Neisseria and Polysaccharide Conjugate Vaccines Flashcards
Neisseria
- Gram -
- diplococci
- aerobic
- N. menigitidis
- N. gonorrhoeae
Similarities:
- All Neisseria are oxidase positive.
- Pili vary in their antigenic composition and multiple classes of outer membrane proteins (OMPs) which also vary antigenically.
- Outer membrane contains LPS and a short chain LPS called lipooligosaccharide (LOS).
- Lipid A and core oligosaccharide are structurally and functionally similar to other gram negative LPS molecules.
Differences:
- Meningococcus has a polysaccharide capsule external to the cell wall.
- Gonococcus grows more slowly and is more fastidious than the meningococcus, which can grow on routine blood agar.
N. meningitidis
- Meningococci are usually quiescent members of the nasopharyngeal microbiota but may produce fulminant infection of the bloodstream and/or central nervous system (CNS).
- There is little warning, as localized infections preceding systemic spread are rarely recognized.
- The major disease is an acute, purulent meningitis with fever, headache, seizures, and mental signs secondary to inflammation and increased intracranial pressure.
- Even when the CNS is not involved, N. meningitidis infections have a marked tendency to be accompanied by rash, purpura, thrombocytopenia and other manifestations associated with endotoxemia.
- It is one of the few infections in which a patient, particularly a child, may progress from normal health to death in less than a day.
N. meningitidis Organism
A dozen serogroups have been defined on the basis of the antigenic specificity of the polysaccharide capsule.
- The most important disease-producing serogroups are A, B, C, W-135, and Y.
- There are two distinct classes of pili, and multiple classes of outer membrane proteins (OMPs).
N. meningitidis Epidemiology
Meningococci are found in the nasopharyngeal flora of approximately 10% of healthy persons. Transmission to others is by inhalation of aerosolized respiratory droplets and is favored by close and prolonged contact such as occurs in families and closed living populations (schools, dorms).
- Attack rate among family members of an index case is 1000-fold higher than in the general population.
- Disease develops only among those lacking group-specific antibody to the infecting strain.
- Most cases are in children under 6 years old.
- Group A strains are rare most years but historically have a more ominous pandemic potential.
N. meningitidis Pathogenesis
N. meningitidis Injury
- LPS blebs
- Hyperproducer of endotoxin
- Endotoxic shock
N. meningitidis Immunity
N. meningitidis Manifestation
- No local infection
- Purpura, shock, meningitis
N. meningitidis Diagnosis
•Culture
– CSF, blood
N. meningitidis Treatment
•penicillin – resistance rare but –> ceftriaxone standard
N. meningitidis Prevention
N. gonorrhoeae
- Genital pathogen - never considered microbiota
- Disease is primarily localized at or adjacent to genital mucosa
- Direct extension to adjacent structures (fallopian tube) is a complication
- Bloodstream invasion is uncommon
N. gonorrhoeae Growth
• Fragile
– drying, pH, temperature
• Fastidious
– chocolate agar required
N. gonorrhoeae Structure
- No capsule, no serotyping system
- Pili – multiple antigenic types
- Outer membrane proteins – OMPs (PorA, PorB) – Opas
- LPS (LOS)
N. gonorrhoeae Epidemiology
• Strict human pathogen
– Asymptomatic patients
- Men – 5%
- Women – 50%
- Sexual transmission
– Mucosal contact
– Sexual intercourse carries 20-50% attack rate
N. gonorrhoeae Pathogenesis Attachement
•Attachment
- Microvilli of nonciliated cells
• Pili
– Epithelium
– Sperm
– Fallopian tube
• Outer membrane Opas
– Epithelium
– Gonococcal cellcell
N. gonorrhoeae Pathogenesis Invasion
- Endocytosis
- OMPs mediate
- Submucosa
– Sticky packets
– Opas
– ? Infectious unit
N. gonorrhoeae Pathogenesis Evasion
- No capsule
- Antigenic variation
N. gonorrhoeae Pathogenesis Injury
- LPS blebs
- Peptidoglycan fragments
– Don’t call it endotoxin
N. gonorrhoeae Diagnosis
Gram smear
• Men
– Diagnostic (CDC)
• Women
– Less sensitive
– Less specific due to other flora
•NAA - PCR
– Sensitivity & specificity comparable to culture
– Combined with Chlamydia
N. gonorrhoeae Treatment/Resistance
N. gonorrhoeae Prevention
- Block transmission - (condoms, foams) Ophthalmia neonatorum
- Erythromycin ointment Case tracing
- Find asymptomatic patients
- No serologic test No vaccine in sight
Polysaccharide Vaccines
T independent – B cells
- Polysaccharides, weak response
- No T helper memory, immunoglobulin class switching
- Matures slowly (>18 mo.)
- OK for adults short term – recruit camp 6 weeks
T dependent – T & B cells
- Proteins, strong response
- Matures earlier
- T helper, memory T cells
- IgM –> IgG
- Booster effect
