Seventeen volunteers in the Netherlands have agreed to host parasitic worms in their bodies for 12 weeks to help advance research towards 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," said Leiden University Medical Centre infectious disease physician Meta Roestenberg, who is directing the research.
But she added that the risk to the student volunteers is "extremely small", especially compared with the potential benefit of 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 would 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 the day, 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 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 gynaecological infection that many researchers believe dramatically increases the risk of being infected by HIV.
Number of people afflicted with schistosomiasis yearly. The chronic disease kills thousands, primarily in sub-Saharan Africa and South America.
At least two potential vaccines for the disease 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, 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 that the vaccine will work in people before committing funds. But it is hard to offer proof without money.
Dr Roestenberg's study, known as a challenge trial, aims to prove that there is a quick and affordable way to test the vaccine in people.
That could help the prototype Dr Hotez has developed, with Texas Children's Hospital Centre for Vaccine Development, advance more quickly. But "there is too much uncertainty", he said.
The first time that 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 causes irreversible neurological damage or death in rare cases.
By dosing young, healthy volunteers with just 20 male larvae - incapable of reproducing inside their host - Dr Roestenberg said she has vastly minimised the risks.
But if the subjects' health can be ensured, Dr Hotez questioned 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, Dr Roestenberg said. As soon as the larvae passed through their skin, all the volunteers displayed a bit of a rash. One had a mild fever. But all this was expected and medical care is available around the clock should a more serious issue arise.
At the end of the study, all will be given Praziquantel, a drug which is supposed to clear any infection and kill the remaining parasites.
Other schistosomiasis researchers were critical of this point.
Professor of microbiology 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' lifespan 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 Centre, said 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. For their trouble, each volunteer was paid about US$1,200 (S$1,580).