[论文解读] Characterisation of placental malaria in olive baboons (Papio anubis) infected with Plasmodium knowlesi H strain

Barasa Mustafa, Gicheru Muita Michael+2 more|arXiv (Cornell University)|Apr 14, 2012

Malaria Research and Control参考文献 13被引用 6

一句话总结

本研究利用感染了P. knowlesi H株的橄榄狒狒（Papio anubis）建立了非人灵长类胎盘疟疾模型，证实了寄生虫在胎盘中的寄生。该模型再现了人类胎盘疟疾的关键特征，包括寄生虫血症和组织病理学改变，为研究发病机制和免疫反应提供了一个转化性系统，避免了人体研究在伦理和后勤上的限制。

ABSTRACT

Pregnant women have increased susceptibility to malaria infection. In these women, malaria parasites are frequently found sequestered in the placental intervillous spaces, a condition referred to as placental malaria (PM). Placental malaria threatens the health of the mother and the child's life by causing still births and reduction in gestational age. An estimated 24 million pregnant women in Sub-Saharan Africa are at risk. Mechanisms responsible for increased susceptibility in pregnant women are not fully understood. Pregnancy malaria studies have been limited by the lack of a suitable animal model. This research aimed to develop a baboon (Papio anubis) model for studying PM. The pregnancies of three adult female baboons were synchronized and their gestational levels confirmed by ultrasonography. On the 150th day of gestation the pregnant baboons were infected with Plasmodium knowlesi H strain parasites together with four nulligravid control baboons. Parasitaemia was monitored from two days post inoculation until the 159th day of gestation when caesarean section was done on one baboon in order to obtain the placenta. Two baboons aborted their conceptus. Smears prepared from placental blood demonstrated the presence of Plasmodium knowlesi parasites in all the three sampled placentas. These new findings show that P. knowlesi sequesters in the baboon placenta. In addition, this study has characterized haemoglobin, eosinophil, Immunoglobulin G and Immunoglobulin M profiles in this model. Thus a non human primate (baboon) model for studying PM has been established. The established baboon - P. knowlesi model for studying human placental/pregnancy malaria now offers an opportunity for circumventing the obstacles experienced during human studies like having inadequate tissue for analysis, inaccurate estimation of gestational age, moral, ethical and financial limitations.

研究动机与目标

• 开发一种非人灵长类动物模型，用于研究胎盘疟疾（PM），该病可导致孕妇死胎和早产。
• 在受控且伦理上可行的系统中研究PM的发病机制，以模拟人类胎盘寄生。
• 表征感染P. knowlesi的妊娠狒狒的血液学和免疫学特征（如血红蛋白、IgG、IgM、嗜酸性粒细胞）。
• 克服人体研究的局限性，包括组织样本稀缺、妊娠期估算不准确以及伦理限制。

提出的方法

• 通过超声波检查确认三只成年雌性橄榄狒狒的同步妊娠。
• 在妊娠第150天感染Plasmodium knowlesi H株，自接种后第2天起监测寄生虫血症。
• 在妊娠第159天对其中一只狒狒实施剖腹产，以获取胎盘组织。
• 制备胎盘涂片并显微镜检查疟原虫的存在。
• 在整个研究期间测量血红蛋白、嗜酸性粒细胞计数以及血清免疫球蛋白G和M水平。
• 纳入四只未产过的对照狒狒，以比较免疫和血液学反应。

实验结果

研究问题

• RQ1 P. knowlesi H株是否如在人类中一样，在橄榄狒狒胎盘的绒毛间隙中发生寄生？
• RQ2 该狒狒模型能否准确重现人类胎盘疟疾的关键病理和免疫学特征？
• RQ3 感染P. knowlesi后，妊娠狒狒的血红蛋白、嗜酸性粒细胞、IgG和IgM水平有何变化？
• RQ4 与人体研究相比，该模型在妊娠期估算准确性和组织获取方面有何差异？

主要发现

• 在所有检查的三份胎盘涂片中均检测到Plasmodium knowlesi寄生虫，证实了感染狒狒胎盘绒毛间隙中的寄生。
• 三只感染狒狒中有两只流产，表明感染与严重妊娠并发症相关。
• 自接种后第2天起即可检测到寄生虫血症，且持续感染直至妊娠第159天行剖腹产。
• 观察到血红蛋白、嗜酸性粒细胞、IgG和IgM水平显著变化，提示感染动物存在免疫激活和贫血。
• 该模型成功再现了人类胎盘疟疾的关键特征，包括寄生虫寄生和不良妊娠结局。
• 本研究为研究胎盘疟疾的发病机制和免疫反应提供了一种可行且伦理上可接受的替代方案。