River Blindness Revealed in Urine

A small parasitic worm is one of the leading causes of blindness in the world. But now researchers have discovered a molecule in the urine of African patients that could help diagnose those infected with the parasite and help eliminate the devastating disease known as river blindness.

The illness, scientifically known as onchocerciasis, is caused by the parasitic worm Onchocerca volvulus. Black fly bites transmit the worm's larvae to humans, and the larvae grow into adults that form nodules beneath the skin all over the human body. Female worms then produce large numbers of larvae called microfilariae that move to the skin to be ingested again by biting black flies. The larvae can also enter the eyes, however, causing blindness. An estimated 500,000 people, mostly in sub-Saharan Africa, have lost their sight because of the parasite.

The World Health Organization has set a goal of eliminating the disease from the Americas by 2017 and from Africa by 2025. Infections with Onchocerca volvulus can be treated with ivermectin, which kills the larvae but not the adult worms. The antibiotic doxycycline, which kills a bacterium called Wolbachia that lives symbiotically with the worm, has shown promise in killing adult worms as well and is sometimes used alone or in combination with ivermectin. Current control strategies rely on the repeated mass treatment of potential patients with ivermectin, however, as diagnosis is often difficult. In some cases, the surviving adult worms can spawn a new generation of larvae.

The gold standard for diagnosis is a so-called skin snip. "You basically cut off a little bit of skin and then you can see the larvae of the worms," says Daniel Globisch, a researcher at the Scripps Research Institute in San Diego, California, and one of the authors of the study. The method is not very sensitive however, particularly in less intense infections, which are becoming more frequent with progress in controlling the disease, says Maria-Gloria Basáñez, a researcher in neglected tropical diseases at Imperial College London.

Now, Globisch and his colleagues have identified a new way to test for the disease. They compared the amounts of hundreds of molecules found in urine samples of infected and healthy Africans and discovered one striking difference: An unknown molecule was present at levels six times higher in the urine samples of infected individuals than in samples from healthy people. The researchers identified the molecule as the remnant of a neurotransmitter that larval stages of the worm excrete and that is then broken down in the human body before being excreted in the urine, they report online this week in the Proceedings of the National Academy of Sciences.

"Finding such a marker was really lucky," Globisch says. "Using this molecule, we could make a diagnostic test that can be put in a backpack and diagnose whether people are infected or not." That would allow doctors to "specifically treat those who are still infected," he says. Globisch estimates that such a portable diagnostic test could be ready in 3 years.

The researchers' approach "to identify biomarkers is certainly elegant and innovative," writes Michel Boussinesq, an onchocerciasis expert at the Institute of Research for Development in Montpellier, France, in an e-mail. But urine samples may not be easier to collect in an African village than skin snips, he cautions. An experienced researcher might collect 40 skin snips in an hour, he says, but with urine the researchers have to wait until each person can produce the sample. To be sure that the new technique provides an advantage, "it would be necessary to compare the quantitative results of the technique described in the paper, and the quantitative results of skin snips," he says.

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