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Lokossou A.G.,CIRAD - Agricultural Research for Development | Lokossou A.G.,University of Paris Descartes | Dechavanne C.,CIRAD - Agricultural Research for Development | Dechavanne C.,University of Paris Descartes | And 19 more authors.
BMC Infectious Diseases | Year: 2013

Background: Particular cytokine gene polymorphisms are involved in the regulation of the antibody production. The consequences of already described IL-4, IL-10 and IL-13 gene polymorphisms on biological parameters and antibody levels were investigated among 576 mothers at delivery and their newborns in the context of P. falciparum placental malaria infection.Methods: The study took place in the semi-rural area of Tori-Bossito, in south-west Benin, where malaria is meso-endemic. Six biallelic polymorphisms were determined by quantitative PCR using TaqMan® Pre-Designed SNP Genotyping Assays, in IL-4 (rs2243250, rs2070874), IL-10 (rs1800896, rs1800871, rs1800872) and IL-13 (rs1800925) genes. Antibody responses directed to P. falciparum MSP-1, MSP-2, MSP-3, GLURP-R0, GLURP-R2 and AMA-1 recombinant proteins were determined by ELISA.Results: The maternal IL-4-590*T/IL-4+33*T haplotype (one or two copies) was associated with favorable maternal condition at delivery (high haemoglobin levels, absence of placental parasites) and one of its component, the IL-4-590TT genotype, was related to low IgG levels to MSP-1, MSP-2/3D7 and MSP-2/FC27. Inversely, the maternal IL-10-1082AA was positively associated with P. falciparum placenta infection at delivery. As a consequence, the IL-10-819*T allele (in CT and TT genotypes) as well as the IL-10-1082*A/IL-10-819*T/IL-10-592*A haplotype (one or two copies) in which it is included, were related to an increased risk for anaemia in newborns. The maternal IL-10-1082AA genotype was related to high IgG levels to MSP-2/3D7 and AMA-1 in mothers and newborns, respectively. The IL-13 gene polymorphism was only involved in the newborn's antibody response to AMA-1.Conclusion: These data revealed that IL-4 and IL-10 maternal gene polymorphisms are likely to play a role in the regulation of biological parameters in pregnant women at delivery (anaemia, P. falciparum placenta infection) and in newborns (anaemia). Moreover, IL-4, IL-10 and IL-13 maternal gene polymorphisms were related to IgG responses to MSP-1, MSP-2/3D7 and MSP-2/FC27 in mothers as well as to AMA-1 in newborns. © 2013 Lokossou et al.; licensee BioMed Central Ltd.

Kedote N.M.,Institute des science Biomedicales Appliquees | Brousselle A.,Universite de Sherbrooke | Champagne F.,University of Montreal | Laudy D.,University of Montreal
Ethique et Sante | Year: 2011

Introduction: In international and national HIV/AIDS policies, free and informed consent is recognized as one of the major components of testing programs. For pregnant women, free and informed consent means that they should get information on prevention of mother-to-child transmission (PMTCT), understand them and make an independent choice after weighing the risks and advantages. However, no PMTCT program looked into the issue of consent. The objective of this paper is to explore the free and informed nature of pregnant women's consent with regard to testing and their rationale for accepting to be tested. Methods: We used data collected within the framework of the analysis of the creation of the PMTCT program in Benin. This analysis is based on multiple case studies that covered six maternity homes selected from 56 operational sites. For the specific analysis of consent, we used both survey data and qualitative research data. Findings: Apart from three cases of secret testing, the free nature of the consent to the test is respected on the PMTCT sites. Twenty-nine cases of refusal were recorded. The reasons put forth by most pregnant women include the fear of a positive test and its consequences on family life in 55.2% of cases and the expectation of their husbands' agreement or disagreement in 27.6% of cases. On the whole, the consent was free on all the sites but its informed nature is less respected. © 2011 Elsevier Masson SAS.

Courtin D.,IRD Montpellier | Courtin D.,University of Paris Descartes | Courtin D.,Institute des science Biomedicales Appliquees | Courtin D.,University of Monastir | And 16 more authors.
Infection, Genetics and Evolution | Year: 2011

High antibody levels directed to Plasmodium falciparum merozoite surface proteins (MSP), including MSP2, as well as genetically related red blood cell defects, have previously been found to be associated with protection against malaria. Here, our main objective was to study the changes in MSP2-specific total IgG, IgG1 and IgG3 responses during a malaria transmission season in order to assess the impact of sickle-cell, α(+)-thalassemia and G6PD variants on antibody kinetics. Repeated parasitological assessments of a cohort of children were conducted during an 8-month period. Antibody responses to recombinant MSP2/3D7 and MSP2/FC27 proteins were measured at the beginning and at the end of transmission season. We found that (i) the period of last Plasmodium falciparum infection during the transmission season was associated with IgG3 anti-MSP2 change. Compared to the IgG3 levels of children infected in January 2003 (end of transmission season), the IgG3 level of children decreased with the length of the period without infection, (ii) G6PD A- carriers had a lower increase of IgG3 levels to MSP2/FC27 and MSP2/3D7 during the transmission season than the noncarriers. This latter finding is suggestive of qualitative and/or quantitative reduction of exposure to malarial antigens related to this genetic variant, leading to weaker stimulation of specific antibody responses. We speculate that cell-mediated immune activity may explain the clinical protection afforded by this genetic trait. © 2011 Elsevier B.V.

Alassane-Kpembi I.,French National Institute for Agricultural Research | Alassane-Kpembi I.,National Polytechnic Institute of Toulouse | Alassane-Kpembi I.,Institute des science Biomedicales Appliquees | Kolf-Clauw M.,French National Institute for Agricultural Research | And 10 more authors.
Toxicology and Applied Pharmacology | Year: 2013

Deoxynivalenol (DON) is the most prevalent trichothecene mycotoxin in crops in Europe and North America. DON is often present with other type B trichothecenes such as 3-acetyldeoxynivalenol (3-ADON), 15-acetyldeoxynivalenol (15-ADON), nivalenol (NIV) and fusarenon-X (FX). Although the cytotoxicity of individual mycotoxins has been widely studied, data on the toxicity of mycotoxin mixtures are limited. The aim of this study was to assess interactions caused by co-exposure to Type B trichothecenes on intestinal epithelial cells. Proliferating Caco-2 cells were exposed to increasing doses of Type B trichothecenes, alone or in binary or ternary mixtures. The MTT test and neutral red uptake, respectively linked to mitochondrial and lysosomal functions, were used to measure intestinal epithelial cytotoxicity. The five tested mycotoxins had a dose-dependent effect on proliferating enterocytes and could be classified in increasing order of toxicity: 3-ADON. <. 15-ADON. ≈. DON. <. NIV. ≪. FX. Binary or ternary mixtures also showed a dose-dependent effect. At low concentrations (cytotoxic effect between 10 and 30-40%), mycotoxin combinations were synergistic; however DON-NIV-FX mixture showed antagonism. At higher concentrations (cytotoxic effect around 50%), the combinations had an additive or nearly additive effect. These results indicate that the simultaneous presence of low doses of mycotoxins in food commodities and diet may be more toxic than predicted from the mycotoxins alone. Considering the frequent co-occurrence of trichothecenes in the diet and the concentrations of toxins to which consumers are exposed, this synergy should be taken into account. © 2013 Elsevier Inc.

Vigan-Womas I.,Institute Pasteur Paris | Vigan-Womas I.,French National Center for Scientific Research | Lokossou A.,CIRAD - Agricultural Research for Development | Lokossou A.,University of Paris Descartes | And 18 more authors.
Malaria Journal | Year: 2010

Abstract. Background. The capacity of Plasmodium falciparum-infected erythrocytes to bind uninfected erythrocytes (rosetting) is associated with severe malaria in African children. Rosetting is mediated by a subset of the variant surface antigens PfEMP1 targeted by protective antibody responses. Analysis of the response to rosette-forming parasites and their PfEMP1 adhesive domains is essential for understanding the acquisition of protection against severe malaria. To this end, the antibody response to a rosetting variant was analysed in children recruited with severe or uncomplicated malaria or asymptomatic P. falciparum infection. Methods. Serum was collected from Beninese children with severe malaria, uncomplicated malaria or P. falciparum asymptomatic infection (N = 65, 37 and 52, respectively) and from immune adults (N = 30) living in the area. Infected erythrocyte surface-reactive IgG, rosette disrupting antibodies and IgG to the parasite crude extract were analysed using the single variant Palo Alto VarO-infected line. IgG, IgG1 and IgG3 to PfEMP1-varO-derived NTS-DBL11, CIDR and DBL2C2 recombinant domains were analysed by ELISA. Antibody responses were compared in the clinical groups. Stability of the response was studied using a blood sampling collected 14 months later from asymptomatic children. Results. Seroprevalence of erythrocyte surface-reactive IgG was high in adults (100%) and asymptomatic children (92.3%) but low in children with severe or uncomplicated malaria (26.1% and 37.8%, respectively). The IgG, IgG1 and IgG3 antibody responses to the varO-derived PfEMP1 domains were significantly higher in asymptomatic children than in children with clinical malaria in a multivariate analysis correcting for age and parasite density at enrolment. They were essentially stable, although levels tended to decrease with time. VarO-surface reactivity correlated positively with IgG reactivity to the rosetting domain varO-NTS-DBL11. None of the children sera, including those with surface-reactive antibodies possessed anti-VarO-rosetting activity, and few adults had rosette-disrupting antibodies. Conclusions. Children with severe and uncomplicated malaria had similar responses. The higher prevalence and level of VarO-reactive antibodies in asymptomatic children compared to children with malaria is consistent with a protective role for anti-VarO antibodies against clinical falciparum malaria. The mechanism of such protection seems independent of rosette-disruption, suggesting that the cytophilic properties of antibodies come into play. © 2010 Vigan-Womas et al; licensee BioMed Central Ltd.

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