Pathogenesis

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Pathogenesis

• Louise S. Thai, M.D.

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OBJECTIVES

• Colonization, Infection, and Disease
• Initiation, Development, and Outcome of an
  Infectious Disease
• Kochs Postulates

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Definitions

• Commensal
• Colonization
• Etiology
• Pathogenicity
• Virulence

• Pathogen
• Pathogenesis
• Infection
• Disease

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Pathogenicity

• Primary Pathogens
• Opportunistic Pathogens

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Primary Pathogens

• Strict or Obligate
• ? Potential in causing disease
• Prevented by immunization
• Responsible for ? morbidity and mortality in
  developing world

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Opportunistic Pathogens

• ? Probability of causing disease in
  immunocompetent host
• ? Probability of causing disease in
  immunocompromised host
• ? High morbidity and mortality in Western world

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Virulence

• A trait of pathogenic bacteria
• ?Virulent or ?virulent strains
• H. influenzae otitis media, sinusitis
• H. influenzae type b meningitis
• Quantitative measure LD50

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Transmission

• Via aerosol TB, Pertussis, Flu
• Fecal-Oral Dysentery, Enterobiasis
• Sexual Chlamydia, Gonorrhea
• Water Legionnaires disease, HAV
• Food Salmonella, HAV
• Vector RMSF, Lyme d., Malaria

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Factors that determine

• Initiation
• Development
• Outcome

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Portals of Entry (Table 1)

• Skin
• Respiratory Tract
• GI Tract
• Urogenital Tract
• Bloodstream

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Evasion of the Host Immune System

• Capsule
• Antigenic mimicry
• Mutation
• Phagosome escape
• Prevention of phagolysosomal fusion
• Prevention of phagolysosomal acidification

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Infectious Dose

• ? Number ? ? likelihood of disease
• ? Pathogenicity ? ? bacteria sufficient to
  initiate disease
• ? Pathogenicity ? ? bacteria required to initiate
  disease

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Virulence Determinants

• Surface Virulence Factors (Table 2)
• Endotoxin
• Exotoxins (Table 3)

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Surface Virulence Factors

• S. pneumoniae Capsule
• N. meningitidis Capsule
• H. influenzae Capsule
• N. gonorrhoeae Pili

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Host Defense System

• Cell-mediated Immune System
• Humoral Immune System
• Complement System

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Stages of Bacterial Pathogenesis

• Transmission
• Penetration of the barrier
• Adherence
• Proliferation ? colonization
• Clinical manifestations
• Host response
• Recovery or death

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Kochs Postulates

• The organism must be isolated from every patient
  with the disease
• The organism must be grown in vitro
• The organism must cause the disease in animal
  model
• The organism must be recovered from the animal

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Stages of Infectious Disease

• Incubation Period
• Prodromal Period
• Specific Illness period
• Convalescent Period

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Extent of Host Involvement

• Localized
• Impetigo
• Ear infection
• Sinusitis
• Systemic
• Bacteremia
• Sepsis
• Septic Shock
• Toxic Shock

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Epidemiologic Classification

• Sporadic
• Endemic
• Epidemic
• Pandemic