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The Duffy binding-like (DBL) domains are common adhesion modules present in Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) variants, which are responsible for immune evasion and cytoadherence. Knowledge about how immune responses are acquired against polymorphic DBL domains of PfEMP1 can aid in the development of vaccines for malaria. A recombinant DBLalpha domain, encoded by R29 var1, which binds complement receptor 1 to mediate rosetting by the P. falciparum laboratory strain R29, was expressed in Escherichia coli, renatured by oxidative refolding to its native form, and purified to homogeneity. Antibody levels in 704 plasmas obtained from residents of areas of different levels of malaria endemicity in Orissa (India) and Manhiça (Mozambique) were assessed by enzyme-linked immunosorbent assay. The refolded DBLalpha domain was pure, homogeneous, and functional in that it bound human erythrocytes with specificity and was capable of inhibiting rosetting. The proportion of individuals who had measurable anti-DBLalpha immunoglobulin G responses was low in areas of low malaria endemicity in Orissa (6.7%) but high in areas of high endemicity in Orissa (87.5%) and Manhiça (74.5%). Seroprevalence and antibody levels against the recombinant protein increased with the age of inhabitants from areas with high transmission rates (P < 0.001). Half of the children in these areas had seroconverted by the age of 5 years. These findings suggest that in spite of the extreme polymorphism of PfEMP1 DBLalpha domains, the acquisition of specific antibodies is rapid and age related and reflects the reduced risk of malaria in areas with high transmission rates. Further studies are required to elucidate the role of these antibodies in protection from malaria.

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.