Suppression of the immune response to diphtheria toxoid in murine schistosomiasis

Abstract

Studies in humans and experimental animals indicate that infection with schistosomes results in impaired immune response to a variety of antigens. Since artificial immunization against a number of infections is frequently attempted in populations in which schistosomiasis is endemic, we have attempted to determine whether this impairment could be demonstrated in response to a commonly used immunogen. We have compared the serum antitoxin response to diphtheria toxoid (DTd) in normal, uninfected mice with that in mice bearing schistosome infections of different duration. Animals were infected with 100 Schistosoma mansoni cercariae 16, 12, 8, 4 and 2 weeks prior to, on the same day as, and 4 weeks after the first of three 1 μg doses of DTd given at 3 week intervals. The antitoxin level of each mouse was taken as the mean of two sera obtained 1 and 2 weeks after the 3rd dose of DTd. The mean antitoxin level in uninfected-immunized control mice was 0.0457 Antitoxin Units (AU) ml −1. 71% of mice in this group developed antitoxin levels ≥0.01 AU ml −1. Only 28% of the infected-immunized mice achieved antitoxin levels ≥0.01 AU ml −1. In infected-immunized mice with infections of all durations, both the percentage of mice with ≥0.01 AU ml −1 (0 to 50%) and mean antitoxin levels (0.003 to 0.016 AU ml −1) were lower than in uninfected-immunized mice. Antitoxin levels in animals infected 16, 12, 8 and 2 weeks prior to, simultaneously with, and 4 weeks after the first dose of DTd were significantly lower ( P=<0.05) than those of controls. Mice infected 4 weeks prior to the first dose of DTd had antitoxin levels 64% below controls but this difference was not significant. If similar immunosuppression occurs in human schistosomiasis, these findings may have implications for childhood immunization programs in areas where schistosomiasis is endemic.