Low prevalence of antibodies to preerythrocytic but not blood-stage Plasmodium falciparum antigens in an area of unstable malaria transmission compared to prevalence in an area of stable malaria transmission

Abstract

In areas where levels of transmission of Plasmodium falciparum are high and stable, the age-related acquisition of high-level immunoglobulin G (IgG) antibodies to preerythrocytic circumsporozoite protein (CSP) and liver-stage antigen 1 (LSA-1) has been associated with protection from clinical malaria. In contrast, age-related protection from malaria develops slowly or not at all in residents of epidemic-prone areas with unstable low levels of malaria transmission. We hypothesized that this suboptimal clinical and parasitological immunity may in part be due to reduced antibodies to CSP or LSA-1 and/or vaccine candidate blood-stage antigens. Frequencies and levels of IgG antibodies to CSP, LSA-1, thrombospondin-related adhesive protein (TRAP), apical membrane antigen 1 (AMA-1), erythrocyte binding antigen 175 (EBA-175), and merozoite surface protein 1 (MSP-1) were compared in 243 Kenyans living in a highland area of unstable transmission and 210 residents of a nearby lowland area of stable transmission. Levels of antibodies to CSP, LSA-1, TRAP, and AMA-1 in the oldest age group (>40 years) in the unstable transmission area were lower than or similar to those of children 2 to 6 years old in the stable transmission area. Only 3.3% of individuals in the unstable transmission area had high levels of IgG (>2 arbitrary units) to both CSP and LSA-1, compared to 43.3% of individuals in the stable transmission area. In contrast, antibody levels to and frequencies of MSP-1 and EBA-175 were similar in adults in areas of stable and unstable malaria transmission. Suboptimal immunity to malaria in areas of unstable malaria transmission may relate in part to infrequent high-level antibodies to preerythrocytic antigens and AMA-1.

FIG. 1.

Prevalence of total IgG antibodies, determined by ELISA, with AU values of >1 for various P. falciparum antigens in areas of stable (a) and unstable (b) malaria transmission across the following age groups: 2 to 5, 6 to 15, 16 to 40, and >40 years old. The number of individuals in each age group is indicated for all antigens, except MSP-1, where the numbers of individuals were 39, 56, 53, and 43, respectively, for stable and 58, 31, 81, and 67, respectively, for unstable transmission areas. An asterisk (*) indicates significant (P < 0.05) differences in age groups between areas by χ² analysis. P values for trend for age by χ² analysis are indicated.

FIG. 2.

Prevalence of total IgG antibodies, determined by ELISA, with AU values of >2 for various P. falciparum antigens in areas of stable (a) and unstable (b) malaria transmission across the following age groups: <6, 6 to 15, 16 to 40, and >40 years old. Numbers of individuals in each age group are indicated for all antigens, except MSP-1, where the numbers of individuals were 39, 56, 53, and 43, respectively, for stable and 58, 31, 81, and 67, respectively, for unstable transmission areas. An asterisk (*) indicates significant (P < 0.05) differences in age groups between areas by χ² analysis. P values for trend for age by χ² analysis are indicated.