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

Diana Ahu Prah,Gordon A Awandare,Linda Eva Amoah,Yaw Bediako,Matthew P Gibbins,Julius Clemence R Hafalla,Aubrey J Cunnington

doi:10.1186/s12936-020-03435-x

Abstract

BackgroundThe 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.MethodsPeripheral 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.ResultsIn 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.ConclusionsSymptomatic 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.

Highlights

The immune mechanisms that determine whether a Plasmodium falciparum infection would be symptomatic or asymptomatic are not fully understood
Characteristics of the study population One hundred and eight children were enrolled from the Obom community: 25 with symptomatic malaria, 67 with asymptomatic infections and 16 uninfected controls
Consistent with haematological data, we observed a significant increase in the proportions and absolute numbers of CD15 + neutrophils in the symptomatic children compared to the asymptomatic (p < 0.0001 for both comparisons) and uninfected (p < 0.0001 proportions and p = 0.0035 for absolute counts) groups

Summary

Introduction

The immune mechanisms that determine whether a Plasmodium falciparum infection would be symptomatic or asymptomatic are not fully understood. The subsequent blood-stage infection leads to acute uncomplicated febrile illness, which can progress to severe life-threatening disease, as the parasite load increases [5]. Individuals who survive and are repeatedly re-infected acquire clinical immunity, which limits parasite load and thereby reduces the likelihood of developing clinical symptoms [6]. Since naturally acquired immunity does not completely clear the parasites, individuals remain susceptible to asymptomatic infections [7]. The highest parasite loads are seen in individuals with severe malaria, lower in symptomatic uncomplicated malaria, and lowest (often-times only positive by molecular methods) in asymptomatic infections. The mechanisms of disease progression remain poorly understood and it is likely that there is either constitutive or acquired variation in the ability of individuals to tolerate a given parasite load without symptoms

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