Prevention and control of microbial infections

Domitory 2222Department of medicine

FromShandong university

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

Three things all viruses must do

1 - Replicate to make progeny2 - Spread and transmission3 - Evade host defenses

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

Types of Prevention and Control

• Natural defenses

• Host immune defenses

• Vaccines- prevent viral infection

• Antiviral chemotherapy- reduce viral

disease after infection

Types of host defenses

• Natural barrier defenses• Innate defenses

(phagocytes, complement, interferon, NK )

• Adaptive immune defenses(antibodies, NK cell)

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

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-• Dendritic cells communicate to adaptive

system by migrating to lymph node

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

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

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

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

Vaccine types• Usually provided before infection

– Live attenuated

adenovirus,measles,rubella

– Killed

influenza,rabies,cholera

– Subunit vaccines

hepatitis B ,tetanus

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

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

Some current anti-virals

– Ribavirin (virazole)– Amantadine (adamantanamine)– Azidothymidine (AZT)– WIN 51711 (Disoxaril)– Ganciclovir (DHPH)

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

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

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