Antibodies to Plasmodium falciparum antigens predict a higher risk of malaria but protection from symptoms once parasitemic

Abstract

Background: Associations between antibody responses to Plasmodium falciparum antigens and protection against symptomatic malaria have been difficult to ascertain, in part because antibodies are potential markers of both exposure to P. falciparum and protection against disease.

Methods: We measured IgG responses to P. falciparum circumsporozoite protein, liver-stage antigen 1, apical-membrane antigen 1 (AMA-1), and merozoite surface proteins (MSP) 1 and 3, in children in Kampala, Uganda, and measured incidence of malaria before and after antibody measurement.

Results: Stronger responses to all 5 antigens were associated with an increased risk of clinical malaria (P < .01) because of confounding with prior exposure to P. falciparum. However, with use of another assessment, risk of clinical malaria once parasitemic, stronger responses to AMA-1, MSP-1, and MSP-3 were associated with protection (odds ratios, 0.34, 0.36, and 0.31, respectively, per 10-fold increase; P < .01). Analyses assessing antibodies in combination suggested that any protective effect of antibodies was overestimated by associations between individual responses and protection.

Conclusions: Using the risk of symptomatic malaria once parasitemic as an outcome may improve detection of associations between immune responses and protection from disease. Immunoepidemiology studies designed to detect mechanisms of immune protection should integrate prior exposure into the analysis and evaluate multiple immune responses.

Figure 1.

Children from Kampala, Uganda, included in the study.

Figure 2.

Accuracy of antibody responses alone and in combination in predicting protection from malaria once parasitemic. Hollow bars indicate predictive accuracy of dichotomous responses; solid bars indicate predictive accuracy of antibody levels. An area under the receiver operating characteristic curve (AUC) value of 0.5 indicates a prediction no better than random, and a value of 1.0 indicates a perfect predictor.