Circulating Endothelial Progenitor Cells and Preeclampsia in Women with Placental Malaria

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dc.contributor.authorObiri, D.
dc.date.accessioned2019-10-23T10:34:04Z
dc.date.available2019-10-23T10:34:04Z
dc.date.issued2019-03
dc.descriptionPhD.Molecular Cell Biology of Infectious Diseasesen_US
dc.description.abstractBackground Placental malaria and preeclampsia are major complications of pregnancy associated with high incidence of maternal/foetal Morbidity and mortality particularly in sub-Saharan Africa. Similarities in pathophysiology such as systemic inflammation and generalized endothelial activation/dysfunction exist and are exacerbated in concurrent situations. The combined pathologic and immunologic effects of these pregnancy disorders, prevalent in malaria endemic regions, have not been tested. This study evaluated the pathologic risk associated with Plasmodium falciparum infection in the placenta and the outcome of preeclampsia. Immune mediators associated with placental malaria and the risk of preeclampsia were evaluated. In addition, the relationship between endothelial cell phenotypes implicated in vascular activation/injury/damage/repair and the factors that mediate their release were assessed. Methods A total of 140 pregnant women (18 - 42 years) diagnosed with and without preeclampsia were recruited into the study in Accra, Ghana. Peripheral blood samples were collected at delivery while cord blood, placental intervillous blood and placental biopsies were collected after delivery. Circulating endothelial cells (cECs) and circulating endothelial progenitor cell phenotypes (cEPCs, mEPCs and iEPCs) were quantified by flow cytometry. Immunological (inflammatory and angiogenic) factors were tested by multiplex ELISA using plasma separated from whole blood. Placental biopsies were histologically evaluated for unique placental lesions and placental malaria (classified as active and past infections). Results Of 133 placentas scored for placental malaria, women diagnosed with preeclampsia had 39 (29.3%) and 15 (11.3%) active and past infections respectively while the non-preeclamptic women had 25 (18.8%) active infections and 6 (4.5%) past infections. Both active (adjusted odds ratio (AOR) 6.7, 95% CI 2.3 – 18.9; P < 0.0001) and past infections (AOR 11.6, 95% CI 3.0 – 45.8; P < 0.0001) increased the risk of preeclampsia. This association was enhanced in primigravidae (AOR 6.6, 95% CI 2.4 – 18.2; P < 0.0001) and in women with pathological alterations in the placenta (AOR 3.0, 95% CI 1.2 – 7.5; P < 0.019). The preeclamptic pregnancies with active placental parasites showed higher levels of proinflammatory and antiangiogenic markers. In multivariate analysis, active parasite infection (AOR = 7.14, 95% CI = 1.1 – 44.7; P = 0.04), past infection (AOR = 12.9, 95% CI = 1.1 – 155.5; P = 0.04), primigravidity (AOR = 7.2, 95% CI = 1.1 – 48.0; P = 0.04) and increased levels of the plasminogen activator inhibitor (PAI)-1 molecule (AOR = 7.1, 95% CI = 1.3 – 38.3; P = 0.02) were all associated with placental malaria. Furthermore, proportions of endothelial cell phenotypes were higher in the placenta and cord compared to peripheral blood. Alterations in their levels correlated strongly with angiogenic factors that stimulate their release mostly in non-preeclamptic compared to preeclamptic pregnancies. Conclusion Findings from this study have demonstrated that the pathophysiology of preeclampsia is pathologically and immunologically exacerbated in women exposed to placental malaria. In addition, endothelial cell phenotypes that contribute to vascular homeostasis and the factors that mediate their release into circulation are altered. Altogether, this study provides a new paradigm in assessing preeclampsia in malaria endemic regions.en_US
dc.identifier.urihttp://ugspace.ug.edu.gh/handle/123456789/33045
dc.language.isoenen_US
dc.publisherUniversity Of Ghanaen_US
dc.subjectPlacental Malariaen_US
dc.subjectFoetal Morbidityen_US
dc.subjectPlasmodium Falciparumen_US
dc.subjectSub-Saharan Africaen_US
dc.titleCirculating Endothelial Progenitor Cells and Preeclampsia in Women with Placental Malariaen_US
dc.typeThesisen_US

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