Michelsen and colleagues1 usefully add to the evidence for the protective effect of BCG against active TB. However, we are puzzled by the conclusion that BCG also prevents Mycobacterium tuberculosis (Mtb) infection. Others have similarly used interferon gamma release assay (IGRA) responses as a surrogate for Mtb infection with similar conclusions.2 3 A positive IGRA response represents a previous interaction with Mtb that was sufficient to lead to an acquired immune response. The authors demonstrate a reduced incidence of IGRA response in individuals vaccinated with BCG despite continued risk of Mtb exposure. The authors’ hypothesis that BCG directly protects against TB infection implies it must limit interaction between Mtb and its host. Although not suggested how this could occur, ...