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Purpose: Summarize the characteristics of a large cohort of BCG disease and compare differences in clinical characteristics and outcomes among different genotypes and between primary immunodeficiency disease (PID) and patients without identified genetic etiology. Methods: We collected information on patients with BCG disease in our center from January 2015 to December 2020 and divided them into four groups: chronic granulomatous disease (CGD), Mendelian susceptibility to mycobacterial disease (MSMD), severe combined immunodeficiency disease (SCID), and gene negative group. Results: A total of 134 patients were reviewed, and most of them had PID. A total of 111 (82.8%) patients had 18 different types of pathogenic gene mutations, most of whom (91.0%) were classified with CGD, MSMD, and SCID. CYBB was the most common gene mutation (52/111). BCG disease behaves differently in individuals with different PIDs. Significant differences in sex (P < 0.001), age at diagnosis (P = 0.013), frequency of recurrent fever (P = 0.007), and vaccination-homolateral axillary lymph node enlargement (P = 0.039) and infection severity (P = 0.006) were noted among the four groups. The CGD group had the highest rate of males and the oldest age at diagnosis. The MSMD group had the highest probability of disseminated infection (48.3%). The course of anti-tuberculosis treatment and the survival time between patients with PID and without identified genetic etiology were similar. Conclusion: Greater than 80% of BCG patients have PID; accordingly, gene sequencing should be performed in patients with BCG disease for early diagnosis. BCG disease behaves differently in patients with different types of PID. Patients without identified genetic etiology had similar outcomes to PID patients, which hints that they may have pathogenic gene mutations that need to be discovered. [ABSTRACT FROM AUTHOR]

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Background: Recurrence and progression of T1 grade 3 (T1G3) urothelial bladder carcinomas (UBCs) treated with bacille Calmette-Guérin (BCG) are common events, but the long-term follow-up of the disease remains controversial. Objective: To evaluate the long-term outcomes of BCG intravesical therapy in relation to disease recurrence and progression in primary T1G3 UBCs and upper tract disease. Patients and methods: A single-institution, retrospective, population-based analysis of 316 patients with primary T1G3 UBC treated with transurethral resection (TUR) and BCG induction intravesical instillations was performed. Response was determined and monitored by routine periodic urine cytology, cystoscopy, and upper tract imaging. Results: The median follow-up was 70 months (maximum 210 months). Among all of the tumours, 49.4 % did not relapse, 48.7 % recurred in the bladder during the first 5 years of surveillance, and only 6 patients (1.9 %) recurred after being free of disease during the first 5 years of follow-up. Nineteen percentage of the UBCs progressed to stage T2, and only 2 patients (1.2 %) progressed after the first 5 years of surveillance. An upper urinary tract recurrence was detected in 9.2 % of the patients; 65.5 % were diagnosed within the upper urinary tract during the first 5 years of follow-up. Conclusions: Following a 5-year tumour-free period, there is minimal risk of recurrence and progression in T1G3 UBCs treated with TUR and BCG induction intravesical instillations. This finding supports a less intensive and potentially less invasive surveillance scheme of bladder follow-up and upper urinary tract imaging in patients without any recurrence. [ABSTRACT FROM AUTHOR]

To describe the demographics, clinical characteristics and microbiologic findings of infant (≤2 years old) tuberculosis (TB) in a high TB burden country. Between Feb, 2007 and Jun, 2015, 115 TB infants who admitted to our hospital were enrolled in the study. Their clinicopathological characteristics were reviewed and analyzed. The mean age was 10.1 ± 7.4 (SD) months, and 84 of 115 infants (73.0 %) were males. 23 patients (20.0 %) had isolated pulmonary TB, 18 patients (15.7 %) had pulmonary and extrapulmonary TB (EPTB), the remaining 74 patients (64.4 %) had exclusively EPTB. The most common site of EPTB was lymph node (n = 61), 54 cases were left axillary lymph node involvement. 49 of 51 patients (96.1 %) were validated by pathological examination, 5 of 57 patients (8.8 %) were positive on acid fast bacilli smear, and 27 of 103 patients (26.2 %) were confirmed by mycobacterial culture. 29 of 59 patients (49.2 %) were PPD positive, 14 of 30 patients (46.7 %) were T-SPOT.TB positive. The most common complaints of patients were lymph node swelling (53.0 %), fever (36.5 %), cough (28.7 %) and dyspnea (10.4 %). There was significant difference in the time before hospital admission among different types of tuberculosis (P < 0.01), fever was also a factor influencing the time (P < 0.05). In infants, the sensitivities of routine TB tests were low and emphasize the need for improved diagnostics; EPTB was more common than pulmonary TB, tuberculous lymphadenitis constituted a high proportion of EPTB; there appears to be an association between the incidence of axillary lymph node TB and BCG vaccination among infants in China. [ABSTRACT FROM AUTHOR]

Background: When administered to an immune-compromised patient, BCG (Bacille Calmette-Guérin) can cause disseminated and life-threatening infections.Objective: To describe the imaging findings in children with primary immunodeficiency and BCG-related infections.Materials and Methods: We reviewed the imaging findings of children with primary immunodeficiency treated at a children's hospital during 2012-2014 with localized or disseminated BCG infection. Imaging modalities included US, CT and radiography.Results: Nine children with primary immunodeficiency had clinical signs of post-vaccination BCGitis; seven of these children showed disseminated disease and two showed only regional lesions with characteristic ipsilateral lymphadenopathy. Overall, lymphadenopathy was the most prevalent feature (n = 8) and characteristically appeared as a ring-enhancing hypodense (CT) or hypoechoic (US) lesion. Visceral involvement with multiple abscesses appeared in the spleen (n = 2), liver (n = 1) and bones (n = 1). All lesions regressed following appropriate anti-tuberculosis treatment.Conclusion: BCG infection needs to be considered in children with typical findings and with suspected primary immunodeficiency. [ABSTRACT FROM AUTHOR]

In the past three decades, intravesical instillation of Mycobacterium bovis bacille Calmette-Guérin (BCG) has been used for treating bladder cancer and it still remains at the forefront of immunotherapy for cancer patients. Although BCG-based therapy is the most effective intravesical therapy for this kind of tumor and represents the only agent known to reduce progression into muscle invasive bladder cancer, BCG is ineffective in approximately 30-40 % of cases and disease recurs in up to 50 % of patients. Since that BCG is considered an effective vehicle for delivery of antigens due to its unique characteristics, the genetic manipulation of these mycobacteria has been appealing in the search for less toxic and more potent therapeutic agents for bladder cancer immunotherapy. Herein, we discuss current advances in recombinant BCG construction, research, concerns, and future directions to promote the development of this promising immunotherapeutic approach for bladder cancer. [ABSTRACT FROM AUTHOR]

We experienced two cases of unrelated Japanese children with bacille Calmette-Guérin (BCG) multiple osteomyelitis with partial interferon (IFN)-γ receptor 1 (IFNGR1) deficiency. Heterozygous small deletions with frame shift (811 del4 and 818 del4) were detected, which were consistent with the diagnosis of partial dominant IFNGR1 deficiency. Case 1: a 2-year-old boy visited us because of limb and neck pain. He had been vaccinated with BCG at 17 months of age. Multiple destructive lesions were observed in the skull, ribs, femur, and vertebral bones. Mycobacterium bovis (BCG Tokyo 172 strain by RFLP technique) was detected in the bone specimen. The BCG multiple osteomyelitis was treated successfully without recurrence. Case 2: an 18-month-old girl developed multiple osteomyelitis 9 months after BCG inoculation. Radiologic images showed multiple osteolytic lesions in the skull, ribs, femur, and vertebrae. M. bovis (BCG Tokyo 172 strain) was detected in the cultures from a bone biopsy. Her clinical course showed recurrent osteomyelitis and lymphadenitis with no pulmonary involvement. The effects of high-dose antimycobacterial drugs and IFN-γ administration were transient, and complete remission has since been achieved by combination antimycobacterial therapy, including levofloxacin. Partial dominant IFNGR1 deficiency is a rare disorder, but it should be considered when a patient presents with multiple osteomyelitis after BCG vaccination. The cases that are resistant to conventional regimens require additional second-line antituberculous drugs, such as levofloxacin. [ABSTRACT FROM AUTHOR]

A cluster of cases of lymphadenitis occurred in Dublin following vaccination with a newly introduced Copenhagen 1331 strain of Bacille Calmette-Guerin (BCG) vaccine during 1989. All cases of BCG lymphadenitis presenting to paediatric surgical clinics over an 11-year period were reviewed to determine the optimum treatment for this problem. Seventeen patients are included, 16 of whom received vaccine in the newborn period; 1 received BCG at 8 months. Nine were treated by initial operation, 6 with antituberculous drugs, and 2 were observed without specific therapy. All but 1 of the medically treated patients and both patients who received observation only required operation for failure to resolve or progression of disease. The best results were obtained with excision and primary closure. We conclude that although sponteneous resolution occurs in a majority of all cases of BCG lymphadenitis in infants, in those patients with more severe disease who require surgical referral, a short trial of anti-microbial therapy is indicated. Patients who fail to improve or develop complications are then best treated by surgical excision of the involved nodes. [ABSTRACT FROM AUTHOR]

Purpose of Review: Many genetic conditions predispose affected individuals to opportunistic infections. A number of immunodeficiency diseases, including genetic defects termed Mendelian susceptibility to mycobacterial disease (MSMD), permit infection from many different strains of mycobacteria that would otherwise not cause disease. These include tuberculous and nontuberculous mycobacteria, and bacille Calmette-Guérin vaccine (BCG). Patients may present with infections from other organisms that depend on macrophage function for containment. Defects in multiple genes in the IL-12 and NFKB signaling pathways can cause the MSMD phenotype, some of which include IL12RB1, IL12B, IKBKG, ISG15, IFNGR1, IFNGR2, CYBB, TYK2, IRF8, and STAT1.Recent Findings: Multiple autosomal recessive and dominant, and 2 X-linked recessive gene defects resulting in the MSMD phenotype have been reported, and others await discovery. This review presents the known gene defects and describes clinical findings that result from the mutations.Summary: If MSMD is suspected, a careful clinical history and examination and basic immunodeficiency screening tests will narrow the differential diagnosis. A specific diagnosis requires more sophisticated laboratory investigation. Genetic testing permits a definitive diagnosis, permitting genetic counseling. Mild cases respond well to appropriate antibiotic therapy, whereas severe disease may require hematopoietic stem cell transplantation. [ABSTRACT FROM AUTHOR]