title: Genetic diversity of Plasmodium falciparum histidine-rich protein 2 (PfHRP2) and its effect on the performance of PfHRP2-based rapid diagnostic tests.
abstract: Rising costs of antimalarial agents are increasing the demand for accurate diagnosis of malaria. Rapid diagnostic tests (RDTs) offer great potential to improve the diagnosis of malaria, particularly in remote areas. Many RDTs are based on the detection of Plasmodium falciparum histidine-rich protein (PfHRP) 2, but reports from field tests have questioned their sensitivity and reliability. We hypothesize that the variability in the results of PfHRP2-based RDTs is related to the variability in the target antigen. We tested this hypothesis by examining the genetic diversity of PfHRP2, which includes numerous amino acid repeats, in 75 P. falciparum lines and isolates originating from 19 countries and testing a subset of parasites by use of 2 PfHRP2-based RDTs. We observed extensive diversity in PfHRP2 sequences, both within and between countries. Logistic regression analysis indicated that 2 types of repeats were predictive of RDT detection sensitivity (87.5% accuracy), with predictions suggesting that only 84% of P. falciparum parasites in the Asia-Pacific region are likely to be detected at densities < or = 250 parasites/microL. Our data also indicated that PfHRP3 may play a role in the performance of PfHRP2-based RDTs. These findings provide an alternative explanation for the variable sensitivity in field tests of malaria RDTs that is not due to the quality of the RDTs.
authors.affiliation: Department of Drug Resistance and Diagnostics, Australian Army Malaria Institute, Brisbane, Australia.
authors.forename: Joanne
authors.initials: J
authors.lastname: Baker
authors.forename: James
authors.initials: J
authors.lastname: McCarthy
authors.forename: Michelle
authors.initials: M
authors.lastname: Gatton
authors.forename: Dennis E
authors.initials: DE
authors.lastname: Kyle
authors.forename: Vicente
authors.initials: V
authors.lastname: Belizario
authors.forename: Jennifer
authors.initials: J
authors.lastname: Luchavez
authors.forename: David
authors.initials: D
authors.lastname: Bell
authors.forename: Qin
authors.initials: Q
authors.lastname: Cheng
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000940:Antigenic Variation; D000953:Antigens, Protozoan / Q000235:genetics*; D001483:Base Sequence; D016054:DNA, Protozoan / Q000737:chemistry / Q000235:genetics; D006801:Humans; D016015:Logistic Models; D016778:Malaria, Falciparum / Q000175:diagnosis* / Q000382:microbiology; D018895:Microsatellite Repeats / Q000235:genetics; D010963:Plasmodium falciparum / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011506:Proteins; D015800:Protozoan Proteins / Q000235:genetics*; D011933:Reagent Kits, Diagnostic; D012680:Sensitivity and Specificity; D017422:Sequence Analysis, DNA; D000099053:Histidine-Rich Glycoprotein
chemical_list: D000953:Antigens, Protozoan; D016054:DNA, Protozoan; C578339:HRP3 protein, Plasmodium falciparum; D011506:Proteins; D015800:Protozoan Proteins; D011933:Reagent Kits, Diagnostic; D000099053:Histidine-Rich Glycoprotein