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

Abstract

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.

Diagnostic Techniques for Soil-Transmitted Helminths – Recent Advances

“… 58 A substantial reduction after albendazole treatment was also seen with a significant association between urine 2-MPC levels and worm/egg counts. 58 However, the same authors did not find this biomarker in infected Indonesian subjects. 59 …”

“…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.…”

“… 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. 58 However, the same authors did not find this biomarker in infected Indonesian subjects.…”

The role of diagnostic technologies to measure progress toward WHO 2030 targets for soil-transmitted helminth control programs

“…Although some of the stool-based technologies have successfully moved toward field testing, the identification and evaluation of biomarkers in non-stool samples have been rather sobering [8]. A proof of principle of 2-methylpentanoyl-carnitine (2-MPC) as metabolite biomarker in urine and serum/plasma was evidenced for A. lumbricoides, but despite intense research efforts, not for the other species [9]. Other research groups are working with success on biomarker discoveries for Schistosoma spp.…”

Metabolite Identification Using Infrared Ion Spectroscopy – Novel Biomarkers for Pyridoxine-Dependent Epilepsy

“…These IR spectra can be matched to reference IR spectra measured from standards or predicted by quantum-chemical computations, which is now routinely done using commercially available software packages. Recently, several proof-of-principle studies have successfully demonstrated the potential for metabolite identification using this technology 6-9, [16][17] . Other studies have demonstrated the coupling of IRIS with online or offline LC and paved the way towards full integration of IRIS in untargeted metabolomics workflows 6,8,13,18 .…”