ABSTRACT
Strain-transcending antibodies against virulence-associated subsets of P. falciparum-infected erythrocyte surface antigens could protect children from severe malaria. However, the evidence supporting the existence of such antibodies is incomplete and inconsistent. One subset of surface antigens associated with severe malaria, rosette-mediating Plasmodium falciparum Erythrocyte Membrane Protein one (PfEMP1) variants, cause infected erythrocytes to bind to uninfected erythrocytes to form clusters of cells (rosettes) that contribute to microvascular obstruction and pathology. Here, we tested plasma from 80 individuals living in malaria-endemic regions for IgG recognition of the surface of four P. falciparum rosetting strains using flow cytometry. Broadly reactive plasma samples were then used in antibody elution experiments in which intact IgG was eluted from the surface of infected erythrocytes and transferred to heterologous rosetting strains to look for strain-transcending antibodies. We found that seroprevalence (percentage of positive plasma samples) against allopatric rosetting strains was high in adults (63%-93%) but lower in children (13%-48%). Strain-transcending antibodies were present in nine out of eleven eluted antibody experiments, with six of these recognizing multiple heterologous rosetting parasite strains. One eluate had rosette-disrupting activity against heterologous strains, suggesting PfEMP1 as the likely target of the strain-transcending antibodies. Naturally acquired strain-transcending antibodies to rosetting P. falciparum strains in humans have not been directly demonstrated previously. Their existence suggests that such antibodies could play a role in clinical protection and raises the possibility that conserved epitopes recognized by strain-transcending antibodies could be targeted therapeutically by monoclonal antibodies or vaccines.
Subject(s)
Antibodies, Protozoan , Immunoglobulin G , Malaria, Falciparum , Plasmodium falciparum , Humans , Plasmodium falciparum/immunology , Antibodies, Protozoan/immunology , Antibodies, Protozoan/blood , Malaria, Falciparum/immunology , Malaria, Falciparum/parasitology , Child , Adult , Immunoglobulin G/immunology , Immunoglobulin G/blood , Child, Preschool , Adolescent , Protozoan Proteins/immunology , Erythrocytes/parasitology , Erythrocytes/immunology , Antigens, Protozoan/immunology , Female , Male , Young Adult , Middle Aged , Seroepidemiologic Studies , Rosette Formation , Flow CytometrySubject(s)
Alemtuzumab/administration & dosage , Graft vs Host Disease/prevention & control , HIV Infections/complications , Immunosuppressive Agents/administration & dosage , Kidney Transplantation/adverse effects , Renal Insufficiency/surgery , Humans , Male , Middle Aged , Transplant Recipients , Treatment OutcomeABSTRACT
Scabies prevalence remains unacceptably high in many regions throughout the world. Infestation with scabies significantly impacts quality of life and is linked to pyoderma and consequently to severe long-term sequelae such as post-streptococcal glomerulonephritis. In the past, control programs using topical treatments have met with poor compliance; however, the highly effective oral agent ivermectin may offer a new paradigm in scabies management. Problems still exist with insensitive diagnostic tests, questions concerning mite reservoirs, and restrictions on who can receive ivermectin. Despite these difficulties, the elimination of scabies in communities worst affected may soon be possible.
