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Plasmodium vivax malaria remains a major public health problem. The requirements for acquisition of protective immunity to the species are not clear. Dendritic cells (DC) are essential for immune cell priming but also perform immune regulatory functions, along with regulatory T cells (Treg). An important function of DC involves activation of the kynurenine pathway via indoleamine 2,3-dioxygenase (IDO). Using a controlled human experimental infection study with blood-stage P. vivax , we characterized plasmacytoid DC (pDC) and myeloid DC (mDC) subset maturation, CD4 + CD25 + CD127 lo Treg activation, and IDO activity. Blood samples were collected from six healthy adults preinoculation, at peak parasitemia (day 14; ∼31,400 parasites/ml), and 24 and 48 h after antimalarial treatment. CD1c + and CD141 + mDC and pDC numbers markedly declined at peak parasitemia, while CD16 + mDC numbers appeared less affected. HLA-DR expression was selectively reduced on CD1c + mDC, increased on CD16 + mDC, and was unaltered on pDC. Plasma IFN-γ increased significantly and was correlated with an increased kynurenine/tryptophan (KT) ratio, a measure of IDO activity. At peak parasitemia, Treg presented an activated CD4 + CD25 + CD127 lo CD45RA - phenotype and upregulated TNFR2 expression. In a mixed-effects model, the KT ratio was positively associated with an increase in activated Treg. Our data demonstrate that a primary P. vivax infection exerts immune modulatory effects by impairing HLA-DR expression on CD1c + mDC while activating CD16 + mDC. Induction of the kynurenine pathway and increased Treg activation, together with skewed mDC maturation, suggest P. vivax promotes an immunosuppressive environment, likely impairing the development of a protective host immune response., (Copyright © 2017 American Society for Microbiology.)

Objectives: Aboriginal children in tropical Australia have a high prevalence of both iron deficiency and acute infections, making it difficult to differentiate their relative contributions to anaemia. The aims of this study were to compare soluble transferrin receptor with ferritin in iron deficiency anaemia (IDA), and to examine how best to distinguish the effect of iron deficiency from infection on anaemia., Methods: We conducted a prospective study of 228 admissions to Royal Darwin Hospital in children from 6 to 60 months of age. Transferrin receptor concentrations were measured by a particle-enhanced immunoturbidimetric assay and ferritin by a microparticle enzyme immunoassay., Results: On multiple regression, the best explanatory variables for haemoglobin differences (r2=33.7%, P<0.001) were mean corpuscular volume (MCV), red cell distribution width (RDW) and C-reactive protein (CRP); whereas transferrin receptor and ferritin were not significant (P>0.4). Using > or =2 abnormal indices (MCV, RDW, blood film)+haemoglobin <110 g/l as the reference standard for IDA, transferrin receptor produced a higher area under the curve on receiver operating characteristic curve analysis than ferritin (0.79 vs. 0.64, P<0.001) or the transferrin receptor-ferritin index (0.77). On logistic regression, the effect of acute infection (CRP) on haemoglobin was significant (P<0.001) at cut-offs of 105 and 110 g/l, but not at 100 g/l when only iron deficiency indicators (MCV, RDW, blood film) were significant., Conclusions: Transferrin receptor does not significantly improve the diagnosis of anaemia (iron deficiency vs. infection) over full blood count and CRP, but in settings with a high burden of infectious diseases and iron deficiency, it is a more reliable adjunctive measure of iron status than ferritin.

Sialic acid is found in especially high concentrations in brain gangliosides, and supplementary sialic acid is associated with increased learning behaviour in animals. It was hypothesised that breast fed infants may have higher concentrations of sialic acid in body fluids and tissues because human milk is a rich source of sialylated oligosaccharides, while formulas contain very little. The aim therefore was to compare the sialic acid content of saliva collected from full term infants who were either solely breast fed or formula fed until weaning at 3-5 months of age. Thirty three infants, 18 breast fed and 15 formula fed, were studied at a mean (SD) age of 5 (2) months. The breast fed infants, when compared with formula fed infants, were found to have almost two times more free sialic acid in saliva (mean (SE) 16.0 (2.7) v 8.2 (2.1) mg/l, p < 0.036) and nearly 50% more total sialic acid (47.3 (3.9) v 32.2 (4.4) mg/l, p < 0.014). The findings provide a preliminary indication that an exogenous source of sialic acids derived from human milk may contribute to higher concentrations of sialic acid in body fluids. There are important implications for the formulation of human milk substitutes.