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.

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。我们开发了一个恒河猴模型来研究怀孕期间疟疾(衣原体)的影响。该项目在NIH R01的支持下，探索母亲的免疫反应、怀孕的影响以及先前存在的免疫对临床疟疾严重程度和胎儿结局的影响。密西西比州立大学和疾病预防控制中心的分包合同支持对婴儿进行FACS分析和每日护理。术语“低出生体重”(LBW)和“小于胎龄儿”(SGA)描述了早产和/或胎儿宫内发育迟缓(IUGR)的婴儿，但没有定义问题的性质。猴子模型表明，有许多复杂的指标表明婴儿结局不佳，仅靠体重并不足以作为唯一的决定因素。人类研究表明，导致IUGR的是疟疾，而不是早产，但这是基于出生体重和临床胎龄评估，而不是通过超声波检查。利用超声检查，我们发现了骨骼异常(异常的成骨)，包括小头测量和表明对称性IUGR的股骨长度(SIUGR)，以及异常的椭圆形头部，头长：头宽比增加。不对称性IUGR(AIUGR)或体脂沉积减少也被发现。出生后，继续对婴儿进行测量，并每月进行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。婴儿表现出疟疾引起的免疫系统的调节，体液(B淋巴细胞)和细胞(T淋巴细胞)的发育都受到影响。在子宫内暴露于疟疾或疟疾抗原可能是原因之一。婴儿对各种微生物制剂的敏感性增加。我们的发现表明，该模型与检查胎儿编程有关，该假说表明成人疾病的起源与子宫内的胎儿环境有关。