Assessing the impact of COVID-19 on routine immunization in Sierra Leone.

BACKGROUND: The COVID-19 pandemic had a profound impact on healthcare systems and services, including routine immunization (RI). To date, there is limited information on the effects of the COVID-19 pandemic on RI in West African countries such as Sierra Leone, which had already experienced public health emergencies that disrupted its healthcare system. Here, we describe the impact of the COVID-19 pandemic on the RI of key antigens in Sierra Leone. METHODS: We used vaccination data from the District Health Information System for BCG, measles-rubella 1 and 2, and pentavalent 1 and 3 antigens. We compared 2019, 2020, 2021, and 2022 annual coverage rates for the selected antigens at the national and district levels. We used the Pearson chi-square test to assess the difference between annual coverage rates between 2019 and 2020, 2020-2021, and 2021-2022. RESULTS: National coverage rates for all antigens declined in 2019-2020, notably measles-rubella 1 and pentavalent 3 (-5.4% and - 4.9%). Between 2020 and 2021, there was an overall increase in coverage (+ 0.2% to + 2.5%), except for measles-rubella 2 (-1.8%). Measles-rubella antigens rebounded in 2021-2022, while others decreased between - 0.5 and - 1.9% in coverage. Overall, all district-level coverage rates in 2022 were lower than those in 2019. Most districts decreased between 2019 and 2022, though a few had a continuous increase; some had an increase/recovery between 2020 and 2021; some districts had recovered 2019 levels by 2022. CONCLUSION: The COVID-19 pandemic impacted Sierra Leone's national BCG, measles-rubella, and pentavalent antigen immunization, which were not fully restored in 2022. Most districts experienced notable coverage declines during the pandemic, though a few reached or surpassed 2019 rates in 2022. Examining pandemic impact can benefit from a focus beyond the national level to identify vulnerable regions. Sierra Leone's post-pandemic RI reestablishment needs targeted strategies and continual investments for equitable access and coverage, as well as to prevent vaccine-preventable diseases.

Models for predicting the risk of illness in leprosy contacts in Brazil: Leprosy prediction models in Brazilian contacts.

OBJECTIVE: This study aims to develop and validate predictive models that assess the risk of leprosy development among contacts, contributing to an enhanced understanding of disease occurrence in this population. METHODS: A cohort of 600 contacts of people with leprosy treated at the National Reference Center for Leprosy and Health Dermatology at the Federal University of Uberlândia (CREDESH/HC-UFU) was followed up between 2002 and 2022. The database was divided into two parts: two-third to construct the disease risk score and one-third to validate this score. Multivariate logistic regression models were used to construct the disease score. RESULTS: Of the four models constructed, model 3, which included the variables anti-phenolic glycolipid I immunoglobulin M positive, absence of Bacillus Calmette-Guérin vaccine scar and age ≥60 years, was considered the best for identifying a higher risk of illness, with a specificity of 89.2%, a positive predictive value of 60% and an accuracy of 78%. CONCLUSIONS: Risk prediction models can contribute to the management of leprosy contacts and the systematisation of contact surveillance protocols.

Macrophages exploit the mannose receptor and JAK-STAT1-MHC-II pathway to drive antigen presentation and the antimycobacterial immune response after BCG vaccination.

Tuberculosis (TB), caused by Mycobacterium tuberculosis ( M. tb), remains one of the leading causes of fatal infectious diseases worldwide. The only licensed vaccine, Mycobacterium bovis Bacillus Calmette-Guérin (BCG), has variable efficacy against TB in adults. Insufficiency of immune cell function diminishes the protective effects of the BCG vaccine. It is critical to clarify the mechanism underlying the antimycobacterial immune response during BCG vaccination. Macrophage mannose receptor (MR) is important for enhancing the uptake and processing of glycoconjugated antigens from pathogens for presentation to T cells, but the roles of macrophage MR in the BCG-induced immune response against M. tb are not yet clear. Here, we discover that macrophage MR deficiency impairs the antimycobacterial immune response in BCG-vaccinated mice. Mechanistically, macrophage MR triggers JAK-STAT1 signaling, which promotes antigen presentation via upregulated MHC-II and induces IL-12 production by macrophages, contributing to CD4 + T cell activation and IFN-γ production. MR deficiency in macrophages reduces the vaccine efficacy of BCG and increases susceptibility to M. tb H37Ra challenge in mice. Our results suggest that MR is critical for macrophage antigen presentation and the antimycobacterial immune response to BCG vaccination and offer valuable guidance for the preventive strategy of BCG immunization.

Immune-checkpoint gene expression and BCG response in non-muscle invasive bladder cancer.

METHODS: One-hundred-six patients diagnosed with non-muscle invasive bladder cancer and treated with intravesical BCG were included and divided into two groups, BCG-responsive (n = 47) and -unresponsive (n = 59). Immunohistochemistry was used to evaluate PD-L1 expression and MSI was assessed by a commercial multiplex PCR kit. The mRNA expression profile of 15 immune checkpoints was performed using the nCounter technology. For in silico validation, two distinct cohorts sourced from the Gene Expression Omnibus (GEO) database were used. RESULTS: Among the 106 patients, only one (<1 %) exhibited MSI instability. PD-L1 expression was present in 9.4 % of cases, and no association was found with BCG-responsive status. We found low gene expression of canonic actionable immune checkpoints PDCD1 (PD-1), CD274 (PD-L1), and CTLA4, while high expression was observed for CD276 (B7-H3), CD47, TNFRSF14, IDO1 and PVR (CD155) genes. High IDO1 expression levels was associated with worst overall survival. The PDCD1, CTLA4 and TNFRSF14 expression levels were associated with BCG responsiveness, whereas TIGIT and CD276 were associated with unresponsiveness. Finally, CD276 was validated in silico cohorts. CONCLUSION: In NMIBC, MSI is rare and PD-L1 expression is present in a small subset of cases. Expression levels of PDCD1, CTLA4, TNFRSF14, TIGIT and CD276 could constitute predictive biomarkers of BCG responsiveness.

The whole genome sequence of Polish vaccine strain Mycobacterium bovis BCG Moreau.

Currently, tuberculosis immunoprophylaxis is based solely on Bacillus Calmette-Guérin (BCG) vaccination, and some of the new potential tuberculosis vaccines are based on the BCG genome. Therefore, it is reasonable to analyze the genomes of individual BCG substrains. The aim of this study was the genetic characterization of the BCG-Moreau Polish (PL) strain used for the production of the BCG vaccine in Poland since 1955. Sequencing of different BCG lots showed that the strain was stable over a period of 59 years. As a result of comparison, BCG-Moreau PL with BCG-Moreau Rio de Janeiro (RDJ) 143 single nucleotide polymorphisms (SNPs) and 32 insertion/deletion mutations (INDELs) were identified. However, the verification of these mutations showed that the most significant were accumulated in the BCG-Moreau RDJ genome. The mutations unique to the Polish strain genome are 1 SNP and 2 INDEL. The strategy of combining short-read sequencing with long-read sequencing is currently the most optimal approach for sequencing bacterial genomes. With this approach, the only available genomic sequence of BCG-Moreau PL was obtained. This sequence will primarily be a reference point in the genetic control of the stability of the vaccine strain in the future. The results enrich knowledge about the microevolution and attenuation of the BCG vaccine substrains. IMPORTANCE: The whole genome sequence obtained is the only genomic sequence of the strain that has been used for vaccine production in Poland since 1955. Sequencing of different BCG lots showed that the strain was stable over a period of 59 years. The comprehensive genomic analysis performed not only enriches knowledge about the microevolution and attenuation of the BCG vaccine substrains but also enables the utilization of identified markers as a reference point in the genetic control and identity tests of the stability of the vaccine strain in the future.

Bacille Calmette-Guérin vaccination to prevent febrile and respiratory illness in adults (BRACE): secondary outcomes of a randomised controlled phase 3 trial.

Background: Bacille Calmette-Guérin (BCG) vaccination has off-target (non-specific) effects that are associated with protection against unrelated infections and decreased all-cause mortality in infants. We aimed to determine whether BCG vaccination prevents febrile and respiratory infections in adults. Methods: This randomised controlled phase 3 trial was done in 36 healthcare centres in Australia, Brazil, the Netherlands, Spain, and the United Kingdom. Healthcare workers were randomised to receive BCG-Denmark (single 0.1 ml intradermal injection) or no BCG in a 1:1 ratio using a web-based procedure, stratified by stage, site, age, and presence of co-morbidity. The difference in occurrence of febrile or respiratory illness were measured over 12 months (prespecified secondary outcome) using the intention-to-treat (ITT) population. This trial is registered with ClinicalTrials.gov, NCT04327206. Findings: Between March 30, 2020, and April 1, 2021, 6828 healthcare workers were randomised to BCG-Denmark (n = 3417) or control (n = 3411; no intervention or placebo) groups. The 12-month adjusted estimated risk of ≥1 episode of febrile or respiratory illness was 66.8% in the BCG group (95% CI 65.3%-68.2%), compared with 63.4% in the control group (95% CI 61.8%-65.0%), a difference of +3.4 percentage points (95% CI +1.3% to +5.5%; p 0.002). The adjusted estimated risk of a severe episode (defined as being incapacitated for ≥3 consecutive days or hospitalised) was 19.4% in the BCG group (95% CI 18.0%-20.7%), compared with 18.8% in the control group (95% CI 17.4%-20.2%) a difference of +0.6 percentage points (95% CI -1.3% to +2.5%; p 0.6). Both groups had a similar number of episodes of illness, pneumonia, and hospitalisation. There were three deaths, all in the control group. There were no safety concerns following BCG vaccination. Interpretation: In contrast to the beneficial off-target effects reported following neonatal BCG in infants, a small increased risk of symptomatic febrile or respiratory illness was observed in the 12 months following BCG vaccination in adults. There was no evidence of a difference in the risk of severe disease. Funding: Bill & Melinda Gates Foundation, Minderoo Foundation, Sarah and Lachlan Murdoch, the Royal Children's Hospital Foundation, Health Services Union NSW, the Peter Sowerby Foundation, SA Health, the Insurance Advisernet Foundation, the NAB Foundation, the Calvert-Jones Foundation, the Modara Pines Charitable Foundation, the UHG Foundation Pty Ltd, Epworth Healthcare, the National Health and Medical Research Council, the Swiss National Science Foundation and individual donors.

Maternal BCG scars and mortality risk for male and female newborns: observational study from Guinea-Bissau.

BACKGROUND: Maternal priming with Bacille Calmette-Guérin (BCG) has been associated with reduced mortality in male offspring. We investigated this association in a cohort of healthy BCG-vaccinated neonates. METHODS: Observational study within a randomized controlled trial comparing different BCG strains conducted in Guinea-Bissau from 2017-2020. As part of trial inclusion procedures, on the day of discharge from the maternity ward, maternal BCG scar status was evaluated by visual inspection, followed by offspring BCG and polio vaccination. Through mortality data collected at telephone interviews at six weeks and six months of age, we assessed all-cause mortality risk in Cox Proportional Hazards models adjusted for maternal schooling and BCG strain, providing adjusted Mortality Rate Ratios (aMRRs). RESULTS: 64% (11,070/17,275) of mothers had a BCG scar, which for females and overall was not associated with neither admission risk, admission severity nor all-cause mortality. By six months of age, the mortality rate (MR) was 4.1 (200 deaths/4,919 person-years) for the maternal BCG scar cohort and 5.2 (139 deaths/2,661 person-years) for no maternal scar, aMRR=0.86 (0.69-1.06). In males, six-month MRs were 4.3 (109/2,531) for maternal BCG scar vs 6.3 (87/1,376) for no scar, the maternal scar/no scar aMRR being 0.74 (0.56-0.99). In females, six-month MRs were 3.8 (91/2,388) vs 4.0 (52(1,286), the aMRR being 1.04 (0.74-1.47), p for interaction with sex=0.16. CONCLUSION: While we cannot rule out an association in females, being born to a mother with a BCG scar reduced the risk of death during early infancy for BCG-vaccinated males, reproducing findings from previous studies.

Efficacy of conduction hyperthermia in the treatment of non-muscle invasive bladder cancer: A systematic review.

INTRODUCTION: Intravesical treatment for non-muscle invasive bladder cancer (NMIBC) aims to reduce recurrences and stop progression. Hyperthermia-enhanced chemotherapy with devices like COMBAT BRS, Unithermia, and BR-TRG-I is a promising alternative to conventional Bacillus de Calmette Guerin (BCG) therapy. OBJECTIVE: To systematically review the efficacy of hyperthermia generated by conduction devices in the treatment of NMIBC. MATERIAL AND METHODS: The review followed the preferred reporting items for systematic reviews and meta-analyses guidelines. A search was performed in the PubMed, Cochrane Library, Scopus, and ClinicalTrials.gov databases. Two reviewers independently assessed the eligibility of candidate studies and abstracted data from studies that met the inclusion criteria. The primary endpoint was assessment of recurrence. Secondary objectives included evaluation of treatment progression and safety. RESULTS: Thirty studies meeting inclusion criteria underwent data extraction. In intermediate-risk NMIBC patients, COMBAT versus mitomycin C (MMC) in normothermia revealed no superiority in reducing recurrence or progression. High-risk NMIBC patients using COMBAT achieved similar or superior outcomes to BCG. BR-TRG-I demonstrated superior results over normothermia in intermediate- and high-risk NMIBC patients. Unithermia proved less effective than BCG in high-risk NMIBC. Progression outcomes were promising with COMBAT and BR-TRG-I, but comprehensive analysis was limited due to inconsistent assessment across studies. Adverse events were primarily mild-moderate, with some device-specific differences. CONCLUSIONS: Studies on conduction hyperthermia present great variability, which do not allow us to determine the superiority of 1 device over another in terms of recurrence, progression, and/or adverse effects. Further research with consistent administration protocols is crucial for definitive conclusions.

Bacillus Calmette-Guérin (BCG)-Induced Protection in Brain Disorders.

The Bacille Calmette-Guerin (BCG) vaccine is one of the most widely used vaccines in the world for the prevention of tuberculosis. Its immunological capacity also includes epigenetic reprogramming, activation of T cells and inflammatory responses. Although the main usage of the vaccine is the prevention of tuberculosis, different works have shown that the effect of BCG can go beyond the peripheral immune response and be linked to the central nervous system by modulating the immune system at the level of the brain. This review therefore aims to describe the BCG vaccine, its origin, its relationship with the immune system, and its involvement at the brain level.

A modified BCG with depletion of enzymes associated with peptidoglycan amidation induces enhanced protection against tuberculosis in mice.

Mechanisms by which Mycobacterium tuberculosis (Mtb) evades pathogen recognition receptor activation during infection may offer insights for the development of improved tuberculosis (TB) vaccines. Whilst Mtb elicits NOD-2 activation through host recognition of its peptidoglycan-derived muramyl dipeptide (MDP), it masks the endogenous NOD-1 ligand through amidation of glutamate at the second position in peptidoglycan side-chains. As the current BCG vaccine is derived from pathogenic mycobacteria, a similar situation prevails. To alleviate this masking ability and to potentially improve efficacy of the BCG vaccine, we used CRISPRi to inhibit expression of the essential enzyme pair, MurT-GatD, implicated in amidation of peptidoglycan side-chains. We demonstrate that depletion of these enzymes results in reduced growth, cell wall defects, increased susceptibility to antibiotics, altered spatial localization of new peptidoglycan and increased NOD-1 expression in macrophages. In cell culture experiments, training of a human monocyte cell line with this recombinant BCG yielded improved control of Mtb growth. In the murine model of TB infection, we demonstrate that depletion of MurT-GatD in BCG, which is expected to unmask the D-glutamate diaminopimelate (iE-DAP) NOD-1 ligand, yields superior prevention of TB disease compared to the standard BCG vaccine. In vitro and in vivo experiments in this study demonstrate the feasibility of gene regulation platforms such as CRISPRi to alter antigen presentation in BCG in a bespoke manner that tunes immunity towards more effective protection against TB disease.

Tuberculosis is the leading cause of death from an infectious disease worldwide, partially due to a lack of access to drug treatments in certain countries where the disease is common. The only available tuberculosis vaccine ­ known as the BCG vaccine ­ is useful for preventing cases in young children, but is ineffective in teenagers and adults. So, there is a need to develop new vaccines that offer better, and longer lasting, durable protection in people of all ages. During an infection, our immune system recognizes markers known as PAMPs on the surface of bacteria, viruses or other disease-causing pathogens. The recognition of PAMPs by the immune system enables the body to distinguish foreign invading organisms from its own cells and tissues, thus triggering a response that fights the infection. If the body encounters the infectious agent again in the future, the immune system is able to quickly recognize and eliminate it before it can cause disease. Vaccines protect us by mimicking the appearance of the pathogen to trigger the first immune response without causing the illness. The BCG vaccine contains live bacteria that are closely related to the bacterium responsible for tuberculosis called Mycobacterium tuberculosis. Both M. tuberculosis and the live bacteria used in the BCG vaccine are able to hide an important PAMP, known as the NOD-1 ligand, from the immune system, making it harder for the body to detect them. The NOD-1 ligand forms part of the bacterial cell wall and modifying the BCG bacterium so it cannot disguise this PAMP may lead to a new, more effective vaccine. To investigate this possibility, Shaku et al. used a gene editing approach to develop a modified version of the BCG bacterium which is unable to hide its NOD-1 ligand when treated with a specific drug. Immune cells trained with the modified BCG vaccine were more effective at controlling the growth of M. tuberculosis than macrophages trained using the original vaccine. Furthermore, mice vaccinated with the modified BCG vaccine were better able to limit M. tuberculosis growth in their lungs than mice that had received the original vaccine. These findings offer a new candidate vaccine in the fight against tuberculosis. Further studies will be needed to modify the vaccine for use in humans. More broadly, this work demonstrates that gene editing can be used to expose a specific PAMP present in a live vaccine. This may help develop more effective vaccines for other diseases in the future.

Protective role of Bacillus Calmette-Guérin vaccine in Alzheimer's disease progression: A systematic review and meta-analysis.

Introduction: Alzheimer's disease (AD) represents a significant societal challenge, highlighting the need to explore effective prevention and treatment approaches. Recent literature has suggested that Bacillus Calmette-Guérin (BCG) vaccine may be a viable therapeutic option for immune disorders associated with AD due to its immunomodulatory properties and protection against various diseases. Methods: This systematic review aimed to evaluate the association of BCG vaccine in the prevention of AD using six medical-scientific databases. A meta-analytical approach was undertaken to estimate the risk of AD incidence in patients with and without BCG vaccine exposure, followed by subgroup analyses. A risk of bias (RoB) assessment was performed using the Newcastle-Ottawa Scale (NOS). Results: Six cohort studies meeting our inclusion criteria were included (47,947 participants) in the study. From our meta-analysis, intravesical BCG vaccine administration lowered the risk of incidence of AD by 26% in non-muscle-invasive bladder cancer (p < 0.00001). Subgroup analyses showed that BCG vaccination showed a potentially notable preventive effect on AD in older adults (>75 years) and female participants. Conversely, significant heterogeneity in results was observed among male participants and those aged <75 years. The RoB was low in three studies and unclear in the remaining studies. Conclusions: Although our results support the potential benefits of BCG vaccine in preventing AD in specific demographics, we remain cautious about interpreting such results. Further research examining the implications of BCG vaccination for prevention and possible treatment of AD should be undertaken in the future.

BCGitis con afectación de aneurisma aortoilíaco: aportación de dos casos y revisión de la literatura / BCGitis with aortoiliac aneurysm involvement: Report of two cases and review of the literature

La BCGitis es una complicación infrecuente del tratamiento intravesical con Bacillus Calmette-Guérin para el cáncer superficial de vejiga de alto grado y el carcinoma in situ. Puede causar afectación vascular. Presentamos 2 casos y una revisión de la literatura de series de casos publicadas en los 10 años previos a la finalización de este trabajo en abril de 2022, que describiesen un caso de aneurisma micótico aortoilíaco tras recibir este tratamiento. De los 51 casos incluidos (49 revisados y 2 originales), el 100% eran hombres, 82% tenían más de 65 años. La mediana del período de latencia fue de 15 meses (RIQ 18). La localización más frecuente fue la aorta abdominal, documentándose rotura en el 45,1%. El síntoma más frecuente fue dolor abdominal o lumbar (61%), seguido de síndrome general (49%). Asoció absceso retroperitoneal un 39,2%. La mortalidad atribuible fue de 13,6%. La BCGitis debería incluirse como diagnóstico diferencial de pacientes que hayan recibido terapia con BCG y presenten afectación vascular, incluso años tras el tratamiento.(AU)

BCGitis is a rare complication after intravesical administration of Bacillus Calmette-Guérin for high-grade superficial bladder cancer and carcinoma in situ. May cause vascular involvement. We present two cases and a review of the literature of the case reports published on the 10 years prior to April of 2022, when this project was finished, which described a case of aortoiliac mycotic aneurysm after receiving this treatment. Of the 51 cases included (49 revised and 2 original), 100% were men, 82% were older than 65 years. The median latency period was 15 months (IQR 18). The most frequent location was the abdominal aorta, rupture occurred in 45.1% of patients. The most frequent symptom was abdominal or lumbar pain (61%), followed by general syndrome (49%). In 39.2% cases, it was associated with retroperitoneal abscesses. Attributable mortality was 13.6%. BCGitis should be included in the differential diagnosis in patients who have received BCG therapy and present vascular involvement, even years after being treated.(AU)

Impact of BCG Vaccination Disruptions During the COVID-19 Pandemic on Tuberculosis Incidence in Infants: A Nationwide Study in Brazil.

Pandemic-related disruptions led to lower Bacille Calmette-Guérin (BCG) vaccine coverage in Brazil. This study highlights a link between reduced vaccinations and increased tuberculosis pulmonary and extrapulmonary cases in infants. Addressing vaccine hesitancy and ensuring healthcare stability is vital for mitigating impacts.

The association between BCG scars and self-reported chronic diseases: A cross-sectional observational study within an RCT of Danish health care workers.

INTRODUCTION: The live-attenuated vaccines Bacillus Calmette-Guérin (BCG) and Vaccinia have been associated with beneficial non-specific effects. We assessed the prevalence of BCG and Vaccinia vaccine scars in a cohort of Danish health care workers and investigated the association between the presence of vaccine scars and self-reported chronic diseases. METHODS: Cross-sectional study utilizing baseline data collected during 2020-2021 at enrollment in a BCG trial aiming to assess the effect of BCG vaccination on absenteeism and infectious disease morbidity during the SARS-COV-2 pandemic. In Denmark, Vaccinia was discontinued in 1977, and BCG was phased out in the early 1980s. We used logistic regression analysis (adjusted for sex, birth year, and smoking status) to estimate the association between scar status and chronic diseases, providing adjusted Odds Ratios (aORs) with 95 % Confidence Intervals, for participants born before 1977, and born from 1965 to 1976. RESULTS: The cohort consisted of 1218 participants (206 males; 1012 females) with a median age of 47 years (Q1-Q3: 36-56). Among participants born 1965-1976 (n = 403), who experienced the phase-outs, having BCG and/or Vaccinia scar(s) vs. having no vaccine scars yielded an aOR of 0.51 (0.29-0.90) of self-reported chronic disease; an effect primarily driven by BCG. In the same birth cohort, having vaccine scar(s) was most strongly associated with a lower prevalence of chronic respiratory and allergic diseases; the aORs being 0.39 (0.16-0.97) and 0.39 (0.16-0.91), respectively. CONCLUSION: Having a BCG scar was associated with a lower prevalence of self-reported chronic disease.

A Case Report of a Cold Chest Wall Abscess Following Bacillus Calmette-Guérin Vaccination.

The Bacillus Calmette-Guérin (BCG) vaccine, a cornerstone in global immunization programs for tuberculosis prevention, has generally proven to be safe and effective. However, rare complications, including localized abscess formation, have been reported. This case report highlights a two-year-old male who developed a painless swelling on the left chest wall, noticed six weeks post-BCG vaccination. Physical and imaging evaluations confirmed a cold abscess. Laboratory tests ruled out alternative diagnoses. Antitubercular therapy led to a favorable response, avoiding surgical intervention. Follow-up revealed complete resolution, showcasing successful management of this rare BCG-related complication in a pediatric patient. The success of antimycobacterial therapy supports a tailored and conservative approach, raising questions about the necessity of surgical intervention. The presented case sheds light on the complex interplay between BCG vaccination, host response, and rare complications, providing valuable insights for further research. Vigilance, robust surveillance, and collaborative efforts are essential to unravel vaccine-related adverse events. This case contributes to a deeper understanding of rare BCG-related complications, guiding clinical practice, and advancing the knowledge base.

Recombinant BCG vaccine expressing multistage antigens of Mycobacterium tuberculosis provides long-term immunity against tuberculosis in BALB/c mice.

Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) persistently kills nearly 1.5 million lives per year in the world, whereas the only licensed TB vaccine BCG exhibits unsatisfactory efficacy in adults. Taking BCG as a vehicle to express Mtb antigens is a promising way to enhance its efficacy against Mtb infection. In this study, the immune efficacy of recombination BCG (rBCG-ECD003) expressing specific antigens ESAT-6, CFP-10, and nDnaK was evaluated at different time points after immunizing BALB/c mice. The results revealed that rBCG-ECD003 induced multiple Th1 cytokine secretion including IFN-γ, TNF-α, IL-2, and IL-12 when compared to the parental BCG. Under the action of PPD or ECD003, rBCG-ECD003 immunization resulted in a significant increase in the proportion of IL-2+ and IFN-γ+IL-2+ CD4+T cells. Importantly, rBCG-ECD003 induced a stronger long-term humoral immune response without compromising the safety of the parental BCG vaccine. By means of the protective efficacy assay in vitro, rBCG-ECD003 showed a greater capacity to inhibit Mtb growth in the long term. Collectively, these features of rBCG-ECD003 indicate long-term protection and the promising effect of controlling Mtb infection.

The spectrum of cytological findings in patients with BCG lymphadenitis: A series of 13 cases.

CONTEXT: Bacillus Calmette-Guérin (BCG) vaccine has been used to prevent tuberculosis and/or its severe complications for long. BCG lymphadenitis is a common complication of the vaccine, which is sometimes subjected to cytological examination. The aim of the study is to describe the cytological findings of BCG lymphadenitis. SETTINGS: The study was conducted in a tertiary care hospital in the western part of India from January 2021 to December 2022. DESIGN: The study was performed on archived material of all patients who were referred to the fine needle aspiration clinic for cytology examination. Clinical and pathological data of cases were retrieved, and cases of BCG lymphadenitis were selected in the study based on these data. Slides of cases were retrieved, and cytological findings were studied. MATERIALS AND METHODS: Papanicolaou, Giemsa, and Hematoxylin & eosin-stained smears, as well as Ziehl-Neelson stain (Z.N. stain) smears of all BCG lymphadenitis cases, were retrieved. Cases were reviewed for individual cytological features and overall cytological diagnostic categories. Z.N. stain smears were evaluated for acid-fast bacilli. RESULTS AND CONCLUSIONS: Diagnostic categories observed in BCG lymphadenitis include suppurative lymphadenitis/abscess (15 %), necrotizing lymphadenitis (23 %), necrotizing granulomatous lymphadenitis (46 %), suppurative granulomatous lymphadenitis (8 %), non-necrotizing granulomatous lymphadenitis (8 %). Acid-fast bacilli were detected by Z.N. stain in 8 cases (62 %). The cytological findings of BCG lymphadenitis closely overlap with those of tuberculous lymphadenitis. So, clinical context is very important while reporting isolated axillary lymphadenopathy, specifically in recently vaccinated infants, to avoid misdiagnosis as tuberculous lymphadenitis.

BCGitis with aortoiliac aneurysm involvement: Report of two cases and review of the literature.

BCGitis is a rare complication after intravesical administration of Bacillus Calmette-Guérin for high-grade superficial bladder cancer and carcinoma in situ. May cause vascular involvement. We present 2 cases and a review of the literature of the case reports pubished on the 10 years prior to April of 2022, when this proyect was finished, which described a case of aortoiliac mycotic aneurysm after receiving this treatment. Of the 51 cases included (49 revised and 2 original), 100% were men, 82% were older than 65 years. The median latency period was 15 months (IQR 18). The most frequent location was the abdominal aorta, rupture occurred in 45,1% of patients. The most frequent symptom was abdominal or lumbar pain (61%), followed by general syndrome (49%). In 39,2% cases, it was associated with retroperitoneal abscesess. Attributable mortality was 13,6%. BCGitis should be included in the differential diagnosis in patients who have received BCG therapy and present vascular involvement, even years after being treated.