Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Malaria during pregnancy and childhood: A focus on soluble mediators and neutrophils
Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
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 [en]
Plasmodium falciparum, pregnancy, childhood, neutrophils, biomarkers, cytokines, chemokines, antibodies, Fulani, Dogon
National Category
Immunology
Research subject
Immunology
Identifiers
URN: urn:nbn:se:su:diva-99916ISBN: 978-91-7447-851-8 (print)OAI: oai:DiVA.org:su-99916DiVA: diva2:689247
Public defence
2014-03-21, Ahlmannsalen, Geovetenskapens hus, Svante Arrhenius väg 12, Stockholm, 10:00 (English)
Opponent
Supervisors
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
List of papers
1. Biomarkers of Plasmodium falciparum infection during pregnancy in women living in Northeastern Tanzania
Open this publication in new window or tab >>Biomarkers of Plasmodium falciparum infection during pregnancy in women living in Northeastern Tanzania
Show others...
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.

National Category
Immunology
Research subject
Immunology
Identifiers
urn:nbn:se:su:diva-86295 (URN)10.1371/journal.pone.0048763 (DOI)000311151900039 ()23155405 (PubMedID)
Available from: 2013-01-11 Created: 2013-01-11 Last updated: 2017-12-06Bibliographically approved
2. Sub-microscopic infections with Plasmodium falciparum during pregnancy and their association with circulating cytokine, chemokine and cellular profiles
Open this publication in new window or tab >>Sub-microscopic infections with Plasmodium falciparum during pregnancy and their association with circulating cytokine, chemokine and cellular profiles
Show others...
(English)Manuscript (preprint) (Other academic)
National Category
Immunology
Research subject
Immunology
Identifiers
urn:nbn:se:su:diva-99856 (URN)
Available from: 2014-01-20 Created: 2014-01-20 Last updated: 2014-01-21
3. Neutrophil migration during placental malaria in vivo and in vitro and distinct neutrophil patterns induced by hemozoin
Open this publication in new window or tab >>Neutrophil migration during placental malaria in vivo and in vitro and distinct neutrophil patterns induced by hemozoin
Show others...
(English)Manuscript (preprint) (Other academic)
National Category
Immunology
Research subject
Immunology
Identifiers
urn:nbn:se:su:diva-99853 (URN)
Available from: 2014-01-20 Created: 2014-01-20 Last updated: 2014-01-21
4. Changes in the levels of cytokines, chemokines and malaria specific antibodies in response to Plasmodium falciparum infection in children living in sympatry in Mali
Open this publication in new window or tab >>Changes in the levels of cytokines, chemokines and malaria specific antibodies in response to Plasmodium falciparum infection in children living in sympatry in Mali
Show others...
2012 (English)In: Malaria Journal, ISSN 1475-2875, E-ISSN 1475-2875, Vol. 11, 109- p.Article in journal (Refereed) Published
Abstract [en]

Background: The Fulani are known to be less susceptible to Plasmodium falciparum malaria as reflected by lower parasitaemia and fewer clinical symptoms than other sympatric ethnic groups. So far most studies in these groups have been performed on adults, which is why little is known about these responses in children. This study was designed to provide more information on this gap. Methods: Circulating inflammatory factors and antibody levels in children from the Fulani and Dogon ethnic groups were measured. The inflammatory cytokines; interleukin (IL)-1beta, IL-6, IL-8, IL-10, IL-12p70, tumor necrosis factor (TNF) and the chemokines; regulated on activation normal T cell expressed and secreted (RANTES), monokine-induced by IFN-gamma (MIG), monocyte chemotactic protein (MCP)-1 and IFN-gamma-inducible protein (IP)-10 were measured by cytometric bead arrays. The levels of interferon (IFN)-alpha, IFN-gamma and malaria-specific antibodies; immunoglobulin (Ig) G, IgM and IgG subclasses (IgG1-IgG4) were measured by ELISA. Results: The results revealed that the Fulani children had higher levels of all tested cytokines compared to the Dogon, in particular IFN-gamma, a cytokine known to be involved in parasite clearance. Out of all the tested chemokines, only MCP-1 was increased in the Fulani compared to the Dogon. When dividing the children into infected and uninfected individuals, infected Dogon had significantly lower levels of RANTES compared to their uninfected peers, and significantly higher levels of MIG and IP-10 as well as MCP-1, although the latter did not reach statistical significance. In contrast, such patterns were not seen in the infected Fulani children and their chemokine levels remained unchanged upon infection compared to uninfected counterparts. Furthermore, the Fulani also had higher titres of malaria-specific IgG and IgM as well as IgG1-3 subclasses compared to the Dogon. Conclusions: Taken together, this study demonstrates, in accordance with previous work, that Fulani children mount a stronger inflammatory and antibody response against P. falciparum parasites compared to the Dogon and that these differences are evident already at an early age. The inflammatory responses in the Fulani were not influenced by an active infection which could explain why less clinical symptoms are seen in this group.

Keyword
cytokines, chemokines, antibodies, Plasmodium falciparum, Fulani, Dogon
National Category
Immunology
Research subject
Immunology
Identifiers
urn:nbn:se:su:diva-80750 (URN)10.1186/1475-2875-11-109 (DOI)000304761300001 ()
Note

AuthorCount:9;

Available from: 2012-10-01 Created: 2012-09-27 Last updated: 2017-12-07Bibliographically approved

Open Access in DiVA

fulltext(1464 kB)495 downloads
File information
File name FULLTEXT01.pdfFile size 1464 kBChecksum SHA-512
6fe0c964de0fc2f4f4df8463f59029479bdfd8c690cd0f70b4beb4f7dd2e69ef7462e73620919b75485132a151641e5c05f148cb741d859b87056032cd418491
Type fulltextMimetype application/pdf

Search in DiVA

By author/editor
Boström, Stéphanie
By organisation
Department of Molecular Biosciences, The Wenner-Gren Institute
Immunology

Search outside of DiVA

GoogleGoogle Scholar
Total: 495 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

isbn
urn-nbn

Altmetric score

isbn
urn-nbn
Total: 594 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf