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Arthroplasty Today Jun 2024Periprosthetic joint infection (PJI) can present challenges in diagnosis and treatment, particularly in the setting of atypical causative organisms such as fungi and...
Periprosthetic joint infection (PJI) can present challenges in diagnosis and treatment, particularly in the setting of atypical causative organisms such as fungi and mycobacteria. Herein, we present a case and provide a review of the diagnosis and treatment of an unusual PJI caused by bacillus Calmette-Guérin, administered during the treatment of bladder cancer 3 years prior to total knee arthroplasty and subsequent PJI. Although the patient's history of bladder cancer was known, neither his Bacillus Calmette-Guérin treatment nor its potential for distant site spread that could lead to PJI were appreciated, leading to a prolonged diagnostic evaluation and treatment course.
PubMed: 38533423
DOI: 10.1016/j.artd.2024.101350 -
Advances in Respiratory Medicine 2019Immunodeficient children are at a high risk of disseminated Bacillus Calmette-Guérin [BCG] infection. We assessed the literature on clinical manifestations of BCGosis...
INTRODUCTION
Immunodeficient children are at a high risk of disseminated Bacillus Calmette-Guérin [BCG] infection. We assessed the literature on clinical manifestations of BCGosis in children with specific primary immunodeficiencies.
MATERIAL AND METHODS
We conducted a systematic review of clinical practice articles by searching Medline, PubMed, Embase, Scopus, Web of Science and Google Scholar from their inception to date.
RESULTS
Thirty-seven articles were included regarding BCG vaccination and its dissemination in children with primary immunodeficiencies. Articles on dissemination after intravesicular BCG were excluded from the study.
CONCLUSIONS
Since disseminated BCG vaccination may be the first manifestation of a primary immunodeficiency disease, a comprehensive search for immunological defects in children developing these problems after BCG vaccination seems rational.
Topics: Adjuvants, Immunologic; BCG Vaccine; Humans; Immunologic Deficiency Syndromes; Mycobacterium bovis; Tuberculosis; Vaccination
PubMed: 31476012
DOI: 10.5603/ARM.2019.0040 -
Frontiers in Pediatrics 2018We report a novel homozygous mutation in two female Brazilian SCID infants from two unrelated kindreds. Patient 1 was referred at 2 months of age due to a family...
We report a novel homozygous mutation in two female Brazilian SCID infants from two unrelated kindreds. Patient 1 was referred at 2 months of age due to a family history of immunodeficiency and the appearance of a facial rash. The infant was screened for TRECs (T-cell receptor excision circles) and KRECs (kappa-deleting recombination excision circles) for the assessment of newly formed naïve T and B cells respectively, which showed undetectable TRECs and normal numbers of KRECs. Lymphocyte immunophenotyping by flow cytometry confirmed the screening results, revealing a T-B+NK- SCID. The patient underwent successful HSCT. Patient 2 was admitted to an intensive care unit at 8 months of age with severe pneumonia, BCGosis, and oral moniliasis; she also had a positive family history for SCID but newborn screening was not performed at birth. At 10 months of age she was diagnosed as a T-B+NK- SCID and underwent successful HSCT. sequencing revealed the same homozygous missense mutation (c.2350G>A) in both patients. This mutation affects the last nucleotide of exon 17 and it is predicted to disrupt the donor splice site. cDNA sequencing revealed skipping of exon 17 missing in both patients, confirming the predicted effect on mRNA splicing. Skipping of exon 17 leads to an out of frame deletion of 151 nucleotides, frameshift and creation of a new stop codon 60 amino acids downstream of the mutation resulting in a truncated protein which is likely nonfunctional.
PubMed: 30177960
DOI: 10.3389/fped.2018.00230 -
The Turkish Journal of Pediatrics 2016Pediatric sarcoidosis comprises a spectrum of childhood granulomatous inflammatory conditions. Pathological hallmark of the disease is granuloma formation that is seen...
Pediatric sarcoidosis comprises a spectrum of childhood granulomatous inflammatory conditions. Pathological hallmark of the disease is granuloma formation that is seen in the affected tissues and almost any organ or system can be involved. There are two forms of pediatric sarcoidosis. One is seen in older children and the clinical picture is very similar to that of adult sarcoidosis and the other one is seen in early childhood. Sarcoidosis in early childhood can be divided as Blau syndrome (familial form) and early onset sarcoidosis (sporadic form). In both of the diseases there is a defect in the NOD2/CARD15 gene. The typical triad of early onset sarcoidosis is polyarthritis, dermatitis and uveitis. Interferon-γ receptor 1 deficiency is caused by defects in the IFNγR1 gene and non-tuberculosis mycobacterial pathogens are the leading causes of infections that start in early childhood. Herein we report a patient who presented with the symptoms of early onset sarcoidosis and also had partial interferon-γ receptor 1 deficiency that presented with BCG-osis. In addition to anti-mycobacterial treatment, methotrexate and prednisolone were used in therapy.
Topics: Arthritis; BCG Vaccine; Humans; Infant; Interferon-gamma; Male; Receptors, Interferon; Sarcoidosis; Synovitis; Tomography, X-Ray Computed; Uveitis; Interferon gamma Receptor
PubMed: 28621099
DOI: 10.24953/turkjped.2016.05.015 -
Frontiers in Cellular and Infection... 2024(BCG) is a live strain of m () for use as an attenuated vaccine to prevent (TB) infection, while it could also lead to an infection in immunodeficient patients.... (Review)
Review
(BCG) is a live strain of m () for use as an attenuated vaccine to prevent (TB) infection, while it could also lead to an infection in immunodeficient patients. could infect patients with immunodeficiency via BCG vaccination. Disseminated BCG disease (BCGosis) is extremely rare and has a high mortality rate. This article presents a case of a 3-month-old patient with disseminated BCG infection who was initially diagnosed with hemophagocytic syndrome (HPS) and eventually found to have X-linked severe combined immunodeficiency (X-SCID). and its drug resistance genes were identified by metagenomics next-generation sequencing (mNGS) combined with targeted next-generation sequencing (tNGS) in blood and cerebrospinal fluid. Whole exome sequencing (WES) revealed a pathogenic variant in the common γ-chain gene (), confirming X-SCID. Finally, antituberculosis therapy and umbilical cord blood transplantation were given to the patient. He was successfully cured of BCGosis, and his immune function was restored. The mNGS combined with the tNGS provided effective methods for diagnosing rare BCG infections in children. Their combined application significantly improved the sensitivity and specificity of the detection of .
Topics: Male; Infant; Child; Humans; Mycobacterium bovis; BCG Vaccine; X-Linked Combined Immunodeficiency Diseases; Tuberculosis; Immunologic Deficiency Syndromes; Latent Tuberculosis; High-Throughput Nucleotide Sequencing
PubMed: 38410723
DOI: 10.3389/fcimb.2024.1341236 -
Clinical Case Reports Oct 2017Intravesical instillation of Bacillus Calmette-Guérin (BCG) has been shown to be an effective form of immunotherapy for bladder cancer. This case report describes a...
Intravesical instillation of Bacillus Calmette-Guérin (BCG) has been shown to be an effective form of immunotherapy for bladder cancer. This case report describes a patient who develops systemic BCG-osis following intravesical BCG instillation and demonstrates the importance of being aware of more severe complications associated with BCG immunotherapy.
PubMed: 29026546
DOI: 10.1002/ccr3.1129 -
MBio Jun 2014The only tuberculosis (TB) vaccine in use today, bacillus Calmette-Guérin (BCG), provides insufficient protection and can cause adverse events in immunocompromised...
UNLABELLED
The only tuberculosis (TB) vaccine in use today, bacillus Calmette-Guérin (BCG), provides insufficient protection and can cause adverse events in immunocompromised individuals, such as BCGosis in HIV(+) newborns. We previously reported improved preclinical efficacy and safety of the recombinant vaccine candidate BCG ΔureC::hly, which secretes the pore-forming listeriolysin O of Listeria monocytogenes. Here, we evaluate a second-generation construct, BCG ΔureC::hly Δpdx1, which is deficient in pyridoxine synthase, an enzyme that is required for biosynthesis of the essential cofactor vitamin B6. This candidate was auxotrophic for vitamin B6 in a concentration-dependent manner, as was its survival in vivo. BCG ΔureC::hly Δpdx1 showed markedly restricted dissemination in subcutaneously vaccinated mice, which was ameliorated by dietary supplementation with vitamin B6. The construct was safer in severe combined immunodeficiency mice than the parental BCG ΔureC::hly. A prompt innate immune response to vaccination, measured by secretion of interleukin-6, granulocyte colony-stimulating factor, keratinocyte cytokine, and macrophage inflammatory protein-1α, remained independent of vitamin B6 administration, while acquired immunity, notably stimulation of antigen-specific CD4 T cells, B cells, and memory T cells, was contingent on vitamin B6 administration. The early protection provided by BCG ΔureC::hly Δpdx1 in a murine Mycobacterium tuberculosis aerosol challenge model consistently depended on vitamin B6 supplementation. Prime-boost vaccination increased protection against the canonical M. tuberculosis H37Rv laboratory strain and a clinical isolate of the Beijing/W lineage. We demonstrate that the efficacy of a profoundly attenuated recombinant BCG vaccine construct can be modulated by external administration of a small molecule. This principle fosters the development of safer vaccines required for immunocompromised individuals, notably HIV(+) infants.
IMPORTANCE
Mycobacterium tuberculosis can synthesize the essential cofactor vitamin B6, while humans depend on dietary supplementation. Unlike the lipophilic vitamins A, D, and E, water-soluble vitamin B6 is well tolerated at high doses. We generated a vitamin B6 auxotroph of the phase II clinical tuberculosis vaccine candidate bacillus Calmette-Guérin ΔureC::hly. The next-generation candidate was profoundly attenuated compared to the parental strain. Adaptive immunity and protection in mice consistently depended on increased dietary vitamin B6 above the daily required dose. Control of vaccine efficacy via food supplements such as vitamin B6 could provide a fast track toward improved safety. Safer vaccines are urgently needed for HIV-infected individuals at high risk of adverse events in response to live vaccines.
Topics: Animals; BCG Vaccine; Dietary Supplements; Disease Models, Animal; Female; Genes, Bacterial; Immunity, Innate; Immunization, Secondary; Immunocompromised Host; Mice; Mutation; Mycobacterium bovis; Mycobacterium tuberculosis; Pyridoxine; Tuberculosis; Vaccination; Vitamin B 6
PubMed: 24895310
DOI: 10.1128/mBio.01262-14 -
The Journal of Infectious Diseases Apr 2009Worldwide, most infants born to mothers infected with human immunodeficiency virus (HIV) receive bacille Calmette-Guérin (BCG) vaccine. Tuberculosis is a major cause of...
BACKGROUND
Worldwide, most infants born to mothers infected with human immunodeficiency virus (HIV) receive bacille Calmette-Guérin (BCG) vaccine. Tuberculosis is a major cause of death among infants infected with HIV in sub-Saharan Africa, and it should be prevented. However, BCG may itself cause disease (known as "BCGosis") in these infants. Information regarding the immunogenicity of BCG is imperative for the risk/benefit assessment of BCG vaccination in HIV-infected infants; however, no such data exist.
METHODS
We compared BCG-induced CD4 and CD8 T cell responses, as assessed by flow cytometry, in HIV-infected (n=20), HIV-exposed but uninfected (n=25), and HIV-unexposed (n=23) infants, during their first year of life.
RESULTS
BCG vaccination of the 2 HIV-uninfected groups induced a robust response, which was characterized by CD4 T cells expressing interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, and/or interleukin (IL)-2. In contrast, HIV-infected infants demonstrated a markedly lower response throughout the first year of life. These infants also had significantly reduced numbers of polyfunctional CD4 T cells coexpressing IFN-gamma, TNF-alpha, and IL-2, a finding that is thought to indicate T cell quality.
CONCLUSIONS
Infection with HIV severely impairs the BCG-specific T cell response during the first year of life. BCG may therefore provide little, if any, vaccine-induced benefit in HIV-infected infants. Considering the significant risk of BCGosis, these data strongly support not giving BCG to HIV-infected infants.
Topics: Adult; BCG Vaccine; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Female; HIV Infections; HIV-1; Humans; Infant; Infant, Newborn; Infectious Disease Transmission, Vertical; Pregnancy
PubMed: 19236280
DOI: 10.1086/597304 -
Iranian Journal of Allergy, Asthma, and... Mar 2003Chronic granulomatous disease is an infrequent primary immunodeficiency characterized by defective intracellular killing of ingested microorganisms thereby making...
Chronic granulomatous disease is an infrequent primary immunodeficiency characterized by defective intracellular killing of ingested microorganisms thereby making patients highly susceptible to recurrent lite threatening bacterial and fungal infections. In this study, we review the medical course of an 8 yrs old girl with AR-CGD. She suffered from recurrent dermal and deep abscesses, retractable salmonellosis, disseminated BCGosis, recurrent aspergillus infection presenting as mandibular osteomyelitis and pulmonary involvement with invasion to rib and vertebral bodies. Despite of longterm IV amphotricin B, itraconazole and IFN-gamma administration, and surgical interventions (drainage and resection), she died in spite of long term antibiotic anti fungal prophylaxis and interferon-gamma administrations, invasive aspergillosis resistant to current conventional therapies is the cause of 1/2 to 1/3 of CGD deaths.
PubMed: 17301351
DOI: No ID Found -
BMJ Case Reports Oct 2012We describe a non-smoker who presented with a persistent cough, weight loss and general malaise, and had a medical history of bladder carcinoma that had been...
We describe a non-smoker who presented with a persistent cough, weight loss and general malaise, and had a medical history of bladder carcinoma that had been successfully treated with intravesical BCG immunotherapy. Radiology revealed hilar lymphadenopathy, a predominantly mid-zone and lower-zone lung parenchymal nodular pattern with a perilymphatic distribution, a few thickened interlobular septae, and small pleural effusions bilaterally. The T-SPOT.TB blood test was negative. Video-assisted thoracoscopic surgery showed multiple pleural nodules, the histopathology of which showed multiple well-defined non-caseating granulomata. The patient was started on antituberculosis medication for presumed BCGosis--a systemic complication of previous BCG immunotherapy--and the patient showed an excellent clinical and radiological response. This case further adds to previous reports and reinforces the recommendation that all patients should be made fully aware of the potential systemic and delayed complications of BCG immunotherapy when they are consented for treatment.
Topics: Adjuvants, Immunologic; Administration, Intravesical; Antineoplastic Agents; BCG Vaccine; Carcinoma, Transitional Cell; Cough; Female; Granuloma; Humans; Immunotherapy; Infections; Lung; Lung Diseases; Lymphatic Diseases; Middle Aged; Mycobacterium bovis; Urinary Bladder Neoplasms
PubMed: 23097577
DOI: 10.1136/bcr-2012-007327