PLASMODIUM COATNEYI IN RHESUS MONKEY AS MODEL OF MALARIA IN PREGNANCY

恒河猴体内的科特尼疟原虫作为妊娠期疟疾模型

• 批准号: 6247293
• 负责人: BILLIE B DAVISON
• 金额: $ 6.02万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-05-09 至 1998-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6247293
• 关键词: Mammalia; Primates; biological products; biomaterials; communicable diseases; growth factor; infant mortality; model design /development; mother /infant health care; parasitism; reproductive system

Pregnant women with malaria due to infection with Plasmodium falciparum suffer more adverse consequences than P. falciparum-infected nonpregnant women. The more common and serious sequelae include anemia and severe malaria with central nervous system complications. Their infants suffer intrauterine growth retardation (IUGR), low birth weight (LBW), congenital infection and high infant mortality. Although much information has been gleaned from human trials, the conditions, and moral and ethical limitations of human studies of pregnancy preclude manipulation of the system and important data are often uninterpretable due to confounding variables. Due to its close similarity to the human in its clinical and immunological responses to Plasmodium, the nonhuman primate has been widely used as a model to study malaria. Nonhuman primates are also the only animals with a villous, hemochorial placenta like that of man and are, therefore, the animal model of choice in studies of pregnancy. We have established a model of malaria during pregnancy by intravenously inoculating 10 rhesus monkeys (Macaca mulatta) during the first trimester with Plasmodium coatneyi, a "falciparum-type parasite". All 10 monkeys became parasitemic 7-14 days post-inoculation (PI). Three aborted 7-10 days PI, coincident with high peak parasitemias (41,088-374,325 parasites per mm3), while 7 monkeys carried their infants to term. These 7 infants weighed significantly less at birth than did infants born to normal mothers (p=.0038). Placental weights in the Plasmodium-infected dams were lower than those of controls (p=.0455). Symmetrical IUGR was detected by ultrasound in 1 fetus with a birth weight of 334 grams. Another LBW infant (300 gms) had ultrasound measurments within the normal range. However, this infant's condition at birth was indicative of asymmetrical growth retardation, which is usually associated with uteroplacental insufficiency. The infant with symmetric IUGR died at 5 days of age while the other is alive but congenitally infected. The cord blood smear in the congenitally-infected infant was negative and parasitemia did not manifest itself until 80 days of age. Failure to recover from anemia during the later half of pregnancy was associated with early infant mortality in 4 infants. Histologically, placental lesions resembled those seen in human placentas infected with P. falciparum. The 6 placentas from P. coatneyi-infected dams had more significant pathologic changes than did the placentas from 5 control animals. Lesions indicative of malaria chronicity were related to IUGR and LBW. No correlation could be made between degree of placental damage and fetal mortality, birth weight, or congenital infection.

因感染疟原虫而患疟疾的孕妇 恶性疟原虫比恶性疟原虫遭受更多的不良后果。 感染恶性疟原虫的未怀孕妇女。越是普遍和严重 后遗症包括贫血和伴有中枢神经系统的严重疟疾 并发症。他们的婴儿患有宫内发育迟缓 (IUGR)、低出生体重儿(LBW)、先天性感染和高婴儿 死亡率。尽管已经从人类那里收集到了许多信息 人类的考验、条件和道德伦理的局限 对怀孕的研究排除了对该系统的操纵，并具有重要意义 由于变量混杂，数据往往无法解释。由于 它在临床和免疫学上与人类非常相似 对疟原虫的反应，非人灵长类已被广泛用作 一个研究疟疾的模型。非人灵长类也是唯一的动物 胎盘呈绒毛状，有血迹，与人类相似， 因此，在妊娠研究中应选择动物模型。我们 通过静脉注射建立了妊娠期疟疾的模型 第一次接种10只恒河猴(Macaca Mulatta) 妊娠三个月，患有“恶性疟原虫”的科特内伊疟原虫。全 10只猕猴在接种后7-14天(PI)成为寄生虫。三 流产7-10天，与寄生虫病高峰期一致 (每立方米41,088-374,325只寄生虫)，而7只猴子携带他们的 婴儿到足月。这7个婴儿出生时体重明显减轻。 与正常母亲所生的婴儿相比(p=0.0038)。胎盘重量 在感染疟原虫的母鸡中的感染率低于对照组。 (P=.0455)。超声检测胎儿对称性宫内发育迟缓1例 出生体重为334克。另一名LBW婴儿(300克)有 超声波测量在正常范围内。不过，这个 婴儿出生时的情况表明发育不对称 发育迟缓，通常与子宫胎盘有关 不够用。对称性宫内发育迟缓婴儿5日龄死亡 而另一个还活着，但先天感染。脐带血 先天感染婴儿的涂片结果为阴性和寄生虫血症 直到80天龄才显露出来。无法恢复 妊娠后半期贫血与早产有关 婴儿死亡4例。组织学上，胎盘病变 与在感染恶性疟原虫的人胎盘中看到的相似。 感染肺炎衣原体的6个母亲的胎盘有更显著的 病理改变优于5只对照动物的胎盘。 表明疟疾慢性化的病变与IUGR和LBW有关。 胎盘损伤程度和胎盘损伤程度之间没有相关性 胎儿死亡率、出生体重或先天性感染。