River Blindness Marker Found In Patients

Onchocerciasis, or river blindness, is a tropical worm infection that causes blindness and other symptoms. It is treatable, and reversible, with medicine. But current immune response-based diagnostics and skin biopsies are unreliable, so it’s difficult to distinguish treated but still-infected patients from those who have been freed of the worms. That means millions of patients are re-treated repeatedly and unnecessarily—a difficult, expensive, and inefficient practice.

The discovery of a worm-based molecule in patients’ urine, by a team from Scripps Research Institute, in California, offers the possibility of a better diagnostic test. Kim D. Janda and coworkers discovered the biomarker, structurally analyzed it, and traced its provenance (Proc. Natl. Acad. Sci. USA, DOI: 10.1073/pnas.1221969110).

River blindness is caused by worm larvae carried by blackflies and then transmitted to people in fly bites. Coadministration of the antiworm drug ivermectin, often donated by Merck & Co., and the antibiotic doxycycline is a fairly effective treatment. But it doesn’t clear all patients of the worm, which can remain dormant for as long as a decade. The drugs are therefore now administered repeatedly to all those who have been treated for less than a decade.

By comparing urine from infected and noninfected Africans, Scripps postdoc Daniel Globisch found a compound that could be monitored to enable treatment to be restricted to those still infected. The Scripps team identified it as N-acetyltyramine-O,β-glucuronide, is a metabolized worm neurotransmitter that is excreted by the human host.

Urine levels of the metabolite are about six times higher in infected than in noninfected patients. It seems to be specific for the river blindness worm when tested in the presence of coinfecting parasites, but its specificity needs to be validated further. A current drawback is that the test works in African onchocerciasis patients but not in infected South Americans. However, 99.9% of river blindness currently occurs in Africa.

Another problem is that the group’s tests were carried out with liquid chromatography/mass spectrometry instruments that would be too difficult and expensive to use in the tropics. The researchers hope to develop a less expensive and more convenient version.

“This is the first clear demonstration of a parasite metabolite that can be detected in easily accessible fluid,” comments Thomas B. Nutman, deputy chief of the Laboratory of Parasitic Diseases at the National Institute of Allergy & Infectious Diseases. But it remains to be seen whether the compound “will ultimately have the kind of positive predictive value Janda and coworkers are hoping for.”

River blindness diagnostics expert Thomas Unnasch of the University of South Florida says that such a marker “is something people have been chasing for about 20 years. This is a really good first step.”