), drug-susceptible tuberculosis (DS-TB), and apparently healthy controls (AHCs). Data collection was through medical records and a structured questionnaire. Statistical analyses compared age, gender, and selected risk factors across the groups. ResultsThe mean age of the DR-TB group was 32 years (SD ≈ 2). A total of 80.0% were ≤40 years of age and four times more likely to have DR-TB; 55% were male, with 1.22 times more likelihood of DR-TB in males. The mean age of the DS-TB group was 34 years (SD ≈ 12); 66.7% were ≤40 years old. The odds ratio of DS-TB in males was 2.16. Only 10% of DR-TB enrolees had BCG scars compared with 65% AHCs. A high percentage of the DR-TB group reported handling raw meat (75%) and drinking unpasteurised milk (70%) compared with the DS-TB group. ConclusionsThe observed gender disparities and age-related factors, particularly among the DR-TB group, highlight the importance of considering age and gender factors in DR-TB prevention, diagnosis, and treatment. Our findings also highlight the need to bridge gaps in awareness as well as for the prevention of zoonotic TB and issues around effective BCG vaccination and coverage.

Enhanced Antimicrobial Peptide Response Following Bacillus Calmette-Guerin Vaccination in Elderly Individuals.

Antimicrobial peptides are an important component of host defense against Mycobacterium tuberculosis. However, the ability of BCG to induce AMPs as part of its mechanism of action has not been investigated in detail. We investigated the impact of Bacillus Calmette-Guerin (BCG) vaccination on circulating plasma levels and TB-antigen stimulated plasma levels of AMPs in a healthy elderly population. We assessed the association of AMPs, including Human Beta Defensin 2 (HBD-2), Human Neutrophil Peptide 1-3 (HNP1-3), Granulysin, and Cathelicidin (LL37), in circulating plasma and TB-antigen stimulated plasma (using IGRA supernatants) at baseline (pre-vaccination) and at Month 1 and Month 6 post vaccination. Post BCG vaccination, both circulating plasma levels and TB-antigen stimulated plasma levels of AMPs significantly increased at Month 1 and Month 6 compared to pre-vaccination levels in the elderly population. However, the association of AMP levels with latent TB (LTB) status did not exhibit statistical significance. Our findings indicate that BCG vaccination is linked to heightened circulating levels of AMPs in the elderly population, which are also TB-antigen-specific. This suggests a potential mechanism underlying the immune effects of BCG in enhancing host defense against TB.

Impact of Bacille Calmette-Guérin vaccination on the therapeutic schedule of infantile epileptic spasms syndrome: A 25-year Japanese single-center survey

Adrenocorticotropic hormone (ACTH) therapy is effective for infantile epileptic spasms syndrome (IESS) but can induce immunosuppression. In Japan, Bacille Calmette-Guérin (BCG) vaccination, modified in 2013 to reduce osteitis/osteomyelitis risk, coincides with the peak onset age of IESS. This raises concerns about infection risks when administering ACTH therapy post-vaccination. To evaluate the impact of BCG vaccination timing on treatment decisions, we retrospectively reviewed the medical records of 86 IESS patients at our hospital (1996–2020). Infants who received ACTH therapy within eight weeks of BCG vaccination experienced no serious adverse events. Four patients deferred or opted out of ACTH therapy, with seizure remission taking 2–15 weeks. The overlap between IESS onset and BCG vaccination period presents clinical challenges in determining the appropriate timing for ACTH therapy. Further epidemiological and immunological research is needed to clarify the relationship between ACTH therapy and BCG-associated adverse events and to optimize treatment strategies and vaccination schedules.

Nutraceuticals and pharmacological to balance the transitional microbiome to extend immunity during COVID-19 and other viral infections

Abstract Scope The underlying medical conditions and gut dysbiosis is known to influence COVID-19 severity in high-risk patients. The current review proposed the optimal usage of nutraceuticals &amp; pharmacological interventions can help regulate the protective immune response and balance the regulatory functionality of gut microbiota. Summary Many studies have revealed that the probiotic interventions viz., Lactobacillus rhamnosus, L. plantarum &amp; other bacterial spp. reduce IFNγ &amp; TNF-α and increase IL-4 &amp; IL-10 secretions to control the immunostimulatory effects in upper respiratory tract infection. Dietary fibres utilized by beneficial microbiota and microbial metabolites can control the NF-kB regulation. Vitamin C halts the propagation of pathogens and vitamin D and A modulate the GM. Selenium and Flavonoids also control the redox regulations. Interferon therapy can antagonize the viral replications, while corticosteroids may reduce the death rates. BCG vaccine reprograms the monocytes to build trained immunity. Bifidobacterium and related microbes were found to increase the vaccine efficacy. Vaccines against COVID-19 and season flu also boost the immunity profile for robust protection. Over all, the collective effects of these therapeutics could help increase the opportunities for faster recovery from infectious diseases. Conclusion The nutraceutical supplements and pharmacological medicines mediate the modulatory functionalities among beneficial microbes of gut, which in turn eliminate pathogens, harmonize the activity of immune cells to secrete essential regulatory molecular receptors and adaptor proteins establishing the homeostasis in the body organs through essential microbiome. Therefore, the implementation of this methodology could control the severity events during clinical sickness and reduce the mortalities.

Organ-preserving treatment for urothelial carcinoma of the upper urinary tract

Urothelial carcinoma of the upper urinary tract is rare but the incidence is currently increasing in western countries. Radical nephroureterectomy has long been the standard treatment; however, it can lead to chronic kidney failure and also the necessity for dialysis. Therefore, organ-preserving treatment is now recommended for selected patients with low-risk tumors. The choice of treatment depends on the tumor characteristics, comorbidities and individual risk factors. Surgical options for organ preservation include ureterorenoscopy (URS), percutaneous treatment and partial ureteral resection. The URS is the most frequently used method for organ preservation. Photodynamic diagnostics (PDD) and narrow band imaging (NBI) can potentially also be used for tumor detection in the upper urinary tract. Conservative options such as topical treatment with mitomycinC or Bacillus Calmette-Guérin (BCG) and systemic treatment options are also possible.

Study on Trend of Immunization Coverage in Mutum Biyu Ward "B" From 2016-2019 in Gassol Local Government Area, Taraba State, Nigeria

This study examines the trend of immunisation coverage for Bacille Calmette-Guerin (BCG), Oral Polio Vaccine (OPV), Measles, and Yellow Fever in Mutum Biyu Ward 'B' of Gassol local Government Area, Taraba State, Nigeria, from 2016 to 2019. The DHIS2 Nigeria platform was used to gather secondary data using a quantitative, cross-sectional approach. In order to analyse the completion and non-completion rates of Routine Immunisation (RI) schedules, vaccination cards and carer recollection were the main sources of immunisation histories. One-way ANOVA testing and descriptive statistics were used in the data analysis. The study's findings showed that vaccination coverage varied over time. The BCG coverage saw notable fluctuations, peaking in the years 2017 and 2019. In 2018, OPV coverage rose on average but somewhat decreased. Measles vaccination rates were steady at first, then they fell in 20l8 and then sharply recovered in 2019. The vaccination rate for yellow fever was low in 20l6, improved slightly in 2017, declined sharply in 2018, and then reached its peak in 2019. The study recommended localized use of geo-mapping to identify and map communities with low immunisation coverage in Mutum Biyu Ward "B" of Gassol LGA, Taraba State.

The potential benefits of concomitant statins treatment in patients with non-muscle-invasive bladder cancer.

To investigate the influence of statins on the survival outcomes of patients with non-muscle-invasive bladder cancer (NMIBC) treated with adjuvant intravesical bacille Calmette-Guérin (BCG) immunotherapy. A retrospective cohort of consecutive patients with NMIBC who received intravesical BCG therapy from 2001 to 2020 and statins prescription were identified. Overall survival (OS), cancer-specific survival (CSS), recurrence-free survival (RFS), and progression-free survival (PFS) were analysed between the Statins Group vs No-Statins Group using Kaplan-Meier method and multivariable Cox regression. A total of 2602 patients with NMIBC who received intravesical BCG were identified. The median follow-up was 11.0 years. On Kaplan-Meier analysis, the Statins Group had significant better OS (P < 0.001), CSS (P < 0.001), and PFS (P < 0.001). Subgroup analysis indicated statins treatment started before BCG treatment had better CSS (P = 0.02) and PFS (P < 0.01). Upon multivariable Cox regression analysis, the 'statins before BCG' group was an independent protective factor for OS (hazard ratio [HR] 0.607, 95% confidence interval [CI] 0.514-0.716), and CSS (HR 0.571, 95% CI 0.376-0.868), but not RFS (HR 0.885, 95% CI 0.736-1.065), and PFS (HR 0.689, 95% CI 0.469-1.013). Statins treatment appears to offer protective effects on OS and CSS for patients with NMIBC receiving adjuvant intravesical BCG.

KNOWLEDGE, ATTITUDE, AND PRACTICE TOWARDS ZOONOTIC BOVINE TUBERCULOSIS AMONG NOMADIC PASTORALISTS IN NASARAWA, NIGERIA

Tuberculosis is a chronic debilitating disease occurring worldwide affecting a wide range of animals and man. In developing countries like Nigeria, the situation is still high among pastoral communities, occupationally related livestock workers, and immune-compromised individuals living with HIV and Aids whose knowledge, practice, and attitude could predispose them to zoonotic tuberculosis (ZTB). In this study, a total of 125 questionnaires were administered to pastoralcommunities in the southern zone of Nasarawa to determine the Knowledge Attitude and Practice among pastoralists towards ZTB, and informed consent was sought among the individuals before the interview was granted. A descriptive statistic was used to calculate and analyze data from the KAP level of response and the socio-demographic variables: Educational Level; duration in Pastoral activities and Age of the respondents. From the KAP level interview, the response indicated that (77.6 %) of respondents with a secondary level of education are aware of the zoonotic transmission of TB from animal to man while (62.4 %) have knowledge that man can contract TB from animals. The participants have some understanding of the signs of TB, but greater awareness (77.6 %) was observed mostly among participants with a secondary level of formal education. Consequently, on the knowledge of how TB is transmitted, there was inadequate knowledge among the participants as (68.8 %) of primary level and (41.6 %) of respondents without formal education said meat is the vehicle for the transmission of TB from animals while only (33.6 %) of the participants with secondary education mention Milk produ cts. All the participants consumed Sour Milk (100 %) while the level of consumption of fresh and boiled milk among the participants was (24.1 % and 27.6%; Table 2) regardless of their educational level. Regarding the practice of using protectives while in contact with animals, (68.0 %) and (61.6 %) of respondents with primary and secondary formal education said they wash their hands after contact with animals while only (20.8 %) of respondents without formal education wash their hands after contact with animals. KAP level observed a divergence of opinion among the participants due to inadequate awareness and knowledge of protection from ZTB.KAP level observed that more than (65 %) of the respondents do not undergo BCG vaccination. Consequently, the study observed a (100 %) consumption of Sour Milk among the respondents. There is a need for an integrated education in line with one health approach to pastoral communities to safeguard them from zoonotic bovine tuberculosis.

Intranasal Immunization with a Recombinant Adenovirus Encoding Multi-Stage Antigens of Mycobacterium tuberculosis Preferentially Elicited CD8+ T Cell Immunity and Conferred a Superior Protection in the Lungs of Mice than Bacillus Calmette-Guerin.

The development of a tuberculosis (TB) vaccine is imperative. Employing multi-stage Mycobacterium tuberculosis (Mtb) antigens as targeted antigens represents a critical strategy in establishing an effective novel TB vaccine. In this investigation, we evaluated the immunogenicity and protective efficacy of a recombinant adenovirus vaccine expressing two fusion proteins, Ag85B-ESAT6 (AE) and Rv2031c-Rv2626c (R2), derived from multi-stage antigens of Mtb via intranasal administration in mice. Intranasal delivery of Ad-AE-R2 induced both long-lasting mucosal and systemic immunities, with a preferential elicitation of CD8+ T cell immunity demonstrated by the accumulation and retention of CD8+ T cells in BALF, lung, and spleen, as well as the generation of CD8+ TRM cells in BALF and lung tissues. Compared to subcutaneous immunization with Bacillus Calmette-Guerin (BCG), Ad-AE-R2 provided superior protection against high-dose intratracheal BCG challenge, specifically within the lungs of mice. Our findings support the notion that empowering T cells within the respiratory mucosa is crucial for TB vaccine development while highlighting targeting CD8+ T cell immunity as an effective strategy for optimizing TB vaccines and emphasizing that eliciting systemic memory immunity is also vital for the successful development of a TB mucosal vaccine. Furthermore, our results demonstrate that the BCG challenge serves as a convenient and efficient method to evaluate candidate vaccine efficacy.

Immunoproteomic discovery of Mycobacterium bovis antigens, including the surface lipoprotein Mpt83 as a T cell antigen useful for vaccine development

Tuberculosis (TB) is one of the leading causes of death from infectious diseases, killing approximately 1.3 million people worldwide in 2022 alone. The current vaccine for TB contains a live attenuated bacterium, Mycobacterium bovis BCG (Bacille Calmette-Guérin). The BCG vaccine is highly effective in preventing severe forms of childhood TB but does not protect against latent infection or disease in older age groups. A new or improved BCG vaccine for prevention of pulmonary TB is urgently needed.In this study, we infected murine bone marrow derived dendritic cells from C57BL/6 mice with M. bovis BCG followed by elution and identification of BCG-derived MHC class I and class II-bound peptides using tandem mass spectrometry. We identified 1436 MHC-bound peptides of which 94 were derived from BCG. Fifty-five peptides were derived from MHC class I molecules and 39 from class II molecules. We tested the 94 peptides for their immunogenicity using IFN- γ ELISPOT assay with splenocytes purified from BCG immunized mice and 10 showed positive responses. Seven peptides were derived from MHC II and three from MHC class I. In particular, MHC class II binding peptides derived from the mycobacterial surface lipoprotein Mpt83 were highly antigenic. Further evaluations of these immunogenic BCG peptides may identify proteins useful as new TB vaccine candidates.

Spatial patterns of maternal and neonatal continuum of care use and its correlations with women’s empowerment

BackgroundThe continuum of care (CoC) in maternal health refers to the continuity of individual reproductive health care across the antenatal, intrapartum, and postnatal periods. The CoC is an indicator of the quality of maternal and newborn health outcomes and women’s empowerment is crucial to improving maternal and neonatal health service access and utilisation.ObjectiveTo examine the spatial patterns of continuum of care use for maternal and neonatal health services and its correlation with women’s empowerment.MethodsWe analysed data from the Ethiopian Demographic and Health Surveys (EDHS) of 2011 and 2016. All women aged 15–49 who had live births in the preceding five years of the DHS surveys were included in the analysis. We measured the continuum of care using the modified co-coverage index (CoCI), which consisted of six indicators. Women’s empowerment was assessed using a validated survey-based Women’s Empowerment (SWPER) index. We used the Getis-Ord-Gi* spatial analysis tool to portray locations with clusters of CoC service use and spatial correlations between CoC use and women empowerment.ResultsNone of the newborn-mother pairs in the 2011 survey received the entire continuum of care and only 2.5% of newborn-mother pairs received the full range of continuum of care services in the 2016 survey. In 2016, 6.9% of mother-newborn pairs received the basic CoC services (four or more antenatal care [ANC] visits, skilled birth attendance [SBA], and postnatal care [PNC]), and no mother-newborn pair received all three services at the same time in 2011. The Amhara, Afar, and Somali regional states had the least CoC service use in both surveys. There was a positive spatial correlation between CoC use and women’s empowerment domains.ConclusionOur analysis showed that the use of four or more ANC visits, SBS, newborn PNC, Bacillus Calmette-Guérin (BCG) vaccine uptake, and tetanus toxoid protection at birth were low in Ethiopia. Women empowerment domains were found to have a positive spatial correlation with CoC services use. To improve and preserve continuity of care, it is critical to leverage every maternal health facility encounter to encourage sustained service usage at each step of the continuum. Government policies should prioritise women’s empowerment and raise public awareness of maternity services.

Bladder-Preserving Trimodality Treatment for High-Grade T1 Bladder Cancer: Results From Phase II Protocol NRG Oncology/RTOG 0926.

To investigate the use of radiation with radiosensitizing chemotherapy following repeated transurethral resection (trimodality therapy) as an alternative to radical cystectomy in T1 bladder cancer which has failed Bacillus Calmette-Guerin (BCG). Patients with recurrent T1 bladders who had failed BCG and were recommended to undergo cystectomy were treated with trimodality therapy. The primary end point was 3-year freedom from cystectomy. Secondary end points were distant metastasis at 3 and 5 years, local recurrence, disease-specific and overall survival (OS), and safety. This single-arm phase II study enrolled 37 patients. Efficacy and safety were evaluated in 34 patients after three exclusions. The median follow-up was 5.1 years. The 3-year freedom from cystectomy rate was 88% (lower one-sided 97.5% confidence limit [CI], 72%), meeting the primary study goal. OS at 3 and 5 years was 69% (95% CI, 54 to 85) and 56% (95% CI, 39 to 74), respectively. The distant metastasis rates at 3 and 5 years were 12% (95% CI, 4 to 26) and 19% (95% CI, 7 to 34), respectively. Eight patients died due to urothelial cancer, 12 exhibited local recurrence at 3 years (cumulative incidence: 32%; 95% CI, 17 to 48), 18 experienced grade 3 adverse events, mostly hematological, and one developed grade 4 neutropenia. Trimodality therapy is an effective potential alternative to radical cystectomy for recurrent high-grade T1 urothelial cancer of the bladder. At 3 years, 88% of the patients remained free of cystectomy.