Lagatie Ole, Njumbe Ediage Emmanuel, Batsa Debrah Linda, Diels Luc, Nolten Christ, Vinken Petra, Debrah Alex, Dillen Lieve, Silber Steven, Stuyver Lieven J
Janssen Diagnostics, Janssen R&D, Turnhoutseweg 30, 2340, Beerse, Belgium.
Bioanalysis, Janssen R&D, Turnhoutseweg 30, 2340, Beerse, Belgium.
Parasit Vectors. 2016 May 23;9(1):302. doi: 10.1186/s13071-016-1582-6.
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.
盘尾丝虫病，又称河盲症，是一种被忽视的热带疾病，主要影响撒哈拉以南非洲的数百万人，由丝状线虫盘尾丝虫引起。目前正在努力消除这种疾病，主要通过大规模药物施用微丝蚴杀虫剂伊维菌素的项目。为了监测这些项目的效果，迫切需要能够识别感染患者的诊断工具。我们研究了尿中N - 乙酰酪胺 - O,β - 葡糖醛酸苷（NATOG）的诊断潜力，这是一种先前通过尿液代谢组分析鉴定出的有前景的盘尾丝虫特异性生物标志物。
采用液相色谱串联质谱（LC - MS/MS）方法评估NATOG的稳定性特征，并评估研究样本中NATOG的水平。还开发了一种LC - 荧光方法。
研究了NATOG的稳定性特征，结果表明其非常适合在热带环境中使用。此外，还开发了一种基于液相色谱与荧光检测联用的简便且更易操作的方法，该方法具有必要的灵敏度（定量限为1 μM）。此外，我们评估了来自加纳的98名结节阳性个体的NATOG水平，这些个体皮肤中无微丝蚴或微丝蚴水平较低，并将其与不同对照组（地方性对照组（n = 50）、非地方性对照组（n = 18）和淋巴丝虫病组（n = 51））中观察到的水平进行比较。只有少数（5%）结节阳性个体的NATOG水平升高（> 10 μM），结节阳性个体与对照组之间无统计学差异（P > 0.05）。
本研究结果表明，NATOG作为无微丝蚴个体盘尾丝虫感染诊断生物标志物的潜力有限。
