1 / 17

Pathogen Study - Design Considerations

Pathogen Study - Design Considerations. Jeffrey T. Gray USDA, ARS,ARRU Athens, GA. Study Design Considerations. Organism Characteristics Host-Range / Clinical Status Study Design Challenge studies Natural inoculations Measuring Effects Confounding Factors. Swine choleraesuis-k C 1

alton
Download Presentation

Pathogen Study - Design Considerations

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. Pathogen Study - Design Considerations Jeffrey T. Gray USDA, ARS,ARRU Athens, GA

  2. Study Design Considerations • Organism Characteristics • Host-Range / Clinical Status • Study Design • Challenge studies • Natural inoculations • Measuring Effects • Confounding Factors

  3. Swine choleraesuis-k C1 typhimurium B derby B choleraesuis C1 typhimurium-c B anatum E1 heidelburg B brandenburg B worthington G2 agona B Human typhimurium B enteritidis D1 heidelburg B newport C2 hadar C2 agona B infantis C1 thompson C1 braenderup C1 javianna D1 Most frequent Salmonella isolates

  4. Organism Characteristics • Salmonella • Broad Host Range “ubiquitous” • Clinical status questionable • Campylobacter • Lack of clinical signs in food animals • E. coli O157:H7 • Narrow host range • No clinical signs in food animals

  5. Organism Characteristics • Invasiveness • Salmonella • “Shedding” • Carrier State • Stress / Diet / Environment • Strain differences among Salmonella isolates • Infectious Dose • Shedding vs. Infectious dose

  6. Study Design • Challenge Studies • Challenge Dose • Dose response curve Salmonella in swine1 • 103cfu- no shedding, no deep tissue infection • 106cfu- 101 shedding peak, 8 weeks carriage • 109cfu- 103 shedding peak, long term carriage • Controlled Natural Infections2 • Seeder Animals 1. Gray et al AJVR Vol. 57, no 3, 1996 2. Gray et al. Appl. Environ. Microbiol. 62: 1996

  7. Study Design • Controlled Natural Infections • 103 shedding peak of seeder animals • All naïve animals infected • 103 shedding peak in ‘naturally’ exposed animals • Long term carrier state • Swine infected with infected, desiccated feces1 • Dose = 105cfu • All naïve animals infected / No shedding • 103/g deep tissue infections 1. Gray et al J. Food Prot. V 64 no 7, 2001.

  8. Measuring Effects • Pathogen Detection Methods • E. coli O157:H7 • 1998-99’ Hancock et al. feedlot prevalence 5%-8% • 2000-2001 Hancock et al. /Smith et al. feedlot prevalence 23-25% • Differences based on detection methods • Are detection methods sensitive enough to detect treatment effects?

  9. Measuring Effects • Temporal Measurements • Salmonella high dose challenge shedding curve - cfu/g of feces • At what point do we intervene?

  10. Measuring Effects • Temporal Measurements • Intervention points • Prior to infection – alterations in flora • During peak shedding - ? Clinical signs • Late in production cycle – Induction of carrier state?

  11. Measuring Effects • Measurement of effect • What measurements are used • Method sensitivity • Feces, Tissue • What time point • For how long • “No” Salmonella • Not currently feasible • Salmonella in many animals – clinical? • Detectable in a few animals at low levels • Likely the norm • Food safety risk

  12. Confounding Factors • Seasonal Changes • E. coli O157:H7 • Seasonal prevalence 3% - 5% • Salmonella • Species, serotype differences • Peak season prevalence 8-12% • Diet • Composition of feedstuffs can effect prevalence and transmission of Foodborne zoonotic pathogens

  13. Confounding Factors • ‘Stress’ • Manner in which stress is measured • Effect on pathogen shedding • Transportation effects • Lairage exposure • Recent swine data indicate lairage may be important exposure point • Deep tissue (lymph node) infections • Salmonella serotype differences

  14. Confounding Factors • Environment • Treatment effects may be environment specific • Mechanism of action of treatment • Temporal relationship of shedding curve • Effect on flora or directly on pathogen • Long term survival and infectivity of Salmonella • Years in desiccated state

  15. Conclusions • Organism Characteristics • Studies must adequetely account for specific characteristics of a foodborne zoonotic pathogen • Study Design • Model a realistic infection cycle in target host species • Measuring Effects • Must be robust enough to show differences under realistic circumstances • Confounding Factors • Study must reasonably account for factors that exist in production systems and pathogen strain differences

More Related