The introduction of BCG vaccination to neonates in Northern Sweden, 1927-31: Re-analysis of historical data to understand the lower mortality among BCG-vaccinated children.
Bacille Calmette-Guérin (BCG) vaccine
Child mortality
History of vaccinology
Non-specific effects of vaccines
Tuberculosis
Vaccine introduction
Journal
Vaccine
ISSN: 1873-2518
Titre abrégé: Vaccine
Pays: Netherlands
ID NLM: 8406899
Informations de publication
Date de publication:
08 03 2022
08 03 2022
Historique:
received:
23
12
2020
revised:
19
05
2021
accepted:
01
06
2021
pubmed:
18
6
2021
medline:
11
3
2022
entrez:
17
6
2021
Statut:
ppublish
Résumé
Following the introduction of oral Bacille Calmette-Guérin (BCG) a century ago, Albert Calmette suggested that BCG both provided protection against death from tuberculosis (TB) and other causes. The findings were not pursued. Today, there is considerable evidence that intradermal BCG have beneficial non-specific effects (NSEs). We re-analyzed data from BCG's introduction 1927-1931 in Sweden hypothesizing that BCG reduced infectious deaths. In three papers published by Dr Carl Näslund, the progress of oral neonatal BCG rollout provided free-of-charge and the effects on child mortality in the highly TB-prevalent region Norrbotten was sequentially updated. We analyzed cause-specific post-neonatal mortality by vaccination status excluding deaths from congenital conditions. Due to apparent differences in effects during study years, effects were assessed overall and separately in two periods (1927-1929, 1930-1931). According to Näslund, TB households were slightly more likely to accept vaccination; fewer newborns that were sick or had congenital problems were vaccinated. BCG coverage was 28.3% (5659/20,012); 8.7% (1746/20,012) died. The BCG/unvaccinated Risk Ratio (RR) of post-neonatal childhood death was 0.53 (0.45-0.62). BCG was associated with 80% (49-92%) reduced mortality from TB. From 1927 to 29, BCG appeared to protect strongly against deaths from all diseases, including the non-infectious, RR = 0.09 (0.02-0.36), presumably reflecting selection bias. From 1930 to 1931, there was no protection against non-infectious deaths, RR = 0.92 (0.49-1.70) indicating less bias (p = 0.004 for same effect). During 1930-1931, BCG was associated with reductions in non-TB infectious deaths (RR = 0.75 (0.58-0.97)); 2/3 were caused by respiratory infections, against which the BCG/unvaccinated RR was 0.61 (0.43-0.84). Other causes of death were less frequent and provided no clear pattern, except that BCG was associated with more meningitis deaths, RR = 6.85 (2.20-21.4). Healthy vaccinee bias, particularly in 1927-1929, resulted in strongly beneficial overall BCG effects. However, the 1930-1931 data provided some support that BCG both protected against TB deaths and deaths from respiratory infections.
Sections du résumé
BACKGROUND
Following the introduction of oral Bacille Calmette-Guérin (BCG) a century ago, Albert Calmette suggested that BCG both provided protection against death from tuberculosis (TB) and other causes. The findings were not pursued. Today, there is considerable evidence that intradermal BCG have beneficial non-specific effects (NSEs). We re-analyzed data from BCG's introduction 1927-1931 in Sweden hypothesizing that BCG reduced infectious deaths.
METHODS
In three papers published by Dr Carl Näslund, the progress of oral neonatal BCG rollout provided free-of-charge and the effects on child mortality in the highly TB-prevalent region Norrbotten was sequentially updated. We analyzed cause-specific post-neonatal mortality by vaccination status excluding deaths from congenital conditions. Due to apparent differences in effects during study years, effects were assessed overall and separately in two periods (1927-1929, 1930-1931).
RESULTS
According to Näslund, TB households were slightly more likely to accept vaccination; fewer newborns that were sick or had congenital problems were vaccinated. BCG coverage was 28.3% (5659/20,012); 8.7% (1746/20,012) died. The BCG/unvaccinated Risk Ratio (RR) of post-neonatal childhood death was 0.53 (0.45-0.62). BCG was associated with 80% (49-92%) reduced mortality from TB. From 1927 to 29, BCG appeared to protect strongly against deaths from all diseases, including the non-infectious, RR = 0.09 (0.02-0.36), presumably reflecting selection bias. From 1930 to 1931, there was no protection against non-infectious deaths, RR = 0.92 (0.49-1.70) indicating less bias (p = 0.004 for same effect). During 1930-1931, BCG was associated with reductions in non-TB infectious deaths (RR = 0.75 (0.58-0.97)); 2/3 were caused by respiratory infections, against which the BCG/unvaccinated RR was 0.61 (0.43-0.84). Other causes of death were less frequent and provided no clear pattern, except that BCG was associated with more meningitis deaths, RR = 6.85 (2.20-21.4).
CONCLUSION
Healthy vaccinee bias, particularly in 1927-1929, resulted in strongly beneficial overall BCG effects. However, the 1930-1931 data provided some support that BCG both protected against TB deaths and deaths from respiratory infections.
Identifiants
pubmed: 34134904
pii: S0264-410X(21)00718-0
doi: 10.1016/j.vaccine.2021.06.006
pii:
doi:
Substances chimiques
BCG Vaccine
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1516-1524Informations de copyright
Copyright © 2021 Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.