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- Ibitokou, Samad A., et al.
(författare)
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Submicroscopic Infections with Plasmodium falciparum during Pregnancy and Their Association with Circulating Cytokine, Chemokine, and Cellular Profiles
- 2014
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Ingår i: Clinical and Vaccine Immunology. - 1556-6811 .- 1556-679X. ; 21:6, s. 859-866
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Tidskriftsartikel (refereegranskat)abstract
- The immunological consequences of pregnancy-associated malaria (PAM) due to Plasmodium falciparum have been extensively investigated in cross-sectional studies conducted at delivery, but there have been very few longitudinal studies of changes due to PAM during pregnancy. We conducted a prospective study in Benin to investigate the changes associated with PAM in groups of 131 and 111 women at inclusion in the second trimester and at delivery, respectively. Infected women were identified by standard microscopic examinations of blood smears and by quantitative PCR (qPCR) assays and were matched to uninfected control women by age, gestational age, and gravidity. We quantified plasma levels of a panel of soluble immunological mediators and other mediators, as well as the frequencies of peripheral blood mononuclear cell types. Comparisons of these variables in infected and uninfected women used multivariate analyses, and we also assessed the predictive value of variables measured at inclusion for pregnancy outcomes at delivery. In multivariate analyses, peripheral plasma interleukin 10 (IL-10) and gamma interferon-inducible protein 10 (IP-10) levels were associated with PAM at inclusion and at delivery, while higher IL-10 levels distinguished qPCR-detectable submicroscopic infections at inclusion but not at delivery. Maternal anemia at delivery was associated with markers of proinflammatory (increased frequency of monocytes) and anti-inflammatory (increased IL-10 levels and increased activation of regulatory T cells) activity measured at inclusion. Elevated concentrations of IL-10 are associated with the majority of P. falciparum infections during pregnancy, but this marker alone does not identify all submicroscopic infections. Reliably identifying such occult infections will require more sensitive and specific methods.
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| 2. |
- Ibitokou, Samad, et al.
(författare)
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Gestational age-related changes in the peripheral blood cell composition of sub-Saharan African women
- 2013
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Ingår i: Journal of Reproductive Immunology. - : Elsevier BV. - 0165-0378 .- 1872-7603. ; 98:1-2, s. 21-28
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Tidskriftsartikel (refereegranskat)abstract
- Gestational age-related changes in the cellular composition of peripheral blood have not been described in sub-Saharan African settings. We conducted longitudinal cohort studies in Beninese and Tanzanian mothers with quantification of peripheral blood mononuclear cell-types ex vivo using flow cytometry. Between the second trimester and delivery the frequency of CD4(+) T cells declined significantly, contrasting with a non-significant increase in CD8(+) T cells, but no changes in T-regulatory, NK or NKT cell frequencies. Antigen-presenting cell profiles were also unaltered, although non-significant trends were evident. These changes resemble in some respects those reported during pregnancies in developed countries, but differ in others.
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| 3. |
- Ibitokou, Samad, et al.
(författare)
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Peripheral Blood Cell Signatures of Plasmodium falciparum Infection during Pregnancy
- 2012
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:12, s. e49621-
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Tidskriftsartikel (refereegranskat)abstract
- Sequestration of Plasmodium falciparum-infected erythrocytes in placental intervillous spaces causes inflammation and pathology. Knowledge of the profiles of immune cells associated with the physiopathology of pregnancy-associated malaria (PAM) is scarce. We conducted a longitudinal, prospective study, both in Benin and Tanzania, including ∼1000 pregnant women in each site with systematic follow-up at scheduled antenatal visits until delivery. We used ex vivo flow cytometry to identify peripheral blood mononuclear cell (PBMC) profiles that are associated with PAM and anaemia, determining the phenotypic composition and activation status of PBMC in selected sub-groups with and without PAM both at inclusion and at delivery in a total of 302 women. Both at inclusion and at delivery PAM was associated with significantly increased frequencies both of B cells overall and of activated B cells. Infection-related profiles were otherwise quite distinct at the two different time-points. At inclusion, PAM was associated with anaemia, with an increased frequency of immature monocytes and with a decreased frequency of regulatory T cells (Treg). At delivery, infected women presented with significantly fewer plasmacytoid dendritic cells (DC), more myeloid DC expressing low levels of HLA-DR, and more effector T cells (Teff) compared to uninfected women. Independent associations with an increased risk of anaemia were found for altered antigen-presenting cell frequencies at inclusion, but for an increased frequency of Teff at delivery. Our findings emphasize the prominent role played by B cells during PAM whenever it arises during pregnancy, whilst also revealing signature changes in other circulating cell types that, we conclude, primarily reflect the relative duration of the infections. Thus, the acute, recently-acquired infections present at delivery were marked by changes in DC and Teff frequencies, contrasting with infections at inclusion, considered chronic in nature, that were characterized by an abundance of immature monocytes and a paucity of Treg in PBMC.
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