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Transcript
Principles of Disease
What are some terms I should know?
• Pathology
• Etiology
• Pathogenesis
– Manner by which a
_________ develops
• Infection
– Invasion of body by
pathogenic
microorganisms
• Disease
– Change from state of
health
• Epidemiology: when,
where and how
transmitted
What are some epidemiological terms I
should know?
• CDC
– US source for epi. Info.
• Morbidity: incidence of notifiable diseases
• Mortality
What other epidemiological terms should I
know?
• Occurrence of disease
– Incidence
• Rate at which people
contract a disease (new
cases)
– Prevalence
• Total number who have the
disease at a specified time
• Includes old, continuing
cases and new cases
– Emerging infectious
diseases: West Nile Virus
What other epidemiological terms should I
know?
– Sporadic
–
–
–
–
Outbreak: SARS
Pandemic: influenza, 1918
Endemic: common cold
Epidemic: HIV?, obesity… see next slide
Trends in Overweight* Prevalence (%), Adults 18 and Older, US, 1992-2003
1992
1995
1998
Less than 50%
50 to 55%
2003
More than 55%
State did not participate in survey
*Body mass index of 25.0 kg/m2or greater
Source: Behavioral Risk Factor Surveillance System, CD-ROM (1984-1995, 1998) and Public Use Data Tape (2003),
National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention,
1997, 2000, 2004.
What kind of microorganisms do I normally
have on me?
• Called normal microbiota
– AKA normal flora
– 1 X 1013 vs. 1 X 1014
– also transient biota
• Introduced at time of birth
and after
– Lactobacilli in birth canal
– E. coli
• See picture for normal
locations
What do normal flora do for me?
• Microbial antagonism
– E. coli bacteriocins
– Vaginal LAB (lactic acid bacteria) maintain low pH
• Flora are symbiotic
– Commensalism
• Corynebacteria on eye
– Mutualism
• E. coli in large intestine makes vitamin K
• But some microorgs can become pathogenic under certain
conditions!
– E. coli in urinary tract
– Called opportunistic pathogens
– Some exhibit parasitism and are not beneficial!
How is disease etiology determined?
• Recall Koch’s
postulate
– Worked with
Bacillus anthracis
– Same pathogen
must be present in
every case of the
disease
– Pathogen must be
isolated from host
and cultured (pure)
– Cultured pathogen
must cause
disease when
injected
– Same pathogen
must be isolated
from inoculated
animal
Are there exceptions?
• Yes
– Some can’t be cultured (e.g. Treponema pallidum)
– Thus, must use alternative methods
• Legionellosis
• Sometimes many bacteria cause same
symptoms
– Pneumonia
• Sometimes one bacteria causes several
diseases
– Streptococcus pyogenes
• Scarlet fever, strep throat, osteomyelitis
How are infectious diseases classified?
• Symptoms:
subjective
• Signs: objective
– Syndrome:
suite of
symptoms or
signs
associated
with a
disease
• Communicable
disease
• Contagious
disease
• Noncommunicable
disease
– C. tetani
What else should I know about diseases?
•
•
•
•
•
Acute disease
Chronic disease
Subacute
Latent disease
Nosocomial
infections
Does vaccination help?
• Yes!
• If ~70% are vaccinated, low likelihood
unvaccinated will contract disease
– Called herd immunity
How else can infections be classified?
•
Degree of host involvement
–
–
–
–
Local infection
Systemic (generalized) infection
Focal infection
Bacteremia
• Sepsis: bacteria multiply in the
blood
• Toxemia
• Viremia
•
•
Primary infection
Secondary infection
– Pneumocystis after HIV infection
•
•
Sub-clinical infection
All can be affected by predisposing factors
What are the stages of disease
development?
• Incubation
period
• Prodromal
period
• Period of illness
• Period of
decline
• Period of
convalescence
During which stages can a disease spread?
• Transmission can
occur:
– In any period,
depending on
pathogen
• Infection reservoir is
needed
– Human
• Those infected
• Carriers also
– Animal
• zoonoses
– Or nonliving
• Soil: B.
anthracis,
Clostridium ssp.
• Water: V.
cholerae, S.
typhi
How are diseases transmitted?
• Contact
transmission
– Direct
– Indirect
• Fomite:
nonliving
object that
helps spread
disease
– Droplet:SARS
• Vehicle
transmission
– Food, water,
soil, air, blood,
drugs, fluids,
body parts
• Vectors
– Arthopods
• Mechanical
• Biological
What about nosocomial infections?
• Increased in last 30 yrs
– 4th leading cause of death
in US!
• Three critical factors
How can nosocomials be controlled?
• Hand washing is most important
• Clean respirators, humidifiers, bathtubs
• Disposable tools, bandages, etc.
Mechanisms of Pathogenicity
How do microbes enter the host?
• Mucous membranes
– Respiratory tract
(easiest)
• TB, cold, flu,
measles, small pox
– digestive tract
• Food, water, fingers
• Poliomyelitis,
hepatitis A, typhoid
fever, shigellosis
– urinary tract
• STDs
– Eyes
• conjunctivitis
How do microbes enter the host?
• Skin
– Sweat glands, hair follicles, on keratin
• Parenteral route
– Injured or penetrated barriers
• Preferred entry route
How many microbes does it take to cause
disease?
• Depends on virulence
– ID50: infective dose for 50 percent of
population
– B. anthracis
• Skin: ID50 = 10-50 endosopres
• Inhaled ID50 = 10,000-20,000
• Gastro ID50 = 250,000-1,000,000
– Toxin potency = LD50 (lethal dose…)
Bacterial pathogenic properties
What happens after entry into the host?
• Attachment
– Usually via
adherence
• Stick to surface
receptors (typically
sugars)
– Biofilm production
• Dental plaque:
mineralized biofilm
– Rolling biofilm
How do pathogens penetrate tissues?
• Capsules
– Prevents phagocytic cells
from attaching
– S. pneumoniae with capsule
= virulent
• Cell wall
– S. pyogenes: m-protein
• attachment and antiphagocytosis
– N. gonorrhoeae: opa
• Attachment, along with
help from fimbriae
– Mycobacterium tuberculosis
• Cell wall waxes
• Resist digestion after
phagocytosis
• animation
How do pathogens penetrate tissues?
• Enzymes
– Coagulases
• Clot fibrinogen
• Protect against phagocytosis
• Staphyloccocus
– Kinases
• Streptokinase (fibrolysin) 
Streptococcus pyogenes
• Staphylokinase 
Staphylococcus aureus
– Hyaluronidase
• Digest matrix in connective tissue
• Clostridium perfringens: gas
gangrene
How do pathogens damage host cells?
• Using host
nutrients
• Directly
damaging cell
at point of
invasion
• Toxin
production
• Causing
hypersensitivity
What about toxins?
• Toxigenicity: ability to produce toxins
• ~220 known bacterial toxins
– 40% cause eukaryotic PM damage
• Two types of toxins
– Exotoxins: mostly gram positive bacteria
– Endotoxins: gram negative bacteria
What do I need to know about exotoxins?
• Are proteins
– Cascade effect
– Genes are usually on plasmids
– Destroy cell parts or interrupt
metabolism
• Antitoxins
– For immunity from exotoxins
• Alter toxins to make toxoids to
stimulate immune system
• Tetanus injection
• Examples
• Leukocidins
• Hemolysins
– Staphylococci and Streptococci
(streptolysins)
• Toxic shock syndrome
– Via superantigen T-cell
overstimulation
What is another example of an exotoxin?
• Botulinum toxin
– Clostridium botulinum
• Released during lysis
• Inhibit ACh release thus paralyzing muscle
What are endotoxins?
• Outer portion of cell wall in
gram negative bacteria
– The LPS part
• Released on lysis
– Antibiotics cause lysis
– Endotoxins cause cytokine
release
• High cytokine levels are toxic
• Can lead to shock
– Septic shock
• Gram negative cause
• Typhoid fever, UTIs,
meningococcal meningitis
Can you summarize all you talked about?