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.
Highlights
Infections with intestinal worms, such as Ascaris lumbricoides, affect hundreds of millions of people in all tropical and subtropical regions of the world
Final proof of the structure was provided by the infrared spectra obtained with infrared ion spectroscopy (IRIS) analysis on ions generated from HPLC purified material and solutions of both synthetic materials (Fig. 2c and Supplementary Fig. S2), which showed the natural marker had exactly the same IR spectrum as 2-methyl pentanoyl carnitine (2-MPC) (Fig. 2d)
In order to confirm that 2-MPC is uniquely associated to A. lumbricoides infection and that other STH (T. trichiura and hookworm) and/or S. mansoni infections are not associated to 2-MPC levels, the samples from Kenya, Indonesia and Ethiopia were grouped according to infection type and one-way ANOVA was performed on the 2-MPC data of the single infected subjects. These analyses demonstrated that there was no significant difference in 2-MPC levels between uninfected subjects and subjects infected with T. trichiura, hookworm or S. mansoni (p > 0.05), while A. lumbricoides infected subjects did differ highly significant from uninfected ones in each of the three countries evaluated (Table 3)
Summary
Infections with intestinal worms, such as Ascaris lumbricoides, affect hundreds of millions of people in all tropical and subtropical regions of the world. Current procedures that are being used in the field are based on the detection and quantification of STH eggs in a stool smear using a compound microscope, the so-called Kato-Katz thick s mear[5,6,7] This microscopic examination lacks standardization, shows day-to-day and intra-stool variability and is not ideal for screening large number of s amples[8]. Target Product Profiles (TPPs) describing the specific requirements for such new STH diagnostic approaches required for different program use cases were published These TPPs indicate that the identification of non-stool-based biomarkers will be essential to enable the development of diagnostic tools for making decisions on whether or not to stop interventions (use case 3) or to verify sustained break in transmission (use case 4)[4]. These findings could not be confirmed in a more recent study on A. lumbricoidesinfected subjects from I ndonesia[11]
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