Prevention and control of microbial infections

1. Prevention and control of microbial infections Domitory 2222 Department of medicine From Shandong university

2. 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

4. Three things all viruses must do 1 - Replicate to make progeny 2 - Spread and transmission • - Evade host defenses

5. 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

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

7. Types of host defenses • Natural barrier defenses • Innate defenses (phagocytes, complement, interferon, NK ) • Adaptive immune defenses (antibodies, NK cell)

8. 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

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

11. 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

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

13. 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

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

15. Vaccine types • Usually provided before infection • Live attenuated • adenovirus,measles,rubella • Killed • influenza,rabies,cholera • Subunit vaccines • hepatitis B ,tetanus

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

17. 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

18. Some current anti-virals • Ribavirin (virazole) • Amantadine (adamantanamine) • Azidothymidine (AZT) • WIN 51711 (Disoxaril) • Ganciclovir (DHPH)

19. 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

20. 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

21. 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