Volunteers agree to be hosts — for parasitic worms
Research to advance vaccine for chronic disease that afflicts hundreds of millions annually
Seventeen volunteers in the Netherlands have agreed to host parasitic worms in their bodies for 12 weeks, in order to help advance research toward a vaccine for schistosomiasis, a chronic disease that afflicts more than 200 million people a year, killing thousands, primarily in sub-Saharan Africa and South America.
“Yes it sounds odd and crazy. The idea of having a worm grow inside you is awful,” says Meta Roestenberg, an infectious disease physician at Leiden University Medical Center, who is directing the research. But she said the risk to the student volunteers is “extremely small,” especially compared with the potential benefit to preventing a disease that burdens millions of the world’s poorest people. A Dutch ethics board agreed. But other researchers of this disease are conflicted about the study’s method, fearing there is no way to be sure that all of the tiny parasites have been evicted from the hosts when the trial ends.
Schistosomiasis is sometimes called bilharzia, or snail fever, because the illness-causing larvae spend their nights tucked away in the shells of snails in freshwater lakes. During daylight, thousands of Schistosoma mansoni head out across the water, penetrating the skin of bathers or fisherman. Over the coming weeks, larvae turn into adult worms and males and females pair up and mate, producing hundreds of eggs a day.
When the offspring hatch, some may get lodged in the liver or bladder, inducing an immune response that can lead to chronic pain, fever, organ failure, internal bleeding or a gynecological infection that many researchers believe dramatically increases the risk of being infected by HIV.
At least two potential vaccines for “schisto” were recently approved for early stage human trials.
The traditional path forward, which would cost millions, requires setting up a study in an afflicted area and using only people who have already been exposed to the worms. Obtaining financing for future development is expected to be a struggle.
“You get yourself in a Catch-22,” said Dr. Peter J. Hotez, the dean of the National School of Tropical Medicine at Baylor College of Medicine in Texas, who has spent the last 15 years trying to develop a vaccine. Donors, he said, want proof the vaccine will work in people before committing funds. But it is hard to offer proof without money.
Roestenberg’s study, known as a challenge trial, aims to prove there is a quick and affordable way to test the vaccine in people. That could help the prototype Hotez has developed with Texas Children’s Hospital Center for Vaccine Development advance more quickly. But “there is too much uncertainty,” he says.
The first time people are exposed to Schistosoma mansoni larvae, they can have an acute reaction known as Katayama fever or develop a central nervous system infection, which in rare cases causes irreversible neurological damage or death.
By dosing young, healthy volunteers with just 20 male larvae — incapable of reproducing inside their host — Roestenberg says she has vastly minimized the risks.
But if the subjects’ health can be ensured, Hotez questions whether there will be enough of a detectable infection to show that a vaccine is working.
So far there has been no reason for alarm in the study underway, Roestenberg said. As soon as the larvae passed through their skin, all of the volunteers displayed a bit of a rash. One had a mild fever. But all this was expected and 24/7 medical care is available should a more serious issue arise.
At the end of the study, all will be given Praziquantel, which is supposed to clear any infection and kill the remaining parasites.
Other schistosomiasis researchers were critical of this point. Daniel Colley at the University of Georgia told Science magazine, which first reported on the study, that the drug is “not terribly effective” and given that the worms’ life span is five to 10 years, “That is a long time to have something as ugly as a schistosome living in your blood vessels, putting out excrement and things.”
But it is precisely because of the drug’s limitations that another researcher, Dr. James Collins at the University of Texas Southwestern Medical Center, said that he is convinced that “the benefits outweigh the risks.”
For now, dozens of male worms have eight weeks until they are expelled from the veins of the Dutch students.
“Yes it sounds odd and crazy. The idea of having a worm grow inside you is awful.” META ROESTENBERG INFECTIOUS DISEASE PHYSICIAN