UNC Water and Health Conference 2011: Professor Glenn Morris, University of Florida

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  • 1. New Frontiers, Old Obstacles
    Pathogens, Genetics, Models, and Public Health
    J. Glenn Morris, Jr., MD, MPH&TM
    Emerging Pathogens Institute
    University of Florida
  • 2. UF Emerging Pathogens Institute
    Created with $60 million appropriation from Florida state legislature, focusing on human, animal, and plant pathogens
    Over 200 faculty members, from 9 UF colleges (including medicine, public health, veterinary medicine, and agriculture)
    Strong global emphasis, reflecting Florida’s sub-tropical location
  • 3. How do you guide optimal allocation of limited public health resources for prevention of diarrheal disease?
  • 4. Why do kids in the developing world get symptomatic diarrhea?
    Driven by specific pathogens, but with occurrence of illness dependent on a complex set of interactions that include:
    Prior exposure to the pathogen /vaccination (immunity)
    Inoculum size
    Nutritional status
    Intestinal microenvironment, driven by local exposures
  • 5. Lindsey et al, EID 2011;17:608-611
    Sample of 2,748 patients with diarrheal disease in Kolkata; samples screened for 26 pathogens using standard microbiological techniques
    Approximately 1/3 had multiple pathogens
    Likelihood of infection with another specific pathogen among patients culture-positive for V. cholerae
  • 6. Global Enterics Multi-Center Study (GEMS)(Levine et al, funded by Gates Foundation)
    3609 samples from children with and without diarrhea, collected at 7 sites in Africa and Southern Asia
    Samples screened for pathogens using standard microbiological techniques
    Sub-Study: Comprehensive genetic analysis/ identification of all microorganisms in samples
    Data to date: analysis of 16S sequence data from samples from 1007 cases (514 children with diarrhea, 493 control children)
    Average of 3,900 sequences per sample
  • 7. Bacterial Identification and Classification by 16S rRNA
    Permits screening of “total community DNA,” and identification of all “OTU” in sample
    Stool samples
    Environmental samples
  • 8. Percentage of Case and Control Samples with Specific Pathogens, as Identified by Genetic vs. Microbiologic Techniques
  • 9. Underlying intestinal flora did not differ by case/control status (although further analysis does suggest that risk can be influenced by flora composition)
    Patterns of intestinal flora (and pathogen distribution) did differ by country
    RedControl
    BlackCase
    Blue – Bangladesh
    Green -Kenya
    Black - Gambia
  • 10. So does pathogen really matter?
    Yes: may be striking differences in public health impact, depending on pathogen
    Report released: April 28, 2011
    Funded by: Robert Wood Johnson Foundation
    Available: epi.ufl.edu
  • 11. U.S. Foodborne Pathogen Incidence*
    *Scallan et al, EID 2011;17:7-15
  • 12.
  • 13. So does pathogen really matter?
    Yes: may be striking differences in public health impact, depending on pathogen
    Yes: transmission pathways (and optimal prevention strategies) may differ dramatically, depending on pathogen
  • 14. Environmental Parameters
    V. cholerae in environment
    including plankton
    Cholera infections in humans
    Cholera Transmission Pathways
    “Slow” transmission: through fecal contamination of environment/water sources
    “Fast” transmission: driven by genetically-induced hyperinfectious state, occurring within a time window of a few hours after passage of stool. Transmission generally occurs within household or immediate environment of patient
  • 15. Zimbabwe
    Spatial Models
    SIR model
    Calculation of R0
    Average number of secondary infections that occur when one infective is introduced into a completely susceptible host population
    Estimation of relative contributions of:
    human/human transmission (short cycle, increased infectivity) vs.
    human/environment/human (long cycle, decreased infectivity)
    Use of these estimates to assess utility of intervention strategies such as vaccination
  • 16. R0 by ProvinceZimbabwe Cholera Epidemic, 2008-9
    Mukandavire et al, PNAS 2011;108:8767-72
  • 17. Mapping ℛ0 values: Haiti Cholera Epidemic, 2010
  • 18. Relative Contribution of “Slow” (Environmental) vs. “Fast” (Human) Sources to Cholera Transmission
    Zimbabwe
    RE (slow cycle) = 0.20 (17%)
    RH (fast cycle) = 0.95 (83%
    R0 = 1.15
    Vaccine coverage to stop epidemic: 17%
    Haiti
    RE(slow cycle) = 0.84 (54%)
    RH (fast cycle) = 0.70 (46%)
    R0 = 1.54
    Vaccination coverage to stop epidemic: 45%
  • 19. How do you guide optimal allocation of limited public health resources for prevention of diarrheal disease?
    Systems are complex
    Mix of pathogens
    Mix of factors driving occurrence of symptomatic infection (disease) in individual patients
    Varying outcomes dependent on pathogen
    Mix of transmission routes, varying by pathogen, country, and region
    Variety of potential interventions, including water systems, sanitation, improved protection of water and food in households, vaccination…..
  • 20. How do you guide optimal allocation of limited public health resources for prevention of diarrheal disease?
    Need for geographically-targeted, data-driven risk analysis, to define optimal approaches to disease prevention