page_title: Non-specific effect of vaccines
section_title: BCG vaccine
hierarchical_section_title: Non-specific effect of vaccines / Live attenuated versus inactivated vaccines / BCG vaccine
caption_attribution_description: My left upper arm which recieved Bacillus Calmette-Guérin for years
context_page_description: Non-specific effects of vaccines are effects which go beyond the specific protective effects against the targeted diseases. Non-specific effects can be strongly beneficial by increasing protection against non-targeted infections. This has been shown with two live attenuated vaccines, BCG vaccine and measles vaccine, through multiple randomized controlled trials. Theoretically, non-specific effects of vaccines may be detrimental, increasing overall mortality despite providing protection against the target diseases. Although observational studies suggest that diphtheria-tetanus-pertussis vaccine may be detrimental, these studies are at high risk of bias and have failed to replicate when conducted by independent groups.
  Ongoing research suggests that non-specific effects of vaccines may depend on the vaccine, the vaccination schedule, and the sex of the infant. For example, one hypothesis suggests that all live attenuated vaccines reduce mortality more than explained by prevention fo target infections, while all inactivated vaccines may increase overall mortality despite providing protection against the target disease.
context_section_description: The live attenuated BCG vaccine developed against tuberculosis has been shown to have strong beneficial effects on the ability to combat non-tuberculosis infections.
  Several studies have suggested that BCG vaccination may reduce atopy, particularly when given early in life. Furthermore, in multiple observational studies BCG vaccination has been shown to provide beneficial effects on overall mortality. These observations encouraged randomised controlled trials to examine BCG vaccination's beneficial non-specific effects on overall health. Since BCG vaccination is recommended to be given at birth in countries that have a high incidence of tuberculosis it would have been unethical to randomize children into 'BCG' vs. 'no BCG' groups. However, many low-income countries delay BCG vaccination for low-birth-weight (LBW) infants; this offered the opportunity to directly test the effect of BCG on overall mortality.
  In the first two randomised controlled trials receipt of BCG+OPV at birth vs. OPV only ('delayed BCG') was associated with strong reductions in neonatal mortality; these effects were seen as early as 3 days after vaccination. BCG protected against sepsis as well as respiratory infections. 
  Among BCG vaccinated children, those who develop a BCG scar or a positive skin test (TST) are less likely to develop sepsis and exhibit an overall reduction in child mortality of around 50%.
  In a recent WHO-commissioned review based on five clinical trials and nine observational studies, it was concluded that "the results indicated a beneficial effect of BCG on overall mortality in the first 6–12 months of life. Relevant follow-up in some of the trials was short, and all of the observational studies were regarded as being at risk of bias, so the confidence in the findings was rated as very low according to the GRADE criteria and "There was a suggestion that BCG vaccination may be more beneficial the earlier it is given". Furthermore, "estimated effects are in the region of a halving of mortality risk" and "any effect of BCG vaccine on all-cause mortality is not likely to be attributable to any great extent to fewer deaths from tuberculosis (i.e. to a specific effect of BCG vaccine against tuberculosis)". Based on the evidence, the WHO's Strategic Group of Experts on Immunization concluded that "the non-specific effects on all-cause mortality warrant further research".
caption: Scar after BCG vaccination
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