Submicroscopic infections with Plasmodium falciparum during pregnancy and their association with circulating cytokine, chemokine, and cellular profiles.
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.
Centre d'Etude et de Recherche sur le Paludisme Associé à la Grossesse et à l'Enfance, Faculté des Sciences de la Santé, Université d'Abomey-Calavi, Cotonou, Benin Institut de Recherche pour le Développement, UMR 216, Mère et Enfant Face aux Infections Tropicales, Paris, France PRES Sorbonne Paris Cité, Université Paris Descartes, Faculté de Pharmacie, Paris, France.
Samad A
SA
Ibitokou
Department of Immunology, Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
Stéphanie
S
Boström
Institut de Recherche pour le Développement, UMR 216, Mère et Enfant Face aux Infections Tropicales, Paris, France PRES Sorbonne Paris Cité, Université Paris Descartes, Faculté de Pharmacie, Paris, France.
Laurent
L
Brutus
Institut de Recherche pour le Développement, UMR 216, Mère et Enfant Face aux Infections Tropicales, Paris, France PRES Sorbonne Paris Cité, Université Paris Descartes, Faculté de Pharmacie, Paris, France.
Nicaise
N
Tuikue Ndam
Centre d'Etude et de Recherche sur le Paludisme Associé à la Grossesse et à l'Enfance, Faculté des Sciences de la Santé, Université d'Abomey-Calavi, Cotonou, Benin.
Bertin
B
Vianou
Centre d'Etude et de Recherche sur le Paludisme Associé à la Grossesse et à l'Enfance, Faculté des Sciences de la Santé, Université d'Abomey-Calavi, Cotonou, Benin.
Carine
C
Agbowaï
Centre d'Etude et de Recherche sur le Paludisme Associé à la Grossesse et à l'Enfance, Faculté des Sciences de la Santé, Université d'Abomey-Calavi, Cotonou, Benin.
Martin
M
Amadoudji Zin
Institut de Recherche pour le Développement, UMR 216, Mère et Enfant Face aux Infections Tropicales, Paris, France PRES Sorbonne Paris Cité, Université Paris Descartes, Faculté de Pharmacie, Paris, France.
Bich Tram
BT
Huynh
Centre d'Etude et de Recherche sur le Paludisme Associé à la Grossesse et à l'Enfance, Faculté des Sciences de la Santé, Université d'Abomey-Calavi, Cotonou, Benin.
Achille
A
Massougbodji
Institut de Recherche pour le Développement, UMR 216, Mère et Enfant Face aux Infections Tropicales, Paris, France PRES Sorbonne Paris Cité, Université Paris Descartes, Faculté de Pharmacie, Paris, France.
Philippe
P
Deloron
Department of Immunology, Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
Marita
M
Troye-Blomberg
Institut de Recherche pour le Développement, UMR 216, Mère et Enfant Face aux Infections Tropicales, Paris, France PRES Sorbonne Paris Cité, Université Paris Descartes, Faculté de Pharmacie, Paris, France.
Nadine
N
Fievet
Institut de Recherche pour le Développement, UMR 216, Mère et Enfant Face aux Infections Tropicales, Paris, France PRES Sorbonne Paris Cité, Université Paris Descartes, Faculté de Pharmacie, Paris, France adrian.luty@ird.fr.
Adrian J F
AJ
Luty
D000328:Adult; D000740:Anemia; D054357:Chemokine CXCL10 / Q000097:blood*; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000097:blood*; D008137:Longitudinal Studies; D008213:Lymphocyte Activation / Q000276:immunology; D016778:Malaria, Falciparum / Q000097:blood* / Q000276:immunology / Q000469:parasitology; D010963:Plasmodium falciparum / Q000276:immunology*; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000469:parasitology; D011256:Pregnancy Outcome; D011446:Prospective Studies; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D055815:Young Adult
C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; C508609:IL10 protein, human; D016753:Interleukin-10