Malaria in Pregnancy Interacts with and Alters the Angiogenic Profiles of the Placenta.

Ricardo Ataíde,Sabrina Epiphanio,Oscar Murillo,Rodrigo M Souza,Angélica D Hristov,Suiane C N Valle,Silvia M Di Santi,Jamille G Dombrowski,Flávia A Lima,Giselle F M C Lima,Claudio R F Marinho,Mauricio Martins Rodrigues

doi:10.1371/journal.pntd.0003824

Ricardo Ataíde, Sabrina Epiphanio + Show 10 more

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https://doi.org/10.1371/journal.pntd.0003824

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Abstract

Malaria in pregnancy remains a substantial public health problem in malaria-endemic areas with detrimental outcomes for both the mother and the foetus. The placental changes that lead to some of these detrimental outcomes have been studied, but the mechanisms that lead to these changes are still not fully elucidated. There is some indication that imbalances in cytokine cascades, complement activation and angiogenic dysregulation might be involved in the placental changes observed. Nevertheless, the majority of studies on malaria in pregnancy (MiP) have come from areas where malaria transmission is high and usually restricted to Plasmodium falciparum, the most pathogenic of the malaria parasite species. We conducted a cross-sectional study in Cruzeiro do Sul, Acre state, Brazil, an area of low transmission and where both P. vivax and P. falciparum circulate. We collected peripheral and placental blood and placental biopsies, at delivery from 137 primigravid women and measured levels of the angiogenic factors angiopoietin (Ang)-1, Ang-2, their receptor Tie-2, and several cytokines and chemokines. We measured 4 placental parameters (placental weight, syncytial knots, placental barrier thickness and mononuclear cells) and associated these with the levels of angiogenic factors and cytokines. In this study, MiP was not associated with severe outcomes. An increased ratio of peripheral Tie-2:Ang-1 was associated with the occurrence of MiP. Both Ang-1 and Ang-2 had similar magnitudes but inverse associations with placental barrier thickness. Malaria in pregnancy is an effect modifier of the association between Ang-1 and placental barrier thickness.

Highlights

Angiogenic Factors Are Changed in Malaria in Pregnancy supported by Universidade Federal do Acre and CNPq
We have recently shown that malaria in pregnancy is associated with placental pathology in this region
In countries endemic for Plasmodium spp., malaria in pregnancy (MiP) remains an important health burden that can result in maternal anaemia, small-for-gestational-age babies, low birth weight, and even miscarriages and stillbirths [1,2,3]

Summary

Introduction

In countries endemic for Plasmodium spp., malaria in pregnancy (MiP) remains an important health burden that can result in maternal anaemia, small-for-gestational-age babies, low birth weight, and even miscarriages and stillbirths [1,2,3]. We are beginning to understand some of the basic pathological processes associated with P. vivax during pregnancy and have recently shown that the placentas of women exposed to P. vivax during pregnancy have increased barrier thickness, syncytial knots and monocyte numbers compared to uninfected placentas, even in the absence of evidence for parasite sequestration (a hallmark for P. falciparum-associated pathology) [25]. What contributes to these histopathological observations is not known. Other studies have observed modifications in the vasculature within the placental villi suggesting that this parasite impacts angiogenic processes [26]

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