The sixty‐year story of Finnish Bacillus Calmette‐Guérin (BCG) osteitis

Abstract

Aim A review published in 2015 showed that 331 Bacillus Calmette‐Guérin (BCG) osteitis cases were globally reported in 1976‐2012. The 222 Finnish cases from 1960 to 1988 formed two‐thirds of all cases. The present narrative review summarises epidemiological, clinical and immunological findings obtained from this Finnish cohort in relation to data from other countries. Methods Six reports including 93 BCG osteitis cases, which were not included in the 2015 review, were identified from PubMed. Results In all, 424 BCG osteitis cases have been published. Population‐based data were available only from Finland and Taiwan. The BCG osteitis incidence in Finnish infants was 6.4/100 000/year in 1960‐1988 compared to 3.4/100 000/year in Taiwanese infants in 1998‐2012. The incidence in Finland increased to 36.9/100 000 in 1971‐1977, and the vaccinations were temporarily discontinued. Over half of lesions were in lower limbs and nearly all were solitary in both cohorts. The outcomes after surgery and chemotherapy were good. Immunology of BCG osteitis was studied only in the Finnish cohort. There were deviations from population data in polymorphisms of genes regulating Toll‐like receptors 1, 2 and 6, mannose‐binding lectin and interleukin‐17A. Conclusion BCG osteitis after vaccination is rare. Preliminary findings in innate immunity raise a question of genetic background.

Toll‐like receptor 10 rs10004195 variation may be protective against Bacillus Calmette‐Guérin osteitis after newborn vaccination

“…In a retrospective study from Taiwan not included in the systematic review covered the years 1998–2014, and the authors identified 70 BCG osteitis cases after newborn vaccination 2 . Globally, 424 BCG osteitis cases have ever been published 3 . As previously published, none of the patients of the present cohort died of tuberculosis, BCG infection or other severe infections, 13 which rules out severe deficiencies in host immunity.…”

“…Osteitis is a rare complication of Bacillus Calmette‐Guérin (BCG) vaccination and needs surgical intervention and an anti‐tuberculous treatment with drug combinations for 9 to 12 months 1,2 . Based on a recent review, over half of all 424 globally ever published BCG osteitis cases were diagnosed in Finnish children 3 . The crucial role of interferon‐gamma (IFN‐γ) in responses to mycobacteria, BCG included, has been known for a long time 4,5 .…”

“…1,2 Based on a recent review, over half of all 424 globally ever published BCG osteitis cases were diagnosed in Finnish children. 3 The crucial role of interferon-gamma (IFN-γ) in responses to mycobacteria, BCG included, has been known for a long time. 4,5 Toll-like receptors (TLR) are molecules of innate immunity that recognise different pathogens.…”