Lecture #11 Prevention and control of microbial infections

1. Lecture #11Prevention and control of microbial infections Microbiology 532 Fall 2002 Prof. Oveta Fuller 647-3830, fullerao@umich.edu

2. Infectious diseases Replication of microbe + host defenses= infectious disease

3. Prevention and Control of Microbial Infection Interaction of microbes with host immune system determines - outcome of an infection and disease - ways to control those infections - effects on populations

5. Three things all viruses must do 1 - Replicate to make progeny 2 - Spread and transmission • - Evade host defenses Outcomes of these determine pathogenesis

6. 3. Evade host defenses • Evade anti-viral defenses • Struggle between virus and host • Virus must evade long enough to replicate and transmit, or establish latent or persistent infection • Disease is unintended consequence of how a virus solves three problems

7. Patterns of disease acute persistent • chronic • latent subclincal

8. Types of Prevention and Control • Natural defenses • Host immune defenses • Vaccines- prevent viral infection • Antiviral chemotherapy- reduce viral • disease after infection

9. Types of host defenses • Natural barrier defenses • Innate defenses (phagocytes, complement, interferon, NK ) • Adaptive immune defenses (antibodies, killer T-cells)

10. Natural host defenses - defend against a variety of microbes - include • skin epidermis layer • pH and enzymes of stomach • ciliation of respiratory tract • mucosal surfaces • blood brain barrier

11. Activation of immune response • Natural barrier is breached • Innate immune system quick response (complement and macrophages) (natural killer, neutrophils, monocytes) • Cytokine activation eg. TNF, IF g • Dendritic cells communicate to adaptive system by migrating to lymph node

12. Adaptive host defenses • Humoral immunity • antibody mediated immune responses • antibodies, IgA, IgM, IgG • interferons • Cellular immunity • cytotoxic T-cells lyse infected cells • Interferons and other cytokines

13. Cooperation of host defenses • Macrophages, monocytes, neutrophils • Complement destroys, signals, recruits • Interferon warning, cell shutdown • Natural killer cells (kill, don’t kill) • Activators- interferon, cytokines • Inflammatory response (fever, fatigue, malaise, tissue damage)

14. Weaknesses of immune defenses • Innate - recognizes bacteria better than viruses - some viruses sneak past detection • Adaptive - specific but slow to react - less efficient in infants and aged

15. Biologicals in viral control • Immunoglobin therapy • Interferons • three types a, b, g • specificity for RNA > DNA • mechanism of action • toxicities

16. Preventions and controls: Vaccines • Prime immune response without causing actually viral disease • Properties of viral vaccines • given usually before disease encounter • can be given once or repeated • can vary in protection

17. Historical perspective • Vaccine success stories • smallpox, yellow fever, polio • measles, mumps, rubella • Criteria for eradication • - no animal reservoire • - effective vaccine available • - one stable virus strain • - easily recognizable disease • - infection provides lifelong immunity

18. Types of vaccines • Usually provided before infection • Live attenuated • Killed • Subunit vaccines • (see Jawetz Table 30.10, 21st)

19. Live vaccines • Use attenuated virus • advantages • active full immune response • longer lasting immunity • disadvantages • reversion of virulence • problems in immunocompromised hosts • spread to contacts

20. Killed virus vaccines • Some process to inactivate virus • advantages • stability • no risk of infection • disadvantages • little cellular or mucosal immunity • shorter duration of immunity • effect of partial immunity

21. Vaccines (cont.) Alternative vaccine types • subunit • engineered live • vector vaccines What are some high priority diseases for development of vaccines or control? What are some complications to successful development?

22. Human vaccines licensed in USA

23. Considerations for vaccine development • What virus component works? • What form of vaccine? live, attenuated, subunit • When to give to host? • Site of inoculation • Safety and storage • Measure response to vaccine

24. Prevention and controls: Anti-virals • Goals of chemotherapy • - reduce severity of disease or outcome • - specifically interrupt events unique to • replication of virus • - do not adversely affect the host • = selective toxicity

25. Anti-viral considerations - give after or during infection - selective toxicity - defined target site - side effects - duration and range of effectiveness - development of resistance - economical market

26. Some current anti-virals • Acyclovir (acycloguanosine) • Vidarabine ( Ara-A, adenosine arabinoside) • Ribavirin (virazole) • Amantadine (adamantanamine) • Azidothymidine (AZT) • WIN 51711 (Disoxaril) • Ganciclovir (DHPH) • Ritonavir • Saquinavir (see Jawetz Table 30.7-6)

27. Criteria for good research model system • Ideally will duplicate pathogenicity of natural host - # or microbes similar or proportionate - see same patterns of pathogenicity - same natural routes of infection

28. How to determine that a virus causes a certain disease: Koch’s postulates • Microbe must be associated with infectious disease • Isolate virus from diseased host and prepare a pure culture • Inoculate pure culture into healthy host who becomes sick with the same disease • Isolate the same microbe from the new sick host

29. Koch’s molecular postulates • Gene or factor should be associated with pathogenic condition or phenotype • Inactivate or alter this gene should lead to measurable decrease in virulence or pathogenicity • Specifically replace gene should restore virulence

30. Viral survival strategies • Gain entry • Multiply at local site • Find suitable niche • Overcome or subvert host defenses - outrun - antigenic change - hide in host - mimic host component - inactivate/down-regulate host response