Lecture

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Lecture 11 Prevention and control of microbial
infections

• Microbiology 532
• Fall 2002
• Prof. Oveta Fuller
• 647-3830, fullerao_at_umich.edu

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Infectious diseases

• Replication of microbe
• host defenses infectious disease

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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

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Three things all viruses must do

• 1 - Replicate to make progeny
• 2 - Spread and transmission
• - Evade host defenses
• Outcomes of these determine
• pathogenesis

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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

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Patterns of disease

• acute
• persistent
• chronic
• latent
• subclincal

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Types of Prevention and Control

• Natural defenses
• Host immune defenses
• Vaccines- prevent viral infection
• Antiviral chemotherapy- reduce viral
• disease after infection

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Types of host defenses

• Natural barrier defenses
• Innate defenses
• (phagocytes, complement, interferon, NK )
• Adaptive immune defenses
• (antibodies, killer T-cells)

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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

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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

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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

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Cooperation of host defenses

• Macrophages, monocytes, neutrophils
• Complement destroys, signals, recruits
• Interferon warning, cell shutdown
• Natural killer cells (kill, dont kill)
• Activators- interferon, cytokines
• Inflammatory response
• (fever, fatigue, malaise, tissue damage)

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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

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Biologicals in viral control

• Immunoglobin therapy
• Interferons
• three types a, b, g
• specificity for RNA gt DNA
• mechanism of action
• toxicities

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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

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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

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Types of vaccines

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

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Live vaccines

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

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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

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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?

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Human vaccines licensed in USA
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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

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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

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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

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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)

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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

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How to determine that a virus causes a certain
disease Kochs 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

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Kochs 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

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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