title: The potential impact of BCG vaccine supply shortages on global paediatric tuberculosis mortality.
abstract: The Bacillus Calmette-Guérin (BCG) vaccine is provided to over 100 million neonates annually to protect against childhood tuberculosis (TB). Recent BCG manufacturing interruptions highlight global supply risks. We estimated the potential impact of BCG shortfalls on global paediatric (<15 years) TB mortality.
  
  
  
  A static mathematical model was employed to estimate the number of paediatric TB deaths avoided by usual levels of BCG coverage, and potential additional TB deaths in the first 15 years of life due to 1-year BCG supply shortfalls of 6.3 % (as occurred in 2015) to 27.6 % (as anticipated without mitigating action in 2015) assuming no catch-up campaigns.
  
  
  
  BCG coverage without shortfalls, estimated at 90 % globally, was estimated to avoid 117,132 (95 % uncertainty range (UR): 5049-306,911) TB deaths globally per birth cohort in the first 15 years of life. An estimated 11,713 (UR: 505-30,691) additional TB deaths would occur in the first 15 years of life per 10 % (26 million dose) annual supply shortfall. A 16.5 million dose (6.3 %) shortfall as reported at the close of 2015, reflecting 84 % global coverage, was estimated as associated with 7433 (95 % UR: 320-19,477) excess TB deaths in the affected cohort in the first 15 years. A possible 24,914 (UR: 1074-65,278) additional deaths were avoided due to prompt shortfall reduction measures in 2015.
  
  
  
  BCG shortages could greatly increase paediatric TB mortality. Although rapid action in 2015 minimised BCG shortfalls, avoiding a large number of potential additional deaths, the possible public health impact of even relatively small shortfalls highlights the critical importance of ensuring secure future manufacturing capacity and global BCG supply continuity.
authors.affiliation: TB Modelling Group, TB Centre and Centre for the Mathematical Modelling of Infectious Diseases, Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, Keppel Street, London, WC1E 7HT, UK. rebecca.harris@lshtm.ac.uk.
authors.forename: Rebecca C
authors.identifier: 0000-0002-2636-1520
authors.initials: RC
authors.lastname: Harris
authors.affiliation: School of Health and Related Research, University of Sheffield, 30 Regent Street, Sheffield, S1 4DA, UK.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Dodd
authors.affiliation: TB Modelling Group, TB Centre and Centre for the Mathematical Modelling of Infectious Diseases, Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, Keppel Street, London, WC1E 7HT, UK.
authors.forename: Richard G
authors.initials: RG
authors.lastname: White
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D001500:BCG Vaccine / Q000600:supply & distribution* / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D006297:Health Services Accessibility / Q000706:statistics & numerical data*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D032541:Mass Vaccination / Q000592:standards / Q000706:statistics & numerical data; D015201:Meta-Analysis as Topic; D008962:Models, Theoretical; D014376:Tuberculosis / Q000401:mortality* / Q000517:prevention & control*; D035501:Uncertainty
chemical_list: D001500:BCG Vaccine
keywords: Bacillus Calmette-Guérin vaccine; Child; Mathematical model; Mortality; Mycobacterium tuberculosis; Paediatric; Shortage; Shortfall; Tuberculosis