River blindness, also called Onchocerciasis, is the result of the infection of several different eye tissues by the nematode Onchocerca volvulus. The bacterium Wolbachia pipientis lives symbiotically in the gut of the nematode, and escapes the small roundworm to cause an inflammatory response in human tissues, which results in damage to the tissue. These infections can occur in a number of different human tissues causing a variety of effects, but when the eye tissues are involved, the result can be river blindness. It is endemic and widespread in several areas of Africa, as well as more restricted areas in South America and the Middle East.
Treatment of the disease involves killing the bacterium, which in turn kills the host nematode, using various anti-biotics. However, as we have learned over recent decades, widespread use of antibiotics can be less than ideal because this can cause selection for resistant strains so that treatment can become generally ineffective across an affected population. Ideally, there would be a reliable test for river blindness infection that would allow more targeted use of treatments.
A research team at Scripps has just published a paper in PNAS that may lead to such a treatment. The team examined urine samples from people who are known to be infected with the nematode Onchocerca volvulus and its attending Wolbachia pipientis bacterium with those who were not thought to be so infected. A massive laboratory based hunt for differences in the contents of the urine was carried out, and one molecule was identified as unique to the infected humans. This was N-acetyltyramine-O,β-glucuronide, which started out as a neurotransmitter found in the nematodes while they are young, which is then converted to N-acetyltyramine-O,β-glucuronide in the human body and eventually secreted in the urine.
The nematode has a somewhat complex lifecycle in which the very young worms infect various tissues and reproduce there, causing the damage to the tissue via the bacterium’s release. This neurotransmitter seems to be unique, or nearly unique, to these young worms. This is important because the nematode is probably widespread in humans in the endemic areas, but as relatively dormant adults found here and there throughout the body. It is only the young reproducing worms that cause the river blindness. Therefore, N-acetyltyramine-O,β-glucuronide specifically identifies individuals at risk of tissue damage to the eyes.
The test is not yet ready for prime time. There needs to be a field test that can be administered easily in conditions where there are only minimal or no clinical facilities. The test materials have to be reasonably inexpensive and not require special handling such as refrigeration. Ideally, this would consist of a urine test strip as have been developed in the past to test for blood sugar levels or pregnancy.
Another important outcome of this finding is the method itself, which the researchers have dubbed “Metabolome-mining.” (The term “metabolome” refers to the full set of metabolites to be found in a particular organism or tissue, similar to the term “genome” for the full set of genes.)
More information will be available at the Scripps Research Institution web site.
Globisch, D, Moreno, A, Hixon, M, Nunes, A., Denery, J., Specth, S., HYoerauf, A, & Jand, K (2013). Onchocerca volvulus-Neurotransmitter Tyramine is a Biomarker for River Blindness PNAS
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