The piglet acute diarrhea model for evaluating efficacy of treatment and control of cryptosporidiosis

Abstract

Cryptosporidium spp. are ranked as the second leading pathogens causing life-threatening diarrhea in children under 2 years of age. Although Cryptosporidium hominis causes three quarters of the cases of cryptosporidiosis, studies on C. hominis are limited since natural disease due to C. hominis is host-restricted to humans only. In this mini-review, we demonstrate the successfully adoption, propagation, and utility of the C. hominis strain TU502, isolated originally from an infant with diarrhea in Uganda, in gnotobiotic piglets. The TU502 C. hominis strain and the gnotobiotic piglet model currently are the only available preclinical tools to evaluate therapeutics that specifically target C. hominis. Infection in this gnotobiotic piglet model displays similar clinical symptoms of diarrhea observed in humans. Here we further describe how this unique model of acute diarrhea, can be used for drug discovery and testing of vaccine candidates against cryptosporidiosis. The shared anatomical, physiological and immunological characteristics between piglets and human infants makes the model ideal for evaluating the efficacy of therapeutics and vaccines against cryptosporidiosis as they become available.

A One Health Approach to Tackle Cryptosporidiosis

“…A further study looked at cross-protective immunity between the two species using an in vivo gnotobiotic pig model and showed than prior infection with C. hominis protected against a further C. hominis challenge and gave partial protection against a C. parvum challenge [68], showing that there is a degree of cross-immunity between the two Cryptosporidium species. The gnotobiotic piglet model shows similar clinical signs of diarrhoea as seen in human infection following challenge with C. hominis and is therefore a relevant clinical model with which to test out new therapies and vaccines [69]. Neonatal cattle [27] and sheep [70] are also relevant clinical models for C. parvum in particular, to improve understanding of host-parasite interactions, to test out novel therapeutic agents, and to provide sources of Cryptosporidium oocysts for research and diagnostic purposes.…”

Intestinal organoid/enteroid-based models for Cryptosporidium

“…Ex vivo organoid/enteroid models can be further refined to permit selection and propagation of transgenic parasites in culture which is currently not possible and relies on the use of immunodeficient mice [ 9 ]. Advances in propagation of C. parvum in ex vivo human organoid/enteroid cultures can be applied to the culture of the anthroponotic species Cryptosporidium hominis , the major species infecting humans [ 50 ] and which can only be propagated with difficulty in gnotobiotic piglets and calves [ 50 ].…”

Cryptosporidium: Host-Parasite Interactions and Pathogenesis

“…Cryptosporidium parvum oocysts (parasite) and hosts are shown for evaluating the protection potential of colostrum, recombinant parasite proteins, and monoclonal antibodies in passive immunization studies as well as for testing the therapeutic efficacy of anti-cryptosporidial compounds [8,[69][70][71][72]. For C. hominis, the gnotobiotic piglet model of acute diarrhea has been the only available model for human cryptosporidiosis due to the high similarity of anatomy, physiology, and immunology between pigs and humans and clinical diarrheal signs [73].…”