Institute of Medical Microbiology, Immunology and Parasitology (IMMIP), University Hospital Bonn, Venusberg-Campus 1, 53127, Bonn, Germany.
Center of Excellence in Plant Sciences (CEPLAS), Mass Spectrometry Platform, University of Cologne, Zülpicher Str. 47b, 50674, Cologne, Germany.
Parasit Vectors. 2021 Aug 11;14(1):397. doi: 10.1186/s13071-021-04893-1.
The tropical disease onchocerciasis (river blindness), caused by Onchocerca volvulus filarial nematodes, is targeted for elimination by mass treatment with nematocidal and antimicrobial drugs. Diagnosis of O. volvulus infections is based on counts of skin-borne microfilariae, but additional diagnostic tools, e.g. worm- or host-derived small RNAs, proteins or metabolites, are required for high-throughput screening. N-acetyltyramine-O,β-glucuronide (NATOG) was suggested as a biomarker for onchocerciasis but its viability as diagnostic tool has been challenged.
We performed a screening program of urine samples from individuals from Cameroon infected with O. volvulus, Loa loa, Mansonella perstans or a combination thereof. Urine metabolites were measured by liquid chromatography-mass spectrometry (LC-MS). Principle component analysis (PCA) revealed that onchocerciasis causes complex changes of the urine metabolome.
The mean NATOG content was elevated in urine of O. volvulus-infected compared with non-infected individuals, but NATOG levels showed considerable variation. However, 13.8% of all O. volvulus-infected individuals had high NATOG levels never reached by individuals without filarial infections or only infected with L. loa or M. perstans. Therefore, the identification of individuals with high NATOG levels might be used to screen for the elimination of onchocerciasis after mass drug application. Additional metabolites, including a compound identified as cinnamoylglycine, had high PC1/PC2 loadings in the data set. Mean levels of cinnamoylglycine were increased in O. volvulus-infected individuals, and 17.2% of all O. volvulus individuals had elevated cinnamoylglycine levels not reached by the controls.
On an individual level, NATOG alone had poor discriminative power distinguishing infected from non-infected individuals. However, 13.8% of all O. volvulus-infected individuals had NATOG levels never reached by individuals without filarial infections or infected with only L. loa or M. perstans. Discrimination of O. volvulus infections from controls or individuals suffering from multiple infections was improved by the measurement of additional metabolites, e.g. cinnamoylglycine. Thus, measuring a combination of urine metabolites may provide a way to assess onchocerciasis on the population level. This provides the possibility to design a strategy for large-scale onchocerciasis epidemiological screening programs based on urine rather than invasive techniques.
由旋盘丝虫（奥氏绕虫）丝状线虫引起的热带病盘尾丝虫病（河盲症），通过大规模使用杀丝虫和抗菌药物进行治疗，目标是消除该病。奥氏绕虫感染的诊断基于皮肤携带的微丝蚴计数，但需要其他诊断工具，例如虫体或宿主来源的小 RNA、蛋白质或代谢物，以进行高通量筛选。N-乙酰酪胺-O，β-葡糖苷酸（NATOG）被提议作为盘尾丝虫病的生物标志物，但它作为诊断工具的可行性受到了挑战。
我们对来自喀麦隆的感染奥氏绕虫、罗阿丝虫、曼森线虫或混合感染的个体的尿液样本进行了筛查。通过液相色谱-质谱（LC-MS）测量尿液代谢物。主成分分析（PCA）显示，盘尾丝虫病会导致尿液代谢组发生复杂变化。
与未感染个体相比，感染奥氏绕虫的个体尿液中的 NATOG 含量升高，但 NATOG 水平存在较大差异。然而，13.8%的所有感染奥氏绕虫的个体的 NATOG 水平从未达到过未感染丝虫的个体或仅感染罗阿丝虫或曼森线虫的个体。因此，识别具有高 NATOG 水平的个体可能用于在大规模药物治疗后筛查盘尾丝虫病的消除。其他代谢物，包括一种鉴定为肉桂酰甘氨酸的化合物，在数据集中有很高的 PC1/PC2 加载。感染奥氏绕虫的个体中肉桂酰甘氨酸的平均水平升高，17.2%的所有感染奥氏绕虫的个体的肉桂酰甘氨酸水平从未达到过对照组。
在个体水平上，NATOG 单独使用时区分感染和未感染个体的能力较差。然而，13.8%的所有感染奥氏绕虫的个体的 NATOG 水平从未达到过未感染丝虫的个体或仅感染罗阿丝虫或曼森线虫的个体。通过测量其他代谢物，例如肉桂酰甘氨酸，可以提高对奥氏绕虫感染与对照或多种感染个体的区分。因此，测量尿液代谢物的组合可能为评估盘尾丝虫病的人群水平提供一种方法。这为基于尿液而不是侵入性技术设计大规模盘尾丝虫病流行病学筛查计划提供了可能性。
