BCG scar and positive tuberculin reaction associated with reduced child mortality in West Africa

Garly, May‐Lill; Martins, Cesário; Balé, Carlitos; Baldé, Mamadu Aliu; Hedegaard, Kathryn; Gustafson, Per; Lisse, Ida Maria; Whittle, Hilton; Aaby, Péter

doi:10.1016/s0264-410x(03)00181-6

Cited by 282 publications

(207 citation statements)

References 39 publications

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“…Children with a BCG scar or a positive tuberculin skin test reaction had a better survival rate than children who had no measurable reaction (27). In the present study, 63.4% of the babies with negative TST failed to develop a visible scar.…”

Section: Discussioncontrasting

confidence: 40%

Scar Formation and Tuberculin Skin Test Response After Bacillus Calmette-Guerin Vaccination: Does Prematurity or Low Birth Weight Have an Impact?

et al. 2017

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Objectives: The present study aimed at evaluating factors affecting scar formation and tuberculin skin test (TST) response in Bacillus Calmette-Guerin (BCG) vaccinated infants. Methods: In the current study, 216 infants with gestational age (GA) of 26 to 40 weeks and birth weight of 730 g to 4590 g were included. The mean corrected age was 6.27 ± 3.79 weeks, and the mean weight was 4442.4 ± 1084.1 g (range 2100 -7700 g) at the time of BCG vaccination. TST was applied at 8 to 16 weeks of vaccination. Factors affecting TST response and BCG scar formation were evaluated. Results: A scar response to BCG vaccination was found in 60%, 49.4%, and 59.7% of the infants with GA < 32 weeks, 33 to 36 weeks, and ≥ 37 weeks, respectively. Of the male infants 65% produced a scar compared to the 45% of the female infants (P = 0.014). The mean weight at the time of vaccination was significantly higher in infants with scar development than in those without scars (6976.94 g vs. 6455.68, P = 0.002). A tuberculin reaction was detected in 57% of the infants (80%, 54%, and 50% according to birth weight > 2500 g, 1500 -2500 g, and < 1500 g, respectively) (P = 0.213). TST response rate was 67%, 55%, and 47% according to GA ≥ 37 w, 33 -36 w, and ≤ 32 w, respectively (P = 0,020). In the present study, 68.4% of the cases with TST of 5 -10 mm, and 100% of the cases with TST > 10 mm developed scars ≥ 2 mm (r = 0.360; P = 0.001).Conclusions: Prematurity or birth weight does not affect BCG scar formation. TST response is lower in preterm babies. The correlation between scar formation and TST response was too low to be interpreted as positive.

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Section: Discussioncontrasting

confidence: 40%

Scar Formation and Tuberculin Skin Test Response After Bacillus Calmette-Guerin Vaccination: Does Prematurity or Low Birth Weight Have an Impact?

et al. 2017

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“…Earlier studies with BCG in experimental schistosomiasis demonstrated similar protection, which was at least partially T-cell independent (29). There appears to be an obvious link between these experimental results and the nonspecific protection against nonmycobacterial disease conferred by BCG (8,9,(12)(13)(14)(15)(16)(17)(18)(19)(20). In the present study, we provide unique mechanistic insights into the processes mediating the adaptive features of innate immunity, or trained immunity, in humans.…”

Section: Discussionmentioning

confidence: 75%

“…Soon after its introduction in the 1930s, epidemiological studies surprisingly demonstrated that BCG also protects against childhood mortality independent of its effect on TB (12)(13)(14)(15). Recent studies corroborated these findings and suggested a reduction in the burden of infections other than TB (16)(17)(18)(19)(20). For example, in a case-control study in Brazil, BCG reduced the risk of death from pneumonia by 50% (17).…”

mentioning

confidence: 89%

Bacille Calmette-Guérin induces NOD2-dependent nonspecific protection from reinfection via epigenetic reprogramming of monocytes

Kleinnijenhuis

Quintin

Preijers

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

1,320

1,550

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Adaptive features of innate immunity, recently described as "trained immunity," have been documented in plants, invertebrate animals, and mice, but not yet in humans. Here we show that bacille Calmette-Guérin (BCG) vaccination in healthy volunteers led not only to a four-to sevenfold increase in the production of IFN-γ, but also to a twofold enhanced release of monocytederived cytokines, such as TNF and IL-1β, in response to unrelated bacterial and fungal pathogens. The enhanced function of circulating monocytes persisted for at least 3 mo after vaccination and was accompanied by increased expression of activation markers such as CD11b and Toll-like receptor 4. These training effects were induced through the NOD2 receptor and mediated by increased histone 3 lysine 4 trimethylation. In experimental studies, BCG vaccination induced T-and B-lymphocyte-independent protection of severe combined immunodeficiency SCID mice from disseminated candidiasis (100% survival in BCG-vaccinated mice vs. 30% in control mice). In conclusion, BCG induces trained immunity and nonspecific protection from infections through epigenetic reprogramming of innate immune cells. mycobacterium tuberculosis vaccine | innate immune memory

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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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BCG scar and positive tuberculin reaction associated with reduced child mortality in West Africa

Cited by 282 publications

References 39 publications

Scar Formation and Tuberculin Skin Test Response After Bacillus Calmette-Guerin Vaccination: Does Prematurity or Low Birth Weight Have an Impact?

Scar Formation and Tuberculin Skin Test Response After Bacillus Calmette-Guerin Vaccination: Does Prematurity or Low Birth Weight Have an Impact?

Bacille Calmette-Guérin induces NOD2-dependent nonspecific protection from reinfection via epigenetic reprogramming of monocytes

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

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