Complement-Mediated Destruction of Red Blood Cells in Children with Plasmodium Falciparum Malaria

Abstract

A total of 484 children aged between 1 -10 years who reported at the emergency unit of the Department of Child Health, Korle Bu Teaching Hospital with clinical malaria were recruited for this study. The children were categorized into four main groups of clinical malaria namely, severe malaria anaemia (SA), cerebral malaria (CM), uncomplicated malaria (UM) and intravascular haemolysis, or bloody urine (IVH). The aim of the study was to determine the role of complement activation in the pathogenesis of malaria anaemia, including intravascular haemolysis. The Coombs test or Direct antiglobulin Test (DAT) was used to detect the binding of C3d alone, IgG alone or both to erythrocytes of P. falciparum malaria patients as well as healthy or asymptomatically infected children (CC). Of the 484 samples tested, 131(27%) were positive for DAT. Out of the 131 DAT positive samples, 115/131 (87%) were positive for C3d alone whiles a small proportion was positive for either IgG alone or both (p<0.05). The results showed that 25/52 (48.1%) of the SA (mean Hb= 4.3g/dl), 23/31 (74.2%) of the IVH (mean Hb=6.1g/dl), 7/25 (28.0%) of the UM (mean Hb=9.0g/dl) and 15/35 (42.8%) of the CM patients (mean Hb=7.3g/dl) were DAT positive. The differences between SA and IVH on one hand and UM on the other for C3d binding were highly significant (p<0.05) suggesting a role for C3d binding and the consequential elimination or destruction of erythrocytes as a cause of the anaemia associated with falciparum malaria. Interestingly, 90% of the DAT positive samples were from children below the ages of five years with mean ages of 3.3 and 3.9 years for SA and IVH cases respectively, confirming that younger children rely on complement activation in response to malaria.