Life cycle of the filarial worm Onchocerca volvulus. Image from WHO: http://www.who.int/tdr/diseases-topics/onchocerciasis/en/
Onchocerciasis, also known as “river blindness,” is a parasitic infection that strikes millions of people in Africa, Latin America and other tropical regions. There are treatment options but monitoring the disease’s progression during treatments and conducting surveillance of the disease in a population are challenging. In a recent paper in the Proceedings of the National Academy of Sciences, researchers described the identification of a unique biomarker in urine that could lay the foundation for a cheap and easy diagnostic tool to track the disease during treatment and eradication campaigns.
Onchocerciasis is caused by the filarial worm Onchocerca volvulus. The worm is transmitted to humans as larvae through the bites of infected blackflies. In humans, the larvae mature to adult worms. After mating, the female adult worm can release up to 1,000 microfilariae a day. These early-stage worms move through the body; when they die, they cause blindness, skin rashes, lesions, intense itching and skin depigmentation.
The combination of an antimicrofiliarial drug called ivermectin and the antibiotic doxycycline can kill the worms. The World Health Organization’s African Programme for Onchocerciasis Control has set a target date of 2025 for the eradication of the disease in that region. Indiscriminate treatment with the drugs could lead to drug resistance and render the treatnent ineffective so it’s important to have a way to track the disease and ensure eliminiation programs are on course.
To track the disease, researchers need a signature molecule that reflects the status of the infection. Kim Janda at The Scripps Research Institute explains that he and his colleagues initially focused on finding biomarkers for O. volvulus infection in blood. They found 14 but what Janda says he really wanted was a single biomarker so that a simple diagnostic tool could be based on this biomarker. “In my opinion, a single biomarker is needed that tracks the progression of onchocerciasis and monitor whether years of mass treatment of people infected by O. volvulus is working toward the goal of its eliminination,” he says.
So the investigators decided to look in urine, with the rationale that the urine-production pathway would generate a different profile of metabolites that was different from those in blood. They analyzed samples from infected and uninfected people by liquid chromatography-mass spectrometry.
The investigators identified a single biomarker, N-acetyltyramine-O,β-glucuronide (NATOG), a metabolite derived from an O. volvulus neurotransmitter. They showed that NATOG is upregulated at the time of infection. If an infected patient gets treated with doxycycline, the level of NATOG goes down. Janda explains that this finding gives “confidence that the biomarker tracks with the worm’s metabolic life cycle.”
The researchers are now working on developing a simple dipstick test based on NATOG.
