Young children are less likely to be hospitalized for infectious disease if their most recent immunization contained live vaccine, according to new research from the US Centers for Disease Control and Prevention (CDC).

“Along with other recent studies, our study raises the possibility that the order in which vaccines are administered may carry benefits in addition to the prevention of the targeted infections,” Dr. Barbara Bardenheier of the CDC’s Immunization Safety Office and her colleagues write. “But the interpretation of our results should be tempered because the extent of potential biases from confounding and selection biases are unknown.”

The findings were published online May 6 in Clinical Infectious Diseases.

“Previous studies have suggested that certain vaccines have beneficial effects on infection beyond those they are targeted to prevent. These studies were primarily conducted in West Africa,” Dr. Bardenheier told Reuters Health by email. “Subsequently, a study in Denmark found that the order in which vaccines (live vs inactivated) are given may have an effect on hospitalization. Our study is the first in the United States and we found similar findings to the studies performed in Denmark.”

Dr. Bardenheier and her team looked at MarketScan US Commercial Claims Database data for 2005 to 2014 on more than 311,000 children 16 to 24 months old.

The hazard ratio for hospitalization for non–targeted infectious diseases for those who had last received live vaccine was 0.50 (95% confidence interval, 0.43 to 0.57) compared to those given inactivated vaccine only. The HR was 0.78 (95% CI, 0.67 to 0.91) for children given live vaccine only compared to those who had last received both inactive and live vaccine.

The mechanisms through which live vaccine might offer additional protection beyond the targeted infections are not clear, Dr. Bardenheier said.

“One possible mechanism involves the concept of ‘trained Immunity,’” the researcher explained. “That is, each person has a unique history of infections and vaccinations and every exposure leaves an imprint on the immune system that can affect future immune responses to pathogens, including the potential to provide protection against unrelated infections.”

Live vaccines may also have a different effect on the immune system than inactivated vaccines, she added.

“One well–known example is BCG (Bacille Calmette–Guerin), a live–attenuated vaccine used for the prevention of tuberculosis,” Dr. Bardenheier noted.” For decades it has also been the predominant immunotherapy for the treatment of non–muscle invasive bladder cancer because of its demonstrated efficacy in reducing tumor recurrence in the majority of treated patients.”

Conducting randomized controlled trials to further investigate the association would be expensive and possibly ethically problematic, according to Dr. Bardenheier.

“Barring the conduct of clinical trials, additional observational studies in other US populations using different databases may provide further evidence on the reliability of our findings,” she said. “If these findings hold up in future research, they would provide additional evidence of the benefits of vaccination beyond the diseases that they are targeted to prevent.”

The study did not include results for unvaccinated children. As a consequence, it was unable to tease out whether receiving inactivated vaccines is associated with more hospitalizations than receiving no vaccines, as other research has suggested.

—Anne Harding