Tuberculin Reaction, BCG Scar, and Lower Female Mortality

Roth, Adam; Sodemann, Morten; Jensen, Henrik; Poulsen, Anja; Gustafson, Per; Weise, Christian F.; Gomes, Justino; Djana, Queba; Jakobsen, Markus Due; Garly, May‐Lill; Rodrigues, Amabélia; Aaby, Péter

doi:10.1097/01.ede.0000231546.14749.ab

Cited by 90 publications

(64 citation statements)

References 32 publications

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“…Our group has consistently found that vaccines, apart from disease-specific effects, may also have so-called "nonspecific effects." The live vaccines bacille Calmette-Guérin (BCG), which is recommended at birth, and measles vaccine (MV), which is recommended at 9 mo of age, are associated with decreased overall mortality (14)(15)(16)(17), whereas diphtheria-tetanus-pertussis vaccine (DTP), which is recommended at 6, 10, and 14 wk of age, is associated with increased mortality in areas where exposure to pertussis is limited because of high vaccination coverage (18)(19)(20). Intriguingly, both beneficial and negative effects of vaccines have been strongest in girls (21)(22)(23).…”

Section: Introductionmentioning

confidence: 99%

Does vitamin A supplementation interact with routine vaccinations? An analysis of the Ghana Vitamin A Supplementation Trial

Benn¹,

Aaby²,

Nielsen³

et al. 2009

The American Journal of Clinical Nutrition

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Background: The World Health Organization recommends vitamin A supplementation (VAS) at vaccination contacts after 6 mo of age to reduce mortality. However, it is unknown whether the effect of VAS is independent of vaccinations. One of the original VAS trials from Ghana had collected vaccination information. Objective: We reanalyzed the data to explore the hypothesis that VAS reduces mortality in children who had bacille Calmette-Guérin or measles vaccine as their most recent vaccine but increased mortality when diphtheria-tetanus-pertussis vaccine (DTP) was the most recent vaccine. On the basis of previous studies, we expected the effects to be strongest in girls. Design: At enrollment, children aged 6-90 mo were randomly assigned to receive VAS or placebo every 4 mo for 2 y. Vaccination status was assessed at enrollment and after 1 and 2 y by reviewing the children's health cards. Lack of a health card was presumed to mean that the child had not been vaccinated. Results: VAS had a beneficial effect only in children with no record of vaccination at enrollment (n = 5066); the mortality rate ratio (MRR) was 0.64 (95% CI: 0.47, 0.88) compared with 0.95 (95% CI: 0.72, 1.26) in children with one or more vaccinations (n = 6656). Among vaccinated children, the effect of VAS differed between boys (MRR: 0.74; 95% CI: 0.51, 1.08) and girls (MRR: 1.18; 95% CI: 0.84, 1.67) (P = 0.046 for interaction). VAS had a negative effect in measles-vaccinated girls who were missing one or more doses of DTP at enrollment, a group who often received DTP during follow-up (MRR: 2.60; 95% CI: 1.41, 4.80). Conclusions: The effect of VAS differed by vaccination status. This is potentially problematic because VAS is provided at vaccination contacts.

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Section: Introductionmentioning

confidence: 99%

Does vitamin A supplementation interact with routine vaccinations? An analysis of the Ghana Vitamin A Supplementation Trial

Benn¹,

Aaby²,

Nielsen³

et al. 2009

The American Journal of Clinical Nutrition

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“…[2][3][4][5] Among BCG-vaccinated children, those having a BCG scar or a positive tuberculin test have lower mortality. 4,6,7 The mechanisms behind these non-specific effects remain unclear. Several studies in humans have observed increased T helper type 1 (Th1) responses, [8][9][10] and at times also Th2 responses, [11][12][13] following BCG vaccination.…”

Section: Introductionmentioning

confidence: 99%

BCG stimulated dendritic cells induce an interleukin‐10 producing T‐cell population with no T helper 1 or T helper 2 bias in vitro

et al. 2007

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SummaryMycobacterium bovis bacillus Calmette-Guérin (BCG) vaccine has been associated with beneficial effects on overall childhood mortality in lowincome countries; this cannot be explained merely by the prevention of tuberculosis (TB) deaths. The beneficial effects of BCG vaccine could be the result of either strengthening of pro-inflammatory mechanisms, helping neonates to fight infections, or the induction of an immune-regulatory network restricting overt inflammation and intense pathology. We aimed to study the effect of live BCG on the ability of dendritic cells (DCs) to polarize T-cell responses. Monocyte-derived DCs were matured in the presence or absence of BCG. The DC phenotype was assessed by CD83 expression, interleukin-12 (IL-12) and IL-10 production, as well as for the ability to polarize T-cell responses. Following stimulation with CD40 ligand, DCs matured in the presence of BCG showed enhanced IL-10 and diminished IL-12 production. These DCs primed naive T cells to develop into IL-10-producing T cells, with no T helper 1 or T helper 2 bias. These results suggest that BCG vaccination might result in the development of IL-10-producing DCs as well as IL-10-producing T cells that could contribute to restricting overt inflammation in infants exposed to pathogens and thus lead to lower infant mortality.

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“…28,29 Albeit conflicting results, studies have shown effects that cannot be attributed to the protection of tuberculosis and a stronger effect for girls compared with boys. [29][30][31][32] On the contrary, previous studies on BCG and T1D found no association, 27,33 but the evidence remains inconsistent. 34 In our study, BCG vaccination was significantly associated with decreased risk for CD (adjusted OR 0.54), but with no difference between girls and boys.…”

Section: Figurementioning

confidence: 89%

Early Vaccinations Are Not Risk Factors for Celiac Disease

Myléus

Stenlund

Hernell³

et al. 2012

Pediatrics

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OBJECTIVES: To investigate if changes in the national Swedish vaccination program coincided with changes in the celiac disease (CD) incidence rate in infants (ie, the Swedish CD Epidemic), and to assess the potential association between these vaccinations and CD risk. METHODS: All studies were based on the National Swedish Childhood Celiac Disease Register. Using an ecological approach, we plotted changes over time in the national vaccination program in the graph displaying CD incidence rate. A population-based incident case-referent study of invited infants was performed. Exposure information was received through a questionnaire and child health clinic records. Vaccines explored were diphtheria/tetanus, pertussis (acellular), polio (inactivated), Haemophilus influenzae type b (conjugated), measles/mumps/rubella, and live attenuated bacillus Calmette-Guérin (BCG) in children with increased tuberculosis risk. Findings were subjected to a birth cohort analysis. RESULTS: Introduction of pertussis vaccine coincided in time with decreasing CD incidence rates. In the infant case-referent study, however, neither vaccination against pertussis (odds ratio 0.91; 95% confidence interval 0.60–1.4), nor against Haemophilus influenzae type b or measles/mumps/rubella was associated with CD. Coverage for the diphtheria/tetanus and polio vaccines was 99%. BCG was associated with reduced risk for CD (adjusted odds ratio 0.54; 95% confidence interval 0.31–0.94). Discontinuation of general BCG vaccination did not affect the cumulative incidence of CD at age 15 years. CONCLUSIONS: Early vaccinations within the national Swedish program were not associated with CD risk, nor could changes in the program explain the Swedish epidemic. A protective effect by BCG was suggested, which could be subject to further studies.

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Tuberculin Reaction, BCG Scar, and Lower Female Mortality

Abstract: A good response to BCG vaccination is related to lower child mortality. The effect seems most pronounced among girls. The findings may have implications for future vaccine trials and policy.

Cited by 90 publications

References 32 publications

Does vitamin A supplementation interact with routine vaccinations? An analysis of the Ghana Vitamin A Supplementation Trial

Does vitamin A supplementation interact with routine vaccinations? An analysis of the Ghana Vitamin A Supplementation Trial

BCG stimulated dendritic cells induce an interleukin‐10 producing T‐cell population with no T helper 1 or T helper 2 bias in vitro

Early Vaccinations Are Not Risk Factors for Celiac Disease

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