Cytoadherence in paediatric malaria: ABO blood group, CD36, and ICAM1 expression and severe Plasmodium falciparum infection.
As a leading cause of childhood mortality worldwide, selection pressure by Plasmodium falciparum continues to shape the human genome. Severe disturbances within the microcirculation result from the adhesion of infected erythrocytes to host receptors on monocytes, platelets, and endothelium. In this prospective study, we compared expression of all major host cytoadhesion receptors among Ugandan children presenting with uncomplicated malaria (n = 1078) versus children with severe malaria (n = 855), including cerebral malaria (n = 174), severe anaemia (n = 522), and lactic acidosis (n = 154). We report a significant survival advantage attributed to blood group O and increased monocyte expression of CD36 and ICAM1 (CD54). The high case fatality rate syndromes of cerebral malaria and lactic acidosis were associated with high platelet CD36 expression and thrombocytopenia, and severe malaria anaemia was characterized by low ICAM1 expression. In a logistic regression model of disease severity, odds ratios for the mitigating effects of blood group O, CD36, and ICAM1 phenotypes were greater than that of sickle haemoglobin. Host genetic adaptations to Plasmodium falciparum suggest new potential malaria treatment strategies.
University Health Network/University of Toronto, Ontario, Canada. christine.cserti@uhn.ca
Christine M
CM
Cserti-Gazdewich
Aggrey
A
Dhabangi
Charles
C
Musoke
Isaac
I
Ssewanyana
Henry
H
Ddungu
Deborah
D
Nakiboneka-Ssenabulya
Nicolette
N
Nabukeera-Barungi
Arthur
A
Mpimbaza
Walter H
WH
Dzik
D000017:ABO Blood-Group System / Q000097:blood*; D000740:Anemia / Q000097:blood / Q000209:etiology / Q000401:mortality; D018955:CD36 Antigens / Q000097:blood*; D002448:Cell Adhesion; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007223:Infant; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood*; D016778:Malaria, Falciparum / Q000097:blood* / Q000150:complications / Q000401:mortality; D008297:Male; D009000:Monocytes / Q000378:metabolism*; D010963:Plasmodium falciparum; D012720:Severity of Illness Index; D015996:Survival Rate; D013921:Thrombocytopenia / Q000097:blood / Q000209:etiology / Q000401:mortality
D000017:ABO Blood-Group System; D018955:CD36 Antigens; C573420:ICAM1 protein, human; D018799:Intercellular Adhesion Molecule-1