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Certain red blood cell (RBC) disorders, including thalassemia, have been associated with an innate protection against malaria infection. However, many in vitro correlative studies have been inconclusive. To better understand the relationship between human RBCs with thalassemia hemoglobinopathies and susceptibility to in vitro infection, we used an in vitro coculture system that involved biotin labeling and flow cytometry to study the ability of normal and variant RBC populations in supporting the growth of Plasmodium falciparummalaria parasites. Results showed that both normal and thalassemic RBCs were susceptible to P falciparuminvasion, but the parasite multiplication rates were significantly reduced in the thalassemic RBC populations. The growth inhibition was especially marked in RBCs from α-thalassemia patients (both α-thalassemia1/α-thalassemia2and α-thalassemia1heterozygote). Our observations support the contention that thalassemia confers protection against malaria and may explain why it is more prevalent in malaria endemic areas.

Hemoglobinopathies have a protective role in malaria that appears to be related to alterations in red blood cell (RBC) properties. Thalassemic RBCs infected with Plasmodium falciparumshowed greatly reduced cytoadherence and rosetting properties as well as impaired growth and multiplication. A significant decrease in the levels of falciparum antigens associated with the membrane of infected β-thalassemic RBCs was observed at trophozoite/schizont stage, but not young ring stage. This reduction was shown when a cytoadherence inhibitory monoclonal antibody, but not a noninhibitory pooled immune serum, was used. These observations suggest that protection against malaria in thalassemia is caused by both reduced parasitemias and altered adherence properties of the infected thalassemic RBCs that promote enhanced clearance of the parasite from the circulation.