title: Pan-Plasmodium band sensitivity for Plasmodium falciparum detection in combination malaria rapid diagnostic tests and implications for clinical management.
abstract: BACKGROUND
  Malaria rapid diagnostic tests (RDTs) are appropriate for case management, but persistent antigenaemia is a concern for HRP2-detecting RDTs in endemic areas. It has been suggested that pan-pLDH test bands on combination RDTs could be used to distinguish persistent antigenaemia from active Plasmodium falciparum infection, however this assumes all active infections produce positive results on both bands of RDTs, an assertion that has not been demonstrated.
  
  
  METHODS
  In this study, data generated during the WHO-FIND product testing programme for malaria RDTs was reviewed to investigate the reactivity of individual test bands against P. falciparum in 18 combination RDTs. Each product was tested against multiple wild-type P. falciparum only samples. Antigen levels were measured by quantitative ELISA for HRP2, pLDH and aldolase.
  
  
  RESULTS
  When tested against P. falciparum samples at 200 parasites/μL, 92% of RDTs were positive; 57% of these on both the P. falciparum and pan bands, while 43% were positive on the P. falciparum band only. There was a relationship between antigen concentration and band positivity; ≥4 ng/mL of HRP2 produced positive results in more than 95% of P. falciparum bands, while ≥45 ng/mL of pLDH was required for at least 90% of pan bands to be positive.
  
  
  CONCLUSIONS
  In active P. falciparum infections it is common for combination RDTs to return a positive HRP2 band combined with a negative pan-pLDH band, and when both bands are positive, often the pan band is faint. Thus active infections could be missed if the presence of a HRP2 band in the absence of a pan band is interpreted as being caused solely by persistent antigenaemia.
authors.affiliation: School of Public Health and Social Work, Queensland University of Technology, GPO Box 2434, Brisbane, Qld 4001, Australia. m.gatton@qut.edu.au.
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Gatton
authors.affiliation: National Institute for Health Research University College London Hospitals Biomedical Research Centre, Hospital for Tropical Diseases, London, UK. roxanne.rees-channer@uclh.nhs.uk.
authors.forename: Roxanne R
authors.initials: RR
authors.lastname: Rees-Channer
authors.affiliation: Malaria Branch, Division of Parasitic Diseases and Malaria, Centers for Disease Control and Prevention, Center for Global Health, Atlanta, USA. khi2@cdc.gov.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Glenn
authors.affiliation: Malaria Branch, Division of Parasitic Diseases and Malaria, Centers for Disease Control and Prevention, Center for Global Health, Atlanta, USA. wzb3@cdc.gov.
authors.forename: John W
authors.initials: JW
authors.lastname: Barnwell
authors.affiliation: Drug Resistance and Diagnostics, Australian Army Malaria Institute, Brisbane, Australia. qin.cheng@defence.gov.au.
authors.forename: Qin
authors.initials: Q
authors.lastname: Cheng
authors.affiliation: National Institute for Health Research University College London Hospitals Biomedical Research Centre, Hospital for Tropical Diseases, London, UK. peter.chiodini@uclh.nhs.uk.|London School of Hygiene and Tropical Medicine, London, UK. peter.chiodini@uclh.nhs.uk.
authors.forename: Peter L
authors.initials: PL
authors.lastname: Chiodini
authors.affiliation: FIND (Foundation for Innovative New Diagnostics), Geneva, Switzerland. sandra.incardona@finddx.org.
authors.forename: Sandra
authors.initials: S
authors.lastname: Incardona
authors.affiliation: FIND (Foundation for Innovative New Diagnostics), Geneva, Switzerland. iveth.gonzalez@finddx.org.
authors.forename: Iveth J
authors.initials: IJ
authors.lastname: González
authors.affiliation: Global Malaria Programme, World Health Organization, Geneva, Switzerland. cunninghamj@who.int.
authors.forename: Jane
authors.initials: J
authors.lastname: Cunningham
mesh_terms: D000953:Antigens, Protozoan / Q000097:blood*; D003955:Diagnostic Tests, Routine / Q000379:methods* / Q000592:standards; D016778:Malaria, Falciparum / Q000175:diagnosis*; D010963:Plasmodium falciparum / Q000302:isolation & purification*
chemical_list: D000953:Antigens, Protozoan