Generalized BCG Tuberculosis With Fatal Course in Two Sisters

Sićević, S

doi:10.1111/j.1651-2227.1972.tb15922.x

Cited by 27 publications

(2 citation statements)

References 9 publications

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“…Lotte et al (22,23) gathered case reports of 39 cases of fatal disseminated BCG disease, and at least 20 additional fatal cases have been reported since those reviews. Fatalities have been caused by BCG strains with acquired resistance to multiple drugs (24,29). An ideal live tuberculosis vaccine should be susceptible to all first-line drugs, including PZA.…”

Section: Discussionmentioning

confidence: 99%

Identification, cloning, and expression of the Escherichia coli pyrazinamidase and nicotinamidase gene, pncA

Frothingham¹,

Meeker-O'Connell

Talbot

et al. 1996

Antimicrob Agents Chemother

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Pyrazinamide (PZA) is one of the three most important drugs for treatment of Mycobacterium tuberculosis infections. The antibacterial activity of PZA requires a bacterial enzyme, pyrazinamidase (PZAase), which hydrolyzes PZA to form pyrazinoic acid and ammonia. Most PZA-resistant clinical M. tuberculosis isolates lack PZAase activity. With the goal of eventually identifying and characterizing the M.tuberculosis PZAase gene, we began with the more tractable organism, Escherichia coli, which also has PZAase activity. We screened a transposon-generated E. coli insertion mutant library, using a qualitative PZAase assay. Two PZAase-negative mutants out of 4,000 colonies screened were identified. In each mutant, the transposon interrupted the same 639-bp open reading frame (ORF), ORF1. The expression of ORF1 on a multicopy plasmid complemented a PZAase-negative mutant, leading to PZAase activity levels approximately 10-fold greater than those of the wild type. PZA has a structure similar to that of nicotinamide, a pyridine nucleotide cycle intermediate, so we tested our strains for nicotinamidase activity (EC 3.5.1.19) (genetic locus pncA). The construct with multiple plasmid copies of ORF1 had an approximately 10-fold increase in levels of nicotinamidase activity. This overexpressing strain could utilize nicotinamide as a sole nitrogen source, through wild-type E. coli cannot. We conclude that a single E. coli enzyme accounts for both PZAase and nicotinamidase activities and that ORF1 is the E.coli PZAase and nicotinamidase gene, pncA.

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Section: Discussionmentioning

confidence: 99%

Identification, cloning, and expression of the Escherichia coli pyrazinamidase and nicotinamidase gene, pncA

Frothingham¹,

Meeker-O'Connell

Talbot

et al. 1996

Antimicrob Agents Chemother

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show abstract

“…It has been reported that inborn errors of immunity like severe combined immunodeficiency (SCID) and other combined immunodeficiency diseases(CID), phagocytic defects including chronic granulomatous disease (CGD) and inborn errors of IFN‐γ immunity (commonly known as Mendelian Susceptibility to Mycobacterial Diseases/MSMD) cause increased susceptibility to mycobacteria 6‐8 . The onset and severity of BCG‐related complications can be different in different IEI 9,10 . In SCID, overwhelming infection post‐BCG might be the first infectious manifestation in these patients and BCG infection in SCID is often accompanied by other opportunistic infections and failure to thrive 11 .…”

Section: Introductionmentioning

confidence: 99%

Spectrum of Inborn errors of immunity in a cohort of 90 patients presenting with complications to BCG vaccination in India

et al. 2021

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World Health Organisation recommends the practice of BCG vaccination at birth in countries which have a high incidence of tuberculosis and/or high leprosy burden. The BCG vaccination is considered safe for a competent immune system. However, in children with weakened immune systems cause of which can be primary or secondary, the vaccine may lead to side effects which can be localized or disseminated. In this study, we report a spectrum of inborn errors of immunity (IEI) commonly referred to as primary immunodeficiency disorders (PIDs) diagnosed in a large cohort of patients presenting with complications to BCG vaccination from India. Retrospective data analysis of patients referred to ICMR‐ National Institute of Immunohematology (ICMR‐NIIH) for IEI workup between 2007 and 2019 was done. IEI was identified in n = 52/90 (57.7%) patients presenting with BCG complications. Of these, n = 13(14.4%) patients were diagnosed with severe combined immune deficiency, n = 15(16.7%) with chronic granulomatous disease, n = 19(21.1%) with Inborn errors of IFN‐γ immunity, n = 4(4.4%) with Combined immunodeficiency and n = 1(1.1%) with Leucocyte Adhesion Deficiency type1. Majority of cases with BCGosis (88%) had an underlying IEI. This study strongly highlights the need for evaluation of patients with BCG complications for underlying IEI. While disseminated BCGosis strongly predicts underlying IEI, even localized persistent adenitis may be a warning sign of underlying IEI. It is also strongly recommended to record a family history of previous sibling death prior to administration of this live vaccine and deferring live vaccine till the diagnosis of IEI is ruled out in cases with a positive family history.

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Fatal Disseminated BCG Infection

Passwell¹,

Katz²,

Frank³

et al. 1976

Am J Dis Child

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A 2-year-old boy had a fatal disseminated BCG infection. Immunologic assessment showed a normal humoral response and normal numbers of E rosettes, normal thymus weight and histological features, but an abnormal response of lymphocytes in vitro and negative skin tests. Histological examination showed the presence of Gram-negative acid-fast bacilli within the macrophages. The possible mechanisms of immunodeficiency in this patient are discussed.

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Generalized BCG Tuberculosis With Fatal Course in Two Sisters

Cited by 27 publications

References 9 publications

Identification, cloning, and expression of the Escherichia coli pyrazinamidase and nicotinamidase gene, pncA

Identification, cloning, and expression of the Escherichia coli pyrazinamidase and nicotinamidase gene, pncA

Spectrum of Inborn errors of immunity in a cohort of 90 patients presenting with complications to BCG vaccination in India

Fatal Disseminated BCG Infection

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