Ascaris
and
Parascaris
are important parasites in the family Ascarididae, large, ubiquitous intestinal-dwelling nematodes infecting all classes of vertebrates. 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 are zoonotic,
e.g.
,
Ascaris
is 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. Here we tested the therapeutic ability of a paraprobiotic or dead probiotic that expresses the
Bacillus thuringiensis
Cry5B protein with known anthelmintic properties, against zoonotic
Ascaris suum
and
Parascaris
spp. This paraprobiotic, known as IBaCC, intoxicated
A. suum
larvae
in vitro
and was highly effective
in vivo
against intestinal
A. suum
infections in a new mouse model for this parasite. Fermentation was scaled up to 350 l to treat pigs and horses. Single dose Cry5B IBaCC nearly completely cleared
A. suum
infections in pigs. Furthermore, single dose Cry5B IBaCC drove fecal egg counts in
Parascaris
-infected foals to zero, showing at least parity with, and potential superiority to, current efficacy of anthelmintics used against this parasite. Cry5B IBaCC therefore 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.