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

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.