2-methyl butyramide, a previously identified urine biomarker for Ascaris lumbricoides, is not present in infected Indonesian individuals

Lagatie, Ole; Ediage, Emmanuel Njumbe; Pikkemaat, Jeroen A.; Djuardi, Yenny; Stuyver, Lieven

doi:10.1186/s13071-017-2600-z

Cited by 4 publications

(4 citation statements)

References 6 publications

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“…In a search for such non-stool-based biomarkers for STH infection, 2-methyl butyramide (2-MBA) and 2-methyl valeramide (2-MVA) were previously identified in urine as promising biomarkers for infection with A. lumbricoides 10 . However, these findings could not be confirmed in a more recent study on A. lumbricoides- infected subjects from Indonesia 11 .…”

Section: Introductioncontrasting

confidence: 67%

“…Similar as observed here for 2-MPC, there seemed to be a correlation between metabolite concentration and worm burden. However, more recent investigation of these proposed biomarkers could not confirm this and in fact has suggested that the original metabolite identification might have been incorrect 11 . Whether (one of) the biomarkers originally detected correspond to 2-MPC is hard to prove but given the similarities in the chemical structures between 2-methyl valeramide and 2-MPC, it could be possible that the same marker was detected but identified as another chemical structure due to differences in analytical techniques available at that time.…”

Section: Discussionmentioning

confidence: 98%

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2-Methyl-pentanoyl-carnitine (2-MPC): a urine biomarker for patent Ascaris lumbricoides infection

Lagatie

Verheyen

Asten

et al. 2020

Sci Rep

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Infections with intestinal worms, such as Ascaris lumbricoides, affect hundreds of millions of people in all tropical and subtropical regions of the world. Through large-scale deworming programs, World Health Organization aims to reduce moderate-to-heavy intensity infections below 1%. Current diagnosis and monitoring of these control programs are solely based on the detection of worm eggs in stool. Here we describe how metabolome analysis was used to identify the A. lumbricoides-specific urine biomarker 2-methyl pentanoyl carnitine (2-MPC). This biomarker was found to be 85.7% accurate in determining infection and 90.5% accurate in determining a moderate-to-heavy infection. Our results also demonstrate that there is a correlation between 2-MPC levels in urine and A. lumbricoides DNA detected in stool. Furthermore, the levels of 2-MPC in urine were shown to rapidly and strongly decrease upon administration of a standard treatment (single oral dose of 400 mg albendazole). In an Ascaris suum infection model in pigs, it was found that, although 2-MPC levels were much lower compared to humans, there was a significant association between urinary 2-MPC levels and both worm counts (p = 0.023) and the number of eggs per gram (epg) counts (p < 0.001). This report demonstrates that urinary 2-MPC can be considered an A. lumbricoides-specific biomarker that can be used to monitor infection intensity.

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Section: Introductioncontrasting

confidence: 67%

Section: Discussionmentioning

confidence: 98%

2-Methyl-pentanoyl-carnitine (2-MPC): a urine biomarker for patent Ascaris lumbricoides infection

Lagatie

Verheyen

Asten

et al. 2020

Sci Rep

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“…57 Recently, urinary biomarkers of A. lumbricoides infection, such as 2-methyl butyramide, 2-methyl pentanoyl carnitine (2-MPC) and 2-methyl-valeramide metabolites have also been evaluated. 58,59 Of these, 2-MPC has been found to have an accuracy of 85.7% for detection of infection with better performance (90.5% accuracy) for moderate to heavy infection. 58 A substantial reduction after albendazole treatment was also seen with a significant association between urine 2-MPC levels and worm/egg counts.…”

Section: Antibody Detectionmentioning

confidence: 99%

Diagnostic Techniques for Soil-Transmitted Helminths – Recent Advances

Khurana¹,

Mewara²

2021

RRTM

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Soil-transmitted helminth (STH) infections (hookworms, Trichuris, Ascaris ) and Strongyloides spp. are associated with a substantial global burden and high morbidity. Sensitive and specific methods for diagnosis of these infections are essential for mapping the burden in communities, accurate assessment of infection levels, to guide interventions and monitoring the success of STH control programs. Despite considerable progress to control STH over several decades, we are still far from identifying a fully adequate diagnostic test. Conventional microscopy-based methods such as direct Kato–Katz smear or mounts after stool centrifugation/flotation-based concentration techniques have been the mainstay of diagnosis, especially in resource-poor countries where these infections abound. However, recently, these are being adapted to closed, easy to perform, digital formats, thereby improving the sensitivity as well as applicability in a remote, resource-limited setting. The use of image analysis systems to identify and quantify helminth eggs, with potential adaptation to smartphones, is also promising. Antibody detection tests have a limited role mostly in the case of Strongyloides hyperinfection. Coproantigen detection tests have been developed and used in veterinary practice for detection of STH, but these have not been evaluated for use in humans. More sensitive molecular diagnostics, including assays developed with new bioinformatic tools and techniques such as polymerase chain reaction (PCR), quantitative PCR (qPCR) and loop-mediated amplification assay, can help in the clear and precise assessment of STH burden during elimination phase and are of immense value for diagnosis in areas with low endemicity and in travelers to endemic regions. Moreover, the molecular techniques will help detect new species that may emerge. Sample preservation and efficient DNA extraction are critical and significantly affect the efficiency of molecular diagnostic tests. In addition to the diagnosis of clinical or asymptomatic infection in humans, detection of STH eggs in environmental samples is imperative to boost STH control efforts. Overall the diagnostic performance, cost-effectiveness, ease of performance, rapidity and in-field applicability of any test should be considered when choosing from the various diagnostic assays in areas with different endemicity, in addition to striving towards the development of novel technologies and optimization of existing methods.

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“…Using this approach, it was reported that two metabolites, 2-methyl-butyramide and 2-methyl-valeramide, can be detected within the urine of individuals infected with Ascaris (Hall and Romanova., 1990). These findings have, however, recently been contested after neither of metabolite was detected in Indonesian individuals harbouring active Ascaris infections (Lagatie et al ., 2017). In addition to liquid chromatography, nuclear magnetic resonance (NMR) spectroscopy has been used to screen urine samples taken from mice experimentally infected with S. mansoni for expelled metabolites (Wang et al ., 2004).…”

Section: Novel Biomarkersmentioning

confidence: 99%

An update on non-invasive urine diagnostics for human-infecting parasitic helminths: what more could be done and how?

et al. 2019

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Parasitology cambridge.org/par Review Cite this article: Archer J, LaCourse JE, Webster BL, Stothard JRussell (2020). An update on non-invasive urine diagnostics for human-infecting parasitic helminths: what more could be done and how? Parasitology 147, 873-888. https://doi. AbstractReliable diagnosis of human helminth infection(s) is essential for ongoing disease surveillance and disease elimination. Current WHO-recommended diagnostic assays are unreliable in lowendemic near-elimination settings and typically involve the invasive, onerous and potentially hazardous sampling of bodily fluids such as stool and blood, as well as tissue via biopsy. In contrast, diagnosis by use of non-invasive urine sampling is generally painless, more convenient and low risk. It negates the need for specialist staff, can usually be obtained immediately upon request and is better accepted by patients. In some instances, urine-based diagnostic assays have also been shown to provide a more reliable diagnosis of infection when compared to traditional methods that require alternative and more invasive bodily samples, particularly in low-endemicity settings. Given these relative benefits, we identify and review current research literature to evaluate whether non-invasive urine sampling is currently exploited to its full potential in the development of diagnostic tools for human helminthiases. Though further development, assessment and validation are needed before their routine use in control programmes, low-cost, rapid and reliable assays capable of detecting transrenal helminthderived antigens and cell-free DNA show excellent promise for future use at the point-ofcare in high-, medium-and even low-endemicity elimination settings.

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2-methyl butyramide, a previously identified urine biomarker for Ascaris lumbricoides, is not present in infected Indonesian individuals

Cited by 4 publications

References 6 publications

2-Methyl-pentanoyl-carnitine (2-MPC): a urine biomarker for patent Ascaris lumbricoides infection

2-Methyl-pentanoyl-carnitine (2-MPC): a urine biomarker for patent Ascaris lumbricoides infection

Diagnostic Techniques for Soil-Transmitted Helminths – Recent Advances

An update on non-invasive urine diagnostics for human-infecting parasitic helminths: what more could be done and how?

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