Nonspecific (Heterologous) Protection of Neonatal BCG Vaccination Against Hospitalization Due to Respiratory Infection and Sepsis

Clin Infect Dis. 2015 Jun 1;60(11):1611-9. doi: 10.1093/cid/civ144. Epub 2015 Feb 27.


Background: Bacille Calmette-Guerin (BCG) vaccination has been suggested to have nonspecific beneficial effects in children from developing countries, reducing morbidity and mortality caused by unrelated pathogens.

Objective: We aimed to assess the heterologous protective effects of BCG vaccination against respiratory infection (RI) and sepsis not attributable to tuberculosis in children born in Spain.

Methods: We conducted a retrospective epidemiological study using data from the Official Spanish Registry of Hospitalizations (CMBD-HA) to identify differences in hospitalization rates (HR) in BCG-vaccinated children (Basque Country, where neonatal BCG is part of the immunization schedule and has a 100% coverage) as compared to non-BCG-vaccinated children (from the rest of Spain, where BCG is not used).

Results: A total of 464 611 hospitalization episodes from 1992 to 2011 were analyzed. The HR due to RI not attributable to tuberculosis in BCG-vaccinated children was significant lower compared to non-BCG-vaccinated children for all age groups, with a total preventive fraction (PF) of 41.4% (95% confidence interval: 40.3-42.5; P-value <.001). According to age group, PF was 32.4% (30.9-33.9; P-value <.001) for children under 1 year old, 60.1% (58.5-61.7; P-value <.001) for children between 1 and 4 years old, 66.6% (62.8-70.2; P-value <.001) for children between 5 and 9 years old, and 69.6% (63.3-75.0; P-value <.001) for children between 10 and 14 years old. The HR due to sepsis not attributable to tuberculosis in BCG-vaccinated children under 1 year of age was also significantly lower, with a PF of 52.8% (43.8-60.7; P-value <.001).

Conclusions: BCG vaccination at birth may decrease hospitalization due to RI and sepsis not related to tuberculosis through heterologous protection.

Keywords: BCG vaccination; children; heterologous effects; nonspecific effects.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • BCG Vaccine / administration & dosage*
  • BCG Vaccine / immunology
  • Child
  • Child, Preschool
  • Cross Protection*
  • Epidemiologic Studies
  • Female
  • Hospitalization*
  • Humans
  • Immunity, Heterologous*
  • Male
  • Respiratory Tract Infections / epidemiology
  • Respiratory Tract Infections / prevention & control*
  • Retrospective Studies
  • Sepsis / epidemiology
  • Sepsis / prevention & control*
  • Spain / epidemiology
  • Treatment Outcome
  • Vaccination


  • BCG Vaccine