Validation of onchocerciasis biomarker N -acetyltyramine- O -glucuronide (NATOG)

Globisch, Daniel; Shirey, Ryan J.; Pfarr, Kenneth; Wanji, Samuel; Debrah, Alexander Yaw; Hoerauf, Achim; Janda, Kim D.

doi:10.1016/j.bmcl.2017.05.082

Cited by 21 publications

(37 citation statements)

References 36 publications

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“…The average urinary NATOG concentration in individuals with active infection in our study was 8.9 µM, which is close to the 8.4 µM observed in Guatemalan samples in a study by Globisch et al [9] ( Table 6). This concentration is below the 13 µM threshold required to identify active O. volvulus infection in Africa, proposed by Globisch et al This high threshold was proposed by Globisch et al because, in a study in Ghana, high urinary NATOG concentrations were observed in O. volvulus uninfected endemic African controls (Table 6) [9,10]. However, the diagnosis of uninfected controls was mainly based on the absence of nodules.…”

Section: Discussionmentioning

confidence: 75%

“…Furthermore, using the previously proposed cut-off value of 13 μM, 17 individuals were correctly classified as having active infection and 47 individuals were correctly classified as not having active infection, leading to a sensitivity of 15.9% and a specificity of 95.9% (Table 5). Using the previously proposed NATOG cut-off value of 13 μM for the diagnosis of active O. volvulus infection and an uninfected state [10], the sensitivity of urinary NATOG was 15.9% and specificity was 95.9% (Table 5). Using the previously proposed NATOG cut-off value of 13 µM for the diagnosis of active O. volvulus infection and an uninfected state [10], the sensitivity of urinary NATOG was 15.9% and specificity was 95.9% (Table 5).…”

Section: Urinary Natog As a Biomarker For Active O Volvulus Infectionmentioning

confidence: 99%

“…Using the previously proposed NATOG cut-off value of 13 μM for the diagnosis of active O. volvulus infection and an uninfected state [10], the sensitivity of urinary NATOG was 15.9% and specificity was 95.9% (Table 5). Using the previously proposed NATOG cut-off value of 13 µM for the diagnosis of active O. volvulus infection and an uninfected state [10], the sensitivity of urinary NATOG was 15.9% and specificity was 95.9% (Table 5).…”

Section: Urinary Natog As a Biomarker For Active O Volvulus Infectionmentioning

confidence: 99%

“…Previous research exploring the metabolomic profile of O. volvulus-infected individuals living in villages in Ghana and Cameroon, revealed that N-acetyltyramine-O,β-glucuronide (NATOG) was enriched in the urine of O. volvulus-infected individuals [9]. NATOG is the inactivated form of the O. volvulus neurotransmitter tyramine, which is excreted in the urine of infected individuals [9,10]. Since the discovery of NATOG, several studies have tried to determine a cut-off value for urinary NATOG concentration to diagnose active O. volvulus infection [9][10][11][12].…”

Section: Introductionmentioning

confidence: 99%

“…NATOG is the inactivated form of the O. volvulus neurotransmitter tyramine, which is excreted in the urine of infected individuals [9,10]. Since the discovery of NATOG, several studies have tried to determine a cut-off value for urinary NATOG concentration to diagnose active O. volvulus infection [9][10][11][12]. However, the results of these studies are conflicting.…”

Section: Introductionmentioning

confidence: 99%

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Urinary N-acetyltyramine-O,β-glucuronide in Persons with Onchocerciasis-Associated Epilepsy

Hotterbeekx

Dusabimana

Mandro³

et al. 2020

Pathogens

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We investigated urinary N-acetyltyramine-O,β-glucuronide (NATOG) levels as a biomarker for active Onchocerca volvulus infection in an onchocerciasis-endemic area in the Democratic Republic of Congo with a high epilepsy prevalence. Urinary NATOG was measured in non-epileptic men with and without O. volvulus infection, and in O. volvulus-infected persons with epilepsy (PWE). Urinary NATOG concentration was positively associated with microfilarial density (p < 0.001). The median urinary NATOG concentration was higher in PWE (3.67 µM) compared to men without epilepsy (1.74 µM), p = 0.017; and was higher in persons with severe (7.62 µM) compared to mild epilepsy (2.16 µM); p = 0.008. Non-epileptic participants with and without O. volvulus infection had similar NATOG levels (2.23 µM and 0.71 µM, p = 0.426). In a receiver operating characteristic curve analysis to investigate the diagnostic value of urinary NATOG, the area under the curve was 0.721 (95% CI: 0.633–0.797). Using the previously proposed cut-off value of 13 µM to distinguish between an active O. volvulus infection and an uninfected state, the sensitivity was 15.9% and the specificity 95.9%. In conclusion, an O. volvulus infection is associated with an increased urinary NATOG concentration, which correlates with the individual parasitic load. However, the NATOG concentration has a low discriminating power to differentiate between infected and uninfected individuals.

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Section: Discussionmentioning

confidence: 75%

Section: Urinary Natog As a Biomarker For Active O Volvulus Infectionmentioning

confidence: 99%

Section: Urinary Natog As a Biomarker For Active O Volvulus Infectionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Urinary N-acetyltyramine-O,β-glucuronide in Persons with Onchocerciasis-Associated Epilepsy

Hotterbeekx

Dusabimana

Mandro³

et al. 2020

Pathogens

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Diagnosis and Assessment of Human Filarial Infections: Current Status and Challenges

Mackenzie¹,

Souza²,

Geary³

2022

Human and Animal Filariases

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Coupled Enzymatic Treatment and Mass Spectrometric Analysis for Identification of Glucuronidated Metabolites in Human Samples

et al. 2019

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Glucuronidation is the most common phase II modification and plays an important role in human clearance metabolism. Glucuronidated metabolites have also been linked to disease development and microbiota–host co‐metabolism. Although many of these compounds have been identified, the total number of unknown glucuronides and their impact on the human host's physiology can only be estimated. Herein, we describe the combination of an untargeted metabolomics analysis and enzymatic metabolic conversion for the selective detection of glucuronide conjugates by using UPLC‐MS/MS in human urine samples. Our study demonstrates that this powerful strategy can be used for the selective identification of glucuronidated molecules and to discover unknown natural metabolites. In total, we identified 191 metabolites in a single sample including microbiota‐derived compounds as well as previously unidentified molecules.

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Validation of onchocerciasis biomarker N -acetyltyramine- O -glucuronide (NATOG)

Abstract: Graphical abstract

Cited by 21 publications

References 36 publications

Urinary N-acetyltyramine-O,β-glucuronide in Persons with Onchocerciasis-Associated Epilepsy

Urinary N-acetyltyramine-O,β-glucuronide in Persons with Onchocerciasis-Associated Epilepsy

Diagnosis and Assessment of Human Filarial Infections: Current Status and Challenges

Coupled Enzymatic Treatment and Mass Spectrometric Analysis for Identification of Glucuronidated Metabolites in Human Samples

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