Circulating IL-6, IL-10, and TNF-alpha and IL-10/IL-6 and IL-10/TNF-alpha ratio profiles of polyparasitized individuals in rural and urban areas of gabon.

Malaria, blood-borne filarial worms and intestinal parasites are all endemic in Gabon. This geographical co-distribution leads to polyparasitism and, consequently, the possibility of immune-mediated interactions among different parasite species. Intestinal protozoa and helminths could modulate antimalarial immunity, for example, thereby potentially increasing or reducing susceptibility to malaria. The aim of the study was to compare the cytokine levels and cytokine ratios according to parasitic profiles of the population to determine the potential role of co-endemic parasites in the malaria susceptibility of populations. Blood and stool samples were collected during cross-sectional surveys in five provinces of Gabon. Parasitological diagnosis was performed to detect plasmodial parasites, Loa loa, Mansonella perstans, intestinal helminths (STHs) and protozoan parasites. Nested PCR was used to detect submicroscopic plasmodial infection in individuals with negative blood smears. A cytometric bead array was used to quantify interleukin (IL)-6, IL-10 and tumour necrosis factor (TNF)-α in the plasma of subjects with different parasitological profiles. Median IL-6 and IL-10 levels and the median IL-10/TNF-α ratio were all significantly higher among individuals with Plasmodium (P.) falciparum infection than among other participants (p<0.0001). The median TNF-α level and IL-10/IL-6 ratio were higher in subjects with STHs (p = 0.09) and P. falciparum-intestinal protozoa co-infection (p = 0.04), respectively. IL-6 (r = -0.37; P<0.01) and IL-10 (r = -0.37; P<0.01) levels and the IL-10/TNF-α ratio (r = -0.36; P<0.01) correlated negatively with age. Among children under five years old, the IL-10/TNF-α and IL-10/IL-6 ratios were higher in those with intestinal protozoan infections than in uninfected children. The IL-10/TNF-α ratio was also higher in children aged 5-15 years and in adults harbouring blood-borne filariae than in their control counterparts, whereas the IL-10/IL-6 ratio was lower in those aged 5-15 years with filariae and intestinal parasites but higher in adults with intestinal parasitic infections. Asymptomatic malaria is associated with a strong polarization towards a regulatory immune response, presenting high circulating levels of IL-10. P. falciparum/intestinal protozoa co-infections were associated with an enhanced IL-10 response. Immunity against malaria could differ according to age and carriage of other parasites. Helminths and intestinal protozoa can play a role in the high susceptibility to malaria currently observed in some areas of Gabon, but further investigations are necessary.

Circulating Cytokines Associated with Poor Pregnancy Outcomes in Beninese Exposed to Infection with Plasmodium falciparum.

Malaria during pregnancy is a major cause of maternal morbidity as well as fetal and neonatal mortality. Previous studies, including our own, suggested that placental and peripheral cytokine and chemokine levels measured at delivery can be used as biomarkers for pregnancy outcomes. However, the timing of malaria infection during pregnancy matters, and these studies do not address the effect of different cytokines in peripheral blood plasma samples taken at early and midpregnancy and at delivery. Here, we aimed to investigate whether peripheral plasma cytokine levels were associated with pregnancy outcomes in a cohort of 400 Beninese pregnant women. Using a high-sensitivity cytometry-based method, we quantified the levels of interleukin-4 (IL-4), IL-5, IL-10, IL-12p70, and gamma interferon (IFN-γ) in peripheral plasma samples taken at two time points during pregnancy and at delivery in various groups of pregnant women identified with Plasmodium falciparum infection, with anemia, with preterm births, or giving birth to babies who are small for their gestational age. We found that, consistently at all time points, elevated levels of IL-10 were strongly and significantly associated with P. falciparum infection, while the levels of IFN-γ at inclusion and delivery were weakly but also significantly associated. Low levels of IL-5 at delivery were associated with a greater risk of both preterm births and small-for-gestational-age babies. The immunosuppressive effects of IL-10 likely affect the overall cytokine equilibrium during pregnancy in women harboring P. falciparum infections. Our findings highlight the peripheral signature of pregnancy outcomes and strengthen the idea of using cytokines as diagnostic or prognostic markers.

Genetic polymorphism of merozoite surface protein-1 and merozoite surface protein-2 in Plasmodium falciparum isolates from children in South of Benin.

The aim of this study was to determine the genetic diversity of Plasmodium falciparum by analyzing the polymorphism of the msp-1 and msp-2 genes and the multiplicity of infection in children with uncomplicated malaria in southern Benin. Blood samples of children with fever or history of fever with thick smear positive P. falciparum were collected on filter paper. After extraction of DNA by Chelex®, the samples underwent nested PCR. 93 isolates from children were genotyped. For the msp-1 gene, the K1 and R033 sequences were the most represented in the study population with 85.2% and 83% prevalence, respectively. Regarding the msp-2 gene, the FC27 family was more highly represented with 99% prevalence against 81.5% for 3D7. Mixed infections accounted for 80.4% of the samples. Twenty-five alleles were identified for msp-1 and 28 for msp-2. Fourteen and ten alleles belonged to the K1 (100-500 bp) and MAD20 (100-500 bp) families, respectively. The RO33 sequence did not show any polymorphism, with only one variant (160 bp) detected. The msp-2 gene was present as 16 FC27 family fragments (250-800 bp) and 12 of the 3D7 family (350-700 bp). The multiplicity of infection was estimated at 3.8 for msp-1 and 3.9 for msp-2 with 77 (87.5%) and 84 (91.3%) samples harboring more than one parasite genotype for msp-1 and msp-2, respectively. The multiplicity of infection (MOI) was influenced neither by age nor by parasite density. This study shows a significant diversity of P. falciparum in southern Benin with an MOI unaffected by age or by parasite density.