Analyses des réponses IgG dirigées contre des antigènes candidats vaccins dans le paludisme urbain non aggravé à Dakar (Sénégal) : variations suivant l’âge et les densités parasitaires

Abstract

Malaria remains a major problem in African countries despite substantial decreases in morbidity and mortality due to sustained control programs. Studies for the evaluation of qualitative or quantitative Ab responses to key targets of anti-plasmodium immunity were mostly done in rural endemic setting compared to urban area. In a cohort of 200 patients with mild malaria and living in Dakar, we analyze total and subclasses IgG responses to a panel of P. falciparum blood stage antigens: MSP1p19, MSP3, EB200, GST-5 and R23. A mean age of 15 yrs (4 to 56 yrs) and parasitemia between 0.1 to 17% were found. Levels of IgG anti-MSP3 were higher in patients with low parasitemia (≤1%) and appear negatively correlated to parasite densities (Rho =. 0.54; p= 0.021). This correlation is more significant in children (≤ 15 yrs). In addition, an increase of IgG responses against MSP1p19 is highly observed in adults having a parasitemia less than 1%. In those patients, we find that IgG1 subclasses were predominant (p <0.01). Our study shows an association between Ab responses and parasitemia. This association is dependant to IgG anti-MSP3 in children and IgG anti-MSP1p19 in adults living in urban area.

Inflammatory cytokine and humoral responses to Plasmodium falciparum glycosylphosphatidylinositols correlates with malaria immunity and pathogenesis

“…In our study, these associations were not observed. Discordances can be explained firstly by the low endemicity in urban area of Dakar 17 and the second explanation can be the fact that our study population was constituted by symptomatic malaria patients and as described previously no significant difference of IgG anti‐ P. falciparum levels were reported between adults and children hospitalized patients 26, 27.…”

Optimization of a magnetic bead-based assay (MAGPIX®-Luminex) for immune surveillance of exposure to malaria using multiple Plasmodium antigens and sera from different endemic settings

“…Discrepancies were especially apparent when analysing antibody responses in CM samples. The profile of antibody responses for low endemic urban malaria was substantially different, with no relationship between age and response level as already observed in this setting [ 45 ]. Such profiles reflect the limited cumulative individual exposition in urban areas, in agreement with the observed antigen dependent longevity of antibody responses which is independent of response magnitude [ 46 ].…”

Relationship between Antibody Levels, IgG Binding toPlasmodium falciparum-Infected Erythrocytes, and Disease Outcome in Hospitalized Urban Malaria Patients from Dakar, Sénégal

“…The flow cytometry technique has been already used as a relevant surrogate marker in IgG binding to iRBC in different contexts: before and after vaccination trials [ 18 ], as function of age and hemoglobin type in Malian children [ 38 ] and as a differential marker in Senegalese individuals living in rural settings with different levels of endemicity [ 17 ]. In urban setting, previous studies focused on relationship between antibody responses to defined antigens and clinicoepidemiology such as age of individuals and severity of outcome [ 23 , 33 ]. However, as reported in rural symptomatic malaria, the amount of sequestered parasites increased with disease severity [ 7 ], and the binding of P. falciparum -infected RBCs to microvascular endothelial cells induces pathological sequelae in microvessels that are associated with the symptoms and severe manifestations such as CM [ 39 ].…”

“…It expresses the C-proximal region of Pf EMP3, a high-molecular weight host membrane-associated protein [ 31 , 32 ]. The control protein was the GST carrier previously reported [ 23 , 33 ].…”

“…The OD signals of the samples were individually corrected for the GST or nRBCm signal. Serum samples with OD ratios greater than 2 (which is over the OD of naïve control + 3 SD) were considered seropositive [ 26 , 32 , 33 ].…”