title: Evaluation of the diagnostic potential of urinary N-Acetyltyramine-O,β-glucuronide (NATOG) as diagnostic biomarker for Onchocerca volvulus infection.
abstract: Onchocerciasis, also known as river blindness is one of the neglected tropical diseases affecting millions of people, mainly in sub-Saharan Africa and is caused by the filarial nematode Onchocerca volvulus. Efforts to eliminate this disease are ongoing and are based on mass drug administration programs with the microfilaricide ivermectin. In order to monitor the efficacy of these programs, there is an unmet need for diagnostic tools capable of identifying infected patients. We have investigated the diagnostic potential of urinary N-acetyltyramine-O,β-glucuronide (NATOG), which is a promising O. volvulus specific biomarker previously identified by urine metabolome analysis.
  
  
  
  A liquid chromatography tandem mass spectrometry (LC-MS/MS) method was used to assess the stability characteristics of NATOG and to evaluate the levels of NATOG in study samples. An LC-fluorescence method was also developed.
  
  
  
  Stability characteristics of NATOG were investigated and shown to be ideally suited for use in tropical settings. Also, an easy and more accessible method based on liquid chromatography coupled to fluorescence detection was developed and shown to have the necessary sensitivity (limit of quantification 1 μM). Furthermore, we have evaluated the levels of NATOG in a population of 98 nodule-positive individuals from Ghana with no or low levels of microfilaria in the skin and compared them with the levels observed in different control groups (endemic controls (n = 50), non-endemic controls (n = 18) and lymphatic filariasis (n = 51). Only a few (5 %) of nodule-positive individuals showed an increased level (> 10 μM) of NATOG and there was no statistical difference between the nodule-positive individuals and the control groups (P > 0.05).
  
  
  
  Results of the present study indicate the limited potential of NATOG as a diagnostic biomarker for O. volvulus infection in amicrofilaridermic individuals.
authors.affiliation: Janssen Diagnostics, Janssen R&D, Turnhoutseweg 30, 2340, Beerse, Belgium. olagatie@its.jnj.com.
authors.forename: Ole
authors.initials: O
authors.lastname: Lagatie
authors.affiliation: Bioanalysis, Janssen R&D, Turnhoutseweg 30, 2340, Beerse, Belgium.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Njumbe Ediage
authors.affiliation: Kumasi Centre for Collaborative Research, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
authors.forename: Linda
authors.initials: L
authors.lastname: Batsa Debrah
authors.affiliation: Bioanalysis, Janssen R&D, Turnhoutseweg 30, 2340, Beerse, Belgium.
authors.forename: Luc
authors.initials: L
authors.lastname: Diels
authors.affiliation: Neuroscience, Janssen R&D, Turnhoutseweg 30, 2340, Beerse, Belgium.
authors.forename: Christ
authors.initials: C
authors.lastname: Nolten
authors.affiliation: Toxicology, Janssen R&D, Turnhoutseweg 30, 2340, Beerse, Belgium.
authors.forename: Petra
authors.initials: P
authors.lastname: Vinken
authors.affiliation: Faculty of Allied Health Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
authors.forename: Alex
authors.initials: A
authors.lastname: Debrah
authors.affiliation: Bioanalysis, Janssen R&D, Turnhoutseweg 30, 2340, Beerse, Belgium.
authors.forename: Lieve
authors.initials: L
authors.lastname: Dillen
authors.affiliation: Janssen Global Public Health, Janssen R&D, 12 W Sunset Ave, Philadelphia, PA, 19118, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Silber
authors.affiliation: Janssen Diagnostics, Janssen R&D, Turnhoutseweg 30, 2340, Beerse, Belgium.
authors.forename: Lieven J
authors.initials: LJ
authors.lastname: Stuyver
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000652:urine; D002853:Chromatography, Liquid; D005260:Female; D020719:Glucuronides / Q000652:urine*; D006801:Humans; D008842:Microfilariae; D017181:Onchocerca volvulus / Q000302:isolation & purification*; D009855:Onchocerciasis / Q000175:diagnosis*; D015827:Onchocerciasis, Ocular / Q000175:diagnosis*; D053719:Tandem Mass Spectrometry; D014439:Tyramine / Q000031:analogs & derivatives* / Q000652:urine
chemical_list: D015415:Biomarkers; D020719:Glucuronides; C054479:N-acetyltyramine; D014439:Tyramine
keywords: Biomarker; Diagnostic; NATOG; Onchocerca volvulus; Onchocerciasis; River blindness; Urine