Tim Anderson, Ph.D., scientist at the Texas Biomedical Research Institute, and Phil LoVerde, Ph.D., biochemistry professor at the University of Texas Health Science Center at San Antonio (UTHSCSA) are taking up the charge to learn more about the tropical disease Schistosomiasis and the drug used to treat it.
Schistosomiasis kills up to 200,000 people every year, mostly in Sub-Saharan Africa and South America. More than 67 million people are infected worldwide. The disease is caused by a worm living in freshwater snails. When a person stands in the water, often to collect water, or when kids play in the water, the worm burrows into the person’s skin. It then becomes an adult living in the victim’s blood vessels, where it lays eggs. The eggs are eventually passed on through the stool, continuing the cycle.
Among the many health issues associated with the disease, infected children can have growth problems and learning difficulties. Long-term infections may cause liver damage, bladder cancer, or kidney failure. Though mostly affecting poor and rural communities in these areas, more and more travelers are becoming affected.
The drug praziquantel, or PZQ, is relatively cheap at $0.30 per adult dose. This means that large-scale treatment programs, such as the Schistosomiasis Control Initiative, have been able to distribute millions of treatments. Initially funded by the Bill and Melinda Gates Foundation in 2002, more than 40 million doses were given in 2013. Unfortunately, the drug only targets adult parasites, so people infected with immature worms remain infected, and the eggs get passed on causing new infections.
As we’ve seen with many other parasites, intensive use of a single drug over time means parasites will develop resistance. Some studies have found increasing levels of drug resistance.
“It’s difficult to know how much resistance there is, since the drug does not kill the immature stages,” Anderson said. “So when a person is still parasite positive after treatment, we don’t know if that’s due to resistance of adult worms or presence of immature worms.”
Parasites have many life cycle stages and different hosts, so studying them in the lab is a huge challenge. Scientists must use samples collected from patients in the field and then study only that stage in the lab. A bonus for Schistosomiasis is that the entire lifecycle can be grown in the laboratory. This is the only human parasite with which we can do this currently. The impact is significant. Scientists can experiment with genetic crosses using markers for drug resistance.
“Think back to your high school biology class and Mendel and his peas,” Anderson explained. They take a parasite that is resistant to PZQ and cross it with one that is not resistant. Then they look at the “offspring.” Advances in technology have played a major role in turning an old story on its head. Thanks to a good genome sequence, the scientists can cheaply sequence the genes in the offspring. The result is a marker identifying the genes involved in resistance.
The team is collaborating with the Kenya Medical Research Institute (KEMRI) and the Ugandan Ministry of Health where they will collect immature worms before and after drug treatment. These field-collected parasites will have their genomes sequenced, which will allow the scientists to see which regions aid in survival, and hence may be responsible for resistance.
We don’t yet know how the drug works against adult parasites or why it doesn’t work against immature parasites, so these studies will not only help identify PZQ-resistance, but may also lead to new targets for other drugs. Furthermore, this research will allow epidemiologists to monitor drug resistance in the field, critical to the efforts of the Schistosomiasis Control Initiative as they continue to distribute millions of doses.
The story of Zika has provided a powerful lesson on how rapidly diseases cross borders. Scientists have known about Zika since the 1950s, but it wasn’t until it began to spread across the globe in 2015 that we paid attention. This has made the world step up and take notice of many diseases.
Finally, long Neglected Tropical Diseases like Schistosomiasis are receiving much needed attention. An excited Anderson said, “This is a golden age for Schistosome genetics.”
Fortunately, San Antonio scientists are on the task.
Top image: San Antonio researchers record microscope findings. Photo by Scott Ball.