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.
Highlights
125 million pregnant women worldwide are exposed to the risks of malaria in pregnancy (MiP) each year, resulting in 200,000 infant deaths [1,2]
In this study we have used ten histological parameters to evaluate the effect of exposure to Plasmodium vivax during pregnancy on the occurrence of placental lesions when compared to placentas from non-exposed women
Placentas from Plasmodium vivaxexposed placentas did not have strong evidence of placental parasites but had increased syncytial knotting, thickness of the placental barrier and mononuclear cells when compared to non-exposed women
Summary
125 million pregnant women worldwide are exposed to the risks of malaria in pregnancy (MiP) each year, resulting in 200,000 infant deaths [1,2]. In areas in which malaria is endemic, pregnant women are more susceptible to Plasmodium infections than their non-pregnant peers. Evidence of Plasmodium (most commonly mature parasites) or Plasmodium products (e.g., hemozoin) in the placenta is considered a defining feature of MiP, often termed placental malaria (PM). This accumulation of parasite material occurs in the intervillous space, a region of low blood flow in the placenta where the maternal blood bathes the syncytiotrophoblast (a cell layer of foetal origin and the site of maternal foetal transfer) [8,9]. A particular emphasis has been placed on the presence of Plasmodium parasites or hemozoin to assess the pathology of malaria during pregnancy and to identify malariaassociated changes in the placenta
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