Allelic dimorphism of the erythrocyte binding antigen-175 (eba-175) gene of Plasmodium falciparum and severe malaria: Significant association of the C-segment with fatal outcome in Ghanaian children.
BACKGROUND
The erythrocyte binding antigen-175 (EBA-175) on Plasmodium falciparum merozoites mediates sialic acid dependent binding to glycophorin A on host erythrocytes and, therefore, plays a crucial role in cell invasion. Dimorphic allele segments have been found in its encoding gene with a 342 bp segment present in FCR-3 strains (F-segment) and a 423 bp segment in CAMP strains (C-segment). Possible associations of the dimorphism with severe malaria have been analysed in a case-control study in northern Ghana.


METHODS
Blood samples of 289 children with severe malaria and 289 matched parasitaemic but asymptomatic controls were screened for eba-175 F- and C-segments by nested polymerase chain reaction.


RESULTS
In children with severe malaria, prevalences of F-, C- and mixed F-/C-segments were 70%, 19%, and 11%, respectively. The C-segment was found more frequently in severe malaria cases whereas mixed infections were more common in controls. Infection with strains harbouring the C-segment significantly increased the risk of fatal outcome.


CONCLUSIONS
The results show that the C-segment is associated with fatal outcome in children with severe malaria in northern Ghana, suggesting that it may contribute to the virulence of the parasite.
Cramer
Jakob P
JP
Berlin Institute of Tropical Medicine, Berlin, Germany. jakob.cramer@charite.de
Mockenhaupt
Frank P
FP
Möhl
Ingo
I
Dittrich
Sabine
S
Dietz
Ekkehardt
E
Otchwemah
Rowland N
RN
Ehrhardt
Stephan
S
Bienzle
Ulrich
U
Jelinek
Tomas
T
D000483:Alleles; D000818:Animals; D000953:Antigens, Protozoan / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D016054:DNA, Protozoan / Q000737:chemistry / Q000302:isolation & purification; D005260:Female; D005869:Ghana / Q000453:epidemiology; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000401:mortality* / Q000469:parasitology*; D008297:Male; D010963:Plasmodium falciparum / Q000235:genetics* / Q000472:pathogenicity; D016133:Polymerase Chain Reaction; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D014774:Virulence
D000953:Antigens, Protozoan; D016054:DNA, Protozoan; D015800:Protozoan Proteins; C065668:erythrocyte-binding antigen 175, Plasmodium