Humoral Response to Defined Plasmodium falciparum Antigens in Cerebral and Uncomplicated Malaria and their Relationship to Parasite Genotype

Fadwa Al-YamanPapua New Guinea Institute of Medical Research, Madang General Hospital, Division of Biochemistry and Molecular Biology, School of Life Sciences, Faculty of Sciences, Australian National University, Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Madang, Papua New Guinea

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Blaise GentonPapua New Guinea Institute of Medical Research, Madang General Hospital, Division of Biochemistry and Molecular Biology, School of Life Sciences, Faculty of Sciences, Australian National University, Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Madang, Papua New Guinea

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John C. ReederPapua New Guinea Institute of Medical Research, Madang General Hospital, Division of Biochemistry and Molecular Biology, School of Life Sciences, Faculty of Sciences, Australian National University, Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Madang, Papua New Guinea

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David MokelaPapua New Guinea Institute of Medical Research, Madang General Hospital, Division of Biochemistry and Molecular Biology, School of Life Sciences, Faculty of Sciences, Australian National University, Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Madang, Papua New Guinea

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Robin F. AndersPapua New Guinea Institute of Medical Research, Madang General Hospital, Division of Biochemistry and Molecular Biology, School of Life Sciences, Faculty of Sciences, Australian National University, Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Madang, Papua New Guinea

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Michael P. AlpersPapua New Guinea Institute of Medical Research, Madang General Hospital, Division of Biochemistry and Molecular Biology, School of Life Sciences, Faculty of Sciences, Australian National University, Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Madang, Papua New Guinea

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The prevalence and concentration of IgG antibodies to defined Plasmodium falciparum antigens were assessed in serum samples of 97 children with cerebral malaria and 146 children with uncomplicated malaria. The antigens used included the schizont extract, ring-infected erythrocyte surface antigen, the C-terminal region of merozoite surface antigen-1 (MSA-1) (BVp42), and three recombinant proteins of MSA-2 (FC27, 3D7, and d3D7). Parasite isolates from 24 children with cerebral malaria and 22 children with uncomplicated malaria were genotyped for MSA-1 and MSA-2. The distribution of parasite genotypes belonging to the different allelic families was similar in both the cerebral and uncomplicated malaria groups. There were higher antibody levels to antigens derived from the infecting parasite genotype than to heterologous genotypes, but this difference was only statistically significant for antibody against the d3D7 antigen among children infected with the 3D7 parasite genotype (mean log = 4.72 versus 3.45 antibody units [AU]; P = 0.029). Those who died were more likely to be infected with the FC27 genotype and had lower antibody levels to MSA-2 of the 3D7 type than had cerebral malaria patients who survived (mean log = 2.94 versus 3.79 AU; P = 0.049). Antibodies against parasites of the 3D7 genotype are associated with a better prognosis among children with cerebral malaria partly because these children are more likely to be infected with parasites of this genotype rather than the FC27 genotype, which appears to be more virulent.

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