Neonatal Bacille Calmette-Guérin vaccination and tuberculin skin test reactions at 2- and 6-months : Effects on mortality up to 1 year of age
(2021) In Vaccine 39(50). p.7286-7294- Abstract
Background: In randomized trials, Bacille Calmette-Guérin (BCG) vaccine has been associated with reduced all-cause mortality. BCG-induced Tuberculin Skin Test (TST) reactions have also been associated with reduced all-cause mortality. We aimed to assess the association between TST responses and subsequent mortality in three birth cohorts and conducted a meta-analysis of existing studies. Methods: Observational study within three Guinea-Bissau BCG trial birth cohorts (conducted 2002–04, 2009–2013 and 2014–18) that encompassed children who were BCG-vaccinated within 28 days with TSTs performed at 2- (n = 1389) and 6-months (n = 2635) of age. We evaluated TST reaction determinants by binomial regression and assessed the association between... (More)
Background: In randomized trials, Bacille Calmette-Guérin (BCG) vaccine has been associated with reduced all-cause mortality. BCG-induced Tuberculin Skin Test (TST) reactions have also been associated with reduced all-cause mortality. We aimed to assess the association between TST responses and subsequent mortality in three birth cohorts and conducted a meta-analysis of existing studies. Methods: Observational study within three Guinea-Bissau BCG trial birth cohorts (conducted 2002–04, 2009–2013 and 2014–18) that encompassed children who were BCG-vaccinated within 28 days with TSTs performed at 2- (n = 1389) and 6-months (n = 2635) of age. We evaluated TST reaction determinants by binomial regression and assessed the association between TSTs > 1 mm (reactors) vs. ≤ 1 mm (non-reactors) and subsequent mortality risk up to age 12 months in Cox-models providing Mortality Rate Ratios (MRRs). We searched PubMed for studies to calculate meta-estimates of the association between TST reactivity by age 2- and 6-months and all-cause mortality. Results: Large post-vaccination wheal size was associated with 6-month TST positivity and so was receiving BCG-Denmark or BCG-Japan, compared with BCG-Russia. By age 2 months, 22% (302/1389) of infants were TST reactors with a 2–12-month mortality risk of 1.7% (5/302) vs. 3.3% (36/1087) for non-reactors, the corresponding reactor/non-reactor MRR = 0.49 (0.19–1.26). By age 6 months, 44% (1149/2635) of infants were reactors and the 6–12-month mortality risk was 0.4% (4/1149) vs. 0.6% (9/1486) for non-reactors, the MRR = 0.87 (0.27–2.86). The literature search provided 3 studies. The meta-analysis revealed a uniform pattern of reduced mortality associated with TST reactivity, a TST response by 2 months being associated with an MRR of 0.59 (0.39–0.90); for 6-month TST responses the MRR was 0.65 (0.43–1.00). Conclusion: Among BCG-vaccinated infants, TST reactions were associated with markedly reduced mortality. Improved vaccination technique and using certain BCG strains could lead to a higher TST reaction prevalence, which would enhance BCG's beneficial non-specific effects.
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- author
- Schaltz-Buchholzer, Frederik ; Roth, Adam LU ; de Bree, L. Charlotte J. ; Biering-Sørensen, Sofie ; Timmermann, Clara Amalie Gade ; Monteiro, Ivan ; Aaby, Peter and Benn, Christine Stabell
- organization
- publishing date
- 2021
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Bacille Calmette-Guérin (BCG), Heterologous effects of vaccines, Infant mortality, Mantoux reaction, Non-specific effects of vaccines, Purified Protein Derivative (PPD), Tuberculin Skin Test (TST)
- in
- Vaccine
- volume
- 39
- issue
- 50
- pages
- 7286 - 7294
- publisher
- Elsevier
- external identifiers
-
- scopus:85109074507
- pmid:34226104
- ISSN
- 0264-410X
- DOI
- 10.1016/j.vaccine.2021.06.077
- language
- English
- LU publication?
- yes
- id
- 4b4ea9ad-2e4f-4957-bf50-4382e82c1330
- date added to LUP
- 2021-08-13 14:26:09
- date last changed
- 2024-07-13 16:34:52
@article{4b4ea9ad-2e4f-4957-bf50-4382e82c1330,
abstract = {{<p>Background: In randomized trials, Bacille Calmette-Guérin (BCG) vaccine has been associated with reduced all-cause mortality. BCG-induced Tuberculin Skin Test (TST) reactions have also been associated with reduced all-cause mortality. We aimed to assess the association between TST responses and subsequent mortality in three birth cohorts and conducted a meta-analysis of existing studies. Methods: Observational study within three Guinea-Bissau BCG trial birth cohorts (conducted 2002–04, 2009–2013 and 2014–18) that encompassed children who were BCG-vaccinated within 28 days with TSTs performed at 2- (n = 1389) and 6-months (n = 2635) of age. We evaluated TST reaction determinants by binomial regression and assessed the association between TSTs > 1 mm (reactors) vs. ≤ 1 mm (non-reactors) and subsequent mortality risk up to age 12 months in Cox-models providing Mortality Rate Ratios (MRRs). We searched PubMed for studies to calculate meta-estimates of the association between TST reactivity by age 2- and 6-months and all-cause mortality. Results: Large post-vaccination wheal size was associated with 6-month TST positivity and so was receiving BCG-Denmark or BCG-Japan, compared with BCG-Russia. By age 2 months, 22% (302/1389) of infants were TST reactors with a 2–12-month mortality risk of 1.7% (5/302) vs. 3.3% (36/1087) for non-reactors, the corresponding reactor/non-reactor MRR = 0.49 (0.19–1.26). By age 6 months, 44% (1149/2635) of infants were reactors and the 6–12-month mortality risk was 0.4% (4/1149) vs. 0.6% (9/1486) for non-reactors, the MRR = 0.87 (0.27–2.86). The literature search provided 3 studies. The meta-analysis revealed a uniform pattern of reduced mortality associated with TST reactivity, a TST response by 2 months being associated with an MRR of 0.59 (0.39–0.90); for 6-month TST responses the MRR was 0.65 (0.43–1.00). Conclusion: Among BCG-vaccinated infants, TST reactions were associated with markedly reduced mortality. Improved vaccination technique and using certain BCG strains could lead to a higher TST reaction prevalence, which would enhance BCG's beneficial non-specific effects.</p>}},
author = {{Schaltz-Buchholzer, Frederik and Roth, Adam and de Bree, L. Charlotte J. and Biering-Sørensen, Sofie and Timmermann, Clara Amalie Gade and Monteiro, Ivan and Aaby, Peter and Benn, Christine Stabell}},
issn = {{0264-410X}},
keywords = {{Bacille Calmette-Guérin (BCG); Heterologous effects of vaccines; Infant mortality; Mantoux reaction; Non-specific effects of vaccines; Purified Protein Derivative (PPD); Tuberculin Skin Test (TST)}},
language = {{eng}},
number = {{50}},
pages = {{7286--7294}},
publisher = {{Elsevier}},
series = {{Vaccine}},
title = {{Neonatal Bacille Calmette-Guérin vaccination and tuberculin skin test reactions at 2- and 6-months : Effects on mortality up to 1 year of age}},
url = {{http://dx.doi.org/10.1016/j.vaccine.2021.06.077}},
doi = {{10.1016/j.vaccine.2021.06.077}},
volume = {{39}},
year = {{2021}},
}