Malaria remains a significant health problem in tropical countries. Malaria is the leading cause of death in African children less than 5 years of age. In hypoendemic areas, cerebral malaria is most problematic and affects children between 36 and 60 months of age. In holoendemic areas, such as sub-Saharan Africa, severe malarial anemia is the leading cause of death in children between 6 and 24 months of age. Anemia in these children does not appear to be related to severe infection, since only a small fraction of all red blood cells (RBCs) are infected. The anemia appears to be due to hemolysis and to be immune-mediated. Severely anemic children with P falciparum infections often have a positive direct antiglobulin test (DAT) due to RBCs coated with IgG and complement. P falciparum infections also change the membranes of RBCs. The expression of complement regulatory proteins CR1 (CD35) and decay accelerating factor (CD55) are decreased on RBCs from children with severe P falciparum anemia, but the expression of the RBC membrane inhibitor of reactive lysis (CD59) is increased. These results suggest that both autoantibodies and RBC membrane changes may contribute to the severe malaria anemia of childhood. The purpose of this study is to investigate the role of RBC autoantibodies and RBC membrane changes in malarial anemia. In collaborative studies with Dr. Stephen Hoffman and Dr. Trevor Jones, malarial anemia is being studied in an aotus monkey model. Monkeys previously immunized by infection or vaccination to P falciparum protein EBA-175 were challenged with low levels of parasites. Animals that experienced low levels or parasitemia experienced a 50 percent fall in hematocrit over 7 to 14 days. The DAT was used to assess the binding of IgG to the RBCs, but none was detected. Further studies are underway which will investigate anemia in infected aotus monkeys using a DAT that will detect C3d and lower levels of IgG. In other studies, in order to assess the effects of P falciparum RBC antigens, RBCs collected from healthy donors will be infected in a laboratory setting with P falciparum. Following infection and culture of the RBCs with P falciparum, RBCs containing parasites will be separated from uninfected RBCs and these RBCs will be tested with a panel of monoclonal and alloantibodies to determine if RBC antigens are changed. The expression of antigens on RBCs that were in culture with P falciparum will be compared with the expression of antigens on RBCs from the same person that were not exposed to P falcipar
| Greco, Victoria A; Byrne, Karen M; Procter, Jo L et al. (2002) Detection of antibodies in acid eluates with the gel microcolumn assay. Transfusion 42:698-701 |
| Caruccio, L; Byrne, K; Procter, J et al. (2002) A novel method using formamide for the elution of antibodies from erythrocytes. Vox Sang 83:63-9 |
