Parasitic worms such as roundworms, whipworms and hookworms affect the health of more than a billion people worldwide, mostly those living in tropical areas of South and Southeast Asia, Africa and Central America.
Among them are filarial nematodes, a type of roundworm transmitted through the bite of an infected mosquito. They can cause a condition called lymphatic filariasis, or elephantiasis, that affects some 120 million people, according to the World Health Organization. Characterized by swelling of the lower limbs, it’s not usually deadly but can cause disfigurement and other health problems. It’s among a group of ailments collectively known as neglected tropical diseases.
Sudhanva Kashyap, an assistant professor in the Creighton University School of Medicine’s microbiology and immunology department, recently received a $410,000 grant from the National Institutes of Health and the National Institute of Allergy and Infectious Disease for basic research to combat drug-resistant infections by such worms.
Kashyap said there are a limited number of drugs to treat nematode infections, most of which are veterinary medicines that have been adapted for human use.
They are effective in controlling the diseases. “But we have nothing at all that can kill the adult worm and cure the disease,†he said.
That means the adult worms can stay in the body and propagate the disease for many years, Kashyap said. People who are infected take the drugs again and again to keep the infection in check. But that leads to drug resistance among the worms, similar to the way repeated, widespread use of antibiotics can cause drug resistance in bacteria.
With the grant, Kashyap and his students are trying to determine what allows the worms to recover even when the drugs are present and find ways to block that mechanism in order to improve the drugs’ effectiveness.
“It’s really important to prevent resistance and reduce the dose and make drugs that can be used more efficiently,†he said.
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Many other parasitic worms are transmitted to humans through contaminated soil. It’s hoped that the work might also apply to them.
For now, the researchers are focused on the drug levamisole, which binds to what are known as nicotinic receptors in the worms’ bodies and paralyzes them.
Once the worms are paralyzed, the human body can get rid of them, he said. But over time, adult worms recover in the presence of the drug, even after more is added. Patients generally have to stop taking the drug for a time, which allows the disease to recur and requires a new round of medication, which can spur resistance.
“The current grant,†Kashyap said, “is to try and understand why this is happening and are there ways we can prevent this from happening and keep the worm paralyzed longer.â€
The researchers are using two different kinds of worms in their studies. One is Brugia malayi, one of the three types of filarial nematode that cause elephantiasis. The other is a model worm called C. elegans that is frequently used in genetic research.
“We’re using both of those models to try and understand how we can prevent the worms from recovering in the presence of the drugs,†he said.
In the longer term, however, Kashyap would like to see such neglected diseases, so termed even though they affect more than a billion people, become eliminated diseases.
Sudhanva Kashyap, an assistant professor in the Creighton School of Medicine’s microbiology and immunology department, received a $410,000 federal grant to combat infections by parasitic worms in humans.
Sudhanva Kashyap, an assistant professor in the Creighton School of Medicine's microbiology and immunology department, received a $410,000 federal grant to combat infections by parasitic worms in humans.