Impact of Pre-Natal Immune Sensitization on Childhood Morbidity

最近和正在进行的人体研究检查了FDA的吡喹酮(PZQ)的安全性和有效性 B类药物，在人类怀孕期间，首次发表的研究支持PZQ在怀孕期间的安全性 怀孕了。我们在菲律宾莱特的随机对照试验(RCT)正在解决PZQ的影响 对母婴结局的影响。总而言之，这些RCT可能会支持PZQ在 怀孕，提供了将妇女作为产前护理的一部分的机会。在推荐之前 然而，妊娠期血吸虫病的治疗，我们需要了解如何治疗。 母体治疗最终会影响血吸虫特异性免疫反应、对感染的抵抗力，以及 他们后代的发病率。 人类对怀孕期间免疫致敏的研究表明，感染了艾滋病的妇女所生的新生儿 蠕虫感染暴露于蠕虫抗原，这种暴露会导致Th2显性免疫。 回应。反过来，这种反应与感染风险的降低有关。此外，子孙后代 未感染的母亲会产生更高水平的促炎细胞因子，这与 血吸虫病相关发病率。很少有研究考察产妇治疗对 在寄生虫病的背景下，超过婴儿期的免疫反应和感染相关发病率。 这项研究将重新招募420名5岁的儿童，他们的母亲参加了随机对照试验。 在怀孕12-16周时服用吡喹酮。我们将研究修改胎儿暴露的影响 蠕虫抗原对日本血吸虫粗蛋白和重组蛋白免疫应答的影响 接受治疗的母亲所生的孩子会产生更低水平的Th2细胞因子来回应抗原，更低的水平 保护性IgE应答水平，感染日本血吸虫和日本血吸虫的强度将更高 钩虫。此外，接受治疗的母亲的孩子将经历更大的疾病，包括营养不良， 贫血和基于感染强度增加和细胞因子偏向的认知障碍 尤其是IL-6和肿瘤坏死因子-α。

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.