title: Malaria in Pregnancy Interacts with and Alters the Angiogenic Profiles of the Placenta.
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.
authors.affiliation: Departamento de Parasitologia, Universidade de São Paulo (ICB/USP), São Paulo, São Paulo, Brazil; Burnet Institute, Centre for Biomedical Research, Melbourne, Victoria, Australia.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Ataíde
authors.affiliation: Departamento de Parasitologia, Universidade de São Paulo (ICB/USP), São Paulo, São Paulo, Brazil.
authors.forename: Oscar
authors.initials: O
authors.lastname: Murillo
authors.affiliation: Departamento de Parasitologia, Universidade de São Paulo (ICB/USP), São Paulo, São Paulo, Brazil.
authors.forename: Jamille G
authors.initials: JG
authors.lastname: Dombrowski
authors.affiliation: Departamento de Parasitologia, Universidade de São Paulo (ICB/USP), São Paulo, São Paulo, Brazil; Centro Multidisciplinar, Campus Floresta, Universidade Federal do Acre, Cruzeiro do Sul, Acre, Brazil.
authors.forename: Rodrigo M
authors.initials: RM
authors.lastname: Souza
authors.affiliation: Departamento de Parasitologia, Universidade de São Paulo (ICB/USP), São Paulo, São Paulo, Brazil.
authors.forename: Flávia A
authors.initials: FA
authors.lastname: Lima
authors.affiliation: Núcleo de Estudos em Malária, Superintendência de Controle de Endemias / Instituto de Medicina Tropical de São Paulo (IMT/USP), São Paulo, São Paulo, Brazil.
authors.forename: Giselle F M C
authors.initials: GF
authors.lastname: Lima
authors.affiliation: Núcleo de Estudos em Malária, Superintendência de Controle de Endemias / Instituto de Medicina Tropical de São Paulo (IMT/USP), São Paulo, São Paulo, Brazil.
authors.forename: Angélica D
authors.initials: AD
authors.lastname: Hristov
authors.affiliation: Centro Multidisciplinar, Campus Floresta, Universidade Federal do Acre, Cruzeiro do Sul, Acre, Brazil.
authors.forename: Suiane C N
authors.initials: SC
authors.lastname: Valle
authors.affiliation: Núcleo de Estudos em Malária, Superintendência de Controle de Endemias / Instituto de Medicina Tropical de São Paulo (IMT/USP), São Paulo, São Paulo, Brazil.
authors.forename: Silvia M
authors.initials: SM
authors.lastname: Di Santi
authors.affiliation: Departamento de Análises Clínicas e Toxicológicas, Universidade de São Paulo (FCF/USP), São Paulo, São Paulo, Brazil.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Epiphanio
authors.affiliation: Departamento de Parasitologia, Universidade de São Paulo (ICB/USP), São Paulo, São Paulo, Brazil.
authors.forename: Claudio R F
authors.initials: CR
authors.lastname: Marinho
mesh_terms: D000803:Angiotensin I / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism; D001938:Brazil / Q000453:epidemiology; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D062665:Epidemiological Monitoring; D005260:Female; D006801:Humans; D008288:Malaria / Q000453:epidemiology* / Q000503:physiopathology*; D018919:Neovascularization, Physiologic / Q000502:physiology*; D010920:Placenta / Q000033:anatomy & histology / Q000098:blood supply*; D011247:Pregnancy; D015995:Prevalence; D042787:Receptor, TIE-2 / Q000378:metabolism; D018709:Statistics, Nonparametric
chemical_list: D016207:Cytokines; D000804:Angiotensin II; D000803:Angiotensin I; D042787:Receptor, TIE-2