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*
Centre for Medical Parasitology at Department of Infectious Diseases, Copenhagen University Hospital (Rigshospitalet) and Institute for Medical Microbiology and Immunology, University of Copenhagen, Copenhagen, Denmark;
Epidemiology and
Immunology Units, Noguchi Memorial Institute, University of Ghana, Legon, Ghana; and
§
Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom
In areas of intense Plasmodium falciparum transmission, clinical immunity is acquired during childhood, and adults enjoy substantial protection against malaria. An exception to this rule is pregnant women, in whom malaria is both more prevalent and severe than in nonpregnant women. Pregnancy-associated malaria (PAM) in endemic areas is concentrated in the first few pregnancies, indicating that protective immunity to PAM is a function of parity. The placenta is often heavily infected in PAM, and placental parasites show a striking preference for chondroitin sulfate A (CSA) as an adhesion receptor. Plasma Abs from malaria-exposed multiparous women are able to interfere with binding of P. falciparum parasites to CSA in vitro, and acquisition of Abs interfering with CSA-specific parasite sequestration thus appears to be a critical element in acquired protection against PAM. Here we show that adults from an area of hyperendemic P. falciparum transmission generally possessed low levels of Abs specifically recognizing surface Ags expressed by a CSA-adhering parasite isolate, while unselected isolates were well recognized. In marked contrast, most third-trimester pregnant women from that area had very high plasma levels of such Abs. Plasma levels of Abs specifically recognizing the CSA-adhering isolate strongly depended on parity, whereas recognition of CSA-nonadhering isolates did not. Finally, we demonstrate a clear correlation between plasma levels of Abs recognizing the CSA-specific isolate and the ability to interfere with its sequestration to CSA in vitro. Our study supports the hypothesis that Abs inhibiting CSA-specific parasite sequestration are important in acquisition of protection against PAM.
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A. Muthusamy, R. N. Achur, V. P. Bhavanandan, G. G. Fouda, D. W. Taylor, and D. C. Gowda Plasmodium falciparum-Infected Erythrocytes Adhere Both in the Intervillous Space and on the Villous Surface of Human Placenta by Binding to the Low-Sulfated Chondroitin Sulfate Proteoglycan Receptor Am. J. Pathol., June 1, 2004; 164(6): 2013 - 2025. [Abstract] [Full Text] [PDF]
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D. W. Taylor, A. Zhou, L. E. Marsillio, L. W. Thuita, E. B. Leke, O. Branch, D. C. Gowda, C. Long, and R. F. G. Leke Antibodies That Inhibit Binding of Plasmodium falciparum-Infected Erythrocytes to Chondroitin Sulfate A and to the C Terminus of Merozoite Surface Protein 1 Correlate with Reduced Placental Malaria in Cameroonian Women Infect. Immun., March 1, 2004; 72(3): 1603 - 1607. [Abstract] [Full Text] [PDF]
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P. E. Duffy and M. Fried Antibodies That Inhibit Plasmodium falciparum Adhesion to Chondroitin Sulfate A Are Associated with Increased Birth Weight and the Gestational Age of Newborns Infect. Immun., November 1, 2003; 71(11): 6620 - 6623. [Abstract] [Full Text] [PDF]
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D. I. Baruch, B. Gamain, and L. H. Miller DNA Immunization with the Cysteine-Rich Interdomain Region 1 of the Plasmodium falciparum Variant Antigen Elicits Limited Cross-Reactive Antibody Responses Infect. Immun., August 1, 2003; 71(8): 4536 - 4543. [Abstract] [Full Text] [PDF]
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A. M. Creasey, T. Staalsoe, A. Raza, D. E. Arnot, and J. A. Rowe Nonspecific Immunoglobulin M Binding and Chondroitin Sulfate A Binding Are Linked Phenotypes of Plasmodium falciparum Isolates Implicated in Malaria during Pregnancy Infect. Immun., August 1, 2003; 71(8): 4767 - 4771. [Abstract] [Full Text] [PDF]
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A. T. R. Jensen, H. D. Zornig, C. Buhmann, A. Salanti, K. A. Koram, E. M. Riley, T. G. Theander, L. Hviid, and T. Staalsoe Lack of Gender-Specific Antibody Recognition of Products from Domains of a var Gene Implicated in Pregnancy-Associated Plasmodium falciparum Malaria Infect. Immun., July 1, 2003; 71(7): 4193 - 4196. [Abstract] [Full Text] [PDF]
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S. T. Agbor-Enoh, R. N. Achur, M. Valiyaveettil, R. Leke, D. W. Taylor, and D. C. Gowda Chondroitin Sulfate Proteoglycan Expression and Binding of Plasmodium falciparum-Infected Erythrocytes in the Human Placenta during Pregnancy Infect. Immun., May 1, 2003; 71(5): 2455 - 2461. [Abstract] [Full Text] [PDF]
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 R. N. Achur, M. Valiyaveettil, and D. C. Gowda The Low Sulfated Chondroitin Sulfate Proteoglycans of Human Placenta Have Sulfate Group-clustered Domains That Can Efficiently Bind Plasmodium falciparum-infected Erythrocytes J. Biol. Chem., March 21, 2003; 278(13): 11705 - 11713. [Abstract] [Full Text] [PDF]
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M. F. Ofori, T. Staalsoe, V. Bam, M. Lundquist, K. P. David, E. N. L. Browne, B. D. Akanmori, and L. Hviid Expression of Variant Surface Antigens by Plasmodium falciparum Parasites in the Peripheral Blood of Clinically Immune Pregnant Women Indicates Ongoing Placental Infection Infect. Immun., March 1, 2003; 71(3): 1584 - 1586. [Abstract] [Full Text] [PDF]
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 M. Cot, J. Y. Le Hesran, T. Staalsoe, N. Fievet, L. Hviid, and P. Deloron Maternally Transmitted Antibodies to Pregnancy-Associated Variant Antigens on the Surface of ErythrocytesInfected with Plasmodium falciparum: Relation to Child Susceptibility to Malaria Am. J. Epidemiol., February 1, 2003; 157(3): 203 - 209. [Abstract] [Full Text] [PDF]
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B. Gamain, S. Gratepanche, L. H. Miller, and D. I. Baruch Molecular basis for the dichotomy in Plasmodium falciparum adhesion to CD36 and chondroitin sulfate A PNAS, July 23, 2002; 99(15): 10020 - 10024. [Abstract] [Full Text] [PDF]
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M. F. Ofori, D. Dodoo, T. Staalsoe, J. A. L. Kurtzhals, K. Koram, T. G. Theander, B. D. Akanmori, and L. Hviid Malaria-Induced Acquisition of Antibodies to Plasmodium falciparum Variant Surface Antigens Infect. Immun., June 1, 2002; 70(6): 2982 - 2988. [Abstract] [Full Text] [PDF]
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M. A. Nielsen, T. Staalsoe, J. A. L. Kurtzhals, B. Q. Goka, D. Dodoo, M. Alifrangis, T. G. Theander, B. D. Akanmori, and L. Hviid Plasmodium falciparum Variant Surface Antigen Expression Varies Between Isolates Causing Severe and Nonsevere Malaria and Is Modified by Acquired Immunity J. Immunol., April 1, 2002; 168(7): 3444 - 3450. [Abstract] [Full Text] [PDF]
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I. O'Neil-Dunne, R. N. Achur, S. T. Agbor-Enoh, M. Valiyaveettil, R. S. Naik, C. F. Ockenhouse, A. Zhou, R. Megnekou, R. Leke, D. W. Taylor, et al. Gravidity-Dependent Production of Antibodies That Inhibit Binding of Plasmodium falciparum-Infected Erythrocytes to Placental Chondroitin Sulfate Proteoglycan during Pregnancy Infect. Immun., December 1, 2001; 69(12): 7487 - 7492. [Abstract] [Full Text] [PDF]
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D. Dodoo, T. Staalsoe, H. Giha, J. A. L. Kurtzhals, B. D. Akanmori, K. Koram, S. Dunyo, F. K. Nkrumah, L. Hviid, and T. G. Theander Antibodies to Variant Antigens on the Surfaces of Infected Erythrocytes Are Associated with Protection from Malaria in Ghanaian Children Infect. Immun., June 1, 2001; 69(6): 3713 - 3718. [Abstract] [Full Text] [PDF]
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