Placental Histopathological Changes Associated with Plasmodium vivax Infection during Pregnancy

Abstract

Histological evidence of Plasmodium in the placenta is indicative of placental malaria, a condition associated with severe outcomes for mother and child. Histological lesions found in placentas from Plasmodium-exposed women include syncytial knotting, syncytial rupture, thickening of the placental barrier, necrosis of villous tissue and intervillositis. These histological changes have been associated with P. falciparum infections, but little is known about the contribution of P. vivax to such changes. We conducted a cross-sectional study with pregnant women at delivery and assigned them to three groups according to their Plasmodium exposure during pregnancy: no Plasmodium exposure (n = 41), P. vivax exposure (n = 59) or P. falciparum exposure (n = 19). We evaluated their placentas for signs of Plasmodium and placental lesions using ten histological parameters: syncytial knotting, syncytial rupture, placental barrier thickness, villi necrosis, intervillous space area, intervillous leucocytes, intervillous mononucleates, intervillous polymorphonucleates, parasitized erythrocytes and hemozoin. Placentas from P. vivax-exposed women showed little evidence of Plasmodium or hemozoin but still exhibited more lesions than placentas from women not exposed to Plasmodium, especially when infections occurred twice or more during pregnancy. In the Brazilian state of Acre, where diagnosis and primary treatment are readily available and placental lesions occur in the absence of detected placental parasites, relying on the presence of Plasmodium in the placenta to evaluate Plasmodium-induced placental pathology is not feasible. Multivariate logistic analysis revealed that syncytial knotting (odds ratio [OR], 4.21, P = 0.045), placental barrier thickness (OR, 25.59, P = 0.021) and mononuclear cells (OR, 4.02, P = 0.046) were increased in placentas from P. vivax-exposed women when compared to women not exposed to Plasmodium during pregnancy. A vivax-score was developed using these three parameters (and not evidence of Plasmodium) that differentiates between placentas from P. vivax-exposed and unexposed women. This score illustrates the importance of adequate management of P. vivax malaria during pregnancy.

Immune responses during gestational malaria: a review of the current knowledge and future trend of research

“…Recent reports supported the concept that detection and treatment of pregnant malaria during early gestation prevents miscarriage both in P. vivax and P. falciparum infections [31,43]. At delivery, placental infection by P. vivax has been confirmed both in cases from America and Asia [35,[45][46][47].…”

Murine Model for Preclinical Studies of Var2CSA-Mediated Pathology Associated with Malaria in Pregnancy

“…This inflammatory environment in the placenta can affect its anatomic structure and normal function. Thickening of the trophoblast basement membrane, which is likely to impair the normal maternal-fetal nutrient and gas exchange, has been observed in both P. falciparum-infected placentas (32) and Plasmodium vivax-infected placentas (33) and is associated with low birth weight (34). Fibrinoid necrosis was also observed in highly infected placentas (35).…”

Effects of Vivax Malaria Acquired Before 20 Weeks of Pregnancy on Subsequent Changes in Fetal Growth

“…A recent study on histopathological analysis of P. vivaxassociated placental lesions 23 concluded that this parasite may induce changes similar to those changes caused by P. falciparum but to a lesser degree of intensity. In that same study, syncytiotrophoblast rupture and syncytial knots as well as fibrinoid deposit and leukocyte infiltrate were observed, and parasitized erythrocytes were found only on P. falciparum infections.…”

“…24 However, P. vivax infection does not seem to be associated with placental volume alterations. 25 Although there is little evidence that P. vivax may contribute to the inflammatory process in the intervillous space, 23 it is possible that the increase of placental thickness occurred because of placental inflammation. This possibility would explain, at least in part, changes in the course of pregnancy during acute malaria attacks, such as the occurrence of vaginal bleeding, uterine contraction, loss of amniotic liquid, Data are shown as mean ± SD.…”