EPIDEMIOLOGY 200B Methods II

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EPIDEMIOLOGY 200BMethods II Prediction and
ValidityScott P. Layne, MD
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PART 1Connecting the Epidemiological, Medical,
and Mathematical Aspectsof Infectious Diseases
March 2010
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As our world grows So do infectious
disease threats
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By 2050 Human population of 9 10
billion
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Emerging Infectious Diseases
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Food Animal Biomass
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What is this lecture about?

• Three viewpoints on infectious diseases.
• Three methods against infectious diseases.

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Macroscopic Perspective

• Public Health, Epidemiology, Care
• Incidence, prevalence, location of infections
  (surveillance)
• Behaviors, practices that cause infections
  (investigation)
• Infection control measures to reduce impacts
  (intervention)
• Health policies to reduce impacts (regulation,
  education)
• Care of sick people and populations (drugs,
  vaccines)

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Microscopic Perspective

• Molecular Biology, Immunology, Pathology
• Mechanisms of disease (pathogenesis)
• Cellular targets (susceptibility, tropism)
• Complexity of agents (genome size)
• Heterogeneity of agents (mutations)
• Resistance (drugs, vaccines)
• Virulence of agents (growth, toxins, adhesions,
  regulation)

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Modeling Perspective

• Mathematical, Computational Biology
• Quantify and analyze variables (parameters)
• Improve data collection (limited resources)
• Relate complex interactions (nonlinear)
• Understand past (validation)
• Predict future (forecast, intervention, time
  scales)
• Guide control, elimination, and eradication
  (intervention)

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Information Domains
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Epitype (outcome)

• Time, location
• Age, sex, race
• Illness severity
• Known contacts
• Cofactors
• Prophylaxis, immunizations

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Phenotype (proteins)

• Cross-reactive immunity
• Enzymatic activity
• Antibiotic resistance
• Antiviral resistance
• Superantigen
• Toxin

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Genotype (DNA / RNA)

• Bacteria (large genomes)
• Viruses (small genomes)
• Whole genomes vs Partial genomes
• Pathogenicity islands
• Individual open reading frames (orfs)
• Regulation

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What Is Life ?

• Factor Humans Bacteria, Viruses
• Reproduction 20 years 1 10 hours
• Mutation 10-6 10-3 10-4
• Selection few many

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Variola major (smallpox)

• Examples of questions that can be addressed
• What is the reproductive number for smallpox
• What is the optimal outbreak control strategy
• What genes and proteins govern virulence
• Who should be vaccinated before outbreak occurs
• How does the pattern of a natural vs terrorist
  outbreak differ
• What are benefits and costs of halting air
  travel to control outbreaks

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Staphylococcus aureus(MRSA)

• Examples of questions that can be addressed
• Risk factors associated with transmission
• Optimal schedules for utilizing antibiotics
• Impacts of hand washing or other control
  measures
• Are there super-spreaders
• What governs spread of virulent clones
• What determines ecological fitness

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HIV / AIDS

• Examples of questions that can be addressed
• Examining and guiding behavioral control
  programs
• Examining and guiding antiviral drug delivery
  drugs
• Optimizing selection of antiviral drugs
• Predicting trends and threats in antiviral
  drug resistance
• Examining efficacy vs impact of vaccines

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Reading
Roy M. Anderson. 2002. The Application of
Mathematical Models in Infectious Disease
Research. in Firepower in the Lab Automation in
the Fight Against Infectious Diseases and
Bioterrorism (S.P. Layne, T.J. Beugelsdijk,
C.K.N. Patel, eds). Washington, DC Joseph Henry
Press, pages 31 - 46.