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Human Vaccines & Immunotherapeutics Aug 2020BCG has been recommended because of its efficacy against disseminated and meningeal tuberculosis. The BCG vaccine has other mechanisms of action besides tuberculosis... (Review)
Review
BCG has been recommended because of its efficacy against disseminated and meningeal tuberculosis. The BCG vaccine has other mechanisms of action besides tuberculosis protection, with immunomodulatory properties that are now being discovered. Reports have shown a significant protective effect against leprosy. Randomized controlled trials suggest that BCG vaccine has beneficial heterologous (nonspecific) effects on mortality in some developing countries. BCG immunotherapy is considered the gold standard adjuvant treatment for non-muscle-invasive bladder cancer. BCG vaccine has also been tested as treatment for diabetes and multiple sclerosis. Erythema of the BCG site is recognized as a clinical clue in Kawasaki disease. BCG administration in the immunodeficient patient is associated with local BCG disease (BCGitis) or disseminated BCG disease (BCGosis) with fatal consequences. BCG administration has been associated with the development of autoimmunity. We present a brief review of the diverse facets of the vaccine, with the discovery of its new modes of action providing new perspectives on this old, multifaceted and controversial vaccine.
Topics: Adjuvants, Immunologic; Autoimmunity; BCG Vaccine; Humans; Immunologic Deficiency Syndromes; Tuberculosis
PubMed: 31995448
DOI: 10.1080/21645515.2019.1706930 -
Journal of Clinical Immunology Jan 2021Bacillus Calmette-Guerin (BCG) is a live attenuated vaccine with the potential of causing severe iatrogenic complications in patients with primary immunodeficiency...
PURPOSE
Bacillus Calmette-Guerin (BCG) is a live attenuated vaccine with the potential of causing severe iatrogenic complications in patients with primary immunodeficiency diseases (PID) before and after hematopoietic stem cell transplantation (HSCT). We aim to investigate risk factors of post-HSCT BCG-related complications in PID patients.
METHODS
A retrospective analysis of pediatric PID patients who had received the BCG vaccine and underwent HSCT at Hadassah-Hebrew University Medical Center, between 2007 and 2019.
RESULTS
We found 15/36 (41.67%) patients who developed post-HSCT BCG-related complications. The most significant risk factor for developing BCG-related complications was T cell deficiency (47.6% of the non-complicated vs 83.3% of the BCGitis and 100% of the BCGosis groups had T cell lymphopenia, p = 0.013). None of the chronic granulomatous patients developed BCG-related manifestation post-transplant. Among T cell-deficient patients, lower NK (127 vs 698 cells/μl, p = 0.04) cell counts and NK-SCID were risk factors for ongoing post-HSCT BCGosis, as was pretransplant disseminated BCGosis (33.3% of patients with BCGosis vs none of the non-BCGosis patients, p = 0.04). Immune reconstitution inflammatory syndrome (IRIS) was observed in 3/5 patients with Omenn syndrome. Prophylactic antimycobacterial treatment was not proven effective.
CONCLUSION
BCG vaccination can cause significant morbidity and mortality in the post-transplant T cell-deficient patient, especially in the presence of pre-transplant disease. Taking a detailed medical history prior to administering, the BCG vaccine is crucial for prevention of this complication.
Topics: BCG Vaccine; Biomarkers; Child, Preschool; Diagnosis, Differential; Disease Susceptibility; Female; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Infant; Infant, Newborn; Male; Patient Outcome Assessment; Primary Immunodeficiency Diseases; Retrospective Studies; Vaccination
PubMed: 33111199
DOI: 10.1007/s10875-020-00892-6 -
Scandinavian Journal of Immunology Oct 2021BCG infections occur more frequently in patients with underlying primary immunodeficiency disease (PIDD). In this study, we aimed to evaluate the ratio of PIDD in the...
BCG infections occur more frequently in patients with underlying primary immunodeficiency disease (PIDD). In this study, we aimed to evaluate the ratio of PIDD in the patients with BCG infections. Patients with BCG infections were analyzed in a tertiary referral centre in the 2015-2020 period. Forty-seven patients with BCGitis/BCGosis were evaluated; thirty-four (72.3%) had BCGitis, and 13 (27.7%) had BCGosis. Common tissue and organs affected are lymph nodes (57.4%), skin and subcutaneous tissue (48.9%), lungs (23.4%) and liver (17%). PIDD was shown in 26 patients (55.3%), including 92.3% of patients with BCGosis and 41.2% of patients with BCGitis. Ten patients had Mendelian susceptibility to Mycobacterial disease (MSMD) (21.2%), six had predominantly antibody deficiency (PAD) (12.7%), five had severe combined immunodeficiency (SCID) (10.6%), three had CGD (6.3%), and two had CID (4.2%). Mortality was reported in two patients (4.2%) with CID (ZAP70 deficiency (n = 1) and PIK3R1 deficiency (n = 1)). Parental consanguinity (84%), axillary lymphadenopathy (65%), mycobacterial lung disease (42%), hepatomegaly (30%) and growth retardation (19%) were significantly high in patients with PIDD diagnosis. Isolated vaccination site infection was also recorded in patients with PIDD (CID (n = 1), SCID (n = 1), PAD (n = 5)). BCG vaccination should be planned with caution for the cases with suspected PIDD. This study indicates that almost all patients (92.3%) with BCGosis and one in every two patients (41.2%) with BCGitis have an underlying PIDD. Parental consanguinity, axillary lymphadenopathy, mycobacterial lung disease, hepatomegaly and growth retardation (19%) are important clinical features in the differential diagnosis of PIDD.
Topics: BCG Vaccine; Child, Preschool; Cohort Studies; Diagnosis, Differential; Disease Susceptibility; Female; Humans; Infant; Male; Mycobacterium bovis; Organ Specificity; Primary Immunodeficiency Diseases; Retrospective Studies; Tuberculosis
PubMed: 34780073
DOI: 10.1111/sji.13084 -
PloS One 2014In this study, the clinical and immunogenetical features in a cohort of Chinese patients with BCGosis/BCGitis were investigated. For the patients with abnormal...
In this study, the clinical and immunogenetical features in a cohort of Chinese patients with BCGosis/BCGitis were investigated. For the patients with abnormal immunological functions, Sanger sequencing was used to identify the involved genes. There were 74 confirmed cases of BCGosis/BCGitis during 2007-2012. Classified by infected tissues and organs, no cases only had local infection, 39 patients had a regional infection, 21 patients had a distant infection and 14 patients had a disseminated infection. Thirty-two patients (43.2%) had definitive primary immunodeficiency diseases (PID) and chronic granulomatous disease (CGD) is the most common PID (n = 23, accounted for 71.9% of all PID patients). For CGD patients, based on the anti-tuberculosis treatment, administration of rhIFN-γ resulted in better control of BCGosis/BCGitis. The results indicate that PIDs are associated with susceptibility to BCG disease. For children with BCGosis/BCGitis, immune function evaluation is necessary, and IFN-γ treatment for BCGosis/BCGitis patients with CGD is effective.
Topics: BCG Vaccine; Child, Preschool; Female; Follow-Up Studies; Humans; Immunogenetics; Immunoglobulins; Immunologic Deficiency Syndromes; Infant; Infant, Newborn; Interferon-gamma; Lymphocyte Subsets; Male; Mycobacterium Infections, Nontuberculous; Severity of Illness Index; Tuberculosis
PubMed: 24722620
DOI: 10.1371/journal.pone.0094485 -
Journal of Microbiology, Immunology,... Aug 2023
Review
Topics: Humans; Granulomatous Disease, Chronic; Hematopoietic Stem Cell Transplantation; Tuberculosis
PubMed: 36702645
DOI: 10.1016/j.jmii.2023.01.002 -
Frontiers in Pediatrics 2022We aimed to assess BCG (Bacillus Calmette-Guérin) complications in patients with Inborn Errors of Immunity (IEI), according to the inherited disorders and associated...
BCG Moreau Polish Substrain Infections in Patients With Inborn Errors of Immunity: 40 Years of Experience in the Department of Immunology, Children's Memorial Health Institute, Warsaw.
OBJECTIVE
We aimed to assess BCG (Bacillus Calmette-Guérin) complications in patients with Inborn Errors of Immunity (IEI), according to the inherited disorders and associated immunological defects, as well as the different BCG substrains.
MATERIAL
We studied adverse reactions to the locally-produced BCG Moreau vaccine, analyzed in patients with IEI diagnosed between 1980 and 2020 in the Department of Immunology, Children's Memorial Health Institute (CMHI), Warsaw. These results were compared with previously published studies.
RESULTS
Significantly fewer disseminated BCG infections (BCGosis) were found in 11 of 72 (15%) SCID (Severe Combined Immunodeficiency) NK (Natural Killer)-phenotype patients, when compared with the 119 out of 349 (34%) ( = 0.0012) patients with SCID with BCG in other countries. Significantly fewer deaths caused by BCGosis were observed ( = 0.0402). A significantly higher number of hematopoietic stem cell transplantations (HSCTs) were performed in the CMHI study ( = 0.00001). BCGosis was found in six patients with Mendelian susceptibility to mycobacterial diseases (MSMD). Other patients with IEI prone to BCG complications, such as CGD (Chronic Granulomatous Disease), showed no case of BCGosis.
CONCLUSION
The BCG Moreau substrain vaccine, produced in Poland since 1955, showed genetic differences with its parental Brazilian substrain together with a superior clinical safety profile in comparison with the other BCG substrains, with no BCGosis in patients with IEI other than SCID and MSMD. Our data also confirmed significantly fewer cases of BCGosis and deaths caused by BCG infection in patients with SCID with this vaccine substrain. Finally, they confirmed the protecting role of NK cells, probably their production of IFN-γ.
PubMed: 35664873
DOI: 10.3389/fped.2022.839111 -
Journal of Surgical Case Reports Dec 2021Bacillus Calmette-Guerin (BCG) immunotherapy is a mainstay of adjunctive therapy for non-muscle-invasive bladder cancer. The instillation of BCG in the upper urinary...
Bacillus Calmette-Guerin (BCG) immunotherapy is a mainstay of adjunctive therapy for non-muscle-invasive bladder cancer. The instillation of BCG in the upper urinary tract after complete tumour eradication has also been studied and used after kidney-sparing management. It is effective in increasing the length of remission. However, it is also associated with rare but severe local and systemic side effects which may potentially become life-threatening. We present a case report of a 37-year-old gentleman who developed BCGosis following intra-renal instillation of BCG immunotherapy. The patient presented with systemic symptoms of jaundice, fever, myalgia and arthralgia, rather than local symptoms. infection was confirmed on blood cultures. The patient also developed hepatosplenomegaly, dyspnoea and pancytopaenia. BCGosis following intravesical instillation has been well documented in literature; to the best of our knowledge, this is the first case report documenting BCGosis following intra-renal instillation.
PubMed: 34934480
DOI: 10.1093/jscr/rjab544 -
International Journal of Infectious... Aug 2020Disseminated Bacillus Calmette-Guérin (BCG) disease (BCGosis) is a classical feature of children with primary immunodeficiency disorders (PIDs). (Review)
Review
BACKGROUND
Disseminated Bacillus Calmette-Guérin (BCG) disease (BCGosis) is a classical feature of children with primary immunodeficiency disorders (PIDs).
METHODS
A 15-year retrospective review was conducted in KK Women's and Children's Hospital in Singapore, from January 2003 to October 2017.
RESULTS
Ten patients were identified, the majority male (60.0%). The median age at presentation of symptoms of BCG infections was 3.8 (0.8 - 7.4) months. All the patients had likely underlying PIDS - four with Severe Combined Immunodeficiency (SCID), three with Mendelian Susceptibility to Mycobacterial Diseases (MSMD), one with Anhidrotic Ectodermal Dysplasia with Primary Immunodeficiency (EDA-ID), one with combined immunodeficiency (CID), and one with STAT-1 gain-of-function mutation. Definitive BCGosis was confirmed in all patients by the identification of Mycobacterium bovis subsp BCG from microbiological cultures. The susceptibility profiles of Mycobacterium bovis subsp BCG are as follows: Rifampicin (88.9%), Isoniazid (44.47%), Ethambutol (100.0%), Streptomycin (100.0%), Kanamycin (100.0%), Ethionamide (25.0%), and Ofloxacin (100.0%). Four patients (40.0%) received a three-drug regimen. Five patients (50.0%) underwent hematopoietic stem cell transplant (HSCT), of which three (60%) have recovered. Overall mortality was 50.0%.
CONCLUSION
Disseminated BCG disease (BCGosis) should prompt immunology evaluation to determine the diagnosis of the immune defect. A three-drug regimen is adequate for treatment if the patient undergoes early HSCT.
Topics: BCG Vaccine; Female; Humans; Infant; Infant, Newborn; Male; Mycobacterium bovis; Primary Immunodeficiency Diseases; Retrospective Studies; Singapore; Tuberculosis
PubMed: 32497805
DOI: 10.1016/j.ijid.2020.05.117 -
Urology Annals 2023Intravesical Calmette-Guérin (BCG) therapy for nonmuscle-invasive bladder cancer rarely leads to the development of granulomatous renal masses (renal BCGosis). The...
Intravesical Calmette-Guérin (BCG) therapy for nonmuscle-invasive bladder cancer rarely leads to the development of granulomatous renal masses (renal BCGosis). The management includes nephroureterectomy, antitubercular therapy (ATT), or both. Here, we present a case of a 62-year-old male who was treated with ATT alone for renal masses. Six months after intravesical BCG therapy for transitional cell carcinoma, he developed high-grade fever and night sweat and had multiple renal parenchymal hypodensities on computed tomography (CT) scan. Repeat CT scan 6 months after ATT revealed full resolution of renal hypodensities. This case report highlights the importance of follow-up for early detection of adverse effects of BCG treatment.
PubMed: 37304506
DOI: 10.4103/ua.ua_117_22 -
JMM Case Reports Aug 2018Guillain Barré Syndrome (GBS) has rarely been associated with tuberculosis and has been previously reported after Bacille Calmette Guérin (BCG) vaccination, but we...
INTRODUCTION
Guillain Barré Syndrome (GBS) has rarely been associated with tuberculosis and has been previously reported after Bacille Calmette Guérin (BCG) vaccination, but we report an association of GBS with intra-vesical BCG instillations followed by the clinical picture of disseminated BCGosis.
CASE PRESENTATION
A 68-year-old man with bladder carcinoma had a transurethral tumour resection followed by repeated BCG instillations. Catheterization for his eighth dose was traumatic, causing frank haematuria. Ten days later he presented with fevers, myalgia and dyspnoea. Chest X-ray on admission showed micronodular shadowing and a computed tomography scan showed miliary changes in the lungs. Disseminated BCGosis infection was suspected and his symptoms did improve after starting rifamipicin, isoniazid and ethambutol. Over 2 weeks post-admission he developed an unsteady gait, reduced pin-prick sensation below both knees and fingertips, reduced proprioception in both toes and ankles, with absent reflexes in his lower limbs and diminished reflexes in his upper limbs. Nerve conduction studies showed a purely demyelinating sensori-motor peripheral neuropathy in upper and lower limbs, characteristic of GBS.
CONCLUSION
To our knowledge this is the first case report of GBS following bladder instillation of BCG. Given the millions of cases of tuberculosis and millions of doses of administered BCG, GBS must be a very rare adverse effect.
PubMed: 30323939
DOI: 10.1099/jmmcr.0.005164