Case Report: Acquired Disseminated BCG in the Context of a Delayed Immune Reconstitution After Hematological Malignancy

Abstract

ContextDisseminated infections due to Mycobacterium bovis Bacillus Calmette-Guérin (BCG) are unusual and occur mostly in patients with inborn error of immunity (IEI) or acquired immunodeficiency. However, cases of secondary BCGosis due to intravesical BCG instillation have been described. Herein, we present a case of severe BCGosis occurring in an unusual situation.Case DescriptionWe report one case of severe disseminated BCG disease occurring after hematological malignancy in a 48-year-old man without BCG instillation and previously vaccinated in infancy with no complication. Laboratory investigations demonstrated that he was not affected by any known or candidate gene of IEI or intrinsic cellular defect involving IFNγ pathway. Whole genome sequencing of the BCG strain showed that it was most closely related to the M. bovis BCG Tice strain, suggesting an unexpected relationship between the secondary immunodeficiency of the patient and the acquired BCG infection.ConclusionThis case highlights the fact that, in addition to the IEI, physicians, as well as microbiologists and pharmacists should be aware of possible acquired disseminated BCG disease in secondary immunocompromised patients treated in centers that administrate BCG for bladder cancers.

Metagenomic sequencing expedites diagnosis of disseminated BCG in an infant with BRAFV600E mutation

“…In countries where BCG is routinely administered in infancy, disseminated Mycobacterium bovis-BCG infection is commonly seen in children with underlying inborn error of immunity (IEI) like severe combined immunodeficiency (SCID) and chronic granulomatous disease [5]. Wang and colleagues evaluated 22 cases of disseminated BCG disease in China for immunodeficiency, and found that at least 16 of them (72.7%) suffered from definite immunodeficiency simultaneously [6].…”

BCG in Immunocompromised Patients: Is it effective? Is it safe?

“…While it's mechanisms of action are not completely understood, it is thought to initiate inflammation and cellular immune activity resulting in an anti-tumor response [6]. Moreover, being a live Mycobacterium, the possibility of it escaping the bladder after intravesical instillation causing a systemic infection ("BCGemia") has been well described [7,8]. Thus, there is understandable concern that in patients who are immunologically compromised, either iatrogenically and/or because of underlying diseases, intravesical instillations of BCG will not be effective and potentially can be unsafe.…”

“…Thus, there is understandable concern that in patients who are immunologically compromised, either iatrogenically and/or because of underlying diseases, intravesical instillations of BCG will not be effective and potentially can be unsafe. While several small, single-institution historical series confirm its safety and efficacy in treating bladder cancer patients who are immunocompromised [7,[9][10][11][12][13][14][15][16], no large-scale assessment has been made, and in large prospective randomized studies testing BCG's efficacy, immunosuppressed patients and/or those receiving corticosteroids chronically have intentionally been excluded from participation (e.g., SWOG S1602 [PRIME]).…”