Antibody responses to a panel of Plasmodium falciparum malaria blood-stage antigens in relation to clinical disease outcome in Sudan.

Despite many intervention programmes aimed at curtailing the scourge, malaria remains a formidable problem of human health. Immunity to asexual blood-stage of Plasmodium falciparum malaria is thought to be associated with protective antibodies of certain immunoglobulin classes and subclasses. We have analysed immunoglobulin G profiles to six leading blood-stage antigens in relation to clinical malaria outcome in a hospital-based study in Sudan. Our results revealed a linear association with anti-AMA-1-IgG1 antibodies in children <5 years and reduced risk of severe malaria, while the responses of the IgG3 antibodies against MSP-2, MSP-3, GLURP in individuals above 5 years were bi-modal. A dominance of IgG3 antibodies in >5 years was also observed. In the final combined model, the highest levels of IgG1 antibodies to AMA-1, GLURP-R0, and the highest levels of IgG3 antibodies to 3D7 MSP-2 were independently associated with protection from clinical malaria. The study provides further support for the potential importance of the studied merozoite vaccine candidate antigens as targets for parasite neutralizing antibody responses of the IgG1 and IgG3 subclasses.

Geographical and temporal conservation of antibody recognition of Plasmodium falciparum variant surface antigens.

The slow acquisition of protection against Plasmodium falciparum malaria probably reflects the extensive diversity of important antigens. The variant surface antigens (VSA) that mediate parasite adhesion to a range of host molecules are regarded as important targets of acquired protective immunity, but their diversity makes them questionable vaccine candidates. We determined levels of VSA-specific immunoglobulin G (IgG) in human plasma collected at four geographically distant and epidemiologically distinct localities with specificity for VSA expressed by P. falciparum isolates from three African countries. Plasma levels of VSA-specific IgG recognizing individual parasite isolates depended on the transmission intensity at the site of plasma collection but were largely independent of the geographical origin of the parasites. The total repertoire of immunologically distinct VSA thus appears to be finite and geographically conserved, most likely due to functional constraints. Furthermore, plasma samples frequently had high IgG reactivity to VSA expressed by parasites isolated more than 10 years later, showing that the repertoire is also temporally stable. Parasites from patients with severe malaria expressed VSA (VSASM) that were better recognized by plasma IgG than VSA expressed by other parasites, but importantly, VSASM-type antigens also appeared to show substantial antigenic homogeneity. Our finding that the repertoire of immunologically distinct VSA in general, and in particular that of VSASM, is geographically and temporally conserved raises hopes for the feasibility of developing VSA-based vaccines specifically designed to accelerate naturally acquired immunity, thereby enhancing protection against severe and life-threatening P. falciparum malaria.

A marked seasonality of malaria transmission in two rural sites in eastern Sudan.

The ecology of Anopheles arabiensis and its relationship to malaria transmission was investigated in two villages in eastern Sudan. Seasonal malaria case incidence was compared with the number of vectors detected and with climatic variables. Following the end of the short rainy season in October the number of A. arabiensis detected dropped gradually until February when neither outdoor human bait trapping nor indoor spray catches revealed any mosquitoes. Vectors re-appeared in June as humidity rose with the onset of rain. Despite the apparent absence of the vector at the height of the long, hot dry season between February and May, sporadic asymptomatic malaria infections were detected in the two villages. The low endemicity of malaria in the area was reflected by the relatively low total September-December parasite and sporozoite rates (15 and 1.4%, respectively) measured in the villages. The entomological inoculation rate (EIR) was estimated to be around two to three infective bites per person per year, although heterogeneity in the transmission indices of malaria between the two villages was observed. The implications of these patterns of anopheline population dynamics for the epidemiology and control of malaria in eastern Sudan are considered.