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Variable outcome of experimental interferon-γ therapy of disseminated Bacillus Calmette-Guerin infection in two unrelated interleukin-12Rβ1-deficient Slovakian children

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Abstract

Mycobacterium bovis Bacillus Calmette-Guerin (BCG) is an attenuated live vaccine that may cause life-threatening clinical disease in children with impaired immunity. In particular, patients with any of the nine known inherited disorders of the interleukin-12/23 interferon-γ (IL-12/23-IFNγ) axis are highly vulnerable to BCG. We describe two unrelated young Slovakian children suffering from disseminated BCG infection which developed shortly after routine BCG vaccination after birth. During treatment with selected anti-BCG antibiotics, resistance against several of these drugs developed. In both children, interleukin-12/23 receptor β1 (IL-12/23Rβ1) deficiency was diagnosed. Thus, in addition to chemotherapy, immunomodulatory treatment with recombinant IFN-γ was performed as the pathogenesis of BCG disease in IL-12Rβ1 deficiency involves impaired IL-12- and IL-23-dependent IFN-γ production by lymphocytes. One child responded to treatment and is presently doing well whereas the second patient died. Conclusion:The marked variability of outcome of disseminated Bacillus Calmette-Guerin disease in interleukin-12/23 receptor β1-deficient children sharing the same ethnic origin and exposed to a similar environment as presented in these case reports has to be taken into consideration for diagnosis and treatment of infections due to this genetic defect.

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Abbreviations

BCG :

Bacillus-Calmette-Guerin

ETH :

ethambutol

IFN-γ :

interferon-γ

IL :

interleukin

IL-12R :

interleukin-12 receptor

INH :

isoniazide

rIFN-y :

recombinant interferon-γ

RMP :

rifampin

SM :

streptomycin

TB :

tuberculosis

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Acknowledgements

The authors thank Sabine Jörg and Lydia Pradl for technical assistance. J-L. C. and C. F. gratefully acknowledge financial support by grants from BNP-Paribas, the Foundation Schlumberger and the EU contract X. S. H. E. K. and T. U. gratefully acknowledge financial support from the EU (FP6 programme). S. H. E. K. acknowledges financial support from BMBF.

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Authors and Affiliations

  1. Department of Immunology, Max-Planck-Institute for Infection Biology, Berlin, Germany

    Timo Ulrichs & Stefan H. E. Kaufmann

  2. Department of Medical Microbiology, Institute for Infection Medicine, Charité, Campus Benjamin Franklin, Berlin, Germany

    Timo Ulrichs & Helmut Hahn

  3. Laboratoire de Génetique Humaine des Maladies Infectieuses, Université de Paris René Descartes, Paris, France

    Claire Fieschi & Jean-Laurent Casanova

  4. Paediatric Pulmonology Department, National Institute of Tuberculosis and Respiratory Diseases (NUTRCH), Krajinska 101, 825 56 , Bratislava, Slovak Republic

    Eva Nevicka, Martin Brezina & Klara Frecerova

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  1. Timo Ulrichs
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  2. Claire Fieschi
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  3. Eva Nevicka
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  4. Helmut Hahn
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  5. Martin Brezina
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  6. Stefan H. E. Kaufmann
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  7. Jean-Laurent Casanova
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  8. Klara Frecerova
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Corresponding author

Correspondence to Klara Frecerova.

Additional information

T. Ulrichs and C. Fieschi, S. H. E. Kaufmann and J-L. Casanova contributed equally to this work

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Ulrichs, T., Fieschi, C., Nevicka, E. et al. Variable outcome of experimental interferon-γ therapy of disseminated Bacillus Calmette-Guerin infection in two unrelated interleukin-12Rβ1-deficient Slovakian children. Eur J Pediatr 164, 166–172 (2005). https://doi.org/10.1007/s00431-004-1599-2

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  • DOI: https://doi.org/10.1007/s00431-004-1599-2

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