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

Prah, D. A., Amoah, L. E., Gibbins, M. P. , Bediako, Y., Cunnington, A. J., Awandare, G. A. and Hafalla, J. C. R. (2020) Comparison of leucocyte profiles between healthy children and those with asymptomatic and symptomatic Plasmodium falciparum infections. Malaria Journal, 19(1), 364. (doi: 10.1186/s12936-020-03435-x) (PMID:33036624) (PMCID:PMC7547495)

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.

• Item Type: Articles
• Additional Information: DAP is supported by a PhD fellowship from a World Bank African Centres of Excellence Grant (ACE02-WACCBIP to GAA) and Wellcome/African Academy of Sciences DELTAS grant (DEL-15-007/107755/Z/15/Z) to GAA. MPG was a recipient of an LSHTM Doctoral Project Travelling Scholarship. AJC was funded by a Clinician Scientist Fellowship (MR/L006529/1—this award is jointly funded by the UK Medical Research Council (MRC) and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement and is also part of the EDCTP2 Programme supported by the European Union). JCRH was funded by grants from The Royal Society (University Research Fellowship UF0762736/UF120026 and Challenge Grant CH160018).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Gibbins, Dr Matt
• Authors: Prah, D. A., Amoah, L. E., Gibbins, M. P., Bediako, Y., Cunnington, A. J., Awandare, G. A., and Hafalla, J. C. R.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Malaria Journal
• Publisher: BMC
• ISSN: 1475-2875
• ISSN (Online): 1475-2875
• Copyright Holders: Copyright © 2020 The Authors
• First Published: First published in Malaria Journal 19(1):364
• Publisher Policy: Reproduced under a Creative Commons License