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Biomarkers of Plasmodium falciparum infection during pregnancy in women living in Northeastern Tanzania
Stockholm University, Faculty of Science, The Wenner-Gren Institute.
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2012 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 11, e48763- p.Article in journal (Refereed) Published
Abstract [en]

In pregnant women, Plasmodium falciparum infections are an important cause of maternal morbidity as well as fetal and neonatal mortality. Erythrocytes infected by these malaria-causing parasites accumulate through adhesive interactions in placental intervillous spaces, thus evading detection in peripheral blood smears. Sequestered infected erythrocytes induce inflammation, offering the possibility of detecting inflammatory mediators in peripheral blood that could act as biomarkers of placental infection. In a longitudinal, prospective study in Tanzania, we quantified a range of different cytokines, chemokines and angiogenic factors in peripheral plasma samples, taken on multiple sequential occasions during pregnancy up to and including delivery, from P. falciparum-infected women and matched uninfected controls. The results show that during healthy, uninfected pregnancies the levels of most of the panel of molecules we measured were largely unchanged except at delivery. In women with P. falciparum, however, both comparative and longitudinal assessments consistently showed that the levels of IL-10 and IP-10 increased significantly whilst that of RANTES decreased significantly, regardless of gestational age at the time the infection was detected. ROC curve analysis indicated that a combination of increased IL-10 and IP-10 levels and decreased RANTES levels might be predictive of P. falciparum infections. In conclusion, our data suggest that host biomarkers in peripheral blood may represent useful diagnostic markers of P. falciparum infection during pregnancy, but placental histology results would need to be included to verify these findings.

Place, publisher, year, edition, pages
2012. Vol. 7, no 11, e48763- p.
National Category
Immunology
Research subject
Immunology
Identifiers
URN: urn:nbn:se:su:diva-86295DOI: 10.1371/journal.pone.0048763ISI: 000311151900039PubMedID: 23155405OAI: oai:DiVA.org:su-86295DiVA: diva2:586590
Available from: 2013-01-11 Created: 2013-01-11 Last updated: 2017-12-06Bibliographically approved
In thesis
1. Malaria during pregnancy and childhood: A focus on soluble mediators and neutrophils
Open this publication in new window or tab >>Malaria during pregnancy and childhood: A focus on soluble mediators and neutrophils
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

In areas where malaria is endemic, pregnant women and children bear the main burden of severe and life-threatening malarial disease. The aim of this work was to study the impact of Plasmodium falciparum infection on inflammatory responses in pregnant women and children residing in African countries. In paper I we investigated peripheral blood samples from pregnant women, living in Tanzania, for potential biomarkers of P. falciparum infection during pregnancy. We found that IL-10 and IP-10 were potential candidates, which increased upon infection, irrespective of gestational age. In addition, increased IL-10 and IP-10 and decreased RANTES levels were predictive of an infection. In paper II we investigated frequencies of peripheral blood-cell types and biomarkers upon infection, in pregnant women living in Benin, and assessed the predictive values of variables measured at inclusion for pregnancy outcomes at delivery. Higher IL-10 levels distinguished quantitative PCR-detectable, sub-microscopic infections, at inclusion, but not at delivery. Maternal anaemia at delivery was associated with increased numbers of circulating monocytes, Treg cells and IL-10 levels measured at inclusion. In paper III we investigated neutrophil functions in the context of pregnancy malaria in vivo and in vitro. Numbers of circulating neutrophils and IL-8 levels were reduced in the infected women, whilst increased levels of IL-8 were found in placental blood of those infected. In vitro assays suggested migration of neutrophils to infected placentas, which also was supported by histological examinations showing the presence of neutrophils containing hemozoin (Hz), in the infected placenta. Stimulation of neutrophils with various Hz preparations revealed distinct patterns of neutrophil activation. In paper IV we investigated cytokines and malaria-specific antibody titres in children belonging to two African ethnic groups, living in Mali, with known different susceptibility to malaria. The Fulani showed increased cytokines (IL-6, IL-8, IL-12, IFN-α, IFN-γ) and higher titres of malaria-specific antibody subclasses (IgG, IgM and IgG1-IgG3), compared to the Dogon. Taken together, this thesis shows that host biomarkers in peripheral blood may represent useful diagnostic markers for malaria during pregnancy. The neutrophil population was shown to be highly affected by the presence of P. falciparum parasites, suggesting a role for neutrophils during malaria infections. The Fulani, showed increased pro-inflammatory and antibody responses against P. falciparum parasites, as compared to Dogon, and these differences are established already at an early age.  

Place, publisher, year, edition, pages
Stockholm: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, 2014. 89 p.
Keyword
Plasmodium falciparum, pregnancy, childhood, neutrophils, biomarkers, cytokines, chemokines, antibodies, Fulani, Dogon
National Category
Immunology
Research subject
Immunology
Identifiers
urn:nbn:se:su:diva-99916 (URN)978-91-7447-851-8 (ISBN)
Public defence
2014-03-21, Ahlmannsalen, Geovetenskapens hus, Svante Arrhenius väg 12, Stockholm, 10:00 (English)
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Note

At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 2: Manuscript. Paper 3: Manuscript.

Available from: 2014-02-27 Created: 2014-01-20 Last updated: 2014-02-17Bibliographically approved

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