title: Rapid diagnostic tests for malaria diagnosis in the Peruvian Amazon: impact of pfhrp2 gene deletions and cross-reactions.
abstract: BACKGROUND
  In the Peruvian Amazon, Plasmodium falciparum and Plasmodium vivax malaria are endemic in rural areas, where microscopy is not available. Malaria rapid diagnostic tests (RDTs) provide quick and accurate diagnosis. However, pfhrp2 gene deletions may limit the use of histidine-rich protein-2 (PfHRP2) detecting RDTs. Further, cross-reactions of P. falciparum with P. vivax-specific test lines and vice versa may impair diagnostic specificity.
  
  
  METHODS
  Thirteen RDT products were evaluated on 179 prospectively collected malaria positive samples. Species diagnosis was performed by microscopy and confirmed by PCR. Pfhrp2 gene deletions were assessed by PCR.
  
  
  RESULTS
  Sensitivity for P. falciparum diagnosis was lower for PfHRP2 compared to P. falciparum-specific Plasmodium lactate dehydrogenase (Pf-pLDH)-detecting RDTs (71.6% vs. 98.7%, p<0.001). Most (19/21) false negative PfHRP2 results were associated with pfhrp2 gene deletions (25.7% of 74 P. falciparum samples). Diagnostic sensitivity for P. vivax (101 samples) was excellent, except for two products. In 10/12 P. vivax-detecting RDT products, cross-reactions with the PfHRP2 or Pf-pLDH line occurred at a median frequency of 2.5% (range 0%-10.9%) of P. vivax samples assessed. In two RDT products, two and one P. falciparum samples respectively cross-reacted with the Pv-pLDH line. Two Pf-pLDH/pan-pLDH-detecting RDTs showed excellent sensitivity with few (1.0%) cross-reactions but showed faint Pf-pLDH lines in 24.7% and 38.9% of P. falciparum samples.
  
  
  CONCLUSIONS
  PfHRP2-detecting RDTs are not suitable in the Peruvian Amazon due to pfhrp2 gene deletions. Two Pf-pLDH-detecting RDTs performed excellently and are promising RDTs for this region although faint test lines are of concern.
authors.affiliation: Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium. jmaltha@itg.be
authors.forename: Jessica
authors.initials: J
authors.lastname: Maltha
authors.forename: Dionicia
authors.initials: D
authors.lastname: Gamboa
authors.forename: Jorge
authors.initials: J
authors.lastname: Bendezu
authors.forename: Luis
authors.initials: L
authors.lastname: Sanchez
authors.forename: Lieselotte
authors.initials: L
authors.lastname: Cnops
authors.forename: Philippe
authors.initials: P
authors.lastname: Gillet
authors.forename: Jan
authors.initials: J
authors.lastname: Jacobs
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000953:Antigens, Protozoan / Q000235:genetics* / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D005260:Female; D017353:Gene Deletion; D005843:Geography; D006801:Humans; D007223:Infant; D008288:Malaria / Q000175:diagnosis* / Q000469:parasitology*; D008297:Male; D008853:Microscopy / Q000379:methods; D008875:Middle Aged; D008957:Models, Genetic; D010568:Peru; D010963:Plasmodium falciparum / Q000235:genetics*; D010966:Plasmodium vivax / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods; D011446:Prospective Studies; D015800:Protozoan Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D000953:Antigens, Protozoan; C514457:HRP-2 antigen, Plasmodium falciparum; C578339:HRP3 protein, Plasmodium falciparum; D015800:Protozoan Proteins