A RHESUS MONKEY MODEL OF MALARIA DURING PREGNANCY

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。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。导致孕妇临床疟疾严重程度增加及其相关胎儿并发症（如低出生体重）的相关因素尚不清楚。 一项利用32只不同胎次的恒河猴通过3次连续妊娠感染疟疾（Plasmodium coatneyi）的研究始于2000年，于2006年结束，共有104例慢性感染（113天）。同一只猴子的重复感染代表了不同的疟疾免疫水平。监测寄生虫血症、CBC、FACS数据和临床体征，并通过超声检查评价胎儿生长和发育。在剖腹产时收集婴儿、胎盘、脐带血、母血和羊水。确定了疟疾严重程度增加或减少及其对胎儿/婴儿影响的相关性。 对照组中不良婴儿结局（PIO）的特征包括：母亲体重低、胎盘小、LBW、对称性宫内生长迟缓（IUGR）以及除绒毛膜炎外无相关胎盘病理学。疟疾感染妊娠中的PIO包括：高寄生虫、小胎盘、胎儿死亡、LBW、对称和不对称IUGR、孕酮和雌二醇不足、低母体体重和疟疾相关胎盘病理学增加。通过FACS分析（2005年发表）和母体血清细胞因子评估，确定了妊娠相关和疟疾诱导的免疫抑制和免疫病理学。 我们测定了外周血血清TNF α水平，其可溶性受体，STNFR 1和STNFR 2，在整个早孕，疟疾感染和两者的组合。TNF α总是与胎儿死亡相关，可溶性TNF受体似乎对胎儿保护很重要，可能通过中和TNF α的毒性作用。我们的研究结果表明，STNFR 2的增加与疟疾特异性相关，而与正常妊娠或因绒毛膜炎导致的LBW妊娠无关。相比之下，STNFR 1在正常妊娠后半期的升高表明，它可能在调节TNF α以准备正常分娩和分娩中很重要。

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).