1. Infection and Disease Fungi Parasites Nosocomial infection Diagnosis of infectious disease

2. Vaccines and antimicrobial agents

3. Vaccines

4. Vaccination to administration of a non-pathogenic antigen or intact virus (as single or multiple doses) in order to elicit an immune response as if that actual pathogen were in the body. Vaccines

5. History Edward Jenner: 1790s – inoculated cow pox virus and demonstrated immunity against small pox. Small pox: 500 million deaths in the 20 th century - now eradicated

6. Factors that contributed to the eradication of small pox Effective vaccine Lifelong immunity No animal reservoir

7. Vaccines – key proteins Usually the surface proteins of microbes are used Bacterial toxins may also be used for vaccination Since antibodies these proteins prevent critical steps in microbial pathogenesis

8. Vaccine Types 3 general types: Attenuated (live) microbe Killed (inactivated) microbe Subunit – a single protein of the microbe is used

9. Attenuated (live) Viral vaccines Live, but weakened (attenuated), viruses. Viruses altered genetically to reduce virulence. Eg. Oral polio vaccine, Varicella zoster vaccine

10. Attenuated (live) vaccines Can replicate to a limited extent in the host but do not cause apparent disease (eg. oral polio vaccine cannot grow well in the neurons) from Flint et al. (2000) Principles of Virology ASM Press

11. Attenuated (live) vaccines: Pros and cons Good Strong immune response Mucosal immunity BAD Immunocompromised Pregnant women Compensatory mutations - reversion to wild type Cold chain required Not recommended

12. Herd immunity Increased vaccination coverage protects unvaccinated individuals Eg. Pulse polio

13. Inactivated (killed) vaccines Chemical inactivation of virulent strain Formalin β -propiolactone Eg. Injectable poliovirus vaccine, Hepatitis A virus

14. Attenuated vs. Killed vaccines Characteristics Live (attenuated) Inactivated (killed) Route oral, nasal or injectionInjection Mucosal immunityYesNo DosesFewMultiple Cold chainRequiredNot required IC host / pregnancyContraindicatedYes. Safe Reversion to WtRarelyNever

15. Subunit vaccines Cloning of viral gene into bacteria to produce immunogenic protein. Recombinant DNA technology. Eg. HBV (HBsAg)

16. Antimicrobial agents

17. Antibiotics Target bacteria

18. Antibiotic usage: Host factors Impaired kidney or liver function – accumulation of toxic levels in the blood /body Hypersensitivity /severe adverse reactions – 1 dose of penicillin can kill – within hours

19. Antibiotic resistance

20. What are plasmids ? Extra chromosomal DNA up to 100,000 bp Replicates when the bacterial DNA replicates Transferred to daughter cells Can be transferred from one bacteria to another bacteria Genes encoded by plasmids often help bacteria

21. Antibiotic resistance and plasmids

22. Transfer of antibiotic resistance plasmids

23. How do farms contribute to antibiotic resistance ?

24. Antibiotic usage in animals

25. How does antibiotic use in animals contribute to superbugs ?

26. More the antibiotic usage – more the drug resistance

27. How does your doctor know which antibiotic to give?

28. Antimicrobial susceptibility testing Bacteria from sample grown in the presence of antibiotics Zone of inhibition – tells whether the bacteria will respond to a drug Zone of inhibition Bacteria resistant to antibiotic

29. Antivirals

30. Challenges in making an antiviral Only few targets are available Viruses replicate using host machinery Toxicity Rapid development of resistance

31. Antiviral agents: targets Viral enzymes Virus polymerases DNA polymerase - DNA viruses RNA polymerase - RNA viruses Reverse trasncriptase– Retroviruses: HIV Integrase – eg. HIV Neuraminidase - orthomyxoviruses

32. Antiviral – how do they work ? AZT = antiviral RT = viral polymerase

33. Antiviral resistance Remains a major problem Mutations make viruses resistant to the antiviral agents How / why does this happen ?

34. Emergence of anti-viral resistance

35. Combination therapy to prevent antiviral resistance Highly active anti-retroviral therapy (HAART) for HIV – is combination therapy

36. Time line and cost - drug development Cost for developing a new drug that hits the market ? 1-2 billion US$