Noninvasive Urine Biomarker Lateral Flow Immunoassay for Monitoring Active Onchocerciasis.

The parasitic disease onchocerciasis is the second leading cause of preventable blindness, afflicting more than 18 million people worldwide. Despite an available treatment, ivermectin, and control efforts by the World Health Organization, onchocerciasis remains a burden in many regions. With an estimated 120 million people living in areas at risk of infection, efforts are now shifting from prevention to surveillance and elimination. The lack of a robust, point-of-care diagnostic for an active Onchocerca infection has been a limiting factor in these efforts. Previously, we reported the discovery of the biomarker N-acetyl-tyramine- O-glucuronide (NATOG) in human urine samples and its ability to track treatment progression between medicated patients relative to placebo; we also established its capability to monitor disease burden in a jird model. NATOG is a human-produced metabolite of tyramine, which itself is produced as a nematode neurotransmitter. The ability of NATOG to distinguish between active and past infection overcomes the limitations of antibody biomarkers and PCR methodologies. Lateral flow immunoassay (LFIA) diagnostics offer the versatility and simplicity to be employed in the field and are inexpensive enough to be utilized in large-scale screening efforts. Herein, we report the development and assessment of a NATOG-based urine LFIA for onchocerciasis, which accurately identified 85% of analyzed patient samples ( N = 27).

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

The Neglected Tropical Disease onchocerciasis is a parasitic disease. Despite many control programmes by the World Health Organization (WHO), large communities in West and Central Africa are still affected. Besides logistic challenges during biannual mass drug administration, the lack of a robust, point-of-care diagnostic is limiting successful eradication of onchocerciasis. Towards the implementation of a non-invasive and point-of-care diagnostic, we have recently reported the discovery of the biomarker N-acetyltyramine-O-glucuronide (NATOG) in human urine samples using a metabolomics-mining approach. NATOG's biomarker value was enhanced during an investigation in a rodent model. Herein, we further detail the specificity of NATOG in active onchocerciasis infections as well as the co-infecting parasites Loa loa and Mansonella perstans. Our results measured by liquid chromatography coupled with mass spectrometry (LC-MS) reveal elevated NATOG values in mono- and co-infection samples only in the presence of the nematode Onchocerca volvulus. Metabolic pathway investigation of l-tyrosine/tyramine in all investigated nematodes uncovered an important link between the endosymbiotic bacterium Wolbachia and O. volvulus for the biosynthesis of NATOG. Based on these extended studies, we suggest NATOG as a biomarker for tracking active onchocerciasis infections and provide a threshold concentration value of NATOG for future diagnostic tool development.

Schistosomiasis and Soil Transmitted Helminths Distribution in Benin: A Baseline Prevalence Survey in 30 Districts.

In 2013, Benin developed strategies to control neglected tropical diseases and one of the first step was the disease mapping of the entire country in order to identify endemic districts of schistosomiasis and soil transmitted helminths (STH). This study was carried out in 30 of the 77 districts of Benin. Of these 30 districts 22 were previously treated for Lymphatic Filariasis (LF) using the Ivermectin and Albendazole combination. In each district, five schools were selected and 50 children aged 8 to 14 years were sampled in each school, making a total of 250 children sampled in the district. The schools were selected mainly according to their proximity to lakes or any bodies of water that were likely to have been used by the children. Samples of faeces and urine were collected from each pupil. Urinary schistosomiasis was identified using the urine filtration technique while STH and intestinal schistosomiasis were identified through the Kato Katz method. Overall a total of 7500 pupils were surveyed across 150 schools with a gender ratio of 1:1. Hookworm was identified in all 30 districts with a prevalence ranging from 1.2% (95%CI: 0.0-2.5) to 60% (95%CI: 53.9-66.1). Ascaris lumbricoides was detected in 19 districts with a prevalence rate between 1% (95%CI: 0.0-2.2) and 39% (95%CI: 32.9-45.0). In addition to these common STH, Trichuris trichiura, Enterobius vermicularis and Strongyloides stercoralis were found at low prevalence. Only 16 districts were endemic to Schistosoma mansoni, while 29 districts were endemic to S. haematobium. The S. haematobium prevalence ranged from 0.8% (95% CI: 0.0-1.9) to 56% (95% CI: 50.2-62.5) while the prevalence of S. mansoni varied from 0.4% (95%CI: 0.0-1.2) to 46% (95% CI: 39.8-52.2). The 22 districts, where LF was successfully eliminated, still require mass drug administration (MDA) of albendazole indicating that school-based MDA would be needed even after LF elimination in districts co-endemic to LF and STH in Benin.