Anemia is frequent in young children infected with Plasmodium falciparum, and severe malarial anemia (SMA) is a leading cause of death. Malarial anemia is caused by two basic mechanisms: hemolysis of both infected and uninfected erythrocytes and inadequate erythropoiesis. In a longitudinal birth cohort, researchers frequently found significant hemoglobin decreases following P falciparum infections, with a small proportion progressing to SMA. They looked for indicators of these processes in plasma samples from 9 P falciparum-infected children, comparing those with lowered hemoglobin (with or without SMA) to those with stable hemoglobin.
In children with low hemoglobin levels, they found larger levels of circulating 20S proteasome and lower levels of insulin-like growth factor-1 (IGF-1). The findings were verified in subgroups of children from the same cohort using separate enzyme-linked immunosorbent assay-based validation tests (20S proteasome, N=71; IGF-1, N=78). They hypothesized that the circulating 20S proteasome aids in the digestion of oxidatively damaged erythrocyte membrane proteins, resulting in hemolysis, whilst reduced IGF-1, a crucial component for erythroid maturation, may lead to inadequate erythropoiesis. Quantitative plasma proteomics uncovered soluble mediators that might play a role in the primary processes generating malarial anemia.
