Elsevier

The Lancet

Volume 350, Issue 9075, 9 August 1997, Pages 400-403
The Lancet

Articles
Early BCG vaccination and development of atopy

https://doi.org/10.1016/S0140-6736(97)02207-1Get rights and content

Summary

Background

The increase in atopic diseases may be partly explicable by a decline of certain infectious diseases, or changes in childhood vaccination programmes, or both. We investigated whether BCG vaccination against tuberculosis influences the development of atopy.

Methods

We did a retrospective cohort study of 216 children with atopic heredity, born in Stockholm between 1989 and 1992, who received BCG vaccination when they were younger than 6 months, and 358 age-matched controls who had not been vaccinated. Both groups attended Sachs' Children's Hospital, Stockholm, Sweden, during 1995–96 for assessment of atopic history and clinical signs of atopic disease. All children also underwent skin-prick testing (SPT) and serum was analysed for allergen-specific IgE antibodies. Serum from parents was also analysed for IgE antibodies.

Findings

77 (36%) children in the BCG group and 145 (41%) in the control group had a positive history or clinical signs of atopic disease. In the vaccinated group, 26 (12%) children had one or more positive SPT, and 61 (31%) had circulating allergen-specific IgE antibodies, whereas in the control group, the numbers were 35 (10%) and 84 (27%) respectively. Atopy was confirmed by serology in parents of almost two-thirds of the children in each group. Other risk factors for atopic disease were evenly distributed between the two groups.

Interpretation

early BCG vaccination in children with atopic heredity does not seem to affect the development of atopic disease before school age.

Introduction

The occurrence of atopic disease mediated by IgE antibodies is increasing in developed countries, and the proportion of children with asthma, atopic dermatitis, rhinoconjunctivitis, or food allergy, is now more than 30%.1, 2, 3 The reasons for this increase are largely unknown, but environmental factors are thought to have an important role. For example, associations with residence in industrial or urban areas and a western lifestyle have been found in comparisons of eastern and western Europe.3, 4

T-helper (Th) lymphocytes have a central regulatory influence on allergic inflammation and can be subdivided according to their production of cytokines.5 Th1 cells, when stimulated with virus or intracellular bacteria, secrete interferon-γ, which can inhibit IgE production by B cells.5, 6 By contrast, Th2 cells, when stimulated with allergens or parasites, release interleukin-4, which promotes IgE production by B cells.5, 6 Th2 activity dominates in atopic individuals.6

BCG vaccine is a potent adjuvant for induction of cell-mediated immunity7 and induces inerferon-γ as one of the major cytokines.8 This action may cause a Th1-activity type immune response.5 BCG vaccine has been used in attempts to modulate the immune response and, thereby, interfere with the pathogenesis of diseases. Studies in diabetes-prone mice have shown that a single injection of BCG vaccine given at an early age can prevent the development of type 1 diabetes.9, 10 In a trial of children with newly diagnosed type 1 diabetes, a single intracutaneous dose of BCG vaccine led to long-term clinical remission.10

The increase in atopic disease may be partly explained by a decline in certain infectious diseases, as well as changes in immunisation programmes. BCG vaccine was given to 95% of all newborn babies in Sweden until 1975, when vaccination was stopped because of side-effects and lower risk of tuberculosis exposure.11 Vaccination is now offered only to high-risk groups, such as children who have a close relative with tuberculosis or immigrants from some areas, or upon parental request. Therefore, the vaccination rate is now less than 4% in Swedish-born children.11 We assessed the influence of BCG vaccination in early life on the development of atopy in children with atopic heredity.

Section snippets

Methods

780 children born between 1989 and 1992 who received BCG vaccination before the age of 6 months were traced from Child Welfare Centre records in the catchment area of Sachs' Children's Hospital in south Stockholm (table 1). In this area, 99·7% of all families with infants visited the Child Welfare Centres.12 Nurses at these centres were asked to exclude children of non-Nordic parents to keep potential confounding to a minimum. A questionnaire about atopic disease among the parents was sent to

Results

Positive history or clinical signs consistent with atopy were seen in 36% of the BCG group and in 41% of controls, of which the youngest were 19 months (range 0–51) and 24 months (1–72), respectively (table 2). The distribution of different atopic symptoms in the two groups did not differ significantly.

12% of infants in the BCG group had positive SPT reactions compared with 10% of controls, with an equal distribution for different allergens between the two groups (table 2). A positive reaction

Discussion

This study shows that early BCG vaccination has no primary preventive effect on the development of atopic disease before school age in children with atopic heredity. To increase the efficiency of our study, only children whose parents had a history of atopy were included. The statistical power was adequate to detect a 50% reduction in the frequency of clinical or serological signs of atopy among the children in the BCG group. The occurrence of clinical symptoms of atopy, and the frequency and

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