Infection and Disease Fungi Parasites Nosocomial infection Diagnosis of infectious disease
Vaccines and antimicrobial agents
Vaccines
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
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
Factors that contributed to the eradication of small pox Effective vaccine Lifelong immunity No animal reservoir
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
Vaccine Types 3 general types: Attenuated (live) microbe Killed (inactivated) microbe Subunit – a single protein of the microbe is used
Attenuated (live) Viral vaccines Live, but weakened (attenuated), viruses. Viruses altered genetically to reduce virulence. Eg. Oral polio vaccine, Varicella zoster vaccine
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
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
Herd immunity Increased vaccination coverage protects unvaccinated individuals Eg. Pulse polio
Inactivated (killed) vaccines Chemical inactivation of virulent strain Formalin β -propiolactone Eg. Injectable poliovirus vaccine, Hepatitis A virus
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
Subunit vaccines Cloning of viral gene into bacteria to produce immunogenic protein. Recombinant DNA technology. Eg. HBV (HBsAg)
Antimicrobial agents
Antibiotics Target bacteria
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
Antibiotic resistance
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
Antibiotic resistance and plasmids
Transfer of antibiotic resistance plasmids
How do farms contribute to antibiotic resistance ?
Antibiotic usage in animals
How does antibiotic use in animals contribute to superbugs ?
More the antibiotic usage – more the drug resistance
How does your doctor know which antibiotic to give?
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
Antivirals
Challenges in making an antiviral Only few targets are available Viruses replicate using host machinery Toxicity Rapid development of resistance
Antiviral agents: targets Viral enzymes Virus polymerases DNA polymerase - DNA viruses RNA polymerase - RNA viruses Reverse trasncriptase– Retroviruses: HIV Integrase – eg. HIV Neuraminidase - orthomyxoviruses
Antiviral – how do they work ? AZT = antiviral RT = viral polymerase
Antiviral resistance Remains a major problem Mutations make viruses resistant to the antiviral agents How / why does this happen ?
Emergence of anti-viral resistance
Combination therapy to prevent antiviral resistance Highly active anti-retroviral therapy (HAART) for HIV – is combination therapy
Time line and cost - drug development Cost for developing a new drug that hits the market ? 1-2 billion US$