title: False positivity of non-targeted infections in malaria rapid diagnostic tests: the case of human african trypanosomiasis.
abstract: BACKGROUND
  In endemic settings, diagnosis of malaria increasingly relies on the use of rapid diagnostic tests (RDTs). False positivity of such RDTs is poorly documented, although it is especially relevant in those infections that resemble malaria, such as human African trypanosomiasis (HAT). We therefore examined specificity of malaria RDT products among patients infected with Trypanosoma brucei gambiense.
  
  
  RESULTS
  Blood samples of 117 HAT patients and 117 matched non-HAT controls were prospectively collected in the Democratic Republic of the Congo. Reference malaria diagnosis was based on real-time PCR. Ten commonly used malaria RDT products were assessed including three two-band and seven three-band products, targeting HRP-2, Pf-pLDH and/or pan-pLDH antigens. Rheumatoid factor was determined in PCR negative subjects. Specificity of the 10 malaria RDT products varied between 79.5 and 100% in HAT-negative controls and between 11.3 and 98.8% in HAT patients. For seven RDT products, specificity was significantly lower in HAT patients compared to controls. False positive reactions in HAT were mainly observed for pan-pLDH test lines (specificities between 13.8 and 97.5%), but also occurred frequently for the HRP-2 test line (specificities between 67.9 and 98.8%). The Pf-pLDH test line was not affected by false-positive lines in HAT patients (specificities between 97.5 and 100%). False positivity was not associated to rheumatoid factor, detected in 7.6% of controls and 1.2% of HAT patients.
  
  
  CONCLUSIONS
  Specificity of some malaria RDT products in HAT was surprisingly low, and constitutes a risk for misdiagnosis of a fatal but treatable infection. Our results show the importance to assess RDT specificity in non-targeted infections when evaluating diagnostic tests.
authors: Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.
authors: Philippe
authors: P
authors: Gillet
authors: Dieudonné
authors: D
authors: Mumba Ngoyi
authors: Albert
authors: A
authors: Lukuka
authors: Viktor
authors: V
authors: Kande
authors: Benjamin
authors: B
authors: Atua
authors: Johan
authors: J
authors: van Griensven
authors: Jean-Jacques
authors: JJ
authors: Muyembe
authors: Jan
authors: J
authors: Jacobs
authors: Veerle
authors: V
authors: Lejon
mesh_terms: D000328:Adult; D003955:Diagnostic Tests, Routine / Q000379:methods*; D005189:False Positive Reactions; D005260:Female; D006801:Humans; D008288:Malaria / Q000175:diagnosis* / Q000469:parasitology; D008297:Male; D011446:Prospective Studies; D060888:Real-Time Polymerase Chain Reaction; D014353:Trypanosomiasis, African / Q000175:diagnosis*
references: N Engl J Med. 1998 Apr 9;338(15):1075
references: 9537883
references: Malar J. 2012 Jul 06;11:224
references: 22770130
references: N Engl J Med. 2013 Mar 14;368(11):1069-70
references: 23484849
references: Clin Exp Immunol. 1976 Aug;25(2):185-90
references: 1085235
references: Trop Med Int Health. 2011 Jul;16(7):869-74
references: 21447063
references: Clin Microbiol Infect. 2011 Jul;17(7):1101-7
references: 20718798
references: Cochrane Database Syst Rev. 2011 Jul 06;(7):CD008122
references: 21735422
references: J Clin Invest. 1981 Jan;67(1):77-85
references: 6969733
references: Malar J. 2011 Oct 18;10:308
references: 22008378
references: N Engl J Med. 1997 Nov 27;337(22):1635-6
references: 9411233
references: Clin Microbiol Rev. 2008 Jan;21(1):97-110
references: 18202438
references: Malar J. 2007 May 16;6:58
references: 17506881
references: Ann Soc Belg Med Trop. 1978;58(2):103-9
references: 361001
references: PLoS Med. 2010 Jun 15;7(6):e1000290
references: 20563310
references: PLoS Med. 2008 Feb;5(2):e55
references: 18303943
references: Malar J. 2010 Dec 22;9:370
references: 21176207
references: Ann Neurol. 2008 Aug;64(2):116-26
references: 18756506
references: J Clin Microbiol. 2000 Mar;38(3):1184-6
references: 10699018
references: J Clin Microbiol. 2011 Jun;49(6):2331-2
references: 21508157
references: J Clin Microbiol. 2010 Aug;48(8):2836-9
references: 20573878
references: J Infect Dis. 2003 May 1;187(9):1475-83
references: 12717630
references: PLoS Negl Trop Dis. 2009 Nov 24;3(11):e471
references: 19936296
references: Lancet. 1999 Jan 23;353(9149):297
references: 9929032