Exposure to pesticides in utero impacts the fetal immune system and response to vaccination in infancy

Mary Prahl,Pamela Odorizzi,Mayimuna Nalubega,Felistas Nankya,Mary Muhindo,Margaret E Feeney,Tara Mcintyre,Esther Sikyomu,Moses R Kamya,Abel Kakuru,Kenneth Musinguzi,Ann Auma,Francesca Aweeka,Rachel Budker,David Gingrich,Lila Farrington,Kate Naluwu,Prasanna Jagannathan,Grant Dorsey

doi:10.1038/s41467-020-20475-8

Abstract

The use of pesticides to reduce mosquito vector populations is a cornerstone of global malaria control efforts, but the biological impact of most pesticides on human populations, including pregnant women and infants, is not known. Some pesticides, including carbamates, have been shown to perturb the human immune system. We measure the systemic absorption and immunologic effects of bendiocarb, a commonly used carbamate pesticide, following household spraying in a cohort of pregnant Ugandan women and their infants. We find that bendiocarb is present at high levels in maternal, umbilical cord, and infant plasma of individuals exposed during pregnancy, indicating that it is systemically absorbed and trans-placentally transferred to the fetus. Moreover, bendiocarb exposure is associated with numerous changes in fetal immune cell homeostasis and function, including a dose-dependent decrease in regulatory CD4 T cells, increased cytokine production, and inhibition of antigen-driven proliferation. Additionally, prenatal bendiocarb exposure is associated with higher post-vaccination measles titers at one year of age, suggesting that its impact on functional immunity may persist for many months after birth. These data indicate that in utero bendiocarb exposure has multiple previously unrecognized biological effects on the fetal immune system.

Highlights

The use of pesticides to reduce mosquito vector populations is a cornerstone of global malaria control efforts, but the biological impact of most pesticides on human populations, including pregnant women and infants, is not known
A total of 294 women were followed through delivery and their infants were followed through 3 years of age
The Ugandan government undertook a campaign of indoor residual spraying (IRS) with bendiocarb to reduce malaria transmission

Summary

Introduction

The use of pesticides to reduce mosquito vector populations is a cornerstone of global malaria control efforts, but the biological impact of most pesticides on human populations, including pregnant women and infants, is not known. Prenatal bendiocarb exposure is associated with higher post-vaccination measles titers at one year of age, suggesting that its impact on functional immunity may persist for many months after birth These data indicate that in utero bendiocarb exposure has multiple previously unrecognized biological effects on the fetal immune system. We examined the systemic absorption and trans-placental transfer of bendiocarb and its impact on the fetal immune system, using samples from mothers and infants enrolled in a randomized trial that compared regimens for intermittent preventive treatment of malaria during pregnancy Among women and their infants whose houses were sprayed during pregnancy, high levels of bendiocarb were present in peripheral and umbilical cord blood, resulting in numerous alterations in fetal immune homeostasis

Methods

Results

Conclusion