The use of crude Plasmodium falciparum antigens for comparison of antibody responses in patients with mild malaria vs. cerebral malaria

Cerebral malaria (CM) is one of the major causes of death in African populations infected with Plasmodium falciparum. Only 1% of infected subjects develop CM. The reasons for these differences are not fully understood, but it is likely that the host humoral response against blood-stage antigens plays a role in protection from malaria, although the precise targets and mechanisms mediating immunity remain unclear. The purpose of this study was to distinguish between defined P. falciparum-specific Ab response patterns in patients presenting with mild malaria (MM) vs. CM. We used a panel of P. falciparum conserved antigens including crude blood-stage extracts schizont, merozoite and parasitised erythrocyte membranes and MSP-1p19, PfEB200, R23 and GST-5 recombinant antigens in a retrospective case-control study of symptomatic adults, one group presenting confirmed CM without fatal outcome and another group with MM. We further matched P. falciparum-specific Ab responses with those from individuals living in an endemic setting known to have protective immunity and considered them as "immune control" subjects (IC). Total IgG, IgM and IgG subclass Ab responses were determined using ELISA method. Substantial Ab responses were found in symptomatic patients, significantly lower than the "immune control" subjects, and with a limited quantitative difference between MM versus CM. Interestingly, asynchronous IgM response was evidenced in CM contrary to MM. Our results suggest that the contribution of an efficient IgG response against parasite multiplication is of importance in the evolution towards CM manifestation without fatal outcome and deserves further analysis for vaccine candidates.