Impact of Pre-Natal Immune Sensitization on Childhood Morbidity

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Recent and ongoing human studies have examined the safety and efficacy of praziquantel (PZQ), an FDA Class B drug, during human pregnancy and the first published study supports the safety of PZQ during pregnancy. Our randomized controlled trial (RCT) in Leyte, The Philippines, is addressing the impact of PZQ on maternal and infant outcomes. Together, these RCTs will likely support the safety of PZQ use during pregnancy, affording the opportunity to treat women as part of their pre-natal care. Before recommending therapy for schistosomiasis during pregnancy, however, we require an informed understanding of how maternal treatment ultimately affects schistosome specific immune responses, resistance to infection, and morbidity in their offspring. Human studies of immune sensitization during pregnany suggest that newborns from women infected with helminth infection are exposed to helminth antigens and this exposure leads to a Th2 dominant immune response. Such responses, in turn, have been associated with decreased risk of infection. Further, offspring of uninfected mothers make higher levels of pro-inflammatory cytokines which have been implicated in schistomsomiasis related morbidity. Few if any studies have examined the impact of maternal treatment on immune responses and infection related-morbidity beyond infancy in the context of parasitic disease. This study will re-enroll 420 children at age five whose mothers participated in a randomized controlled trial of praziquantel during at 12-16 weeks gestation. We will examine the impact of modification of fetal exposure to helminth antigens on immune responses to S. japonicum crude and recombinant proteins, hypothesizing that children born to treated mothers will make lower levels of Th2 cytokines in response to antigen, lower levels of protective IgE responses, and will have higher intensities of infection with both S. japonicum and hookworm. In addition, children of treated mothers will experience greater moribidity including malnutrition, anemia, and cognitive impairment based on incrased infection intensities and a Thi cytokine bias, in particular IL-6 and TNF -alpha. RELEVANCE (See instructions): Studies of praziquantel during pregnancy are likely to support its safety. This study will therefore inform risk- benefit analyses with respect to targeting women for treatment with praziquantel during pregnancy by providing important data regarding how treatment may or may not place young children at increased risk of infection with helminths and related morbidities: