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Review of non-specific effects of vaccines

WHO recently conducted a review to evaluate CVIVA researchers' hypothesis that vaccines - beyond their disease protective effect - may also have so-called "non-specific" effects on the immune system, which may have important implications for overall health.
The review has just been published in the renowned journal, British Medical Journal, and supports the Danish researchers' hypotheses.

Researchers from the Center for Vitamins and Vaccines, Bandim Health Project, Statens Serum Institut, have put forward the hypothesis that vaccines, in addition to their well-known disease protective effect may have non-specific effects, which may have important implications for overall health.

The studies, primarily conducted at the research station in Guinea-Bissau, but subsequently also in other low-income countries, have shown that the live vaccines, BCG vaccine against tuberculosis and measles vaccine, appear to induce general protection against other infectious diseases, which means that the vaccinated children survive far better than can be expected from the specific effect of the vaccines. In contrast, the non-live vaccine against diphtheria, tetanus and pertussis, DTP vaccine, seems to increase overall mortality from other diseases among girls. The researchers have also shown that the non-specific effects are strongest, as long as a given vaccine is the most recently received vaccine. This means that the sequence and the combination of vaccines is important for their overall effect on mortality; it is best to end with a live vaccine as the most recently received vaccine.

These figures mean that with more than 30 million children below 1 year in Sub-Saharan Africa, providing BCG vaccine for all could save anywhere between 150,000 and 300,000 children per year, while DTP vaccine is associated with 120,000 to 240,000 extra deaths per year.
Christine Benn, CVIVA

The findings have been seen as highly controversial and have met much resistance, but recently WHO decided to undertake a systematic literature review of the evidence for non-specific effects of BCG, measles and DTP vaccines on overall mortality. The review has just been published in the renowned scientific journal, British Medical Journal (http://www.bmj.com/content/355/bmj.i5170?etoc).

The conclusions of the review support the Danish researchers' hypotheses. The overall conclusion reads: "Evidence suggests that receipt of BCG and MCV [measles vaccine] reduce overall mortality by more than would be expected through their effects on the diseases they prevent, and receipt of DTP may be associated with an increase in all cause mortality".

Based on the reviewers’ calculation BCG vaccine is associated with 5-10 fewer deaths/1000 children; DTP vaccine is conversely associated with 4-8 additional deaths/1,000 children. These figures mean that with more than 30 million children below 1 year in Sub-Saharan Africa, providing BCG vaccine for all could save anywhere between 150,000 and 300,000 children per year, while DTP vaccine is associated with 120,000 to 240,000 extra deaths per year.

With regard to sequence and combination of vaccines the review concludes - also in accordance with the Danish researchers' hypotheses - that the data indicate that it is better to receive vaccines, so the live vaccines are provided after the non-live vaccines, rather than vice versa.

The reviewers remark that in the studies that have evaluated several vaccines, the same pattern is seen consistently: live vaccines are associated with increased survival, non-live vaccines with increased mortality, and they write: "We are unable to explain these patterns using information relating to potential risks of bias available in the study reports, and regard the findings to be a cause for concern".

The reviewers come with a very clear recommendation: "the data raise sufficient concerns for us to strongly recommend further studies on the possible effects of immunisations on the immune system and on the risk of morbidity and mortality, particularly in relation to DTP".

The review ends: "The evidence does not support a change to existing vaccination recommendations but does indicate a need for randomised trials to examine the positioning of DTP in the vaccine schedule. Until the results of such studies are available, every effort should be made to ensure that infants receive routine immunisations on schedule and in the sequence recommended by WHO".

Thus, there is no need to change the vaccination program here and now, but there is a need for further studies. So far it is recommended that children receive vaccines on time and in the recommended order - which in most countries, including Denmark, will mean that the children have a live vaccine, MMR vaccine, as the most recently received vaccine in most of the first years of life.

Eksternt link

Higgins JP, Soares-Weiser K, López-López JA, Kakourou A, Chaplin K, Christensen H, Martin NK, Sterne JA, Reingold AL. Association of BCG, DTP, and measles containing vaccines with childhood mortality: systematic review. BMJ. 2016 Oct 13;355:i5170. doi: 10.1136/bmj.i5170.

Link to open access article: https://goo.gl/NokiXb