It was also found that the adherence of infected red blood cells to certain cell receptors is also implicated - under the influence of other genes. Increased binding of parasites to the receptor, ICAM-1, may also be associated with severity of disease.
Severe malaria is found significantly more frequently in heterozygotes.
Indeed, only two homozygote individuals were found to have severe malaria among the several hundred patients studied. Patients with severe malaria were also observed to exhibit higher adherence of infected red blood cells, due to an increased expression of the ligand ICAM-1, while the adherence to cells expressing the CD36 marker did not differ significantly. Plasma from patients with cerebral malaria resulted in a greater expression of ICAM-1 than did plasma from patients with uncomplicated malaria or with multiple organ failure. There was no difference in the regulation of CD36 expression between these groups, suggesting that the binding of infected red cells to ICAM-1, but not CD36, plays an important role in the pathogenesis of severe, complicated malaria. Results also showed that binding of ICAM-1 is specifically involved in the pathogenesis of cerebral malaria and that the causal pathogenic mechanism may be different from that causing multiple organ failure.