A RHESUS MONKEY MODEL OF MALARIA DURING PREGNANCY

怀孕期间疟疾的恒河猴模型

• 批准号: 7348973
• 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/7348973
• 关键词: RHESUS; MONKEY; MODEL; MALARIA; DURING

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. The associated factors responsible for the increased severity of clinical malaria in pregnant women and its associated fetal complications such as low birth weight (LBW) are unknown. A study utilizing 32 rhesus monkeys of differing parities through 3 sequential pregnancies with malaria (Plasmodium coatneyi) began in 2000 and ended in 2006 with a total of 104 chronic infections (113 days). Repeated infections in the same monkey represented different levels of malaria immunity. Parasitemia, CBCs, FACS data, and clinical signs were monitored and fetal growth and development evaluated by ultrasonography. The infants, placentas, cord blood, maternal blood, and amniotic fluid were collected during cesarean section. Correlates of increased or decreased severity of malaria and its effect on the fetus/infant were identified. Features of poor infant outcome (PIO) in controls included: low weight mother, small placenta, LBW, symmetric intrauterine growth retardation (IUGR), and no associated placental pathology other than chorioamnionitis. PIO in malaria-infected pregnancies included: high parasites, small placenta, fetal death, LBW, symmetric and asymmetric IUGR, insufficient progesterone and estradiol, low maternal weight, and increased malaria-associated placental pathology. Pregnancy-related and malaria-induced immunosuppression and immunopathology were identified though FACS analysis (published 2005) and assessment of maternal serum cytokines. We determined peripheral blood serum levels of TNF alpha, its soluble receptors, STNFR1 and STNFR2, throughout primigravid pregnancy, malaria infection and a combination of the two. TNF alpha was always associated with fetal death and soluble TNF receptors appear to be important for fetal protection possibly through neutralizing the toxic effects of TNF alpha. Our findings showed that increased STNFR2 was associated specifically with malaria and not normal pregnancy or even pregnancy with LBW due to chorioamnionitis. In contrast, elevations in STNFR1 during the later half of normal pregnancy indicate that it may be important in regulating TNF alpha in preparation for normal labor and delivery (in press).

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子弹和调查员（PI）可能已经从其他NIH来源获得了主要资金，因此可以在其他清晰的条目中代表。列出的机构适用于该中心，这不一定是调查员的机构。导致孕妇临床疟疾严重程度增加的相关因素及其相关的胎儿并发症（例如低出生体重（LBW））尚不清楚。 一项利用32只恒河猴通过3种顺序怀孕（疟疾疟原虫）的研究始于2000年，于2006年结束，总共有104种慢性感染（113天）。在同一猴子中反复感染代表了不同水平的疟疾免疫力。监测寄生虫，CBC，FACS数据和临床体征，并通过超声检查评估胎儿生长和发育。在剖宫产期间，收集了婴儿，胎盘，脐带血，孕妇血液和羊水。确定了疟疾严重程度升高或降低的相关性及其对胎儿/婴儿的影响。 对照组中婴儿预后不良（PIO）的特征包括：低体重母亲，小胎盘，LBW，对称性宫内生长迟缓（IUGR），除绒毛膜炎以外没有相关的胎盘病理学。疟疾感染妊娠的PIO包括：高寄生虫，小胎盘，胎儿死亡，LBW，对称和不对称的IUGR，孕酮和雌二醇不足，孕妇体重低以及与疟疾相关的胎盘病理学增加。通过FACS分析（2005年出版）和孕妇血清细胞因子的评估，发现了与妊娠相关和疟疾诱导的免疫抑制和免疫病理学的发现。 我们确定了TNFα的外周血血清水平，其可溶性受体STNFR1和STNFR2，整个原发性妊娠，疟疾感染以及两者的组合。 TNFα始终与胎儿死亡有关，可溶性TNF受体对于胎儿保护似乎很重要，这可能是通过中和TNF alpha的毒性作用。我们的发现表明，由于绒毛膜炎，STNFR2的增加与疟疾特别是正常的妊娠，甚至不是正常的妊娠，甚至与LBW妊娠有关。相比之下，正常怀孕后期的STNFR1升高表明，这对于调节TNF alpha以准备正常劳动和分娩可能很重要（在印刷中）。