1. 1 EPIDEMIOLOGY 200B Methods II – Prediction and Validity Scott P. Layne, MD

2. 2 PART 1 Connecting the Epidemiological, Medical, and Mathematical Aspects of Infectious Diseases March 2010

3. As our world grows So do infectious disease threats

4. By 2050 Human population of 9 – 10 billion

5. 5 Emerging Infectious Diseases

6. Food Animal Biomass

8. 8 What is this lecture about? Three viewpoints on infectious diseases. Three methods against infectious diseases.

9. 9 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)

10. 10 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)

11. 11 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)

12. 12 Information Domains

13. 13 Epitype (outcome) Time, location Age, sex, race Illness severity Known contacts Cofactors Prophylaxis, immunizations

14. 14 Phenotype (proteins) Cross-reactive immunity Enzymatic activity Antibiotic resistance Antiviral resistance Superantigen Toxin

15. 15 Genotype (DNA / RNA) Bacteria (large genomes) Viruses (small genomes) Whole genomes vs Partial genomes Pathogenicity islands Individual open reading frames (orfs) Regulation

16. 16 What Is Life ? FactorHumansBacteria, Viruses Reproduction20 years1 – 10 hours Mutation10 -6 10 -3 – 10 -4 Selectionfewmany

17. 17 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

18. 18 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

19. 19 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

20. 20 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.