Case Report: Disseminated, rifampicin resistant Mycobacterium bovis (BCG) infection in an immunocompromised child

<ns4:p><ns4:bold>Background: </ns4:bold><ns4:italic>Bacillus Calmette–Guérin</ns4:italic> (BCG) is a live-attenuated vaccine used world-wide for prevention of tuberculosis disease. In some immunocompromised hosts it has the potential to cause disease. As with other members of the <ns4:italic>M. tuberculosis </ns4:italic>complex it has the potential for acquiring drug resistance.</ns4:p><ns4:p> <ns4:bold>Methods: </ns4:bold>We reviewed 10 years of paediatric clinical BCG strains referred to our clinical microbiology laboratory in Oxford where they underwent whole genome sequencing. We present a case series comparing clinical, pathogen genetic and pathogen phenotypic data, and consider the clinical implications.</ns4:p><ns4:p> <ns4:bold>Results: </ns4:bold>We identified 15 BCG isolates from 8 children under 16 years old. Only one child had clinical disease with the other seven reported as local inoculation-site reactions. Case 1 suffered disseminated disease secondary to an undiagnosed IL-12/IFNγ receptor defect and the BCG isolates evolved two different rifampicin resistance mutations. Across all 15 isolates, phenotypic resistance to each first line drug was seen. </ns4:p><ns4:p> <ns4:bold>Conclusions: </ns4:bold>BCG is a safe and effective vaccine in children. Most clinical specimens in our series were not related to disease. However, in the context of rare pathogen-specific immunocompromise, BCG can cause pathology and acquire drug resistance under selection from therapy.</ns4:p>