Bacillus Calmette-Guérin vaccination against bovine tuberculosis: Is Perfect the Enemy of Good?

More than 50 million cattle are likely exposed to bovine tuberculosis (bTB) worldwide, highlighting a need for vaccination in regions where bTB is endemic and test-and-slaughter approaches are unfeasible. Bacillus Calmette-Guérin (BCG) was first evaluated as a vaccine in cattle even before its widespread use in humans, yet its efficacy in cattle remains poorly understood. We performed a systematic review and meta-analysis on the efficacy of BCG against bTB challenge in cattle, which demonstrated a relative risk of infection of 0.75 (95% CI: 0.69, 0.82) in 1873 vaccinates as compared with 1632 controls, corresponding to a vaccine efficacy of 25% (95% CI: 18, 31), as measured by the presence of visible lesions and/or culture. We also assessed the evidence for BCG in reducing transmission of bTB in cattle from experimental challenge and field trials, and used herd level transmission dynamic models to explore the overall impact of BCG in cattle populations in low- and middle-income countries (LMICs). These analyses suggest that BCG vaccination has the potential to substantially accelerate control of bTB in endemic settings, and that early implementation may be of particular utility in the face of dairy intensification in LMICs.