CONSORTIUM FOR ANTIMALARIAL DEVELOPMENT

抗疟开发联盟

• 批准号: 7348998
• 负责人: BILLIE B DAVISON
• 金额: $ 3.1万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7348998
• 关键词: CONSORTIUM; ANTIMALARIAL; DEVELOPMENT

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We developed a rhesus monkey model to examine the effects of malaria (Plasmodium coatneyi) during pregnancy. This project, supported by an NIH R01, explores maternal immunologic responses, the effects of gravidity, and preexisting immunity on the severity of clinical malaria and fetal outcome. The FACS analysis and per diem for the infants is supported by a subcontract through Mississippi state university and the CDC. The terms ¿low birth weight¿ (LBW) and ¿small for gestational age¿ (SGA) describe infants born prematurely and/or with intrauterine growth retardation (IUGR), but do not define the nature of the problem. The monkey model shows that there are complex indicators of poor infant outcome and weight alone is not sufficient as the sole determinant. Human studies show that malaria, not prematurity, leads to IUGR but this has been based on birth weight with clinical assessment of gestational age, not on ultrasonography. Utilizing ultrasonography, we demonstrated skeletal abnormalities (dysregulated osteogenesis) including small head measurments and femur length indicative of symmetric IUGR (SIUGR), as well as abnormal elliptical shaped heads with increased head length :head width ratios. Asymmetric IUGR (AIUGR) or reduced body fat deposition was also identified. After birth the infants continued to be measured and monthly FACs analysis was performed. Malaria was associated not only with impaired fetal growth but impaired infant growth and persistent immunologic alterations. Infants displayed malaria-induced modulation of their immune systems, whereby both humoral (B-lymphocytes) and cellular (T-lymphocyte) development was affected. In utero exposure to malaria or malaria antigens are likely responsible. Infants displayed increased susceptibility to a variety of microbial agents. Our findings indicate that the model is relevant for the examination ¿fetal programming¿ a hypothesis which states that the origins of adult disease are related to the fetal environment in utero.

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。我们开发了一个恒河猴模型来检查疟疾（疟原虫）在怀孕期间的影响。该项目由美国国立卫生研究院R01支持，探索母体免疫反应，妊娠的影响，以及预先存在的免疫对临床疟疾严重程度和胎儿结局的影响。FACS的分析和婴儿的每日津贴由密西西比州立大学和疾病预防控制中心的分包合同提供支持。术语“低出生体重”（LBW）和“小于胎龄”（SGA）描述了早产和/或有宫内生长迟缓（IUGR）的婴儿，但没有定义问题的性质。猴子模型表明，有复杂的指标，不良的婴儿结局和体重单独是不够的，作为唯一的决定因素。人类研究表明，疟疾而不是早产导致IUGR，但这是基于出生体重和胎龄的临床评估，而不是超声检查。利用超声检查，我们发现了骨骼异常（成骨失调），包括小头测量和表明对称IUGR （SIUGR）的股骨长度，以及异常的椭圆形头，头长：头宽比增加。不对称IUGR （AIUGR）或体脂沉积减少也被发现。出生后继续测量婴儿，并进行每月FACs分析。疟疾不仅与胎儿生长受损有关，而且与婴儿生长受损和持续的免疫改变有关。婴儿表现出疟疾诱导的免疫系统调节，体液（b淋巴细胞）和细胞（t淋巴细胞）的发育都受到影响。在子宫内接触疟疾或疟疾抗原可能是原因。婴儿对多种微生物制剂的易感性增加。我们的研究结果表明，该模型与检查“胎儿编程”有关，“胎儿编程”是一种假设，认为成人疾病的起源与子宫内的胎儿环境有关。