title: Identification of sVSG117 as an immunodiagnostic antigen and evaluation of a dual-antigen lateral flow test for the diagnosis of human African trypanosomiasis.
abstract: BACKGROUND
  The diagnosis of human African trypanosomiasis (HAT) caused by Trypanosoma brucei gambiense relies mainly on the Card Agglutination Test for Trypanosomiasis (CATT). There is no immunodiagnostic for HAT caused by T. b. rhodesiense. Our principle aim was to develop a prototype lateral flow test that might be an improvement on CATT.
  
  
  RESULTS
  Pools of infection and control sera were screened against four different soluble form variant surface glycoproteins (sVSGs) by ELISA and one, sVSG117, showed particularly strong immunoreactivity to pooled infection sera. Using individual sera, sVSG117 was shown to be able to discriminate between T. b. gambiense infection and control sera by both ELISA and lateral flow test. The sVSG117 antigen was subsequently used with a previously described recombinant diagnostic antigen, rISG65, to create a dual-antigen lateral flow test prototype. The latter was used blind in a virtual field trial of 431 randomized infection and control sera from the WHO HAT Specimen Biobank.
  
  
  CONCLUSIONS
  In the virtual field trial, using two positive antigen bands as the criterion for infection, the sVSG117 and rISG65 dual-antigen lateral flow test prototype showed a sensitivity of 97.3% (95% CI: 93.3 to 99.2) and a specificity of 83.3% (95% CI: 76.4 to 88.9) for the detection of T. b. gambiense infections. The device was not as good for detecting T. b. rhodesiense infections using two positive antigen bands as the criterion for infection, with a sensitivity of 58.9% (95% CI: 44.9 to 71.9) and specificity of 97.3% (95% CI: 90.7 to 99.7). However, using one or both positive antigen band(s) as the criterion for T. b. rhodesiense infection improved the sensitivity to 83.9% (95% CI: 71.7 to 92.4) with a specificity of 85.3% (95% CI: 75.3 to 92.4). These results encourage further development of the dual-antigen device for clinical use.
authors.affiliation: Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dundee, United Kingdom.
authors.forename: Lauren
authors.initials: L
authors.lastname: Sullivan
authors.affiliation: Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dundee, United Kingdom.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Fleming
authors.affiliation: Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dundee, United Kingdom.
authors.forename: Lalitha
authors.initials: L
authors.lastname: Sastry
authors.affiliation: Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dundee, United Kingdom.
authors.forename: Angela
authors.initials: A
authors.lastname: Mehlert
authors.affiliation: BBI Solutions, Alchemy House, Dundee, United Kingdom.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Wall
authors.affiliation: Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dundee, United Kingdom.
authors.forename: Michael A J
authors.initials: MA
authors.lastname: Ferguson
mesh_terms: D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods*; D006801:Humans; D011933:Reagent Kits, Diagnostic / Q000469:parasitology*; D014353:Trypanosomiasis, African / Q000175:diagnosis* / Q000276:immunology* / Q000469:parasitology*; D014643:Variant Surface Glycoproteins, Trypanosoma / Q000276:immunology*
chemical_list: D011933:Reagent Kits, Diagnostic; D014643:Variant Surface Glycoproteins, Trypanosoma