Impact of Pre-Natal Immune Sensitization on Childhood Morbidity

产前免疫敏化对儿童发病率的影响

• 批准号: 8716654
• 负责人: Luz Acosta
• 金额: $ 15.53万
• 依托单位: RESEARCH INSTITUTE FOR TROPICAL MEDICINE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8716654
• 关键词: 5 year old; Address; Adult; Affect; Age; Age-Months; Anemia; Anemia due to Chronic Disorder; Animal Model; Anorexia; Antibodies; Antibody Formation; Antigens; Area; Benefits and Risks; Biological Assay; Birth; Cachexia; Caring; Child; Childhood; Cognitive; Data; Detection; Double-Blind Method; Enrollment; Exposure to; Fetus; Funding; Helminth Antigens; Helminths; Hookworm Infections; Hookworms; Human; IgE; Immune; Immune response; Immunoglobulin G; Immunoglobulin Idiotypes; Impaired cognition; Infant; Infection; Inflammatory; Injury; Interferons; Interleukin-13; Interleukin-4; Interleukin-5; Interleukin-6; Iron; Iron deficiency anemia; Lead; Life Cycle Stages; Link; Longevity; Lymphocyte; Malnutrition; Modification; Morbidity - disease rate; Mothers; National Institute of Allergy and Infectious Disease; Newborn Infant; Outcome; Parasites; Parasitic Diseases; Pathology; Pattern; Performance; Perinatal Exposure; Peripheral; Pharmaceutical Preparations; Philippines; Placebos; Praziquantel; Pregnancy; Prevalence; Production; Publishing; Randomized Controlled Trials; Recombinant Proteins; Reporting; Resistance; Resistance to infection; Risk; Safety; Sampling; Schedule; Schistosoma; Schistosoma japonicum; Schistosoma mansoni; Schistosomiasis; Serum; TNF gene; Tumor Necrosis Factor-alpha; Umbilical Cord Blood; Whole Blood; Woman; base; cohort; cytokine; early childhood; egg; experience; hepcidin; human TNF protein; immune resistance; immunogenic; in utero; infancy; infant outcome; neonate; offspring; response; vaccine development

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.

最近和正在进行的人体研究已经检查了吡喹酮（PZQ）的安全性和有效性， B类药物，在人类妊娠期间，第一项发表的研究支持PZQ在妊娠期间的安全性。 怀孕我们在菲律宾莱特进行的随机对照试验（RCT）旨在研究PZQ的影响 对母婴的影响总之，这些随机对照试验将可能支持PZQ使用的安全性， 怀孕，为妇女提供治疗机会，作为产前护理的一部分。在推荐 然而，我们需要了解如何在怀孕期间治疗血吸虫病， 母体治疗最终会影响某些特定的免疫反应，对感染的抵抗力， 其后代的发病率。 对哺乳期免疫致敏的人体研究表明， 蠕虫感染暴露于蠕虫抗原，这种暴露导致Th 2显性免疫 反应反过来，这种反应与感染风险降低有关。此外，后代 未感染的母亲产生更高水平的促炎细胞因子， 口腔相关疾病。很少有研究检查了母体治疗对 免疫反应和感染相关的发病率超过婴儿期的寄生虫病的情况下。 这项研究将重新招募420名5岁的儿童，他们的母亲参加了一项随机对照试验 吡喹酮在妊娠12-16周期间。我们将研究修改胎儿暴露的影响， 蠕虫抗原对免疫应答的影响。日本血吸虫粗蛋白和重组蛋白，推测 接受治疗的母亲所生的孩子会使Th 2细胞因子水平降低， 保护性IgE应答水平，并且将具有较高的感染强度。茉莉酮酸且 钩虫此外，接受治疗的母亲的子女将经历更严重的死亡，包括营养不良， 贫血和认知障碍，基于感染强度增加和Thi细胞因子偏倚， 特别是IL-6和TNF -α。