Evaluation of immunotherapy to reverse sequestration in the treatment of severe Plasmodium falciparum malaria.
Sequestration and the attachment of Plasmodium falciparum malaria-infected RBC to venous endothelial cells involves parasite-encoded ligands interacting with up to nine host receptors. Antisequestration immunotherapy as an adjunct to quinine did not alter the dynamics of parasite clearance or prove beneficial for the patient. Estimated concentrations of antibody likely to reverse adherence in patients were based on the concentrations of parasite ligands, host receptors and patient equivalents derived from in vitro observations. Calculations presented here indicate that concentrations in excess of a fivefold increase in antibody concentrations used in the immunotherapy trial and equivalent to doubling normal peripheral blood antibody concentrations are anticipated for the successful reversal of sequestration to occur. It is suggested that immunotherapy aimed at either parasite ligands or host receptors to reverse sequestration in the treatment of severe malaria infections is unlikely to be successful given the complexity and number of receptors and ligands and the calculated concentrations of antibodies required.
Biochemistry, School of Molecular and Cellular Biosciences, University of KwaZulu-Natal (PMB), Scottsville, South Africa. goldringd@ukzn.ac.za
J P Dean
JP
Goldring
D000818:Animals; D000906:Antibodies / Q000494:pharmacology / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D000913:Antibodies, Protozoan / Q000097:blood / Q000627:therapeutic use; D000962:Antimalarials / Q000627:therapeutic use; D004730:Endothelium, Vascular / Q000378:metabolism; D004912:Erythrocytes / Q000469:parasitology; D006801:Humans; D008024:Ligands; D016778:Malaria, Falciparum / Q000175:diagnosis / Q000276:immunology / Q000628:therapy*; D008962:Models, Theoretical; D011971:Receptors, Immunologic / Q000378:metabolism
D000906:Antibodies; D000911:Antibodies, Monoclonal; D000913:Antibodies, Protozoan; D000962:Antimalarials; D008024:Ligands; D011971:Receptors, Immunologic