BioEd Online

A bacterial protein used in a common pesticide kills intestinal parasitic roundworms in mice and may become a treatment option for humans, researchers say.

Intestinal roundworms, including hookworms and whipworms, infect well over one billion people, lowering immune systems for HIV, malaria and tuberculosis and debilitating both physically and cognitively.

The new approach, published today in PLoS Neglected Tropical Diseases¹, uses crystal proteins from the soil bacterium Bacillus thuringiensis (Bt). Organic farmers have used Bt to kill insects for decades, and plants have been genetically modified with Bt genes since 1996 so crops such as corn and potato can produce the crystal proteins, protecting themselves from insects without any pesticides.

"This bacterium is a natural soil predator of nematodes," says author Raffi Aroian from the University of California, San Diego. "The bacterium can kill the worm," he adds, "and it has a great track record for safety around vertebrates."

Hookworms and some other parasitic nematodes have shown signs of resistance to albendazole, the current treatment approved by the World Health Organization. "Compared to the best drugs people have developed to treat human parasitic worms, this natural protein is at least three times better," Aroian says.

Of mice and men

The parasitic worm Heligmosomoides bakeri naturally infects mice and is a common laboratory model organism for studying human diseases caused by roundworms, such as river blindness and elephantiasis. The researchers orally infected mice and waited for the parasites to mature and become reproductively active adults before treating the mice with the crystal protein. A few days after treatment, the mice had 98% fewer parasite eggs in their faecal samples and 70% fewer adult parasites in their intestines compared to untreated mice.

Aroian's previous study² using a type of human intestinal roundworm parasite to infect hamsters showed a 90% reduction in three doses of Bt. "Taken together, the two in vivo studies have shown significant therapeutic activity of a crystal protein against two species of nematode," says Andrew Kotze from the livestock industries division of Australia's Commonwealth Scientific and Industrial Research Organisation (CSIRO) in St Lucia, Queensland.

Aroian hopes that these mouse and hamster studies will pave the way to human trials within two to four years. Nearly all of the current drugs to treat nematode diseases were invented for veterinary purposes, he says, and then were approved for use in humans. "Do you ever say to your doctor, give me the best vet drug you have for treating my condition?" he says. "This is the only disease I can think of when that's what we do."

According to Aroian, this treatment can be grown cheaply in large quantities. Bt is grown in fermenters that hold thousands of litres for use as an agricultural spray and to control mosquitoes and blackflies.

The cost to treat one child with Bt would be 28 cents, Aroian estimates. It could be driven down more with optimizations in production, such as making sure more of the protein reaches the intestine without being dissolved in the stomach first. "The issue of protecting the toxin as it passes through the stomach to be released in the intestine will have to be addressed but does not seem to be insurmountable," says Ray Akhurst from the entomology division of CSIRO in Canberra.

Aroian adds, "Even at a quarter a pop, it's a cheap way to treat all those children."