Association of msp-1, msp-2 and pfcrt genes with the severe complications of Plasmodium falciparum malaria in children

The pathogenesis of severe malaria is still not clearly understood and there are few substantial data describing the association of specific parasite genotypes with the severity of Plasmodium falciparum infection in humans. The merozoite surface proteins 1 and 2 (MSP-1 and MSP-2) of P. falciparum play a crucial role in the parasite's invasion of the human host and the subsequent manifestation of the complications of severe malaria. Attempts at associating msp-1 and msp-2 genotypes with the severity of P. falciparum malaria therefore appear worthwhile. In the present study, based in the malaria-endemic district of Sundergarh, in the Indian state of Orissa, the msp-1, msp-2 and pfcrt genotypes of P. falciparum infecting children were investigated and compared against the severity of malaria in each donor child. The two major complications seen in the subjects, cerebral malaria and severe anaemia, were each found to be significantly associated with the RO33 subtype of msp-1 and the 3D7 subtype of msp-2. Although the study isolates showed a high degree of multiclonicity (multiplicity of infection = 1.9) and of polymorphism in msp- 1 and -2, almost all (95%) of the isolates had the K76T mutation in their pfcrt genes.