title: Duration of BCG protection against tuberculosis and change in effectiveness with time since vaccination in Norway: a retrospective population-based cohort study.
abstract: BACKGROUND
  Little is known about how long the BCG vaccine protects against tuberculosis. We assessed the long-term vaccine effectiveness (VE) in Norwegian-born individuals.
  
  
  METHODS
  In this retrospective population-based cohort study, we studied Norwegian-born individuals aged 12-50 years who were tuberculin skin test (TST) negative and eligible for BCG vaccination as part of the last round of Norway's mandatory mass tuberculosis screening and BCG vaccination programme between 1962 and 1975. We excluded individuals who had tuberculosis before or in the year of screening and those with unknown TST and BCG status. We obtained TST and BCG information and linked it to the National Tuberculosis Register, population and housing censuses, and the population register for emigrations and deaths. We followed individuals up to their first tuberculosis episode, emigration, death, or Dec 31, 2011. We used Cox regressions to estimate VE against all tuberculosis and just pulmonary tuberculosis by time since vaccination, adjusted for age, time, county-level tuberculosis rates, and demographic and socioeconomic indicators.
  
  
  RESULTS
  Median follow-up was 41 years (IQR 32-49) for 83 421 BCG-unvaccinated and 44 years (41-46) for 297 905 vaccinated individuals, with 260 tuberculosis episodes. Tuberculosis rates were 3·3 per 100 000 person-years in unvaccinated and 1·3 per 100 000 person-years in vaccinated individuals. The adjusted average VE during 40 year follow-up was 49% (95% CI 26-65), although after 20 years, the VE was not significant (up to 9 years VE [excluding tuberculosis episodes in the first 2 years] 61% [95% CI 24-80]; 10-19 years 58% [27-76]; 20-29 years 38% [-32 to 71]; 30-40 years 42% [-24 to 73]). VE against pulmonary tuberculosis up to 9 years (excluding tuberculosis episodes in the first 2 years) was 67% (95% CI 27-85), 10-19 years was 63% (32-80), 20-29 years was 50% (-19 to 79), and 30-40 years was 40% (-46 to 76).
  
  
  CONCLUSIONS
  Findings are consistent with long-lasting BCG protection, but waning of VE with time. The vaccine could be more cost effective than has been previously estimated
  
  
  BACKGROUND
  Norwegian Institute of Public Health and London School of Hygiene & Tropical Medicine.
authors.affiliation: Department of Infectious Disease Epidemiology, Faculty of Epidemiology and Population Health, and Tuberculosis Centre, London School of Hygiene & Tropical Medicine, London, UK. Electronic address: patrick.nguipdop-djomo@lshtm.ac.uk.
authors.forename: Patrick
authors.initials: P
authors.lastname: Nguipdop-Djomo
authors.affiliation: Norwegian Institute of Public Health, Oslo, Norway.
authors.forename: Einar
authors.initials: E
authors.lastname: Heldal
authors.affiliation: Department of Infectious Disease Epidemiology, Faculty of Epidemiology and Population Health, and Tuberculosis Centre, London School of Hygiene & Tropical Medicine, London, UK.
authors.forename: Laura Cunha
authors.initials: LC
authors.lastname: Rodrigues
authors.affiliation: Institute of Epidemiology and Health, and Centre for Infectious Disease Epidemiology, Faculty of Population Health Sciences, University College London, London, UK.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Abubakar
authors.affiliation: Department of Infectious Disease Epidemiology, Faculty of Epidemiology and Population Health, and Tuberculosis Centre, London School of Hygiene & Tropical Medicine, London, UK.
authors.forename: Punam
authors.initials: P
authors.lastname: Mangtani
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D001500:BCG Vaccine / Q000276:immunology*; D002648:Child; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008403:Mass Screening / Q000706:statistics & numerical data*; D008875:Middle Aged; D009163:Mycobacterium bovis / Q000187:drug effects*; D009664:Norway / Q000453:epidemiology; D011159:Population Surveillance; D012189:Retrospective Studies; D012959:Socioeconomic Factors; D013997:Time Factors; D014376:Tuberculosis / Q000453:epidemiology* / Q000517:prevention & control*; D055815:Young Adult
chemical_list: D001500:BCG Vaccine