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Peer-reviewedCC BYVaccines

Pediatric Mycobacterium bovis Infection: Clinical Spectrum, BCG-Related Disease, Primary Immunodeficiency, and a Comprehensive Review of the Literature.

  1. 1Department of Pediatric Infection Diseases, Istanbul University Faculty of Medicine, Capa, Fatih, Istanbul 34093, Turkey.
  2. 2Department of Medical Microbiology, Istanbul University Faculty of Medicine, Çapa, Fatih, Istanbul 34093, Turkey.

Abstract

Objectives: Mycobacterium bovis (M. bovis) infection in children is uncommon but may remain unrecognized because routine laboratory methods often fail to distinguish it from Mycobacterium tuberculosis. In addition, Bacillus Calmette-Guérin (BCG)-associated M. bovis infection may represent the first manifestation of an underlying primary immunodeficiency. This study aimed to describe the clinical spectrum, diagnostic features, treatment, and outcomes of pediatric M. bovis infection and to review the contemporary literature on BCG-associated disease and primary immunodeficiency. Methods: We retrospectively reviewed 388 pediatric patients diagnosed with tuberculosis at a tertiary referral center between 1998 and 2025 and identified three children with culture- or PCR-confirmed M. bovis infection. Clinical presentation, microbiological findings, immunological evaluation, treatment, and outcomes were analyzed. In addition, a narrative review of representative pediatric studies on M. bovis infection, BCG-associated disease, and Mendelian susceptibility to mycobacterial disease (MSMD) was performed. Results: Two BCG-vaccinated 2-year-old children presented with persistent BCG-related lymphadenitis and were subsequently diagnosed with genetically confirmed IL12RB1 deficiency after identification of M. bovis BCG. The third patient, a previously healthy 15-year-old girl, developed pulmonary and gastrointestinal tuberculosis caused by non-BCG M. bovis. Recognition of M. bovis facilitated the optimization of antimycobacterial therapy, including the discontinuation of pyrazinamide where appropriate. Treatment decisions were individualized according to disease extent and the underlying immune status. Adjunctive interferon-γ therapy was administered to both children with IL12RB1 deficiency. All three patients achieved favorable clinical outcomes. A review of the published literature demonstrated that disseminated BCG disease is strongly associated with defects of the IL-12/IFN-γ pathway and frequently represents the first manifestation of primary immunodeficiency. Conclusions: Pediatric M. bovis infection should be considered in children with persistent or disseminated disease following BCG vaccination or with unusual manifestations of tuberculosis. Early species-level microbiological identification is essential because it directly influences antimicrobial therapy, while BCG-associated M. bovis infection should prompt comprehensive immunological and genetic evaluation for underlying primary immunodeficiency. Integration of microbiological diagnosis with immunological assessment enables individualized management and may improve clinical outcomes.

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BibTeX
@article{atasever2026pediatric,
  title = {{Pediatric Mycobacterium bovis Infection: Clinical Spectrum, BCG-Related Disease, Primary Immunodeficiency, and a Comprehensive Review of the Literature.}},
  author = {Neslihan Mete Atasever and Elif Dede and Kaya Köksalan and Ayper Somer and Selda Hançerli Törün},
  journal = {Vaccines},
  year = {2026},
  month = oct,
  doi = {10.3390/vaccines14100867},
  url = {https://europepmc.org/article/MED/42931396},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Pediatric Mycobacterium bovis Infection: Clinical Spectrum, BCG-Related Disease, Primary Immunodeficiency, and a Comprehensive Review of the Literature.
AU  - Neslihan Mete Atasever
AU  - Elif Dede
AU  - Kaya Köksalan
AU  - Ayper Somer
AU  - Selda Hançerli Törün
PY  - 2026
DA  - 2026/10/01
JO  - Vaccines
DO  - 10.3390/vaccines14100867
UR  - https://europepmc.org/article/MED/42931396
AB  - Objectives: Mycobacterium bovis (M. bovis) infection in children is uncommon but may remain unrecognized because routine laboratory methods often fail to distinguish it from Mycobacterium tuberculosis. In addition, Bacillus Calmette-Guérin (BCG)-associated M. bovis infection may represent the first manifestation of an underlying primary immunodeficiency. This study aimed to describe the clinical spectrum, diagnostic features, treatment, and outcomes of pediatric M. bovis infection and to review the contemporary literature on BCG-associated disease and primary immunodeficiency. Methods: We retrospectively reviewed 388 pediatric patients diagnosed with tuberculosis at a tertiary referral center between 1998 and 2025 and identified three children with culture- or PCR-confirmed M. bovis infection. Clinical presentation, microbiological findings, immunological evaluation, treatment, and outcomes were analyzed. In addition, a narrative review of representative pediatric studies on M. bovis infection, BCG-associated disease, and Mendelian susceptibility to mycobacterial disease (MSMD) was performed. Results: Two BCG-vaccinated 2-year-old children presented with persistent BCG-related lymphadenitis and were subsequently diagnosed with genetically confirmed IL12RB1 deficiency after identification of M. bovis BCG. The third patient, a previously healthy 15-year-old girl, developed pulmonary and gastrointestinal tuberculosis caused by non-BCG M. bovis. Recognition of M. bovis facilitated the optimization of antimycobacterial therapy, including the discontinuation of pyrazinamide where appropriate. Treatment decisions were individualized according to disease extent and the underlying immune status. Adjunctive interferon-γ therapy was administered to both children with IL12RB1 deficiency. All three patients achieved favorable clinical outcomes. A review of the published literature demonstrated that disseminated BCG disease is strongly associated with defects of the IL-12/IFN-γ pathway and frequently represents the first manifestation of primary immunodeficiency. Conclusions: Pediatric M. bovis infection should be considered in children with persistent or disseminated disease following BCG vaccination or with unusual manifestations of tuberculosis. Early species-level microbiological identification is essential because it directly influences antimicrobial therapy, while BCG-associated M. bovis infection should prompt comprehensive immunological and genetic evaluation for underlying primary immunodeficiency. Integration of microbiological diagnosis with immunological assessment enables individualized management and may improve clinical outcomes.
SN  - 2076-393X
ER  -