"It was interesting that although we reviewed an astonishing number (over 11,000) of scientific papers we were not able to find any robust evidence for off-target immune effects following childhood vaccination that could be related to an epidemiological outcome," Dr Rama Kandasamy from the University of Oxford and Churchill Hospital in the UK told Reuters Health.

"Off-target immune effects of vaccines are those effects on the immune system that occur after vaccination and which are not related to protection against the germ to which the vaccine is designed against," he said. "We were particularly interested in looking for any proof of such effects on the immune system after childhood vaccination and if these effects could be related to community-wide observations, for example disease or death," Dr. Kandasamy said.

The research team identified 11,168 studies that reported nonspecific immunological effects after vaccination against BCG, measles, diphtheria, tetanus, pertussis, and MMR (mumps, measles, and rubella).

All of the studies had a high risk of bias, with no study rated low risk across all assessment criteria, according to the October 13th BMJ online report.

Based on a careful analysis of 77 studies, the investigators could not identify consistent findings to confirm or discard the occurrence of nonspecific immunological effects after vaccination with these vaccines.

Moreover, the data were not presented in a form that allowed the researchers to assess the effect of sex on nonspecific immunological effects.

"Although it is recognized that off-target immune effects following vaccines are plausible," Dr. Kandasamy concluded, "the findings from our review of the literature show that there is no evidence for the vaccines that we studied having off-target immune effects that would alter childhood mortality."

In a related paper, Dr. Julian P. T. Higgins from University of Bristol, UK and colleagues report on their systematic review of 68 articles, conducted to investigate the effects of BCG, DTP (diphtheria, tetanus, pertussis), and measles-containing vaccines on mortality from causes other than those vaccines.

Receipt of BCG and measles-containing vaccine was associated with a lower risk of all-cause mortality, whereas receipt of DTP was associated with a higher risk of mortality in seven studies and a lower risk in two studies.

Measles-containing vaccines appeared to provide greater mortality benefits among girls than among boys.

"The evidence does not support a change to existing vaccination recommendations but does indicate a need for randomized trials to examine the positioning of DTP in the vaccine schedule," the researchers conclude. "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."

"It is important to emphasize that the systematic reviews were not intended or designed to assess if these vaccines are safe or should continue to be recommended for children," writes Dr. Chee Fu Yung from KK Women's and Children's Hospital, Singapore in a related editorial. "It is beyond debate that BCG, diphtheria, tetanus, pertussis (DPT), and measles containing vaccines (MCV) are safe. These vaccines have saved the lives of millions of children. The reviews' findings must not be hijacked to argue against their recommended use."

Dr. Yung told Reuters Health by email, "Overall, evidence of nonspecific effects (clinical or immunological) of childhood vaccines remains weak and highly susceptible to biases. Parents should continue to ensure that their children get vaccinated and adhere to the local immunisation schedule. BCG, diphtheria, tetanus, pertussis (DTP), and measles containing vaccines (MCV) are safe and effective."

"To move the evidence forward, researchers need to come together to develop better studies, designed to minimise bias across various settings and countries," he concluded. "Future immunological research on nonspecific effects of vaccines should be coordinated with clinical studies and adopt a systems approach."

Dr. Higgins was unable to respond to a request for comments.

SOURCE: http://bit.ly/2edHRwh, http://bit.ly/2evJIzV and http://bit.ly/2eASDfM