BCG vaccines Report on BCG vaccine use for protection against mycobacterial infections including tuberculosis, leprosy, and other nontuberculous mycobacteria (NTM) infections Prepared by the SAGE Working Group on BCG Vaccines and WHO Secretariat 22. September 2017 List of abbreviations AFR. african region MDR-TB. multidrug-resistant TB AMR. antimicrobial resistances MDT. multi-drug therapy, multidrug therapy BCG. bacillus calmette-guérin MICs. middle income countries BUD. buruli ulcera disease MICS. multiple indicator cluster surveys CFU. colony forming units MOTT. mycobacteria other than tuberculosis DHS. demographic health surveys NRA. national regulatory authority DRDR. drug resistance determining regions NS. needle and syringe DSJI. disposable-syringe jet injectors NTM. non-tuberculous mycobacterial DST. drug susceptibility testing OPV. oral polio vaccine EID. early infant HIV diagnosis PB. pauci-bacillary EMR. eastern mediterranean region PEP. post-exposure prophylaxis EUR. european region PMTCT. prevention of mother to child transmission G2D. grade-2 disabilities POC. point-of-care GLP. global leprosy programm PQ’d. prequalified GTB. global TB programme PTB. pulmonary tuberculosis HBsAg. hepatitis B surface antigen R&D. research and development HCWs. health care workers SAGE. strategic advisory group of experts on immunization HICs. high income countries SDGs. sustainable development goals IRIS. immune reconstitution inflammatory syndrome SEAR. south east asian region IUATLD. international union against TB and lung disease TB. tuberculosis JRF. WHO/UNICEF Joint Reporting UHC. universal health coverage LBW. low birth weight VENICE. vaccine european new integrated collaboration effort LICs. low income countries WPR. western pacific region LMICs. lower-middle income countries WUENIC. WHO/UNICEF estimates of national immunization MB. multi-bacillary Coverage MDGs. millennium development goals XDR-TB. extensively drug-resistant TB 1 BCG vaccines – Table of contents Table of Contents 1. Executive summary ........................................................................................................................................................................ 3 2. BCG Working Group Recommendations ......................................................................................................................................... 5 3. Background ................................................................................................................................................................................. 10 4. Tuberculosis ................................................................................................................................................................................ 11 4.2. Epidemiology of TB ................................................................................................................................. 11 4.3. TB control in the era of the UN Sustainable Development Goals ........................................................... 12 4.4. Trends in antibiotic resistance of TB ....................................................................................................... 14 5. Leprosy ................................................................................................................................................................................................. 16 5.2. Epidemiology of Leprosy ......................................................................................................................... 16 5.3. Global Leprosy Strategy 2016-2020 ........................................................................................................ 19 5.4. Antimicrobial resistance in Leprosy ........................................................................................................ 21 6. Non-tuberculous mycobacterial (NTM) infections .............................................................................................................................. 21 6.2. Buruli ulcer disease ................................................................................................................................. 22 7. Current WHO recommendations (2004 and addition of 2007) ...................................................................................................... 24 8. Country policies and implementation .......................................................................................................................................... 25 8.2. Country policies on the use of BCG against leprosy ................................................................................ 25 8.3. Review of BCG vaccine policies in countries with low TB burden ........................................................... 26 8.4. Switching vaccination policy – from universal to selective vaccination .................................................. 27 8.5. BCG vaccine coverage estimate .............................................................................................................. 28 8.6. Timeliness of BCG vaccination ................................................................................................................ 30 9. Vaccine strains and other factors that are influencing safety and effectiveness of BCG vaccines .................................................. 32 10. Market update BCG Vaccines ....................................................................................................................................................... 35 10.2. Impact of BCG vaccine shortages ............................................................................................................ 37 10.3. How to mitigate the impact of BCG shortages........................................................................................ 38 11. BCG efficacy and effectiveness against TB .................................................................................................................................... 38 12. BCG efficacy and effectiveness against leprosy ............................................................................................................................ 41 13. Non-specific (‘heterologous’ or ’non-targeted') effects of BCG ..................................................................................................... 43 14. Duration of Protection ................................................................................................................................................................. 45 15. Need for revaccination, vaccination in adolescent and adults ...................................................................................................... 46 16. Safety of BCG vaccination ............................................................................................................................................................ 53 17. Route of administration ............................................................................................................................................................... 55 18. Co-administration with other vaccines......................................................................................................................................... 57 19. Update on the status of the pediatric HIV epidemic and implications for BCG administration policies in countries with high burden of HIV ....................................................................................................................................................................................... 59 20. Vaccination of low birth weight and premature infants ............................................................................................................... 62 21. Vaccination of travelers from non TB endemic countries to TB endemic countries ....................................................................... 63 22. Cost-effectiveness of BCG vaccination ......................................................................................................................................... 63 23. Innovations and new vaccines under development ...................................................................................................................... 65 23.2. Innovations and research are critical to break the trajectory of the TB epidemic .................................. 65 23.3. Diagnostic and treatment tools on the horizon ...................................................................................... 65 23.4. What research is required to end the TB epidemic and eliminate TB?................................................... 66 23.5. New vaccines under development.......................................................................................................... 66 23.5.1. Status of TB Vaccine Development - highlights ...................................................................................... 66 23.5.2. Status of Leprosy Vaccine Development................................................................................................. 68 24. Additional research needs on BCG ............................................................................................................................................... 68 25. Working Group members, other experts and WHO secretariat .................................................................................................... 68 26. Appendix ....................................................................................................................................................................................