Transcript Bacteria Pathogenicity Ability to Cause Infection Infectious Diseases • • • • Encounter-bug meets host (reservoir) Bug adheres to host Entry-bug enters host Multiplication- bug multiplies in host –

Bacteria Pathogenicity
Ability to Cause Infection
Infectious Diseases
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Encounter-bug meets host (reservoir)
Bug adheres to host
Entry-bug enters host
Multiplication- bug multiplies in host
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Infectious Diseases
• Damage to host
– Virulence of bug or host response
• Outcome- bug or host wins or
• Coexist- chronic infection
Reservoir
• Exposure to microbe
– Humans
– Animals
– Environment
Virulence Factors
• Enhance colonization & growth
• # of cells required to establish infection
• Measure of pathogenicity
Adherence (Virulence Factor)
• Attachment to host cells
• Adhesins on pathogen (proteins)
– Bind to complimentary surface receptor
Adherence
• Prevent infection
• Influenza changes adhesions over time
• Neisseria gonorrhoeae -variety of
adhesions
Portals of Entry
• Mucous membranes
– Respiratory
– GI
– Genitourinary
• Conjunctiva
Portals of Entry
• Skin
• Bugs have preferred portal
• C. tetani spores in soil --- anaerobic wound
Inoculum
• Number of microbes-dose
• Greater dose, more chance infection will
occur
• ID50 or LD50 expresses virulence
– Infectious or lethal dose for 50% of population
– LD50 used for toxins
ID50
• ID50 for B.anthracis via skin is 10 to 50
endospores
• Via which route is infection more likely?
• Via which route is infection more lethal?
Invasins
• Adherence of microbe to surface
• Activates factors that let microbe inpenetration
• Microbes produce invasins (proteins)
• Endocytosis
Colonization
• Requires multiplication
• Compete with normal flora for space &
nutrients
Colonization
• Overcome local host defenses
– IgA (mucosal surfaces)
• Avoid IgA
– Rapid turnover of fimbriae/pili
– Antigenic variation in type of pili
– IgA proteases (enzymes) destroy IgA
Multiplication
• Need Fe to multiply
– Most is bound in host
– Have own iron-binding molecules that compete
for Fe-siderophores
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Avoid Phagocytosis
• Avoid recognition & attachment
• Capsule
– Impairs phagocytosis DT negative charges
– Produce antibodies to capsule
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Avoiding Phagocytosis
• Components of cell wall –virulence
– Mycolic acids in M. tuberculosis
Surviving Within Phagocyte
• Escape from phagosome, vesicle, before
fuses with lysosome
• Prevent fusion with lysosome
• Grow inside phagocyte protected from host
Tuberculosis
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Ancient disease
1/3 of world population infected
8 million develop active TB each year
2 million die each year
AIDs increases activation of latent TB
Tuberculosis
• Dependent upon virulence of strain & host
resistance
• Produces cell mediated immunity which
prevents active disease in many people
• Multi drug resistance has developed
S & S of Pulmonary TB
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Chronic disease
Progressive weight loss
Night sweats
Chronic cough
Hemoptysis
Mycobacterium tuberculosis
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Acid fast bacillus (AFB)
Resistant to drying
Aerobic, slow growth
Airborne transmission
Mycobacterium tuberculosis
• Inhale airborne droplets
• Ingested by alveolar macrophages
• Multiply in macrophages even with ongoing
immune response
TB Response
• Host immune response-delayed type
hypersensitivity reaction
• Tissue damage DT Inflammatory response
TB Conversion
• TST skin reaction is positive
• Occurs within 24 – 48 hours after exposure
to TB antigens
• Purified protein derivative of bacillus
• Cell mediated immunity
• Sensitized T cells react with proteins
QuantiferonGold
• Blood test
• Detects interferon gamma
How to Confirm Diagnosis
• Sputum cultures for AFB smear & culture
• Chest xray
Pathogenesis
• LTBI (latent TB infection)
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Immune defenses contain organism
Formation of tubercle
TB converter
No S&S of disease
Active Disease
• Low resistance
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Disease not controlled
Cytokines damage lung
Acute pulmonary infection
Can spread & cause death
TB Outcomes
• Primary infection- positive skin test
– 90% immune system controls infection via
cellular immunity
• TB germs isolated within tubercles( Activated
macrophages)
TB Outcomes
• 10% progressive primary infection-not
controlled
– Illness or death if not treated
– Cavities in lungs
– Spread throughout body
Secondary or Reactivation Infection
• Reinfection-2nd exposure or
• Bacteria escape immune systemreactivation
• Activated macrophages release cytokines
• Delayed hypersensitivity reaction
Prevention of Transmission
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Negative pressure rooms
Respirator masks-fit tested
Admit staff aware of symptoms of TB
Yearly TST of staff
Conversions treated with 6-9 months of
INH
Treatment
• INH for LTBI or TB conversion
• TB disease-active TB
– 4 drugs till drug sensitivities return
– DOT
• 9- 12 months of treatment
– Slow growing
– Impedes abx entering cell wall
Resistant TB
• MDR TB
– Resistant to INH, & 1 other TB drug
• XDR TB
– Resistant to all 1st line drugs
– Use 2nd line drugs for several years
– Often leads to death
• DT improper treatment
BCG
• Live culture of M. bovis
– Attenuated strain
– Used in other countries to protect children from
miliary disease
– Can cause positive reaction on TST
Latent vs Active
• Latent TB
– Infected but no S&S
– Not infectious
• Active TB
– S&S of disease
– Infectious if pulmonary TB
Leprosy
• Hanson’s disease- discovered in 1873
• Seen in tropics and underserved countries
• U.S.-150 new cases per year
Leprosy
• Infection of nervous system
• Infects the peripheral nerves within skin
• 2 forms of disease dependent upon immune
response
M. leprae
• Tuberculoid form
– Regions of skin, lost sensation surrounded by
nodules
– Lose pigmentation
– Causes strong cell mediated response
– Activated macrophages keep microbe under
control
Lepromatous Form
• Weak immune response & microbe spreads
• Skin & nerve cells infected
• Shed large #s in nasal secretions and oozing
sores-more infectious
Invasion via Enzymes
• Exoenzymes- excreted to outside
• Coagulases-clot fibrinogen in blood
Kinases
• Breakdown fibrin
– Produced by strep
– Invades tissues & spreads
– Used to isolate infections
Enzymes
• Hyaluronidases – hydrolyzes hyaluronic
acid (polysaccharide)
• IgA proteases
– Destroys IgA antibodies in secretions
Enzymes
• Leukocidins
– Kill neutrophils
• Hemolysins-staph & strep
– Dissolve RBCs
– Able to obtain Fe
Invasion via Toxins
• Toxins
– Poisonous substances damage tissues
– Cause shock, fever, inhibit protein synthesis
• Two types
– Exotoxins
– Endotoxins
Exotoxins
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Produced inside cell
Mostly proteins, kill in low concentrations
Mainly gram positive
Gene on plasmids or phages
– Not bacterial genes
Exotoxins
• Destroy part of cell or inhibit metabolic
processes
– Specific for each exotoxin
• Toxin responsible for S &S of disease
Exotoxins
• Antitoxins
– Antibodies to toxin
• Toxoid
– Inactivated exotoxin
– Use to induce immunity to toxins
– Vaccines
A-B Toxins
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2 parts-polypeptides
A-active or enzyme component
B-binding component
B binds toxin to host cell
A-B toxin enters
Components separate & A kills host
– Disrupts protein synthesis
Superantigens
• Bacterial toxins provoke intense response
• Stimulate nonspecifically T cells
• T cells release cytokines
– Fever, N & V, diarrhea
– System wide effect with organ failure
Naming of Exotoxins
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Neurotoxins attack nerve cells
Cardiotoxins-heart cells
Hepatoxins-liver cells
Leukotoxins-WBCs
Enterotoxins-release of fluids-nausea,
vomiting & diarrhea
• Cytotoxins-variety of cells
Endotoxin
• Lipid A
• Stimulates macrophages to release
cytokines
– High levels are toxic
• Activate complement & immune defenses
S&S
• Chills, fever, weakness, aches
• Later shock and death
• Activate blood clotting
– Clots obstruct capillaries
– Death of tissues-DIC
• Endotoxin shock sepsis
Shock
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Loss of blood pressure
Gram negatives-endotoxin shock
Cytokine-tumor necrosis factor (TNF)
Damages blood vessels -leaky
Endotoxins
• Do not promote antitoxins ( abs to Lipid A)
• Antibodies produced to bug don’t affect
toxin
• Assay to detect minute amounts of
endotoxins in drugs & body fluids
Staphylococci
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Staph divided based upon coagulase
S. aureus is coagulase positive
S. epidermidis (CNS)
Found on humans and animals
S. aureus
• Named for yellow pigmented colonies
• Facultative anaerobe, catalase positive
• Grows well in nares-colonization
S. aureus
• If infected, shed high numbers
– Don’t work around food or patients
• Survives well in environment-resists drying
• Now resistant to most antibiotics
• MRSA
Epidemiology
• Nasal carriers have 2-7 times greater risk of
infection than non carriers
• Screening of high risk pts
Successful Pathogen
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Biofilm
Capsule
Exoenzymes
Toxins
Biofilm
• Protective growth medium for
microorganisms
– WBCs, antibodies, antibiotics
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ET & trach tubes-PNA
IV catheters-BSIs
Implants- SSIs
Facilitates transfer of resistant genes
Capsule
• Protection from phagocytes
• Attachment
• Prevents dehydration
Enzymes
• Proteases
– Degrade fibrous protein in collagen
• Hyaluronidase
– Degrades cement between cells
• Promote spread in tissues
Enzymes
• Lipases
– Colonize hair follicles
– Breaks down sebum
• Leukocidins
– Kill WBCs
– Pus formation (pyogenic)
Skin Infections
• Pimples, boils, abscesses
– Impetigo of newborn, blisters
– Infection of insect bites, burns, scrapes etc.
• Cellulitis
– Spread of bug through skin and soft tissue
• Wound infections-major cause
• Use of antibiotics
• Resistant MRSA
Invasion via Toxins
• Produce many exotoxins
• Secreted to outside
– Increase ability to invade tissue and cause
damage
• Exfoliatin toxin-scalded skin syndrome
– Occurs in infants
Toxic shock syndrome
• Superantigen
• Symptoms
– High fever, hypotension, vomiting, rash &
death
• Female normal flora
– Use of tampons abrade wall
S. aureus Intoxication
• Enterotoxin causes food poisoning
– Restricted to GI tract
• S&S
– Vomiting, diarrhea, abdominal cramps
• Prevention-hand hygiene & refrigerate food
– Toxin not produced
Treatment
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Use of antibiotics for infections only
Over use/misuse
Resulted in selection of MRSA in hospitals
Isolate these patients
CA-MRSA
• MRSA in community
• Patient lacks risk factors for HA-MRSA
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Hospitalization
Surgery
Long term care
Dialysis
Indwelling catheters
Outbreaks in Community
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Sports participants
Daycare, elementary schools
Inmates
Military recruits
Men having sex with men (MSM)
Tattoo recipients
CA-MRSA
• Susceptible to more antibiotics
• Gene for Panton-Valentine leukocidin
(PVL)
• Causes skin & soft tissue infections
PVL Gene
• May be associated with severe necrotizing
infections
• HA MRSA & S. aureus strains rarely carry
this gene
Preventing Transmission
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Exclude from work, school, sports, etc.
Dispose of used bandages in trash
Avoid sharing personal items
Shower every day with Dial or antibacterial soap
Clostridium botulinum
• Gram positive rod
• Soil and vegetation
• Produces several exotoxins- neurotoxin
Neurotoxin
• Toxin causes flaccid paralysis of muscles
• Prevents release of neurotransmitter,
acetylcholine
– Muscles can’t contract
Botulism-Foodborne Disease
• Disease caused by exposure to toxin
– Microbe can’t compete with normal gut flora in adults
• Infant botulism-don’t have protective gut flora
– Associated with honey
• Treatment-supportive care
– Ventilator
– Antitoxins-trivalent
Toxin
• 1 pt kills everyone in world
• 1 oz kills everyone in US
• Botox –type A
Clostridium tetani
• Gram positive, endospore forming rod
• Found in soil contaminated with animal
feces
• Encounter- deep puncture wounds with dirt
Neurotoxin
• Released by lysis of bacteria
• Binds to nerve cells that control contraction
of skeletal muscles
• Toxin blocks relaxing pathway so both
muscles contract  spasm
• Jaw muscles first, can’t open mouth
Lockjaw
• Death from spasms of respiratory tract
– Pneumonia & regurgitation of stomach contents
• Prevention
– DPT -toxoid, inactivated toxin
– Anti toxin neutralizes toxin
Clostridium difficile
• Anaerobe
• Endospore forming rod
• Vegetative cells
– Survive for at least 24 hr on inanimate surfaces
Epidemiology
• Present in soil and water
• Found in gut of humans & animals
• Hospitals are a major reservoir
– 20-40% of pts become colonized
• Recently, found in pork
Range of Disease
• Asymptomatic carriage ( outnumber those
with disease)
• Clostridium difficile infection (CDI)
• Pseudomembranous colitis
• Toxic megacolon
• Sepsis
• Death
Pathogenesis of CDI
• C. difficile ingested either as vegetative
form or spores
• Spores germinate in small intestine
• Normal flora disrupted by antibiotic
therapy, disease can occur
• C. difficile releases toxins causing severe
inflammation of colon
New Issues
• CDI rates are increasing
• Epidemic strain found in US, Canada, &
Europe
• More severe disease
– Higher mortality
– Higher rates of colectomy
Treatment
• Stop the inciting antibiotics
• 25% recover without further treatment
• Flagyl is first line of therapy
Treatment
• Must monitor response to therapy
• Vanco po for moderate to severe disease
• Both antibiotics disrupt the normal flora
– Susceptible to relapses or re-infection
Transmission
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Fecal-oral route
Contaminated hands of HCWs
Contaminated hands of patients
Contaminated environment
Environment
• Clean and disinfect surfaces in close
proximity of the patient
• Patient care equipment.
• Use bleach for C. difficile
• Privacy drapes