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August 2005 People with hemoglobin type C are less prone to severe malaria because it impairs the ability of malaria parasites to cause disease symptoms, according to research published in Nature from the National Institute of Allergy and Infectious Diseases.
In parts of West Africa, where malaria is endemic, one-fourth of the population has at least one gene for hemoglobin C. Children with at least one hemoglobin C gene are less prone to deadly cerebral malaria. But how hemoglobin C confers this protection has puzzled scientists until now. To solve the mystery, researchers studied laboratory-infected red blood cells and blood drawn from Mali children with malaria. Genetically, the samples fell into three groups: those with two genes for hemoglobin A (AA), those with two genes for hemoglobin C (CC) or those with one gene for each type of hemoglobin (AC). The scientists measured agglutination, rosetting and cytoadherence to determine how well parasitized red blood cells can be made to stick to one another, to uninfected red blood cells and to blood vessel walls. All three phenomena depend on a parasite protein called PfEMP-1. To evade the immune system, malaria parasites produce proteins, including PfEMP-1, that remodel the red blood cell’s surface to their advantage. For example, when spikes of PfEMP-1 are distributed evenly over the surface of an infected AA red blood cell, they act like grappling hooks, allowing the parasitized cells to stick in tiny capillaries and avoid being cleared from the bloodstream. When parasite-infected red blood cells stick to blood vessel walls, the resulting inflammation may increase the severity of malarial symptoms, according to the researchers. Researchers found uneven and reduced distribution of PfEMP-1 on the surface of parasite-infected red blood cells from children with one hemoglobin C gene. This abnormal distribution of PfEMP-1 significantly impairs the infected cells’ stickiness. For instance, laboratory-grown, parasitized AC blood cells agglutinated at a 75% lower rate than AA red blood cells did, while parasitized CC blood cells did not stick to each other at all. Rosette formation, in which parasitized cells attach to non-parasitized cells, also occurred less often with AC and CC blood cells than with AA blood cells. Rosettes can impede blood flow in small vessels of the brain, contributing to cerebral malaria and death, according to the study. For more information: |
