title: Effect of sequence variation in Plasmodium falciparum histidine- rich protein 2 on binding of specific monoclonal antibodies: Implications for rapid diagnostic tests for malaria.
abstract: The ability to accurately diagnose malaria infections, particularly in settings where laboratory facilities are not well developed, is of key importance in the control of this disease. Rapid diagnostic tests (RDTs) offer great potential to address this need. Reports of significant variation in the field performance of RDTs based on the detection of Plasmodium falciparum histidine-rich protein 2 (HRP2) (PfHRP2) and of significant sequence polymorphism in PfHRP2 led us to evaluate the binding of four HRP2-specific monoclonal antibodies (MABs) to parasite proteins from geographically distinct P. falciparum isolates, define the epitopes recognized by these MABs, and relate the copy number of the epitopes to MAB reactivity. We observed a significant difference in the reactivity of the same MAB to different isolates and between different MABs tested with single isolates. When the target epitopes of three of the MABs were determined and mapped onto the peptide sequences of the field isolates, significant variability in the frequency of these epitopes was observed. These findings support the role of sequence variation as an explanation for variations in the performance of HRP2-based RDTs and point toward possible approaches to improve their diagnostic sensitivities.
authors.affiliation: Australian Centre for International and Tropical Health and Nutrition, Queensland Institute of Medical Research and School of Population Health, University of Queensland, Queensland, Australia.
authors.forename: Nelson
authors.initials: N
authors.lastname: Lee
authors.forename: Joanne
authors.initials: J
authors.lastname: Baker
authors.forename: Kathy T
authors.initials: KT
authors.lastname: Andrews
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Gatton
authors.forename: David
authors.initials: D
authors.lastname: Bell
authors.forename: Qin
authors.initials: Q
authors.lastname: Cheng
authors.forename: James
authors.initials: J
authors.lastname: McCarthy
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000913:Antibodies, Protozoan / Q000276:immunology; D015153:Blotting, Western; D016054:DNA, Protozoan / Q000737:chemistry / Q000235:genetics; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D005188:False Negative Reactions; D006801:Humans; D016778:Malaria, Falciparum / Q000175:diagnosis*; D025202:Molecular Diagnostic Techniques; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D010963:Plasmodium falciparum / Q000235:genetics* / Q000276:immunology*; D011110:Polymorphism, Genetic; D011506:Proteins / Q000235:genetics* / Q000276:immunology*; D015800:Protozoan Proteins / Q000235:genetics* / Q000276:immunology*; D012680:Sensitivity and Specificity; D017422:Sequence Analysis, DNA; D000099053:Histidine-Rich Glycoprotein
chemical_list: D000911:Antibodies, Monoclonal; D000913:Antibodies, Protozoan; D016054:DNA, Protozoan; D000939:Epitopes; D011506:Proteins; D015800:Protozoan Proteins; D000099053:Histidine-Rich Glycoprotein