Effect of helminth infections and antihelminthic treatment during pregnancy on antibody response to Tetanus immunisation in women and their babies

Abstract

Uganda is still among the 46 countries that have not yet achieved neonatal tetanus (NT) global elimination target despite its adoption of the WHO strategy to vaccinate against tetanus during pregnancy. Immunisation of pregnant women with tetanus toxoid boosts immunity against the tetanus but a number of factors may influence the efficacy of tetanus toxoid immunisation in boosting immunity against tetanus. We examined the possible influence of helminth infections and antihelminthic treatment during pregnancy on levels of antibodies against tetanus toxoid.

The study was conducted using archived serum samples that were collected from infants at one year of age and their mothers who were enrolled in the Entebbe Mother and Baby Study (EMABS) during their pregnancy in a randomised, double-blind, placebo-controlled study of deworming during pregnancy with albendazole or praziquantel. Levels of total IgG and subclasses IgG1, 2, 3 and IgG4 against tetanus toxoid were measured by ELISA for women during pregnancy and at delivery and for their offsprings in cord blood and at the age of one year. The data was analysed using median, ranksum test, Chi-square test, signrank test and Spearman’s test.

The prevalence of helminth infections among the enrolled pregnant women was 65% with most of them having light infection intensity. The predominant worms were hookworm (40%), Schistosoma mansoni (17%) and Mansonella perstans (20%). Sixty six percent (66%) and 90% of the women had detectable total IgG levels at enrolment and delivery respectively. The median total IgG, IgG 1, 2, 3, and 4 antibody levels at enrolment were 4.4 (0 - 15) IU/ml, 731 (266 - 1378) µg/ml, 64 (28 - 148 ) µg/ml, 188 (0 - 424) µg/ml and 57 (0 - 376) µg/ml, respectively. There was a significant increase in total IgG and all its isotypes at delivery except IgG3 (p =0.374). The cord blood antibody levels positively correlated with delivery antibody levels but not with levels at one year. Antibody levels for infants at one year were lower than the cord blood levels for all the antibodies. Maternal helminth infections and antihelminthic treatment had no significant effect on all the maternal and offspring’s antibody levels except for IgG2 where albendazole treatment during pregnancy in hookworm infected women was associated with reduced IgG2 levels in infants at one year. However, since it was not consistent with our study hypothesis and not related to any other findings, it may have been due to individual variation in immune system or due to other factors which were not part of this study such as nutrition.

Hence helminth infections and antihelminthic treatment during pregnancy did not have effects on maternal and infant response to tetanus immunisation likely to be of significant public health importance. This conclusion is based on results obtained from a cohort of pregnant women where the majority had light helminth infection intensity. Further studies with a cohort of women with heavy helminth infection intensity are necessary to explore effects of helminth infections and antihelminthic treatment on immune response to tetanus immunisation. Studies to explore how infancy and childhood helminth infections and their treatment could affect the immune response to tetanus immunisation in clinical controlled trials are also needed.