Dose Of BCG Research Articles

The role of community health and nutrition volunteers in improving the health and nutrition status of infant and young children in remote areas, Hajjah, Yemen

BackgroundIn Yemen, morbidity and malnutrition are major public health problems. The Community Health and Nutrition Volunteers (CHNVs) program was launched to tackle these problems through providing services to mothers and their children residing in remote villages. Since establishment of the CHNVs program in Yemen, its outcome has never been evaluated. Therefore, the aim of this study was to assess the role of CHNVs in improving the immunization, morbidity and nutritional status of infant and young children (IYC).MethodsA comparative cross-sectional study design was conducted in Al-Maghrabah and Bani-Qais districts, Hajjah governorate. It was carried out between January and April 2023. A three-stage cluster sampling method was used. A total of 926 IYC with their mothers were interviewed using a pre-tested questionnaire. SPSS 26 was used for data analysis. The multinomial logistic regression and chi-square or fisher exact tests were used to compare the vaccination, morbidity and nutritional status of IYC between the volunteer and non-volunteer villages. Odds Ratio (OR) with 95% Confidence Interval (CI) were calculated. A p value < 0.05 was considered statistically significant.ResultsThe IYC in volunteer villages were more likely to be fully or partially vaccinated compared to those in non-volunteer villages [OR = 2.3, 95% CI: 1.5–3.7, p < 0.0001, and OR = 1.9, 95% CI: 1.3–2.8, p = 0.001, respectively]. The specific coverage rates for BCG, and the 1st and 2nd doses of OPV/Pentavalent/Pneumo/Rota vaccines were significantly higher in the volunteer compared to non-volunteer villages [(OR = 1.8, 95% CI: 1.3–2.5, p < 0.0001), (OR = 1.5, 95% CI: 1.2–2.1, p = 0.003), and (OR = 1.5, 95% CI: 1.2-2.0, p = 0.002), respectively]. Moreover, the prevalence of diarrhea and fever among IYC was significantly lower in the volunteer compared to non-volunteer villages [(OR = 0.7, 95% CI: 0.5–0.9, p = 0.004) and (OR = 0.7 95% CI: 0.5–0.9, p = 0.045), respectively].ConclusionsThe study found that CHNVs play a significant role in improving vaccination status and the coverage rate for BCG, and 1st and 2nd doses of OPV/Pentavalent/Pneumo/Rota vaccines, and reducing the prevalence of diarrhea and fever among IYC in their villages compared to non-volunteer villages, in Hajjah governorate. Future follow-up study and expansion to other settings in different governorates is recommended.

Safety of a controlled human infection model of tuberculosis with aerosolised, live-attenuated Mycobacterium bovis BCG versus intradermal BCG in BCG-naive adults in the UK: a dose-escalation, randomised, controlled, phase 1 trial

Mycobacterium tuberculosis is the main causative agent of tuberculosis. BCG, the only licensed vaccine, provides inadequate protection against pulmonary tuberculosis. Controlled human infection models are useful tools for vaccine development. We aimed to determine a safe dose of aerosol-inhaled live-attenuated Mycobacterium bovis BCG as a surrogate for M tuberculosis infection, then compare the safety and tolerability of infection models established using aerosol-inhaled and intradermally administered BCG. This phase 1 controlled human infection trial was conducted at two clinical research facilities in the UK. Healthy, immunocompetent adults aged 18-50 years, who were both M tuberculosis-naive and BCG-naive and had no history of asthma or other respiratory diseases, were eligible for the trial. Participants were initially enrolled into group 1 (receiving the BCG Danish strain); the trial was subsequently paused because of a worldwide shortage of BCG Danish and, after protocol amendment, was restarted using the BCG Bulgaria strain (group 2). After a dose-escalation study, during which participants were sequentially allocated to receive either 1 × 103, 1 × 104, 1 × 105, 1 × 106, or 1 × 107 colony-forming units (CFU) of aerosol BCG, the maximum tolerated dose was selected for the randomised controlled trial. Participants in this trial were randomly assigned (9:12), by variable block randomisation and using sequentially numbered sealed envelopes, to receive aerosol BCG (1 × 107 CFU) and intradermal saline or intradermal BCG (1 × 106 CFU) and aerosol saline. Participants were masked to treatment allocation until day 14. The primary outcome was to compare the safety of a controlled human infection model based on aerosol-inhaled BCG versus one based on intradermally administered BCG, and the secondary outcome was to evaluate BCG recovery in the airways of participants who received aerosol BCG or skin biopsies of participants who received intradermal BCG. BCG was detected by culture and by PCR. The trial is registered at ClinicalTrials.gov, NCT02709278, and is complete. Participants were assessed for eligibility between April 7, 2016, and Sept 29, 2018. For group 1, 15 participants were screened, of whom 13 were enrolled and ten completed the study; for group 2, 60 were screened and 33 enrolled, all of whom completed the study. Doses up to 1 × 107 CFU aerosol-inhaled BCG were sufficiently well tolerated. No significant difference was observed in the frequency of adverse events between aerosol and intradermal groups (median percentage of solicited adverse events per participant, post-aerosol vs post-intradermal BCG: systemic 7% [IQR 2-11] vs 4% [1-13], p=0·62; respiratory 7% [1-19] vs 4% [1-9], p=0·56). More severe systemic adverse events occurred in the 2 weeks after aerosol BCG (15 [12%] of 122 reported systemic adverse events) than after intradermal BCG (one [1%] of 94; difference 11% [95% CI 5-17]; p=0·0013), but no difference was observed in the severity of respiratory adverse events (two [1%] of 144 vs zero [0%] of 97; 1% [-1 to 3]; p=0·52). All adverse events after aerosol BCG resolved spontaneously. One serious adverse event was reported-a participant in group 2 was admitted to hospital to receive analgesia for a pre-existing ovarian cyst, which was deemed unrelated to BCG infection. On day 14, BCG was cultured from bronchoalveolar lavage samples after aerosol infection and from skin biopsy samples after intradermal infection. This first-in-human aerosol BCG controlled human infection model was sufficiently well tolerated. Further work will evaluate the utility of this model in assessing vaccine efficacy and identifying potential correlates of protection. Bill & Melinda Gates Foundation, Wellcome Trust, National Institute for Health Research Oxford Biomedical Research Centre, Thames Valley Clinical Research Network, and TBVAC2020.

IJCM_87A: Immunization status among children living in streets of Chennai - A cross sectional study

Background: The homeless population of Chennai is the people who are living in the platforms, bus stands and other unused buildings in Chennai for more than three generations. Many of them lack basic amenities for their living, which makes them a vulnerable population especially the women and children. The children especially are prone to many communicable diseases as a result of their way of living Objective: To estimate the immunization status among the children of homeless population in Chennai. Methodology: The information about the clusters of homeless population is obtained from the Greater Chennai Corporation enumeration. Individual clusters are mapped in Zone 5 of Greater Chennai Corporation. Almost all the mothers of children of age up to 5 years are interviewed. Data collected using Epicollect5 data collection software. Results: The mean age of the children was 34.59 + 17.73 months. 45.4% were male children and 54.6% were female children.98.9% of the mothers registered their pregnancy and 100% delivered in the public facility. 93.4% registered their birth. 87.4 % of the children got enrolled in Anganwadis. 90.5% of the children were immunized up to age. Only one child (0.4%) didn’t get the birth dose of BCG. 18 children (6.6%) didn’t get their Measles Rubella vaccine not even once. 28 children (10.3%) didn’t get their second dose of Measles Rubella vaccine and Diptheria Pertussis Tetanus vaccine. Conclusion: The immunization coverage among homeless children upto 5 years is 90.5%. The coverage has to be strengthened in order to improve their quality of life

Determinant of Complete Basic Immunization of Children

&#x0D; &#x0D; &#x0D; &#x0D; Abstract&#x0D; WHO mention about 1.5 million children die each year because diseases that can be prevented by immunization. Immunization is one of the health interventions that has proven to be the cheapest, because it can prevent and reduce the incidence number of morbidity, disability, and death due to PD3I (Ministry of Health RI, 2020). Infants aged 0-11 months must receive complete basic immunization consisting of 1 dose of Hepatitis B, 1 dose of BCG, 3 doses of DPT-HB-HiB, 4 doses of polio drops (OPV), 1 dose of injectable polio (IPV) and 1 dose of measles rubella. In 2020, complete basic immunization in the city of palembang is 81.9% and this means that it has not reached the 2023 national target of 100%. The immunization coverage of Boom Baru Health Center reached 96.4%. The purpose of this study was to find out what factors are related to the coverage of complete basic immunization in children at the Boom Baru Health Center in Palembang City. This study used quantitative methods with a cross sectional approach. Data collectiom used a questionnaire and analyzed univariately to describe distribution and proportion, and bivariate used Chi Square. This study found that there was no relationship between mother’s last education with complete basic immunization coverage (p = 0.143), and there was a relationship between mother’s knowledge (p = 0.000), Trust (p = 0.000), family support (p = 0.000). This study suggest for health workers provide counseling and increase the motivation of mothers regarding the importance of immunization and do monitor the completeness of their immunization, while mothers who have babies should take the time to immunize their chidren. to immunize their children.&#x0D; &#x0D; &#x0D; &#x0D;

Faktor Penentu Imunisasi Dasar Lengkap pada Anak di Wilayah Kerja Puskesams di Kota Palembang

WHO mention about 1.5 million children die each year because diseases that can be prevented by immunization. Immunization is one of the health interventions that has proven to be the cheapest, because it can prevent and reduce the incidence number of morbidity, disability, and death due to PD3I (Ministry of Health RI, 2020). Infants aged 0-11 months must receive complete basic immunization consisting of 1 dose of Hepatitis B, 1 dose of BCG, 3 doses of DPT-HB-HiB, 4 doses of polio drops (OPV), 1 dose of injectable polio (IPV) and 1 dose of measles rubella. In 2020, complete basic immunization in the city of palembang is 81.9% and this means that it has not reached the 2023 national target of 100%. The immunization coverage of Boom Baru Health Center reached 96.4%. The purpose of this study was to find out what factors are related to the coverage of complete basic immunization in children at the Boom Baru Health Center in Palembang City. This study used quantitative methods with a cross sectional approach. Data collectiom used a questionnaire and analyzed univariately to describe distribution and proportion, and bivariate used Chi Square. This study found that there was no relationship between mother’s last education with complete basic immunization coverage (p = 0.143), and there was a relationship between mother’s knowledge (p = 0.000), Trust (p = 0.000), family support (p = 0.000). This study suggest for health workers provide counseling and increase the motivation of mothers regarding the importance of immunization and do monitor the completeness of their immunization, while mothers who have babies should take the time to immunize their chidren.&#x0D; &#x0D; Bibliography : 2010-2023&#x0D; Keywords : Basic Immunizations, Education, Knowledge, Trust, Family Support

Understanding household-level risk factors for zero dose immunization in 82 low- and middle-income countries.

In 2021, an estimated 18 million children did not receive a single dose of routine vaccinations and constitute the population known as zero dose children. There is growing momentum and investment in reaching zero dose children and addressing the gross inequity in the reach of immunization services. To effectively do so, there is an urgent need to characterize more deeply the population of zero dose children and the barriers they face in accessing routine immunization services. We utilized the most recent DHS and MICS data spanning 2011 to 2020 from low, lower-middle, and upper-middle income countries. Zero dose status was defined as children aged 12-23 months who had not received any doses of BCG, DTP-containing, polio, and measles-containing vaccines. We estimated the prevalence of zero-dose children in the entire study sample, by country income level, and by region, and characterized the zero dose population by household-level factors. Multivariate logistic regressions were used to determine the household-level sociodemographic and health care access factors associated with zero dose immunization status. To pool multicountry data, we adjusted the original survey weights according to the country's population of children 12-23 months of age. To contextualize our findings, we utilized United Nations Population Division birth cohort data to estimate the study population as a proportion of the global and country income group populations. We included a total of 82 countries in our univariate analyses and 68 countries in our multivariate model. Overall, 7.5% of the study population were zero dose children. More than half (51.9%) of this population was concentrated in African countries. Zero dose children were predominantly situated in rural areas (75.8%) and in households in the lowest two wealth quintiles (62.7%) and were born to mothers who completed fewer than four antenatal care (ANC) visits (66.5%) and had home births (58.5%). Yet, surprisingly, a considerable proportion of zero dose children's mothers did receive appropriate care during pregnancy (33.5% of zero dose children have mothers who received at least 4 ANC visits). When controlled for other factors, children had three times the odds (OR = 3.00, 95% CI: 2.72, 3.30) of being zero dose if their mother had not received any tetanus injections, 2.46 times the odds (95% CI: 2.21, 2.74) of being zero dose if their mother had not received any ANC visits, and had nearly twice the odds (OR = 1.87, 95% CI: 1.70, 2.05) of being zero dose if their mother had a home delivery, compared to children of mothers who received at least 2 tetanus injections, received at least 4 ANC visits, and had a facility delivery, respectively. A lack of access to maternal health care was a strong risk factor of zero dose status and highlights important opportunities to improve the quality and integration of maternal and child health programs. Additionally, because a substantial proportion of zero dose children and their mothers do receive appropriate care, approaches to reach zero dose children should incorporate mitigating missed opportunities for vaccination.

Defining the Zero Dose Child: A Comparative Analysis of Two Approaches and Their Impact on Assessing the Zero Dose Burden and Vulnerability Profiles across 82 Low- and Middle-Income Countries.

While there is a coordinated effort around reaching zero dose children and closing existing equity gaps in immunization delivery, it is important that there is agreement and clarity around how 'zero dose status' is defined and what is gained and lost by using different indicators for zero dose status. There are two popular approaches used in research, program design, and advocacy to define zero dose status: one uses a single vaccine to serve as a proxy for zero dose status, while another uses a subset of vaccines to identify children who have missed all routine vaccines. We provide a global analysis utilizing the most recent publicly available DHS and MICS data from 2010 to 2020 to compare the number, proportion, and profile of children aged 12 to 23 months who are 'penta-zero dose' (have not received the pentavalent vaccine), 'truly' zero dose (have not received any dose of BCG, polio, pentavalent, or measles vaccines), and 'misclassified' zero dose children (those who are penta-zero dose but have received at least one other vaccine). Our analysis includes 194,829 observations from 82 low- and middle-income countries. Globally, 14.2% of children are penta-zero dose and 7.5% are truly zero dose, suggesting that 46.5% of penta-zero dose children have had at least one contact with the immunization system. While there are similarities in the profile of children that are penta-zero dose and truly zero dose, there are key differences between the proportion of key characteristics among truly zero dose and misclassified zero dose children, including access to maternal and child health services. By understanding the extent of the connection zero dose children may have with the health and immunization system and contrasting it with how much the use of a more feasible definition of zero dose may underestimate the level of vulnerability in the zero dose population, we provide insights that can help immunization programs design strategies that better target the most disadvantaged populations. If the vulnerability profiles of the truly zero dose children are qualitatively different from that of the penta-zero dose children, then failing to distinguish the truly zero dose populations, and how to optimally reach them, may lead to the development of misguided or inefficient strategies for vaccinating the most disadvantaged population of children.

The efficacy and safety outcomes of lower dose BCG compared to intravesical chemotherapy in non-muscle-invasive bladder cancer: A network meta-analysis.

This study aimed to assess both efficacy and safety outcomes of lowering the dose of BCG compared to intravesical chemotherapies in non-muscle-invasive bladder cancer (NMIBC) patients using a systematic review, meta-analysis, and network meta-analysis approach. A comprehensive literature search was performed through Pubmed®, Web of Science™, and Scopus® in December 2022 to identify randomized controlled trials comparing the oncologic and/or safety outcomes of reduced dose intravesical BCG and/or intravesical chemotherapies according to the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) statement. The outcomes of interest were risk of recurrence, progression, treatment-related adverse events, and discontinuation. Overall, 24 studies were eligible for quantitative synthesis. Among 22 studies that adopted induction followed by maintenance intravesical therapy, with reference to the lower-dose BCG, epirubicin was associated with a significantly higher risk of recurrence (Odds ratio [OR]: 2.82, 95% CI: 1.54-5.15), but not other intravesical chemotherapies. There were no significant differences in risk of progression among the intravesical therapies. On the other hand, standard-dose BCG was associated with a higher risk of any AEs (OR: 1.91, 95% CI: 1.07-3.41) but other intravesical chemotherapies had a comparable risk of AEs compared to lower-dose BCG. The discontinuation rate did not significantly differ between lower-dose and standard-dose BCG (OR: 1.40, 95% CI: 0.81-2.43) as well as other intravesical. According to the surface under the cumulative ranking curve, gemcitabine, and standard-dose BCG were preferable to lower-dose BCG in terms of recurrence risk; gemcitabine was also preferable to lower-dose BCG in terms of risk of AEs. In patients with NMIBC, lowering the dose of BCG decreases the risks of AEs and discontinuation rate compared to standard-dose BCG, but there is no difference in these endpoints compared to other intravesical chemotherapies. Standard-dose of BCG is preferred for all intermediate and high-risk NMIBC patients based on oncologic efficacy; however, lower-dose BCG and intravesical chemotherapies, especially gemcitabine, could be considered a reasonable alternative to BCG in selected patients who suffer from significant AEs or in case standard-dose BCG is not available.

A novel self-adjuvanted mRNA vaccine expressing the Antigen-85B-p25 epitope of Mycobacterium tuberculosisprotects mice against tuberculosis

Abstract Mycobacterium tuberculosis (Mtb) is a leading cause of death due to infections. BCG is the most used vaccine despite having partial efficacy against the tuberculosis. We have developed a synthetic mRNA vaccine, SelmRp25-C5, which expresses the p25 epitope of Mtb-derived Antigen-85B and a TLR-2 stimulating C5 adjuvant peptide from CFP-10 protein. We evaluated its efficacy both ex vivo and in mice. Methods: Mouse and human macrophages (MΦ) and mouse dendritic cells (DCs) were treated with SelmRp25-C5 vaccine or EGFP-mRNA control followed by antigen presentation assays and assessment of cytokine secretion. C57Bl/6 mice were vaccinated subcutaneously with two doses (5μg per mouse) of SelmRp25-C5 vaccine, or EGFP-mRNA and one dose of subcutaneous BCG (10 6CFU per mouse) as a control, followed by aerosol infection with Mtb. Four weeks after Mtb challenge, mice were sacrificed, and organs were analyzed for Mtb CFU, RNAseq, Ag85B-p25 tetramer-specific CD4 T cells and memory T cells. Results: SelmRp25-C5 vaccine induced robust antigen presentation to T cells in both mouse MΦs and DCs and in human MΦs, and enhanced Th1 cytokine secretion. Two doses of SelmRp25-C5 vaccine protected mice by reducing Mtb burden by 1log 10. Protection induced by SelmRp25-C5 vaccine was associated with an increase in Ag85B-p25-specific CD4 T cells, increased IFN-γ and IL-2 secreting T cells and CD4 effector memory T cells. Lung and spleens of protected mice showed an upregulation of Spleen tyrosine kinase (Syk) and genes of the C-type lectin receptor-pathway compared to control mice. Conclusions: We propose that the new generation self-adjuvanted mRNA vaccine strengthen both innate and adaptive immunity to provide protection against tuberculosis. Supported by NIAID, NIH AI122070, AI138587; AI161015.

Low Vaccine Coverage and Factors Associated with Incomplete Childhood Immunization in Racial/Ethnic Minorities and Rural Groups, Central Brazil.

Discrimination and limited access to healthcare services in remote areas can affect vaccination coverage. Therefore, this study aimed to estimate vaccination coverage for children living in quilombola communities and rural settlements in the central region of Brazil during their first year of life and to analyze the factors associated with incomplete vaccination. An analytical cross-sectional study was conducted on children born between 2015 and 2017. The percentage of children who received all vaccines recommended by the National Immunization Program in Brazil by 11 months and 29 days was used to calculate immunization coverage. Children who received the following vaccines were considered as having a complete basic vaccination schedule: one dose of BCG; three doses of Hepatitis B, of Diphtheria-Tetanus-Pertussis (DPT), of Haemophilus influenzae type b (Hib), and of Poliovirus (Polio); two doses of Rotavirus, of 10-valent pneumococcal (PCV10), and of Serogroup C meningococcal conjugate (MenC); and one dose of Yellow Fever (YF). Measles-mumps-rubella (MMR) and other doses recommended at or after 12 months were not included. Consolidated logistic regression was used to identify factors associated with incomplete vaccination coverage. Overall vaccination coverage was 52.8% (95% CI: 45.5-59.9%) and ranged from 70.4% for the Yellow Fever vaccine to 78.3% for the Rotavirus vaccine, with no significant differences between the quilombola and settler groups. Notably, the likelihood of incomplete general vaccination coverage was higher among children who did not receive a visit from a healthcare professional. Urgent strategies are required to achieve and ensure health equity for this unique and traditionally distinct group with low vaccination coverage.

PD29-03 COMPARISON OF REDUCED AND FULL BCG DOSING IN THE TREATMENT OF NON-MUSCLE INVASIVE BLADDER CANCER

You have accessJournal of UrologyCME1 Apr 2023PD29-03 COMPARISON OF REDUCED AND FULL BCG DOSING IN THE TREATMENT OF NON-MUSCLE INVASIVE BLADDER CANCER Matthew Buck, Andrew Salib, Edward Kloniecke, Rishabh Simhal, Anne Calvaresi, Costas Lallas, Leonard Gomella, and Joseph Izes Matthew BuckMatthew Buck More articles by this author , Andrew SalibAndrew Salib More articles by this author , Edward KlonieckeEdward Kloniecke More articles by this author , Rishabh SimhalRishabh Simhal More articles by this author , Anne CalvaresiAnne Calvaresi More articles by this author , Costas LallasCostas Lallas More articles by this author , Leonard GomellaLeonard Gomella More articles by this author , and Joseph IzesJoseph Izes More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003315.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The BCG shortage era has prompted the need for rethinking of the classic treatment paradigm for non-muscle invasive bladder cancer (NMIBC). Among other approaches, reduced BCG dosage protocols have been implemented across various institutions with conflicting evidence on their efficacy. We retrospectively evaluated patients at out institution with NMIBC and hypothesized that reduced dose protocols would have no significant impact on the development of BCG-relapsing disease, BCG-refractory disease, or progression to muscle invasive bladder cancer. METHODS: We evaluated 300 patients treated at our institution during the BCG shortage era (01/2017–05-2021). After obtaining institutional IRB approval, we retrospectively reviewed the charts of 300 patients and recorded pathology at diagnosis, size of tumor at initial resection, BCG induction dose (25 mg vs. 50 mg), BCG maintenance dose (25 mg vs 50 mg), pathology and date of recurrence. We evaluated baseline differences between full and reduced dose groups utilizing chi-squared tests, t-test, and ANOVA where appropriate. We then compared time to recurrence between the two dosing strategies with log-rank tests and Cox proportional hazards models. RESULTS: 203 patients with complete data were treated with BCG during the period of the study (115 high risk, 73 intermediate risk). Patients who received a lower induction dose of were more likely to develop a recurrence during the study period (log-rank test, p<0.001, Figure 1). On multivariable Cox proportional-hazards modelling, those who received reduced dose BCG were more likely to experience a recurrence during the study period (HR: 1.88, 95% CI 1.08–3.26) while adjusting for number of inductions, maintenance dosing, and AUA risk category. CONCLUSIONS: In this cohort of mainly high-risk NMIBC patients, those treated with reduced induction dose of BCG were more likely to experience a recurrence within the study period. Additional research and prospective trials can shed light on which patients are able to safely be treated with reduced dose BCG in the shortage era. Source of Funding: Institutional funding. © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e824 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Matthew Buck More articles by this author Andrew Salib More articles by this author Edward Kloniecke More articles by this author Rishabh Simhal More articles by this author Anne Calvaresi More articles by this author Costas Lallas More articles by this author Leonard Gomella More articles by this author Joseph Izes More articles by this author Expand All Advertisement PDF downloadLoading ...

A trial of intra-pleural bacterial immunotherapy in malignant pleural mesothelioma (TILT) — a randomised feasibility study using the trial within a cohort (TwiC) methodology

BackgroundMalignant pleural mesothelioma (MPM) is an aggressive thoracic malignancy with a poor prognosis. Systemic immunotherapy is an effective frontline treatment for MPM, and there is a scientific rationale supporting the possible efficacy of local, i.e. intra-pleural immune modulators. Trial of intra-pleural bacterial immunotherapy (TILT) investigated the feasibility of performing a randomised trial of intra-pleural bacterial immunotherapy in people with MPM, using the trials within cohorts (TwiC) methodology.MethodsTILT was a multicentre, three-armed, randomised, feasibility TwiC of intra-pleural OK432, BCG, or usual care in people with MPM. Eligible participants were identified from within the ASSESS-meso study, a prospective, longitudinal, observational cohort study, and were randomly selected to be offered a single dose of OK432 or BCG, via an indwelling pleural catheter. The primary outcome was feasibility, evaluated against prespecified recruitment, attrition and data completeness targets. The acceptability of trial processes and interventions was assessed during qualitative interviews with participants and family members at the end of the trial. TILT was registered prospectively on the European Clinical Trials Registry (EudraCT number 2016–004,727-23) and the ISRCTN Register on 04 December 2017.ResultsSeven participants were randomised from a planned sample size of 12; thus, the 66% recruitment rate target was not met. Two participants withdrew after randomisation, breaching the pre-stated attrition threshold of 10%. It was not possible to maintain blinding of control participants, which negated a fundamental tenet of the TwiC design. The trial processes and methodology were generally acceptable to participants and relatives, despite several recipients of intra-pleural bacterial agents experiencing significant local and systemic inflammatory responses.ConclusionIt was possible to design a clinical trial of an investigational medicinal product based on the TwiC design and to obtain the necessary regulatory approvals. However, whilst acceptable to participants and relatives, the TwiC design was not a feasible method of investigating intra-pleural bacterial immunotherapy in people with MPM. Future trials investigating this topic should consider the eligibility constraints and recruitment difficulties encountered.Trial registrationTILT was registered prospectively on the European Clinical Trials Registry (EudraCT number 2016-004727-23) and the ISRCTN Register (10432197) on 04 December 2017.

A hospital-based cross-sectional study of clinico-epidemiological aspects of childhood leprosy with disability in the post-elimination era

Background Childhood leprosy is an important indicator of active foci of transmission in the community in the post-elimination era. Childhood leprosy cases with disabilities are still prevalent, but are often undertreated or misdiagnosed due to diminishing awareness and the available studies on the same are limited. Aims and objectives To study the clinical presentation, WHO grading, duration, relation with lepra reaction, smear positivity and neurological correlation of childhood leprosy cases with disability. Materials and methods A cross-sectional study was conducted in the dermatology department of a tertiary care center including all recent cases of childhood leprosy (less than or equal to 13 years) with WHO grade 1 and grade 2 disability from October 2018 to June 2020. Results Disability among childhood leprosy cases was detected in 18 (32.1%) out of 56 children. The most common type of disability observed was visible muscle wasting (26.7%). Based on WHO disability grading, 3 children (16.6%) had grade 1 disability and 15 children (83.4%) had grade 2 disability. Children with borderline tuberculoid lesions had maximum disability (17.8%). All had thickened peripheral nerves with increased incidence of lepra-reaction (27.7%) and slit skin smear positivity (38.8%). None of the children with disability had a second dose of BCG or rifampicin prophylaxis, even if leprosy cases were reported in the family earlier. Conclusion Development of deformity was dependent on various factors including increasing age, delay in accessing health care, multiple skin lesions, multibacillary disease, smear positivity, multiple nerve involvement, and lepra reaction at the time of presentation. Active school surveys and campaigns are needed for early detection of leprosy and prevention of disability, with appropriate distribution of post-exposure prophylaxis.

Association between clinical forms of leprosy and contacts with the vaccination state with BCG in five endemic municipalities in the Brazilian Amazon

Introduction: The World Health Organization (WHO) strategy for leprosy control from 2021 to 2030 focuses on interrupting transmission, reducing autochthonous cases to zero, and using a safe and effective vaccine and chemoprophylaxis. In 2020, 127,396 new cases were registered in the world, 19,195 new cases in the Americas, and, of these, 17,979 cases in Brazil, about 93.66% of the total in the Americas. Brazil is classified as a country with a high burden of the disease, occupying the 2nd place in the world, behind only India (WHO, 2020). Análise do período de 2010-2015 em publicação recente9, apresenta as seguintes cidades no estado do Pará nas quais se observou maiores taxas de incidência (detecção): Marituba, Belém, Marabá, Parauapebas e Altamira [9]. Material and method: This is an analytical retrospective study carried out in a database - Epi-Info resulting from records of Surveillance and Seroprevalence actions in five endemic municipalities for leprosy located in the Southeast and West of Pará. The following variables were analyzed: age, sex, Clinical Classification, vaccination status with BCG, and the result of the search for IgM antibodies against PGL-1 of Mycobacterium leprae by the “In house” ELISA technique. Results: We evaluated 1551 records examined in the laboratory from 2014 to 2016, which were classified into 123 Multibacillary -MB patients (123/1551 = 7.93%); 71 Paucibacillary-PB patients (71/1551 = 4.57%); 451 Intradomicilliary Consanguineous Contacts - CCOSI (451/1551 = 29.07%) and 906 Non Consanguineous Contacts - CNCOS (906/1551 = 58.41%). 57 MB patients (13.47%), 13 PB patients (3.07%), 133 CCOSI (31.44%) and 220 CNCOS (52.00%) were positive for PGL-1. The correlation of the Classification with the vaccination status showed 57 MB patients without any BCG (57/125 = 45.6%) and only 3 patients with two doses of BCG (3/125 = 2.4%); 17 PB patients without any dose of BCG (17/69 = 24.63%); 80 CCOSI without any BCG (80/455 = 17.58%) and 171 CNCOS (171/906 = 18.87%). The odds ratio (OR) in the analysis between unvaccinated MB patients compared to CCOSI was statistically significant (OR = 14.25; p ˂ 0.0001). The study shows the importance of using the BCG vaccine in healthy contacts of patients with leprosy, as it shows the probability of unvaccinated individuals being 14.25 times more likely to become ill with Multibacillary forms compared to CCOSI. In addition, the BCG vaccine has been in use for 80 years and is the only vaccine that we can use in leprosy control programs. Conclusion: Although the leprosy epidemiological data analyzed recently (2010 - 2015) show a downward trend in the main indicators in Pará, such as the detection of new cases and prevalence, the endemic municipalities are still classified as hyperendemic for the population under 15 years of age and This proves that Surveillance is essential, as well as BCG vaccination according to the Ministry of Health Standards.

Final clinical results of pivotal trial of IL-15RαFc superagonist N-803 with BCG in BCG-unresponsive CIS and papillary nonmuscle-invasive bladder cancer (NMIBC).

4508 Background: Patients with NMIBC CIS unresponsive to BCG have limited treatment options. N-803 (Anktiva) is a mutant IL-15-based immunostimulatory fusion protein complex (IL15RaFc) that promotes proliferation and activation of natural killer (NK) cells and CD8+ T cells, but not regulatory T cells. Phase 1b data in BCG-naïve patients with NMIBC demonstrate that intravesical administration of N-803 with BCG induced complete response in all patients, without recurrences for the study duration of 24 months. Pembrolizumab was approved in 2020 with a 41% complete response (CR) rate in a single arm phase 2 trial of 96 patients. We report data on 160 subjects from an open-label, 3 cohort multicenter study (QUILT 3.032) of intravesical BCG plus N-803 in patients with BCG-unresponsive high-grade NMIBC (NCT03022825). Methods: All treated patients received intravesical N-803 plus BCG, consistent with the standard induction/maintenance treatment schedule. The primary endpoint for Cohort A (CIS) is incidence of CR of CIS at any time. The primary endpoint for Cohort B (Papillary) is disease-free rate (DFS) at 12 months. Results: To date, we enrolled 160 patients (83 CIS, 77 Papillary). In the overall population, median age is 72.3 years, 81% male, with mean number of prior TURBT = 4. Median number of prior BCG doses = 12. CIS patients have a CR rate of 71% (59/83), with a mediation duration of CR of 24.1 months in responders; 91% avoided cystectomy and 96% 24 month bladder cancer specific progression free survival (defined as progression to MIBC). Papillary patients have a 57% 12 month DFS rate, 48% 24 month DFS rate, and 95% avoided cystectomy. Median time to cystectomy in responders (N = 4) is 12.9 months versus 7.8 in non-responders (N = 8) for a 5.1 month delay in cystectomy. PK data shows no systemic levels of N-803; activity is confined to the bladder. Low grade treatment related AEs (grade 1-2) include dysuria (22%), pollakiurua (19%), hematuria (18%), fatigue (16%), and urgency (12%), all other AEs were seen at 7% or less. No treatment related grade 4 or 5 AE were seen. No SAE's were considered treatment related. No immune related SAE's have been seen. Conclusions: In 160 patients with BCG-unresponsive NMIBC, there is a 99% bladder cancer specific overall survival at 2 years. In CIS patients 71% CR rate with 24.1 months median duration of response, and 53% DFS rate at 18 months in Papillary disease. Cystectomy was avoided in over 90% of patients with 2 years of follow-up. The efficacy and safety profile of N-803+BCG exceeds that of other available intravesical and systemic options for BCG-unresponsive NMIBC. Clinical trial information: NCT03022825.

Efficacy of High and Low Dose of BCG and Their Complications in Superficial Transtional Cell Carcinoma of Urinary Bladder

Background: Bladder cancer patients mostly (75%) present with non-muscle invasive bladder tumors. Aim: To compare tumor recurrence and side effects between high and low dose of BCG in NMIBC. Study Design: Randomized controlled trial. Methodology: Patients (n=30 each group) were enrolled with expected percentage of side effects with low dose (40 mg) as 2.5 % and high dose (80 mg) as 25.8%. Patients of all age groups with both genders having NMIBC (Ta, T1, Tis) and high grade tumors (G3) determined on histopathology of TURBT sample. Patients with history of renal transplant and chemotherapy were excluded. The difference between both groups was analyzed using Chi Square test with P- value of &lt; 0.05 was considered statistically significant. Results: The mean age of patients in group A was 55.83 ± 9.17 and group B was 59.17 ± 8.13 years. There was no significant difference in the age of two groups (P= 0.142). There was no difference in gender distribution in two groups (P=0.688). Regarding the stage of tumor there were 13 cases of stage Ta and T1 in both groups. Conclusion: It was concluded that 40 mg dose of intra-vesical BCG in patients with NMIBC had lower recurrence and side effects as compared to higher dose of intra-vesical BCG. Key words: Recurrence, Side Effects, Low dose BCG and High Dose BCG.

PLLBA-01 FINAL CLINICAL RESULTS OF PIVOTAL TRIAL OF IL-15RΑFC SUPERAGONIST N-803 WITH BCG IN BCG-UNRESPONSIVE NON-MUSCLE INVASIVE BLADDER CANCER (NMIBC) CIS AND PAPILLARY COHORTS

You have accessJournal of UrologyCME1 May 2022PLLBA-01 FINAL CLINICAL RESULTS OF PIVOTAL TRIAL OF IL-15RΑFC SUPERAGONIST N-803 WITH BCG IN BCG-UNRESPONSIVE NON-MUSCLE INVASIVE BLADDER CANCER (NMIBC) CIS AND PAPILLARY COHORTS Sam Chang, Karim Chamie, Mark Hidalgo, Eugene Kramolowsky, Wade Sexton, Sandeep Reddy, and Patrick Soon-Shiong Sam ChangSam Chang More articles by this author , Karim ChamieKarim Chamie More articles by this author , Mark HidalgoMark Hidalgo More articles by this author , Eugene KramolowskyEugene Kramolowsky More articles by this author , Wade SextonWade Sexton More articles by this author , Sandeep ReddySandeep Reddy More articles by this author , and Patrick Soon-ShiongPatrick Soon-Shiong More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002671.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Patients with NMIBC CIS unresponsive to BCG have limited treatment options. N-803 (Anktiva) is a mutant IL-15-based immunostimulatory fusion protein complex (IL15RaFc) that promotes proliferation and activation of natural killer (NK) cells and CD8+ T cells, but not regulatory T cells. Phase 1b data in BCG-naïve patients with NMIBC demonstrate that intravesical N-803 with BCG induced complete response in all patients, without recurrences for the study duration of 24 months. An open-label, 3 cohort multicenter study (QUILT 3.032) of intravesical BCG plus N-803 in patients with BCG-unresponsive high-grade NMIBC (NCT03022825) was opened. We report data on 160 subjects. METHODS: All treated patients received intravesical N-803 plus BCG, consistent with the standard induction/maintenance treatment schedule. The primary endpoint for Cohort A (CIS) is incidence of complete response (CR) of CIS at any time. The primary endpoint for Cohort B (Papillary) is disease-free rate (DFS) at 12 months. RESULTS: To date, 83 patients have enrolled in cohort A, 77 in Cohort B. In the overall population, median age is 72.3 years, 81% male, with mean number of prior TURBT=4. Median number of prior BCG doses = 12. CIS patients have a CR rate of 71% (59/83), with a mediation duration of CR of 24.1 months in responders; 91% avoided cystectomy and 96% 24 month bladder cancer specific progression free survival (defined as progression to MIBC). Papillary patients have a 57% 12 month DFS rate, 48% 24 month DFS rate, and 95% avoided cystectomy. Median time to cystectomy in responders (N=4) is 12.9 months versus 7.8 in non-responders (N=8) for a 5.1 month delay in cystectomy. PK data shows no systemic levels of N-803; thus activity is confined to the bladder. Low grade treatment related AEs (grade 1-2) include dysuria (22%), pollakiurua (19%), hematuria (18%), fatigue (16%), and urgency (12%), all other AEs were seen at 7% or less. No treatment related grade 4 or 5 AE were seen. No treatment emergent SAE's were considered treatment related. No immune related SAE's have been seen. Final data will be presented at AUA. CONCLUSIONS: In 160 patients with BCG-unresponsive NMIBC, there is a 99% bladder cancer specific overall survival at 2 years. In CIS patients 71% CR rate with 24.1 months median duration of response and 96% absence of progression to MIBC at 24 months. 53% DFS rate at 18 months in Papillary disease, N-803+BCG efficacy and safety profile exceeds other available intravesical and systemic options. Source of Funding: ImmunityBio © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e1047 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Sam Chang More articles by this author Karim Chamie More articles by this author Mark Hidalgo More articles by this author Eugene Kramolowsky More articles by this author Wade Sexton More articles by this author Sandeep Reddy More articles by this author Patrick Soon-Shiong More articles by this author Expand All Advertisement PDF DownloadLoading ...

Real-world treatment patterns, survival outcomes, and health care resource utilization among individuals with nonmuscle-invasive bladder cancer in Canada.

470 Background: Real-world evidence pertaining to high-risk Non-Muscle Invasive Bladder Cancer (NMIBC) is limited. We aimed to describe real-world treatment patterns and outcomes of this study population within a Canadian setting. Methods: A retrospective cohort study was conducted by linking various population-based administrative datasets from a large Canadian province. The study population consisted of all individuals ≥ 18 years who were diagnosed with Tis or high-grade Ta/T1 NMIBC in Alberta, Canada between 2010-2019. High-grade disease was defined using the WHO 1973 system. Individuals who initiated BCG therapy were classified as having received adequate induction therapy if they completed 5+ cycles. BCG unresponsive was defined as receipt of TURBT, intravesical chemotherapy, cystectomy, or radiation within 1 year of the last BCG dose. Overall survival (OS), cystectomy-free survival (CFS), progression-free survival (PFS), and healthcare resource utilization (HCRU) were examined from the time of being classified as BCG unresponsive following adequate induction therapy. CFS was defined as time until death or radical cystectomy and PFS was defined as time until death or disease progression. Disease progression was classified using a proxy based on subsequent receipt of cystectomy, systemic therapy, or radiation. Kaplan-Meier survival curves were estimated for OS, CFS, and PFS and the mean number of healthcare encounters within each year of follow-up were estimated for HCRU. Results: 5369 individuals were diagnosed with NMIBC in Alberta between 2010-2019, of whom 2679 (49.9%) had Tis or HG Ta/T1 disease at initial diagnosis. Among individuals with high-risk NMIBC, 1044 (39%) initiated BCG therapy. 885 (84.8%) individuals received 5+ BCG doses. Despite receiving adequate induction treatment, 249 (28.1%) individuals became unresponsive. The mean age at BCG unresponsive was 72.9 years and 213 (58.5%) were males. Among those who were BCG unresponsive, 25.7% underwent radical cystectomy (median time to cystectomy: 4.4 months, IQR: 1.7 to 8.2). Median OS was 50.7 months (95% CI: 37.2-65.5), CFS was 22.4 months (18.9-31.1), and PFS was 14.4 months (11.6-20.9). Within the first year of becoming BCG unresponsive, individuals spent an average of 6.2 days in hospital, had 28.8 visits with healthcare practictitioners, and had 2.2 emergency and 13.6 non-emergency encounters with ambulatory care services. Conclusions: A considerable proportion of individuals with high-risk NMIBC became unresponsive to BCG therapy despite adequate treatment. The time from becomining BCG unresponsive to radical cystectomy was relatively short. These findings highlight an unmet need in this patient population for alternative therapeutic options.

Analysis of the Frequency of the Toll-like 2 Gene Polymorphism in Leprosy

Polymorphisms in genes that are responsible for encoding cytokines and receptors involved in the immune response, such as Toll-like Receptor (TLR) 2 in leprosy, are of great interest for immunogenetic studies. This work aimed to analyze the possible association of single nucleotide polymorphism (SNP), synonymous, rs3804100 of the TLR2 gene with leprosy. The study was conducted in Bacteriology and Mycology section of Evandro Chagas Institute, Brazil between August 2020 and July 2021.The scope of the study consisted of 122 subjects from cities of Goianésia, Rondon, Curionópolis, Altamira, Parauapebas and Redenção of the State of Pará, Brazil. Genotyping was performed by conventional PCR and sequencing in the ABI 3130 Genetic Analyzer (Applied Biosystems®) using primer nucleotides designed by the Primer3Plus program from the genomic region “Homo sapiens toll like receptor 2 (TLR2) transcript variant X6, mRNA”, deposited in GenBank with reference XM_011532216.2. The analyzes were performed based on Fisher's exact test. It was managed in accordance with Helsinki Declaration and the Brazilian National Health Council and with approval of the ethics committee at Evandro Chagas Institute, under opinion number: 3.950.570. No associations between gender and leprosy were possible (P&gt; 0.05). However, associations were observed between age groups, which were significant between those over 46 years old (P=0.004) and the 2nd dose of BCG as a more protective agent between the groups analyzed (P=0.004). For the subjects with the typed genotypes, 68 contacts had T/T genotype and only 4 T/C genotypes, while in multibacillary (MB) group only 1 T/C genotype was found and none in paucibacillary (PB) (P&gt; 0.05). We conclude that there is no association between the TLR2 SNP rs3804100 and leprosy in the Pará population, which still indicates the need for new immunogenetic studies with other genes involved in the immune response and a greater number of polymorphisms.

A single dose, BCG-adjuvanted COVID-19 vaccine provides sterilising immunity against SARS-CoV-2 infection

Global control of COVID-19 requires broadly accessible vaccines that are effective against SARS-CoV-2 variants. In this report, we exploit the immunostimulatory properties of bacille Calmette-Guérin (BCG), the existing tuberculosis vaccine, to deliver a vaccination regimen with potent SARS-CoV-2-specific protective immunity. Combination of BCG with a stabilised, trimeric form of SARS-CoV-2 spike antigen promoted rapid development of virus-specific IgG antibodies in the blood of vaccinated mice, that was further augmented by the addition of alum. This vaccine formulation, BCG:CoVac, induced high-titre SARS-CoV-2 neutralising antibodies (NAbs) and Th1-biased cytokine release by vaccine-specific T cells, which correlated with the early emergence of T follicular helper cells in local lymph nodes and heightened levels of antigen-specific plasma B cells after vaccination. Vaccination of K18-hACE2 mice with a single dose of BCG:CoVac almost completely abrogated disease after SARS-CoV-2 challenge, with minimal inflammation and no detectable virus in the lungs of infected animals. Boosting BCG:CoVac-primed mice with a heterologous vaccine further increased SARS-CoV-2-specific antibody responses, which effectively neutralised B.1.1.7 and B.1.351 SARS-CoV-2 variants of concern. These findings demonstrate the potential for BCG-based vaccination to protect against major SARS-CoV-2 variants circulating globally.