title: Circulating antibodies against Plasmodium falciparum histidine-rich proteins 2 interfere with antigen detection by rapid diagnostic tests.
abstract: BACKGROUND
  Rapid diagnostic tests (RDTs) for detection of Plasmodium falciparum infection that target P. falciparum histidine-rich protein 2 (PfHRP2), a protein that circulates in the blood of patients infected with this species of malaria, are widely used to guide case management. Understanding determinants of PfHRP2 availability in circulation is therefore essential to understanding the performance of PfHRP2-detecting RDTs.
  
  
  METHODS
  The possibility that pre-formed host anti-PfHRP2 antibodies may block target antigen detection, thereby causing false negative test results was investigated in this study.
  
  
  RESULTS
  Anti-PfHRP2 antibodies were detected in 19/75 (25%) of plasma samples collected from patients with acute malaria from Cambodia, Nigeria and the Philippines, as well as in 3/28 (10.7%) asymptomatic Solomon Islands residents. Pre-incubation of plasma samples from subjects with high-titre anti-PfHRP2 antibodies with soluble PfHRP2 blocked the detection of the target antigen on two of the three brands of RDTs tested, leading to false negative results. Pre-incubation of the plasma with intact parasitized erythrocytes resulted in a reduction of band intensity at the highest parasite density, and a reduction of lower detection threshold by ten-fold on all three brands of RDTs tested.
  
  
  CONCLUSIONS
  These observations indicate possible reduced sensitivity for diagnosis of P. falciparum malaria using PfHRP2-detecting RDTs among people with high levels of specific antibodies and low density infection, as well as possible interference with tests configured to detect soluble PfHRP2 in saliva or urine samples. Further investigations are required to assess the impact of pre-formed anti-PfHRP2 antibodies on RDT performance in different transmission settings.
authors.forename: Mei-Fong
authors.initials: MF
authors.lastname: Ho
authors.forename: Joanne
authors.initials: J
authors.lastname: Baker
authors.forename: Nelson
authors.initials: N
authors.lastname: Lee
authors.forename: Jennifer
authors.initials: J
authors.lastname: Luchavez
authors.forename: Frédéric
authors.initials: F
authors.lastname: Ariey
authors.forename: Sina
authors.initials: S
authors.lastname: Nhem
authors.forename: Wellington
authors.initials: W
authors.lastname: Oyibo
authors.forename: David
authors.initials: D
authors.lastname: Bell
authors.forename: Iveth
authors.initials: I
authors.lastname: González
authors.forename: Peter
authors.initials: P
authors.lastname: Chiodini
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Gatton
authors.forename: Qin
authors.initials: Q
authors.lastname: Cheng
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Australia. j.mccarthy@uq.edu.au.
authors.forename: James S
authors.initials: JS
authors.lastname: McCarthy
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000913:Antibodies, Protozoan / Q000097:blood*; D000953:Antigens, Protozoan / Q000032:analysis* / Q000276:immunology*; D002160:Cambodia; D002648:Child; D002675:Child, Preschool; D003951:Diagnostic Errors; D003955:Diagnostic Tests, Routine / Q000379:methods*; D005260:Female; D006801:Humans; D016778:Malaria, Falciparum / Q000175:diagnosis* / Q000276:immunology; D008297:Male; D008542:Melanesia; D008875:Middle Aged; D009549:Nigeria; D010679:Philippines; D015800:Protozoan Proteins / Q000032:analysis* / Q000276:immunology*; D012680:Sensitivity and Specificity; D055815:Young Adult
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; C514457:HRP-2 antigen, Plasmodium falciparum; D015800:Protozoan Proteins