High hopes for a naturally occurring bacterial dewormer have been vindicated, after recently published research showed it was highly effective against large roundworms in foals.
The results of the research, published in the journal One Health, represent an important step towards the development of a commercially available dewormer.
The research centers on a free-living bacterium, Bacillus thuringiensis, which produces a family of crystal proteins to combat its competitors. Some of these proteins have potent activity against parasitic worms.
The findings are the result of a collaboration between scientists at the University of Kentucky’s Maxwell H. Gluck Equine Research Center, the University of Massachusetts and the US Department of Agriculture.
They are the culmination of an innovative crowdfunding project led by equine parasitologist Dr Martin Nielsen, of the Gluck Center, titled “Let the Germs get the Worms.” The initial crowdfunded research delivered promising results which in turn attracted federal funding.
The researchers described their testing of the recombinant paraprobiotic in several species, targeting Ascaris and Parascaris. Both are important parasites in the family Ascarididae. They are large, common, intestinal-dwelling nematodes capable of infecting a wide range of animals.
Ascarids are some of the most common and damaging parasites of humans and animals.
Parasitic nematode drug resistance in veterinary medicine and drug recalcitrance in human medicine are increasing worldwide, with few if any new therapeutic classes on the horizon.
Some of these parasites can be passed between species. For example, Ascaris can be passed from humans to pigs and vice versa.
“The development of new therapies against this family of parasites would have major implications for both human and livestock health,” the study team said.
“However, to be therapeutically deployable in both human and veterinary medicine in the developed and developing world, such therapies need to be safe, broadly active against this class of parasite, inexpensive, and massively scalable.
“We are unaware of any new drugs that meet these criteria that are in the commercial pipeline.”
The recombinant paraprobiotic they tested, dubbed Cry5B IBaCC, has great promise to fulfill this void, the researchers said.
In their study, they delivered Cry5B IBaCC to animals in the form of a “dead bacterial ghost” — the bacterium was dead but the protein crystals were still intact.
It proved highly effective against intestinal Ascaris suum infections in mice. In pigs, a single dose completely cleared A. suum infections.
Furthermore, a single dose drove fecal egg counts of Parascaris in five foals to zero, showing at least parity with, and potential superiority to, current dewormers used against this parasite.
The researchers said the new agent represents a new, paraprobiotic One Health approach towards targeting Ascarididae that is safe, effective, massively scalable, stable, and useful in human and veterinary medicine in both the developed and developing regions of the world.
They said their findings indicate that the treatment could make a significant contribution to the long-term, safe, and effective control of ascarid parasites of humans and other animals.
“The scalability, adaptability, safety, and ease of manufacture of Cry5B IBaCC make it ideally suited for promoting One Health against ascarid parasites equally in humans and livestock in developed and developing countries,” they said.
“The research reported here more generally points towards the suitability and great potential of paraprobiotics to treat pathogens of humans and livestock, that is also likely to include ascarids of companion animals such as dogs and cats.”
Turning to toxicity, the authors said a pilot toxicology study in hamsters showed that five consecutive daily doses of IBaCC at 200 mg Cry5B/kg body weight was completely safe and non-toxic, with no deviation from normal histopathology and blood chemistry.
Nielsen told Horsetalk that the study team has not been able to get any efficacy in horses against strongyle parasites from the crystal protein.
“In the lab, it kills them right away, and we have publications on this too. But it doesn’t seem to do anything, when we administer it to horses.
“We think this is because strongyles are hindgut parasites.
“The ascarids, on the other hand, live in the small intestine. So when the protein is administered orally, it degrades before it reaches the large intestine, but there is still enough of it to work in the small intestine.
“If this is true, we could still get it to work against strongyles, if we find the right formulation.
“But, for now, we can say that it is very potent against ascarids.”
Joseph F. Urban, Martin K. Nielsen, David Gazzola, Yue Xie, Ethiopia Beshah, Yan Hu, Hanchen Li, Florentina Rus, Kelly Flanagan, Austin Draper, Sridhar Vakalapudi, Robert W. Li, Gary R. Ostroff, Raffi V. Aroian.
An inactivated bacterium (paraprobiotic) expressing Bacillus thuringiensis Cry5B as a therapeutic for Ascaris and Parascaris spp. infections in large animals,
One Health, Volume 12, 2021, 100241, ISSN 2352-7714, https://doi.org/10.1016/j.onehlt.2021.100241.