Molecular Principles of Intrauterine Growth Restriction in Plasmodium Falciparum Infection.

Johanna Seitz,Henning Schneider,Udo Rudolf Markert,Diana Maria Morales-Prieto,Rodolfo R. Favaro

doi:10.3389/fendo.2019.00098

Johanna Seitz, Henning Schneider + Show 3 more

Open Access

https://doi.org/10.3389/fendo.2019.00098

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Abstract

Malaria in pregnancy still constitutes a particular medical challenge in tropical and subtropical regions. Of the five Plasmodium species that are pathogenic to humans, infection with Plasmodium falciparum leads to fulminant progression of the disease with massive impact on pregnancy. Severe anemia of the mother, miscarriage, stillbirth, preterm delivery and intrauterine growth restriction (IUGR) with reduced birth weight are frequent complications that lead to more than 10,000 maternal and 200,000 perinatal deaths annually in sub-Saharan Africa alone. P. falciparum can adhere to the placenta via the expression of the surface antigen VAR2CSA, which leads to sequestration of infected erythrocytes in the intervillous space. This process induces a placental inflammation with involvement of immune cells and humoral factors. Especially, monocytes get activated and change the release of soluble mediators, including a variety of cytokines. This proinflammatory environment contributes to disorders of angiogenesis, blood flow, autophagy, and nutrient transport in the placenta and erythropoiesis. Collectively, they impair placental functions and, consequently, fetal growth. The discovery that women in endemic regions develop a certain immunity against VAR2CSA-expressing parasites with increasing number of pregnancies has redefined the understanding of malaria in pregnancy and offers strategies for the development of vaccines. The following review gives an overview of molecular processes in P. falciparum infection in pregnancy which may be involved in the development of IUGR.

Highlights

Pregnant women are more susceptible to infection with Plasmodium falciparum and present a more severe form of the disease than non-pregnant women [1]
P. falciparum expresses a special Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP-1), the VAR2CSA antigen, which can bind to chondroitin sulfate A (CSA) produced by trophoblast cells
P. falciparum infected erythrocytes expressing VAR2CSA but not those binding to endothelial protein C receptor (EPCR) or lacking PfEMP1 disappear from the maternal circulation and accumulate in the perfused tissue, mostly in the intervillous space and to a less extend on the syncytiotrophoblast [163]

Summary

Introduction

Pregnant women are more susceptible to infection with Plasmodium falciparum and present a more severe form of the disease than non-pregnant women [1]. Increased concentrations of TNF are associated with high placental parasite density and pregnancy complications such as LBW, IUGR, preterm birth and maternal anemia [50, 86, 87, 91].

Results

Conclusion