Lymphocyte Perturbations in Malawian Children with Severe and Uncomplicated Malaria.

Wilson L Mandala,Paul Pensulo,James J Gilchrist,Stephen M Graham,Meraby Banda,Grace Mwimaniwa,Steven A Ward,Malcolm E Molyneux,Calman A Maclennan,Chisomo L Msefula,Esther N Gondwe,Mark T Drayson,Elizabeth E Molyneux,Terrie E Taylor,M F Pasetti

doi:10.1128/cvi.00564-15

Abstract

Lymphocytes are implicated in immunity and pathogenesis of severe malaria. Since lymphocyte subsets vary with age, assessment of their contribution to different etiologies can be difficult. We immunophenotyped peripheral blood from Malawian children presenting with cerebral malaria, severe malarial anemia, and uncomplicated malaria (n = 113) and healthy aparasitemic children (n = 42) in Blantyre, Malawi, and investigated lymphocyte subset counts, activation, and memory status. Children with cerebral malaria were older than those with severe malarial anemia. We found panlymphopenia in children presenting with cerebral malaria (median lymphocyte count, 2,100/μl) and uncomplicated malaria (3,700/μl), which was corrected in convalescence and was absent in severe malarial anemia (5,950/μl). Median percentages of activated CD69+ NK (73%) and γδ T (60%) cells were higher in cerebral malaria than in other malaria types. Median ratios of memory to naive CD4+ lymphocytes were higher in cerebral malaria than in uncomplicated malaria and low in severe malarial anemia. The polarized lymphocyte subset profiles of different forms of severe malaria are independent of age. In conclusion, among Malawian children cerebral malaria is characterized by lymphocyte activation and increased memory cells, consistent with immune priming. In contrast, there are reduced memory cells and less activation in severe malaria anemia. Further studies are required to understand whether these immunological profiles indicate predisposition of some children to one or another form of severe malaria.

Highlights

Lymphocytes are implicated in immunity and pathogenesis of severe malaria
Lymphocyte Changes in Severe Malaria guish memory and naive T cells, respectively, we found a high ratio of memory to naive CD4ϩ lymphocytes in cerebral and uncomplicated malaria compared with controls and children with severe malarial anemia (Table 4; Fig. 4)
Using careful malaria subtype case definitions and analysis of results with age, we have confirmed that the immunophenotype profiles of different forms of severe malaria are linked to the infection itself rather than patient age

Summary

Introduction

Lymphocytes are implicated in immunity and pathogenesis of severe malaria. Since lymphocyte subsets vary with age, assessment of their contribution to different etiologies can be difficult. We immunophenotyped peripheral blood from Malawian children presenting with cerebral malaria, severe malarial anemia, and uncomplicated malaria (n ‫ ؍‬113) and healthy aparasitemic children (n ‫ ؍‬42) in Blantyre, Malawi, and investigated lymphocyte subset counts, activation, and memory status. We found panlymphopenia in children presenting with cerebral malaria (median lymphocyte count, 2,100/␮l) and uncomplicated malaria (3,700/␮l), which was corrected in convalescence and was absent in severe malarial anemia (5,950/␮l). A number of clinical studies of lymphocyte populations have been conducted in African children [11,12,13,14,15] The results of these studies can be difficult to interpret, because large studies usually do not discriminate between different clinical manifestations of malaria and the lymphocyte subsets investigated are often limited. We investigated absolute and percent lymphocyte counts and lymphocyte activation and memory status

Methods

Results

Conclusion