The impact of prenatal exposure to parasitic infections and to anthelminthic treatment on antibody responses to routine immunisations given in infancy: Secondary analysis of a randomised controlled trial

Stephen Nash,Fiona R M Van Der Klis,Swaib A Lule,Dennison Kizito,Alexander J Mentzer,Alison M Elliott,Gaby Smits,David Joseph Diemert

doi:10.1371/journal.pntd.0005213

Abstract

BackgroundChronic parasitic infections are associated with active immunomodulation which may include by-stander effects on unrelated antigens. It has been suggested that pre-natal exposure to parasitic infections in the mother impacts immunological development in the fetus and hence the offspring’s response to vaccines, and that control of parasitic infection among pregnant women will therefore be beneficial.Methodology/Principal findingsWe used new data from the Entebbe Mother and Baby Study, a trial of anthelminthic treatment during pregnancy conducted in Uganda, to further investigate this hypothesis. 2705 mothers were investigated for parasitic infections and then randomised to albendazole (400mg) versus placebo and praziquantel (40mg/kg) during pregnancy in a factorial design. All mothers received sulfadoxine/pyrimethamine for presumptive treatment of malaria. Offspring received Expanded Programme on Immunisation vaccines at birth, six, 10 and 14 weeks. New data on antibody levels to diphtheria toxin, three pertussis antigens, Haemophilus influenzae type B (HiB) and Hepatitis B, measured at one year (April 2004 –May 2007) from 1379 infants were analysed for this report. Additional observational analyses relating maternal infections to infant vaccine responses were also conducted. Helminth infections were highly prevalent amongst mothers (hookworm 43.1%, Mansonella 20.9%, Schistosoma mansoni 17.3%, Strongyloides 11.7%, Trichuris 8.1%) and 9.4% had malaria at enrolment. In the trial analysis we found no overall effect of either anthelminthic intervention on the measured infant vaccine responses. In observational analyses, no species was associated with suppressed responses. Strongyloidiasis was associated with enhanced responses to pertussis toxin, HiB and Hep B vaccine antigens.Conclusions/SignificanceOur results do not support the hypothesis that routine anthelminthic treatment during pregnancy has a benefit for the infant’s vaccine response, or that maternal helminth infection has a net suppressive effect on the offspring’s response to vaccines.Trial RegistrationISRCTN.com ISRCTN32849447

Highlights

There is substantial evidence that pre-natal exposures are important in shaping immunological development [1]
Parasitic infections, such as worms and malaria, have potent effects on the human immune system. These effects include modification of immune responses in the fetus and infant if a mother has a parasitic infection during pregnancy
We found no evidence that the parasitic infections were associated with reduced responses in the children

Summary

Introduction

There is substantial evidence that pre-natal exposures are important in shaping immunological development [1]. This includes strong evidence that prenatal exposure and sensitisation to parasite antigens determines susceptibility to the same parasite in the offspring [1] and that immunisation during pregnancy influences the infant response to the same vaccine [2]. There is evidence that prenatal exposures may influence the offspring’s response to unrelated antigens [1]. It has been suggested that pre-natal exposure to parasitic infections in the mother impacts immunological development in the fetus and the offspring’s response to vaccines, and that control of parasitic infection among pregnant women will be beneficial

Methods

Results

Discussion

Conclusion