Association of the ICAM-1(Kilifi) 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. Espec ially 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 th e 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, lympho cytes, and parasitized red blood cells. Surprisingly, this mutation was sho wn to increase susceptibility of Kenyan children to severe malaria in one s tudy. When we compared the distribution of ICAM-1(Kilifi) in two groups of Gabonese children enrolled in a case-control, matched-pair study who presen ted with either mild or severe malaria, we found that 55% of the patients w ith mild malaria were carriers whereas only 39% of those with severe malari a were carriers. The difference in the distribution of ICAM-1(Kilifi) homoz ygous pairs between the groups, as well as the distribution of ICAM-1(Kilif i) 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 indi viduals was found. In a survey for the ICAM-1(Kilifi) in other malaria-ende mic regions, this allele was also found in Nigeria and Papua New Guinea, bu t not in Thailand.