Comparison of leucocyte profiles between healthy children and those with asymptomatic and symptomatic Plasmodium falciparum infections

Abstract

Background The immune mechanisms that determine whether a Plasmodium falciparum infection would be symptomatic or asymptomatic are not fully understood. Several studies have been carried out to characterize the associations between disease outcomes and leucocyte numbers. However, the majority of these studies have been conducted in adults with acute uncomplicated malaria, despite children being the most vulnerable group. Methods Peripheral blood leucocyte subpopulations were characterized in children with acute uncomplicated (symptomatic; n = 25) or asymptomatic (n = 67) P. falciparum malaria, as well as malaria-free (uninfected) children (n = 16) from Obom, a sub-district of Accra, Ghana. Leucocyte subpopulations were enumerated by flow cytometry and correlated with two measures of parasite load: (a) plasma levels of P. falciparum histidine-rich protein 2 (PfHRP2) as a proxy for parasite biomass and (b) peripheral blood parasite densities determined by microscopy. Results In children with symptomatic P. falciparum infections, the proportions and absolute cell counts of total (CD3 +) T cells, CD4 + T cells, CD8 + T cells, CD19 + B cells and CD11c + dendritic cells (DCs) were significantly lower as compared to asymptomatic P. falciparum-infected and uninfected children. Notably, CD15 + neutrophil proportions and cell counts were significantly increased in symptomatic children. There was no significant difference in the proportions and absolute counts of CD14 + monocytes amongst the three study groups. As expected, measures of parasite load were significantly higher in symptomatic cases. Remarkably, PfHRP2 levels and parasite densities negatively correlated with both the proportions and absolute numbers of peripheral leucocyte subsets: CD3 + T, CD4 + T, CD8 + T, CD19 + B, CD56 + NK, γδ + T and CD11c + cells. In contrast, both PfHRP2 levels and parasite densities positively correlated with the proportions and absolute numbers of CD15 + cells. Conclusions Symptomatic P. falciparum infection is correlated with an increase in the levels of peripheral blood neutrophils, indicating a role for this cell type in disease pathogenesis. Parasite load is a key determinant of peripheral cell numbers during malaria infections.

‘Bouncing Back’ From Subclinical Malaria: Inflammation and Erythrocytosis After Resolution of P. falciparum Infection in Gambian Children

“…This is consistent with data from Burkina Faso (8), as are our findings that the prevalence of mild to moderate anaemia did not differ between children with persistent subclinical infections and uninfected control children, and that persistently infected children had raised levels of circulating IL-10. Prah et al also found no significant differences in haemoglobin concentrations between uninfected children and those with asymptomatic infections in Ghana (37). However, in contrast to our previous study (8), the only obvious abnormalities in markers of haemolysis, iron handling and inflammation in the persistently infected group were modestly, but significantly, higher concentrations of CD163 and IL-10.…”

Dry season prevalence of Plasmodium falciparum in asymptomatic Gambian children, with a comparative evaluation of diagnostic methods

“…Persistent, low density infections have been linked to low grade in ammation, speci cally raised plasma concentrations of C-reactive protein [47], 49], CXCL1 [50], 51], and IL-6 [49,51]. Low grade anaemia may also be more common in those with subpatent infections than among those without detectable infection [48] although this is not a universal nding [17,52]. Differences between studies in the immunological and haematological status of people with asymptomatic/subpatent infections likely re ect different epidemiological and cohort characteristics and/or the method by which the uninfected control group is de ned.…”

Dry season prevalence of Plasmodium falciparum in asymptomatic Gambian children, with a comparative evaluation of diagnostic methods

“…Persistent, low density infections have been linked to low grade inflammation, specifically raised plasma concentrations of C-reactive protein [ 45 ], IFN-γ [ 46 , 47 ], CXCL1 [ 48 ], IL-10 [ 46 , 49 ], and IL-6 [ 47 , 49 ]. Low grade anaemia may also be more common in those with subpatent infections than among those without detectable infection [ 46 ] although this is not a universal finding [ 16 , 50 ]. Differences between studies in the immunological and haematological status of people with asymptomatic/subpatent infections likely reflect different epidemiological and cohort characteristics and/or methods by which the uninfected control group is defined.…”