title: Survival analysis of diagnostic assays in Plasmodium falciparum malaria.
abstract: BACKGROUND
  Rapid diagnostic tests (RDT) and real-time PCR (qPCR) assays are sensitive for diagnosing malaria, but because they detect antigen and DNA, respectively, positivity may not reflect active infection. Performance characteristics of RDT and qPCR in Plasmodium falciparum positive specimens were evaluated over time to elucidate duration of positivity following conversion to microscopy negative.
  
  
  METHODS
  Specimens from patients with at least one specimen that was positive for P. falciparum by microscopy, and at least one specimen that was negative for P. falciparum within a 1-month period were identified. Survival distributions of the diagnostic tests over time were compared. Performance characteristics for each test were calculated.
  
  
  RESULTS
  Ninety specimens were included, with 48 initially positive for P. falciparum, and 42 subsequently negative. Of 42 specimens that converted to microscopy-negative following an initial positive, 26 (61.9 %) and 41 (97.6 %) were positive by qPCR and RDT, respectively. Survival curves of microscopy versus qPCR, as well as microscopy vs RDT differed significantly (p = 0.0002 and p < 0.0001, respectively). Compared to microscopy, sensitivity of qPCR was 100.0 % (95 % CI 90.8-100.0 %), and that of RDT was 100.0 % (95 % CI 90.8-100.0 %).
  
  
  CONCLUSIONS
  Due to slow clearance of circulating antigen and DNA from bloodstream, RDT and qPCR have low positive predictive value for clinically relevant asexual parasitaemia in post-treatment specimens. Thus, microscopy remains the only available malaria diagnostic that can reliably distinguish true asexual parasitaemia from prolonged clearance of antigen and nucleic acid in a convalescing patient.
authors.affiliation: Faculty of Health Sciences, McMaster University, Hamilton, Canada. phuongm@mcmaster.ca.
authors.forename: Melissa
authors.initials: M
authors.lastname: Phuong
authors.affiliation: Public Health Ontario Laboratories, Public Health Ontario, Toronto, Canada. rachel.lau@oahpp.ca.
authors.forename: Rachel
authors.initials: R
authors.lastname: Lau
authors.affiliation: Public Health Ontario Laboratories, Public Health Ontario, Toronto, Canada. filip.ralevski@oahpp.ca.
authors.forename: Filip
authors.initials: F
authors.lastname: Ralevski
authors.affiliation: Public Health Ontario Laboratories, Public Health Ontario, Toronto, Canada. andrea.boggild@utoronto.ca.|Tropical Disease Unit, Division of Infectious Diseases, UHN-Toronto General Hospital, 200 Elizabeth Street, 13EN-218, Toronto, ON, M5G 2C4, Canada. andrea.boggild@utoronto.ca.|Department of Medicine, University of Toronto, Toronto, Canada. andrea.boggild@utoronto.ca.
authors.forename: Andrea K
authors.initials: AK
authors.lastname: Boggild
mesh_terms: D006801:Humans; D016778:Malaria, Falciparum / Q000175:diagnosis*; D008853:Microscopy; D010274:Parasitology / Q000379:methods* / Q000592:standards*; D010963:Plasmodium falciparum / Q000235:genetics / Q000302:isolation & purification*; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D011933:Reagent Kits, Diagnostic
chemical_list: D011933:Reagent Kits, Diagnostic