Calf Clinical Model of Cryptosporidiosis for Efficacy Evaluation of Therapeutics

Riggs, Michael W.; Schaefer, Deborah A.

doi:10.1007/978-1-4939-9748-0_15

Cited by 14 publications

(11 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We chose to evaluate the in vivo efficacy of trtE using a neonatal mouse model of C. parvum infection [40]. This cost-effective model has been shown to have positive predictive value for justifying anti-cryptosporidial efficacy testing in the neonatal calf model [41,42]. In a preliminary experiment, ten, 8 day old mice were infected with C. parvum and then treated with four doses of 2 mg/kg of trtE (purification method 1) given orally every 12 hours for 2 days.…”

Section: Trte Is Effective In Vivo Against the Gastrointestinal Parasite C Parvummentioning

confidence: 99%

A symbiotic bacterium of shipworms produces a compound with broad spectrum anti-apicomplexan activity

et al. 2020

Self Cite

View full text Add to dashboard Cite

Apicomplexan parasites cause severe disease in both humans and their domesticated animals. Since these parasites readily develop drug resistance, development of new, effective drugs to treat infection caused by these parasites is an ongoing challenge for the medical and veterinary communities. We hypothesized that invertebrate-bacterial symbioses might be a rich source of anti-apicomplexan compounds because invertebrates are susceptible to infections with gregarines, parasites that are ancestral to all apicomplexans. We chose to explore the therapeutic potential of shipworm symbiotic bacteria as they are bona fide symbionts, are easily grown in axenic culture and have genomes rich in secondary metabolite loci [1,2]. Two strains of the shipworm symbiotic bacterium, Teredinibacter turnerae, were screened for activity against Toxoplasma gondii and one strain, T7901, exhibited activity against intracellular stages of the parasite. Bioassay-guided fractionation identified tartrolon E (trtE) as the source of the activity. TrtE has an EC 50 of 3 nM against T. gondii, acts directly on the parasite itself and kills the parasites after two hours of treatment. TrtE exhibits nanomolar to picomolar level activity against Cryptosporidium, Plasmodium, Babesia, Theileria, and Sarcocystis; parasites representing all branches of the apicomplexan phylogenetic tree. The compound also proved effective against Cryptosporidium parvum infection in neonatal mice, indicating that trtE may be a potential lead compound for preclinical development. Identification of a promising new

show abstract

Section: Trte Is Effective In Vivo Against the Gastrointestinal Parasite C Parvummentioning

confidence: 99%

A symbiotic bacterium of shipworms produces a compound with broad spectrum anti-apicomplexan activity

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…Bovine cryptosporidiosis is a commonly used natural model of Cryptosporidium infections (Riggs & Schaefer, 2020). Cattle are commonly infected with four Cryptosporidium spp.…”

Section: E1711mentioning

confidence: 99%

Age and episode‐associated occurrence of Cryptosporidium species and subtypes in a birth‐cohort of dairy calves

Wan

Huang

et al. 2022

Transbounding Emerging Dis

View full text Add to dashboard Cite

The role of species‐specific immunity in infection patterns of Cryptosporidium spp. in humans and farm animals is not well understood. In the present study, the dynamics of Cryptosporidium infections in a natural cryptosporidiosis model was examined using genotyping, subtyping and whole genome sequencing tools. In a cross‐sectional survey of Cryptosporidium spp. in 934 dairy cattle on one farm, marked age‐associated differences in the distribution of Cryptosporidium species and C. bovis subtypes were observed. In a closely followed longitudinal birth cohort study of 81 calves over a 9‐month period, shedding of C. parvum oocysts by the IIdA19G1 subtype started at 4 days, peaked at 2 weeks and ended mostly by 4 weeks. In contrast, the shedding of C. bovis oocysts started at 2 weeks, peaked initially at 6 weeks and had a second wave during 15th to 23rd weeks. For C. ryanae, calves had mostly only one episode of infection by one subtype, with accumulative infection increasing much slower than C. parvum and C. bovis. Overall, the accumulative infection rates and mean duration of oocyst shedding for calves in the cohort were 97.4% (76/78) and 2.3 weeks, 100.0% (80/80) and 3.9 weeks, and 78.7% (63/80) and 3.2 weeks for C. parvum, C. bovis and C. ryanae, respectively. The oocyst shedding intensity was much lower in C. bovis and C. ryanae infections compared with C. parvum infection, and in the second episode of C. bovis infection compared with the first episode. The two episodes of C. bovis infections were caused by different genome types that differed mostly in nine genes. Cryptosporidium parvum infection was associated with the occurrence of watery diarrhoea. Data from the natural history study of cryptosporidiosis indicate that despite the existence of acquired immunity against homologous pathogens, neonatal animals experience waves of Cryptosporidium infections by different species and genome types.

show abstract

“…1 Interactions between Cryptosporidium and host determines pathogenesis or protection from disease. 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].…”

Section: Cryptosporidium-host Cell Interactionsmentioning

confidence: 99%

Cryptosporidium: Host-Parasite Interactions and Pathogenesis

Pinto

Vinayak

2021

Curr Clin Micro Rpt

View full text Add to dashboard Cite

Purpose of Review Cryptosporidium spp. ( C. hominis and C. parvum ) are a major cause of diarrhea-associated morbidity and mortality in young children globally. While C. hominis only infects humans, C. parvum is a zoonotic parasite that can be transmitted from infected animals to humans. There are no treatment or control measures to fully treat cryptosporidiosis or prevent the infection in humans and animals. Our knowledge on the molecular mechanisms of Cryptosporidium -host interactions and the underlying factors that govern infectivity and disease pathogenesis is very limited. Recent Findings Recent development of genetics and new animal models of infection, along with progress in cell culture platforms to complete the parasite lifecycle in vitro, is greatly advancing the Cryptosporidium field. Summary In this review, we will discuss our current knowledge of host-parasite interactions and how genetic manipulation of Cryptosporidium and promising infection models are opening the doors towards an improved understanding of parasite biology and disease pathogenesis.

show abstract

Calf Clinical Model of Cryptosporidiosis for Efficacy Evaluation of Therapeutics

Cited by 14 publications

References 30 publications

A symbiotic bacterium of shipworms produces a compound with broad spectrum anti-apicomplexan activity

A symbiotic bacterium of shipworms produces a compound with broad spectrum anti-apicomplexan activity

Age and episode‐associated occurrence of Cryptosporidium species and subtypes in a birth‐cohort of dairy calves

Cryptosporidium: Host-Parasite Interactions and Pathogenesis

Contact Info

Product

Resources

About