Association of the ICAM-1Kilifi mutation with protection against severe malaria in Lambarene, Gabon

The intercellular adhesion molecule-1 (ICAM-1) is thought to be a receptor that mediates binding of Plasmodium falciparum-infected erythrocytes. Especially in vital organs, the binding of parasitized cells to the endothelium via ICAM-1 may lead to severe disease and death. Recently, a mutation in the coding region of ICAM-1, termed ICAM-1(Kilifi), was described, causing a change from Lys to Met in the loop that interacts with rhinoviruses, lymphocytes, and parasitized red blood cells. Surprisingly, this mutation was shown to increase susceptibility of Kenyan children to severe malaria in one study. When we compared the distribution of ICAM-1(Kilifi) in two groups of Gabonese children enrolled in a case-control, matched-pair study who presented with either mild or severe malaria, we found that 55% of the patients with mild malaria were carriers whereas only 39% of those with severe malaria were carriers. The difference in the distribution of ICAM-1(Kilifi) homozygous pairs between the groups, as well as the distribution of ICAM-1(Kilifi) carriers, was statistically highly significant (P = 0.027 and P = 0.012, by the McNemar test). In a group of healthy school children from the same region, a distribution of 52% ICAM-1(Kilifi) carriers to 48% wild-type individuals was found. In a survey for the ICAM-1(Kilifi) in other malaria-endemic regions, this allele was also found in Nigeria and Papua New Guinea, but not in Thailand.