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Infection and Immunity, September 2002, p. 5045-5051, Vol. 70, No. 9
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.9.5045-5051.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Prevalence and Boosting of Antibodies to Plasmodium falciparum Glycosylphosphatidylinositols and Evaluation of Their Association with Protection from Mild and Severe Clinical Malaria

Department of Immunology and Molecular Pathology, Royal Free and University College London Medical School, London W1T 4JF,¹ Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT,² University Department of Paediatrics, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom,⁴ Department of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine, Milton S. Hershey Medical Center, Hershey, Pennsylvania 17033³

Received 17 April 2002/ Returned for modification 18 May 2002/ Accepted 11 June 2002

Glycosylphosphatidylinositols (GPIs), the anchor molecules of some membrane proteins of Plasmodium species, have been implicated in the induction of immunopathology during malaria infections. Hence, neutralization of GPIs by antibodies may reduce the severity of clinical attacks of malaria. To test this hypothesis, we have assessed the levels of anti-GPI antibodies in plasma from children and adults living in areas of seasonal malaria transmission in The Gambia. In a prospective study of susceptibility to clinical or asymptomatic infection, the levels of anti-GPI antibodies were measured before and after the transmission season. Samples were also obtained from children recruited into a hospital-based study of severe malaria. We find that in malaria-exposed individuals both the prevalence and the concentration of anti-GPI antibodies increase with age and that antibody levels are significantly higher at the end of the malaria transmission season than at the start of the season. Antibody levels are also higher in children with asymptomatic infections (i.e., those with a degree of clinical immunity) than in children who developed clinical malaria and high parasitemia, although this difference is not statistically significant. Importantly, antibodies appear to be rapidly boosted by clinical malaria infection, but children under the age of two years are seronegative for anti-GPI antibodies, even during an acute infection. While GPIs may be involved in the pathogenesis of human malaria, the data from this study do not provide any strong evidence to support the notion that anti-GPI antibodies confer resistance to mild or severe malarial disease. Further case-control studies, ideally of a prospective nature, are required to elucidate the role of antiglycolipid antibodies in protection from severe malaria.

Editor: W. A. Petri, Jr.

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