BCG vaccination among West African infants is associated with less anergy to tuberculin and diphtheria–tetanus antigens

Abstract

To examine risk factors for anergy, delayed-type hypersensitivity was assessed among 884 infants participating in a vaccine trial in Guinea-Bissau. The infants were skin-tested at 7.5 months of age with a panel of seven intradermal antigens. Risk factors for anergy to tuberculin or anergy to both the diphtheria and tetanus antigens were determined in relation to Bacillus Calmette-Guérin (BCG) vaccination, diphtheria–tetanus–pertussis (DTP) vaccination, and measles vaccination. We found sick children to be more anergic to tuberculin and diphtheria–tetanus antigens than healthy children (OR=2.49 (95% confidence interval 1.40–4.55)). There was a higher prevalence of anergy to tuberculin in the rainy season than in the dry season (OR=1.67 (1.25–2.23)). Children who had taken antimalarials within the last week had a higher prevalence of anergy to tuberculin (OR=1.41 (1.02–1.92)). BCG vaccination was significantly associated with less anergy to tuberculin and diphtheria–tetanus antigens (OR=0.42 (0.28–0.63), OR=0.77 (0.60–0.99), respectively). Children vaccinated with BCG before 1 month of age were more anergic to tuberculin than children vaccinated after 1 month (OR=1.61 (1.19–2.19)). DTP vaccination was associated with less anergy to diphtheria–tetanus antigens (OR=0.40 (0.32–0.49)), but not to tuberculin. Children with a positive reaction to tuberculin were less likely to be anergic to diphtheria–tetanus antigens (OR=0.36 (0.26–0.49)) than children with a negative tuberculin reaction. Children who were vaccinated with BCG before they received their last DTP vaccine were less anergic to diphtheria–tetanus antigens (OR=0.40 (0.16–0.88)) than other DTP-vaccinated children. In conclusion, current disease, rainy season, age below 1 month of age at the time of BCG vaccination, and administration of chloroquine or quinimax within the last 7 days were risk factors for anergy to tuberculin among 7.5-month-old infants. BCG vaccination and a positive tuberculin reaction were associated with a lower prevalence of anergy to both tuberculin and diphtheria–tetanus. Thus, BCG vaccination may contribute to better cell-mediated immune responses among infants.

Introduction

In studies from Bangladesh and Peru, anergy to panels of antigens was found to be a risk factor for childhood diarrhoea [1], [2], [3] and acute lower respiratory infection [4], which are important causes of childhood mortality in developing countries. Therefore, anergy might be a risk factor for child mortality in general. A study among initially healthy elderly persons showed anergy to candida, mumps, streptokinase/streptonordase and trichophyton to be associated with all-cause mortality [5], and anergy to various antigens has been shown to be associated with increased mortality in surgical patients and patients with ischemic heart failure [6], [7], [8]. It is important to determine underlying conditions for anergy, because prevention of these conditions may improve child health in developing countries.

The Bacillus Calmette-Guérin (BCG) vaccination has been associated with better survival among infants in Guinea-Bissau [9], and in the Gambia BCG vaccination within the first days of life induced a strong Th1-type response, whereas non-vaccinated infants developed a Th2-type response [10]. The BCG vaccine is known to stimulate cell-mediated immunity and delayed-type hypersensitivity in adults by inducing a Th1-type response among helper T-cells [11], [12].

As these observations indicate that the BCG vaccine may have a more general effect on the immune system, we examined whether this and other routine childhood vaccines had an impact on anergy status.