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: 8897971
• 负责人: Luz Acosta
• 金额: $ 11.48万
• 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/8897971
• 关键词: 5 year old; Address; Adult; Affect; Age; Age-Months; Anemia; Anemia due to Chronic Disorder; Animal Model; Anorexia; Antibodies; Antibody Response; Antigens; Area; Benefits and Risks; Biological Assay; Birth; Cachexia; Caring; Child; Childhood; 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; 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; cognitive performance; 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检验了 FDA 批准的吡喹酮 (PZQ) 的安全性和有效性 B 类药物，在人类怀孕期间和第一个发表的研究支持 PZQ 在怀孕期间的安全性 怀孕。我们在菲律宾莱特岛进行的随机对照试验 (RCT) 正在研究 PZQ 的影响 关于孕产妇和婴儿的结局。总之，这些 RCT 可能会支持 PZQ 在 怀孕，为妇女提供治疗作为产前护理的一部分的机会。推荐之前 然而，怀孕期间血吸虫病的治疗，我们需要充分了解如何治疗 产妇治疗最终会影响血吸虫特异性免疫反应、对感染的抵抗力和 他们的后代发病。 对怀孕期间免疫敏化的人体研究表明，感染艾滋病毒的妇女所生的新生儿 蠕虫感染暴露于蠕虫抗原，这种暴露导致 Th2 显性免疫 回复。反过来，这种反应又与感染风险降低有关。进一步说，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。很少有研究探讨孕产妇治疗对婴儿的影响。 在寄生虫病的背景下，婴儿期以后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 岁儿童，他们的母亲参加了一项随机对照试验 妊娠 12-16 周期间服用吡喹酮。我们将研究改变胎儿暴露的影响 蠕虫抗原对日本血吸虫粗蛋白和重组蛋白免疫反应的影响，假设 接受治疗的母亲所生的孩子会产生较低水平的 Th2 细胞因子来应对抗原， 保护性 IgE 反应水平，并且日本血吸虫和 钩虫。此外，接受治疗的母亲的孩子将经历更大的发病率，包括营养不良、 贫血和基于感染强度增加和 Thi 细胞因子偏向的认知障碍 特别是IL-6和TNF-α。