On the Occurrence of Epithelioid Cell Granulomas in the Organs of Bcg‐vaccinated Human Beings

Gormsen, H

doi:10.1111/j.1600-0463.1956.tb06761.x

Cited by 42 publications

(17 citation statements)

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“…In fact, dissemination of M. bovis BCG is a normal sequel as shown by autopsies on M. bovis BCGvaccinated infants and children who died of unrelated causes; histological examination of tissues demonstrated granulomas in many distant organs, including lungs, liver, kidneys, and spleen. Organisms were found up to 3 years after vaccination without evidence of clinical disease (16,34). Moreover, reactivation of M. bovis BCG in a patient with AIDS 30 years after vaccination has been reported (33).…”

Section: Discussionmentioning

confidence: 99%

Dependence of Mycobacterium bovis BCG on Anaerobic Nitrate Reductase for Persistence Is Tissue Specific

Fritz¹,

Maass²,

Kreft

et al. 2002

Infect Immun

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Mycobacterium bovis BCG, the only presently available vaccine against tuberculosis, was obtained from virulent M. bovis after serial passages in vitro. The vaccine strain retained at least some of its original virulence, as it persists in immune-competent hosts and occasionally may cause fatal disease in immunedeficient hosts. Mycobacterial persistence in vivo is thought to depend on anaerobic metabolism, an apparent paradox since all mycobacteria are obligate aerobes. Here we report that M. bovis BCG lacking anaerobic nitrate reductase (NarGHJI), an enzyme essential for nitrate respiration, failed to persist in the lungs, liver, and kidneys of immune-competent (BALB/c) mice. In immune-deficient (SCID) mice, however, bacilli caused chronic infection despite disruption of narG, even if growth of the mutant was severely impaired in lungs, liver, and kidneys. Persistence and growth of BCG in the spleens of either mouse strain appeared largely unaffected by lack of anaerobic nitrate reductase, indicating that the role of the enzyme in pathogenesis is tissue specific. These data suggest first that anaerobic nitrate reduction is essential for metabolism of M. bovis BCG in immune-competent but not immune-deficient mice and second that its role in mycobacterial disease is tissue specific, both of which are observations with important implications for pathogenesis of mycobacteria and vaccine development.Mycobacterium tuberculosis claims more human lives each year than any other bacterial pathogen. Mycobacterium bovis BCG, the only presently available vaccine against tuberculosis, belongs phylogenetically to the M. tuberculosis complex. In humans, M. bovis BCG, like M. tuberculosis, forms granulomas and abscesses in various tissues. Following vaccination in immune-competent individuals, M. bovis BCG may persist for extended periods (34). In immune-compromised individuals the vaccine strain may even lead to fatal disease (2,3,10,11,14,21,27,30,36,39).Mycobacteria become firmly established within host tissues, adapting their metabolism to the available source of carbohydrates, nitrogen, and energy (4). Although the acquisition of essential nutrients by mycobacteria is an area of considerable interest, our knowledge of bacterial metabolism throughout the course of infection remains rudimentary. A recent study revealed that metabolism of fatty acids serves as a source of carbohydrates and is required for persistence of M. tuberculosis in mice and activated macrophages (25). Nitrate, through nitrate respiration, could provide energy for bacterial metabolism in an anaerobic environment, because anaerobic nitrate reductase (NarGHJI) couples the reduction of nitrate (NO 3 ) to the generation of ATP by replacing oxygen as a terminal electron acceptor (29). Anaerobic nitrate reductase coding sequences (narGHJI) have been identified in both obligate aerobes such as Bacillus and Pseudomonas and facultative anaerobes such as Escherichia coli (5, 17, 28). However, a role of this enzyme in virulence was not established. In mycobacteria,...

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Section: Discussionmentioning

confidence: 99%

Dependence of Mycobacterium bovis BCG on Anaerobic Nitrate Reductase for Persistence Is Tissue Specific

Fritz¹,

Maass²,

Kreft

et al. 2002

Infect Immun

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“…Haematogenous spread of BCG and formation of epithelioid cell granulomas of different localizations is an ordinary consequence of the BCG-vaccination (GORMSEN 1955, SENECAL et coll. 1956, STOJANOV & ZAGUROV 1963animal experiments: STROM & WIDSTROM 1951, VOGELSANG et coll.…”

Section: Discussionmentioning

confidence: 99%

Radiologic Aspects of Bcg-Osteomyelitis in Infants and Children

Mortensson¹,

Eklöf²,

Jorulf³

1976

Acta Radiologica. Diagnosis

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An account is given of results of the radiologic examination of 29 infants and children with bone tuberculosis caused by the Bacilli Calmette-Guérin (BCG) as a complication to intradermal vaccination. The diagnosis is based on radiologic appearances, microscopy and bacteriologic examination of specimens obtained from the bone lesions. The radiologic appearance of the bone lesions is in most cases characteristic and differs decisively from that of pyogenic osteomyelitis and malignant disease.

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“…Gormsen [14] found that 13 of 20 patients who had received BCG and died incidentally had granulomas in the lung, liver or lymph nodes. Aungst et al [ 15] reviewed 300 cases of patients receiving BCG immunotherapy for a neoplasm and found only 1 patient who developed pul monary granulomas.…”

Section: Discussionmentioning

confidence: 99%

Disseminated Pulmonary Granulomas after Intravesical Bacillus Calmette-Guérin Immunotherapy

Diego

Rogado²,

Prieto³

et al. 1997

Respiration

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On the Occurrence of Epithelioid Cell Granulomas in the Organs of Bcg‐vaccinated Human Beings

Cited by 42 publications

References 0 publications

Dependence of Mycobacterium bovis BCG on Anaerobic Nitrate Reductase for Persistence Is Tissue Specific

Dependence of Mycobacterium bovis BCG on Anaerobic Nitrate Reductase for Persistence Is Tissue Specific

Radiologic Aspects of Bcg-Osteomyelitis in Infants and Children

Disseminated Pulmonary Granulomas after Intravesical Bacillus Calmette-Guérin Immunotherapy

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