Genotypic and antigenic diversity of Plasmodium falciparum merozoite proteins in Malawian children with severe and uncomplicated malaria.

BACKGROUND

Malaria disease presentation and severity could be influenced in part by differential virulence among Plasmodium falciparum genotypes and/or by the multiplicity of infection (MOI).

METHODS

Using polymorphic merozoite surface proteins MSP-1 and MSP-2, the genetic and serological diversity of P. falciparum parasites infecting children with different clinical presentations of malaria was characterized during two transmission seasons in Malawi. Plasmodium falciparum isolates were obtained from 93 patients with cerebral malaria (CM), 50 with severe anaemia (SMA), 26 with CM and SMA, and 92 with uncomplicated malaria (UM).

RESULTS

There was more parasite genetic diversity amongst patients with SMA (mean ± SD 2.70 ± 1.20) than amongst those with CM (2.25 ± 0.89) (p < 0.01). The MSP-1 dimorphic K1-type was more frequent in parasites from SMA cases but almost absent in parasites from CM patients (p = 0.03). The MSP-1 MAD20 block 2 type was less common in CM than in UM patients (p < 0.05). Presence of MSP-2 FC27-type parasites was associated with SMA (66%) whereas MSP-2 IC1-type parasites were associated with CM (61.5%) (p < 0.025). The DNA sequence polymorphisms were largely reflected in antigenic diversity as defined by distinct serological recognition of anti-MSP-1 and MSP-2 antibodies.

CONCLUSIONS

Patients with CM, SMA and UM could be partly distinguished on the basis of the merozoite proteins in parasite isolates. The differences in MOI as well as the genetic and antigenic differences in the clinically defined groups are consistent with a role for parasite antigenic variability in malaria pathogenesis.