This study and clinical descriptions of severe and fatal knowlesi malaria suggest that up-regulation of ICAM-1 observed in P. falciparum infections is less evident in P. knowlesi malaria and that direct or indirect induction of ICAM-1 may be a defining Plasmodium species-specific virulence factor in severe malaria with coma. Here, ICAM1 is linked to type 2 diabetes mellitus.