Key Concept

Key Evidence: This 2013 review summarizes data from several randomized trials in which measles and tuberculosis vaccines were associated with a substantial reduction in overall child mortality, which cannot be solely explained by prevention of the target disease. These studies suggest that in addition to disease-specific effects, some live vaccines may also provide “nonspecific effects” that enhance the immune system’s ability to protect against additional pathogens.

Benn, C. S., Netea, M. G., Selin, L. K., & Aaby, P. 2013. A small jab – a big effect: Nonspecific immunomodulation by vaccines. Trends in Immunology. 34(9).
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Key Evidence: In a study of data from England & Wales, Denmark, and the US, it was shown that measles infection suppresses the immune system for up to 3 years after infection, increasing the risk of death due to other childhood infections during that time. This means that prevention of measles significantly impacts overall health during critical childhood years.

Mina, M.J., Metcalf, C.J. de Swart, R.L., et al 2015. Long-term measles-induced immunomodulation increases overall childhood infectious disease mortality. Science. 348(6235).
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Key Evidence: An analysis of children aged 12-59 months in rural India showed that children who were not vaccinated against measles vaccine in infancy had a three times higher likelihood of death, with unvaccinated children from lower caste households having the highest risk of mortality (odds ratio, 8.9). However, the results also revealed a nonspecific reducing effect of the vaccine on the overall child mortality in this region. This indicates that vaccination against measles can benefit the overall population, especially those in lower castes who have not received the vaccine in infancy. Thus, making them the group that would receive the highest benefit.

Kabir, K., Long, J., Reddaiah, V.P., et al 2003. Non-specific effect of measles vaccination on overall child mortality in an area of rural India with high vaccination coverage: a population-based case-control study. Bulletin of the World Health Organization. 81(4).
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Key Evidence: Three randomized controlled trials enrolling a total of over 6500 infants over 12 consecutive years in Guinea-Bissau found a 38% reduction in all-cause neonatal mortality associated with early vaccination with BCG. Revisiting these trials to explore the seasonal variation in this effect, it was found that early vaccination with BCG was particularly beneficial when administered between November and January, coincident with peaking malaria infections.

Jensen, K. J., Biering-Sørensen, S., Ursing, J., Kofoed, P. E. L., Aaby, P., & Benn, C. S. 2020. Seasonal variation in the non-specific effects of BCG vaccination on neonatal mortality: Three randomised controlled trials in Guinea-Bissau. BMJ Global Health. 5(3).
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Key Evidence: In a 2014 review of the non-specific effects of measles vaccines, among others, the WHO Strategic Advisory Group of Experts indicated that some studies of measles vaccine were suggestive (but not conclusive) of a beneficial effect of measles vaccine on overall mortality beyond the expected direct effect of the vaccine against measles. In particular, randomized control trials of children in Guinea- Bissau which looked at mortality up to the age of 9 months showed a low number of deaths post administration of the 3 doses of the measles vaccine over the study follow up period. Another trial in Nigeria also showed similar results.

World Health Organization, Strategic Advisory Group of Experts 2014. Systematic review of the non-specific effects of BCG, DTP and measles-containing vaccines.
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