Bordetella pertussis characteristics
negative, coccobacilli, encapsulated, obligate aerobe
What does pertussis adhere to in the nasopharynx?
Ciliated epithelial cells
Bordetella pertussis epidemoiology
All age groups affected (<1 years old most - non-immunized)
How is pertussis transmitted?
Respiratory aerosol droplets
Bordetella pertussis pathogenesis and virulence factors
Attachment
FHA (filamentous hemagglutinin): mediates adherence to ciliated epithelial cells
Fimbriae
Pertactin
Toxins
TCT (tracheal cytotoxin)
ACT (adenylate cyclase toxin)
PTX (pertussis toxin - type IV secreted AB)
TCT
Inhibits DNA synthesis in epithelial cells
Leads to epithelial cell necrosis and disruption of ciliary elevator
ACT
-Affects AC activity to catalyze ATP to cAMP»causes localized edema through loosening of the tissues and alters host response»inhibits PMN/macrophage phagocytosis and chemotaxis
PTX
AB5 structural arrangement that covalently adds and ADP-ribose to G alpha i»inhibition of inhibitory G protein results in adenylyl cyclase activity»increased cAMP
Effects of pertussis toxin
Acts on beta cells of pancreatic islets (hyperinsulinemia, hypoglycemia), lymphocytosis, inhibition of chemotaxis at macrophage
3 stages of pertussis disease
Catarrhal - nonspecific symptoms, 1-2 weeks, highly infectious
Paroxysmal - duration 2-10 weeks, most damage, whooping cough (can cause cyanosis, sub-conjunctival hemorrhage, bulging eyes, protrusion of tongue, distension of neck veins), vomiting and exhaustion, lymphocytosis, NO ANTIBIOTICS
Convalescence - diminished coughing fits, secondary complications (pneumonia, seizures, encephalopathy)
How does erythromycin increase GI motility?
It is a receptor agonist for motilin, which promotes gastric emptying
Side effects of macrolides
- Increase GI motility
- Hypertrophic pyloric stenosis (erythromycin)
- Arrhythmia (erythromycin)
- Inhibit CYP450 (except azithromycin)
SMX MOA
Inhibit dihydropteroate synthase
TMP MOA
Inhibit dihydrofolate reductase
SMX+TMP use
- MSSA and MRSA (mild to moderate)
- UTI
- Respiratory tract infections
- Otitis media
Sulfa drug allergies most drastic
Steven Johnson syndrome (toxic epidermal necrolysis)
SMX+TMP major side effects
Hematological disorders (hemolytic anemia in G6PD), kernicterus in newborns
When are the function of passive immunizations?
- When immediate protection is required
- Immunodeficiencies – hypo or agammaglobulinemias
- Antibody-mediated protection in the fetus and from breast milk
What are two examples of artificial passive immunizations?
- Antitoxins, antiserums, antivenoms
- IVIG
What are disadvantages to artificial passive immunizations?
No memory, transient immunity, type III hypersensitivity reactions
What are general vaccine characteristics?
- Targeting natural mode of infection is most effective
- Live organism most effective
- Inducing long-lasting memory is most effective
What are characteristics of live attenuated vaccine?
- induce good cell-mediated immunity and antibody response
- reversion to wild-type/virulent
- unsafe in immunocompromised individuals
- adjuvants not usually required
What are characteristics of inactivated vaccines?
- weak to moderate antibody response
- safe for immunocompromised
- adjuvants usually required
- no reversion to virulent form
What are the components of subunit vaccines?
Non-toxin protein, toxoid, polysaccharide, conjugate
