title: Accuracy of PfHRP2 versus Pf-pLDH antigen detection by malaria rapid diagnostic tests in hospitalized children in a seasonal hyperendemic malaria transmission area in Burkina Faso.
abstract: BACKGROUND
  In most sub-Saharan African countries malaria rapid diagnostic tests (RDTs) are now used for the diagnosis of malaria. Most RDTs used detect Plasmodium falciparum histidine-rich protein-2 (PfHRP2), though P. falciparum-specific parasite lactate dehydrogenase (Pf-pLDH)-detecting RDTs may have advantages over PfHRP2-detecting RDTs. Only few data are available on the use of RDTs in severe illness and the present study compared Pf-pLDH to PfHRP2-detection.
  
  
  METHODS
  Hospitalized children aged one month to 14 years presenting with fever or severe illness were included over one year. Venous blood samples were drawn for malaria diagnosis (microscopy and RDT), culture and complete blood count. Leftovers were stored at -80 °C and used for additional RDT analysis and PCR. An RDT targeting both PfHRP2 and Pf-pLDH was performed on all samples for direct comparison of diagnostic accuracy with microscopy as reference method. PCR was performed to explore false-positive RDT results.
  
  
  RESULTS
  In 376 of 694 (54.2%) included children, malaria was microscopically confirmed. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value were 100.0, 70.9, 69.4 and 100.0%, respectively for PfHRP2-detection and 98.7, 94.0, 91.6 and 99.1%, respectively for Pf-pLDH-detection. Specificity and PPV were significantly lower for PfHRP2-detection (p <0.001). For both detection antigens, specificity was lowest for children one to five years and in the rainy season. PPV for both antigens was highest in the rainy season, because of higher malaria prevalence. False positive PfHRP2 results were associated with prior anti-malarial treatment and positive PCR results (98/114 (86.0%) samples tested).
  
  
  CONCLUSIONS
  Among children presenting with severe febrile illness in a seasonal hyperendemic malaria transmission area, the present study observed similar sensitivity but lower specificity and PPV of PfHRP2 compared to Pf-pLDH-detection. Further studies should assess the diagnostic accuracy and safety of an appropriate Pf-pLDH-detecting RDT in field settings and if satisfying, replacement of PfHRP2 by Pf-pLDH-detecting RDTs should be considered.
authors.affiliation: Department of Clinical Sciences, Institute of Tropical Medicine, Nationalestraat 155, B 2000, Antwerp, Belgium. jessicamaltha@gmail.com.
authors.forename: Jessica
authors.initials: J
authors.lastname: Maltha
authors.forename: Issa
authors.initials: I
authors.lastname: Guiraud
authors.forename: Palpouguini
authors.initials: P
authors.lastname: Lompo
authors.forename: Bérenger
authors.initials: B
authors.lastname: Kaboré
authors.forename: Philippe
authors.initials: P
authors.lastname: Gillet
authors.forename: Chris
authors.initials: C
authors.lastname: Van Geet
authors.forename: Halidou
authors.initials: H
authors.lastname: Tinto
authors.forename: Jan
authors.initials: J
authors.lastname: Jacobs
mesh_terms: D000293:Adolescent; D000953:Antigens, Protozoan; D002050:Burkina Faso / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D003955:Diagnostic Tests, Routine / Q000379:methods*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007770:L-Lactate Dehydrogenase; D016778:Malaria, Falciparum / Q000175:diagnosis* / Q000453:epidemiology / Q000469:parasitology; D008297:Male; D016133:Polymerase Chain Reaction; D015995:Prevalence; D015800:Protozoan Proteins; D012621:Seasons; D012680:Sensitivity and Specificity
chemical_list: D000953:Antigens, Protozoan; C514457:HRP-2 antigen, Plasmodium falciparum; D015800:Protozoan Proteins; D007770:L-Lactate Dehydrogenase