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: 2795489
• 金额: $ 3.18万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2795489
• 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P. 感染恶性疟原虫的非妊娠妇女。 越是常见和严重的 后遗症包括贫血和严重疟疾， 并发症 他们的婴儿患有宫内发育迟缓 （IUGR）、低出生体重（LBW）、先天性感染和高婴儿 mortality. 尽管从人类身上收集到了很多信息， 审判，条件，以及人类的道德和伦理限制 怀孕的研究排除了对系统的操纵， 由于混杂的变量，数据通常是不可解释的。 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，非人灵长类动物已被广泛用作 一个研究疟疾的模型 非人类灵长类动物也是唯一 有绒毛状血绒膜胎盘， 因此，动物模型的选择在研究怀孕。 我们 通过静脉注射建立了一个怀孕期间的疟疾模型， 10只恒河猴（Macaca mulatta）在第一次 三个月内感染了疟原虫，一种“恶性疟原虫型寄生虫”。 所有 10只猴在接种后7-14天（PI）出现寄生虫血症。 三 感染后7-10天流产，与寄生虫血症的高峰一致 (41 088 - 374，325个寄生虫/mm 3），而7只猴子携带它们的 婴儿足月。 这7名婴儿出生时体重明显较轻 正常母亲所生的婴儿（p= 0.0038）。 胎盘重量 在疟原虫感染的母鼠中， （p=.0455）。 超声检出对称性IUGR 1例 出生体重334克 另一名LBW婴儿（300 g） 超声波测量值在正常范围内。 但这 婴儿出生时的情况表明生长不对称 发育迟缓，通常与子宫胎盘有关 不足。 对称性IUGR婴儿5日龄死亡 而另一个活着但先天感染 脐带血 先天性感染婴儿涂片阴性， 直到80日龄才出现。 未能从 妊娠后半期贫血与妊娠早期 4名婴儿死亡。 组织学上，胎盘病变 与感染恶性疟原虫的人类胎盘相似。 来自感染Coatneyi的母鼠的6个胎盘具有更显著的 病理变化比5只对照动物的胎盘。 指示疟疾慢性的病变与IUGR和LBW相关。 胎盘损伤程度与 胎儿死亡率、出生体重或先天性感染。