Center Detude Et Of Recherche Sur Le Paludisme Associe Grossesse Et Lenfance Cerpage

Cotonou, Benin

Center Detude Et Of Recherche Sur Le Paludisme Associe Grossesse Et Lenfance Cerpage

Cotonou, Benin
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Bertin G.I.,Institute Of Recherche Pour Le Developpement Ird | Bertin G.I.,University of Paris Descartes | Lavstsen T.,Copenhagen University | Guillonneau F.,University of Paris Descartes | And 18 more authors.
PLoS ONE | Year: 2013

Background:Plasmodium falciparum erythrocyte membrane protein-1 (PfEMP-1) is a highly polymorphic adherence receptor expressed on the surface of infected erythrocytes. Based on sequence homology PfEMP-1 variants have been grouped into three major groups A-C, the highly conserved VAR2CSA variants, and semi-conserved types defined by tandem runs of specific domains ("domain cassettes" (DC)). The PfEMP-1 type expressed determines the adherence phenotype, and is associated with clinical outcome of infection.Methods:Parasite isolates from Beninese children or women presenting with, respectively, CM or PAM were collected along with samples from patients with uncomplicated malaria (UM). We assessed the transcript level of var genes by RT-qPCR and the expression of PfEMP-1 proteins by LC-MS/MS.Results:Var genes encoding DC8 and Group A PfEMP-1 were transcribed more often and at higher levels in cerebral malaria vs. uncomplicated malaria patients. LC-MS/MS identified peptides from group A, DC8 PfEMP-1 more frequently in cerebral malaria than in uncomplicated malaria and pregnancy-associated malaria samples.Conclusion:This is the first study to show association between PfEMP-1 subtype and disease outcome by direct analysis of parasites proteome. The results corroborate that group A and specifically the PfEMP-1 types DC8 are universally associated with cerebral malaria. This is a crucial observation for promoting studies on malaria pathogenesis. © 2013 Bertin et al.


PubMed | Mother and child hospital HOMEL, CIRAD - Agricultural Research for Development, Center Detude Et Of Recherche Sur Le Paludisme Associe Grossesse Et Lenfance Cerpage, University of Paris Descartes and University of Benin
Type: | Journal: Scientific reports | Year: 2016

Plasmodium falciparum is responsible of severe malaria, including cerebral malaria (CM). During its intra-erythrocytic maturation, parasite-derived proteins are expressed, exported and presented at the infected erythrocyte membrane. To identify new CM-specific parasite membrane proteins, we conducted a mass spectrometry-based proteomic study and compared the protein expression profiles between 9 CM and 10 uncomplicated malaria (UM) samples. Among the 1097 Plasmodium proteins identified, we focused on the 499 membrane-associated and hypothetical proteins for comparative analysis. Filter-based feature selection methods combined with supervised data analysis identified a subset of 29 proteins distinguishing CM and UM samples with high classification accuracy. A hierarchical clustering analysis of these 29 proteins based on the similarity of their expression profiles revealed two clusters of 15 and 14 proteins, respectively under- and over-expressed in CM. Among the over-expressed proteins, the MESA protein is expressed at the erythrocyte membrane, involved in proteins trafficking and in the export of variant surface antigens (VSAs), but without antigenic function. Antigen 332 protein is exported at the erythrocyte, also involved in protein trafficking and in VSAs export, and exposed to the immune system. Our proteomics data demonstrate an association of selected proteins in the pathophysiology of CM.


Badaut C.,Institute Of Recherche Biomedicale Des Armees Irba | Guyonnet L.,Institute Of Recherche Pour Le Developpement | Guyonnet L.,University of Paris Descartes | Milet J.,Institute Of Recherche Pour Le Developpement | And 15 more authors.
Malaria Journal | Year: 2015

Background: The three members of the ring-infected erythrocyte surface antigen (RESA) proteins family share high sequence homologies, which impair the detection and assignment to one or another protein of some pathogenic processes inherent to Plasmodium falciparum malaria. The present study was intended to determine if the antibody and inflammatory responses of children living in a malaria-endemic area varied depending on the RESA-1, RESA-2 or RESA-3 proteins and the severity of the disease, two groups of severe and uncomplicated malaria cases being considered. Methods: Two synthetic peptides representing predicted B cell epitopes were designed per RESA protein, all located outside of the 3′ and 5′ repetition blocks, in order to allow an antibody detection specific of each member of the family. Recombinant rRESA-1B and rRESA-3B proteins were also engineered. Two groups of Beninese children admitted to hospital in 2009 for either uncomplicated or severe malaria were compared for their plasma levels of IgG specifically recognizing each recombinant RESA protein or synthetic peptide, and for their plasma inflammatory cytokine levels (IFN-γ, TNF-α and IL-10), taking into account host and parasite genetic factors. Results: The absence of IgG cross-reactivity between rRESA proteins and their protein carrier as well as between each RESA peptide and a non-epitopic RESA control peptide validated the use of the engineered recombinant proteins and peptides for the measurement of plasma IgG. Taking into account age, fever duration and parasitaemia, a multiple logistic regression performed on children clustered according to their antibody responses' profiles concluded to an increased risk of severe malaria for P2 (representative of RESA-1) responders (P = 0.007). Increased IL-10 plasma levels were found in children harbouring multiclonal P. falciparum infections on the basis of the T1526G resa2 gene polymorphism (P = 0.004). Conclusions: This study provided novel tools to dissect the seroreactivity against the three members of the RESA protein family and to describe its relation to protection against malaria. It suggested the measurement of plasma antibodies raised against specific peptides to serve as predictive immunologic markers for disease severity. Lastly, it reinforced previous observations linking the T1526G resa2 gene mutation to severe malaria. © 2015 Badaut et al.


Dechavanne C.,Institute Of Recherche Pour Le Developpement | Dechavanne C.,University of Paris Descartes | Pierrat C.,Barcelona Center for International Health Research | Renard E.,University of Paris Descartes | And 13 more authors.
Infection, Genetics and Evolution | Year: 2013

Introduction: Infants born to mothers with placental malaria at delivery develop Plasmodium falciparum parasitemia earlier than those born to mothers without placental infection. This phenomenon may be explained by the development of immune tolerance due to exposure to P. falciparum antigens in utero. The hypothesis of this study is that this increased susceptibility might be related to infections by parasites expressing the same blood stage allele's antigens as those to which the infants were exposed in utero. Methods: The comparison of P. falciparum msp2 (. 3D7 and FC27) and glurp gene polymorphisms of infected mothers at delivery to those of their offspring's infections during infancy was realized and the possible associations of the different polymorphisms with clinical outcomes were assessed. A second approach consisted in the use of a Geographic Information System to determine whether the antigen alleles were homogeneously distributed in the area of study. This was necessary to analyze whether the biological observations were due to high exposure to a particular antigen allelic form in the environment or to high infant permissiveness to the same allelic antigen polymorphism as the placental one. Results: Infants born to mothers with placental malaria at delivery were more susceptible to infections by parasites carrying the same glurp allele as encountered in utero compared to distinct alleles, independently of their geographic distribution. Conclusion: The increased permissiveness of infants to plasmodial infections with shared placental-infant glurp alleles sheds light on the role that P. falciparum blood stage antigen polymorphisms may play in the first plasmodial infections in infancy. © 2013 The Authors.


Rafiou A.,Center Detude Et Of Recherche Sur Le Paludisme Associe Grossesse Et Lenfance Cerpage | Rafiou A.,Institute Of Recherche Pour Le Developpement | Rafiou A.,University of Paris Descartes | Francine C.,Center Detude Et Of Recherche Sur Le Paludisme Associe Grossesse Et Lenfance Cerpage | And 34 more authors.
Acta Tropica | Year: 2016

Antibodies that impede the invasion of Plasmodium falciparum (P. falciparum) merozoites into erythrocytes play a critical role in anti-malarial immunity. The Growth Inhibition Assay (GIA) is an in vitro measure of the functional capacity of such antibodies to limit erythrocyte invasion and/or parasite growth. Up to now, it is unclear whether growth-inhibitory activity correlates with protection from clinical disease and there are inconsistent results from studies performed with GIA. Studies that have focused on the relationship between IgGs and their in vitro parasite Growth Inhibition Activity (GIAc) in infants aged less than two years old are rare. Here, we used clinical and parasitological data to precisely define symptomatic or asymptomatic infection with P. falciparum in groups of infants followed-up actively for 18 months post-natally. We quantified the levels of IgG1 and IgG3 directed to a panel of candidate P. falciparum vaccine antigens (AMA-1, MSP1, 2, 3 and GLURP) using ELISA and the functional activity of IgG was quantified using GIA. Data were then correlated with individuals' infection status. At 18 months of age, infants harbouring infections at the time of blood sampling had an average 19% less GIAc than those not infected (p = 0.004, multivariate linear regression). GIAc decreased from 12 to 18 months of age (p = 0.003, Wilcoxon matched pairs test). Antibody levels quantified at 18 months in infants were strongly correlated with their exposure to malarial infection, however GIAc was not correlated with malaria infectious status (asymptomatic and symptomatic groups). In conclusion, both infection status at blood draw and age influence parasite growth inhibition mediated by IgG in the GIA. Both factors must be taken into account when correlations between GIAc and anti-malarial protection or vaccine efficacy have to be made. © 2016 Elsevier B.V.


PubMed | Biomedical Primate Research Center, Center Detude Et Of Recherche Sur Le Paludisme Associe Grossesse Et Lenfance Cerpage, University of Paris Descartes and University Abomey Calavi
Type: | Journal: Acta tropica | Year: 2016

Antibodies that impede the invasion of Plasmodium falciparum (P. falciparum) merozoites into erythrocytes play a critical role in anti-malarial immunity. The Growth Inhibition Assay (GIA) is an in vitro measure of the functional capacity of such antibodies to limit erythrocyte invasion and/or parasite growth. Up to now, it is unclear whether growth-inhibitory activity correlates with protection from clinical disease and there are inconsistent results from studies performed with GIA. Studies that have focused on the relationship between IgGs and their in vitro parasite Growth Inhibition Activity (GIAc) in infants aged less than two years old are rare. Here, we used clinical and parasitological data to precisely define symptomatic or asymptomatic infection with P. falciparum in groups of infants followed-up actively for 18 months post-natally. We quantified the levels of IgG1 and IgG3 directed to a panel of candidate P. falciparum vaccine antigens (AMA-1, MSP1, 2, 3 and GLURP) using ELISA and the functional activity of IgG was quantified using GIA. Data were then correlated with individuals infection status. At 18 months of age, infants harbouring infections at the time of blood sampling had an average 19% less GIAc than those not infected (p=0.004, multivariate linear regression). GIAc decreased from 12 to 18 months of age (p=0.003, Wilcoxon matched pairs test). Antibody levels quantified at 18 months in infants were strongly correlated with their exposure to malarial infection, however GIAc was not correlated with malaria infectious status (asymptomatic and symptomatic groups). In conclusion, both infection status at blood draw and age influence parasite growth inhibition mediated by IgG in the GIA. Both factors must be taken into account when correlations between GIAc and anti-malarial protection or vaccine efficacy have to be made.


PubMed | Biomedical Primate Research Center, Institute Of Recherche Pour Le Developpement, Center Detude Et Of Recherche Sur Le Paludisme Associe Grossesse Et Lenfance Cerpage, Statens Serum Institute and 2 more.
Type: | Journal: Scientific reports | Year: 2016

To our knowledge, effects of age, placental malaria infection, infections during follow-up, nutritional habits, sickle-cell trait and individual exposure to Anopheles bites were never explored together in a study focusing on the acquisition of malaria antibody responses among infants living in endemic areas.Five hundred and sixty-seven Beninese infants were weekly followed-up from birth to 18 months of age. Immunoglobulin G (IgG), IgG1 and IgG3 specific for 5 malaria antigens were measured every 3 months. A linear mixed model was used to analyze the effect of each variable on the acquisition of antimalarial antibodies in 6-to18-month old infants in univariate and multivariate analyses. Placental malaria, nutrition intakes and sickle-cell trait did not influence the infant antibody levels to P. falciparum antigens. In contrary, age, malaria antibody levels at birth, previous and present malaria infections as well as exposure to Anopheles bites were significantly associated with the natural acquisition of malaria antibodies in 6-to18-month old Beninese infants. This study highlighted inescapable factors to consider simultaneously in an immuno-epidemiological study or a vaccine trial in early life.

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