54. Neisseria Flashcards
Neisseria general characteristics?
small, non-motile, GN diplococci, piliated (fresh isolates), aerobes, oxidase +, lab growth on Thayer-Martin (selective) or chocolate agar
N. Meningitides general characteristics?
- polysacch. capsule
- invades non-ciliated cells of epithelial layer
N. meningitides epi?
- asymptomatic carrier state common
- trans by respiratory aerosols
- mostly kids
- acquired immunity but inc. incidence ~ age 20 re: dense living conditions like college/ military
N. meningitides RFs?
- immune deficiencies esp Ab-dependent complement-mediated lysis (MAC C5-C9 deficiencies)
- crowded living
- respiratory viral infection
- genetic factors (IL-1B genotype assoc w/fatality, complement factor H)
- relationship b/w carrier and disease states/strains poorly understood
N. meningitidis pathogenesis and virulence?
- colonize nasopharynx by attaching to non-ciliated epithelial cells
- pass through cells in vesicles and disseminate via bloodstream - intracellular survival
- cross BBB to initiate meningeal infection
- inflammatory response w/high levels of inflammatory cytokines
- polysacch. Capsule (serogroup determinants; A, B, C most commonly linked w/disease, B is polysialic acid and no vaccine coverage so most commonly causes infection; protection from phagocytosis, carrier strains unencapsulated)
- type IV pili (mediate attachment to respiratory epith, binds to CD46 – C’ regulatory protein)
- LOS = potent endotoxin
- complement factor H binding protein (GWAS identified CFH variants assoc w/susceptibility to meningococcal disease)
N. meningitidis disease?
Meningitis
- high mortality untreated
- headache, fever, vomiting, meningeal signs
- increased ICP (LOC possible)
Meningococcemia
- bacteremia/ sepsis (25% mortality)
- rash w/petechial lesions
- progress rapidly to endotoxic shock (DIC, hypotensive, adrenal hemorrhage, multiorgan failure)
Chronic meningococcemia (arthritis/dermatitis syndrome), pneumonia, urethritis
N. meningitidis dx and tx?
Identification crucial for rapid tx initiation
- gram stain of CSF specimen
- culture from blood or CSF specimen
- rapid initiation of treatment essential
- ceftriaxone
- prophylaxis (rifampin) for indivs w/increased risk of infection
- capsule polysaccharides are vaccines, except serogroup B
- ineffective in kids
N. gonorrhoeae epi and risk factors?
usu asymptomatic
No immune response: untreated infection persists, repeat infections common, uncomplicated local infection raises poor Ab response
So need sexual counseling and screening of partners
N. gonorrhoeae pathogenesis and virulence?
- similar to meningococcus but less invasive
- no polysaccharide capsule, but serum resistant
- initial attachment to GU epithelium via pili
- invasion of cells, transcytosis across epith, dissemination rare
- can survive w/in neutrophils
virulence factors:
- Pili: type 4 pilus, promotes adherence to epith cells, PilE major subunit, PilC adhesion
- Por (PI) porin, major OMP, stable expression, may translocate into membranes
- Opa (PII): adherence factors for epithelial cells and neutrophils, binding promotes invasion of epith cells, suppresses lymphocyte functions
- LOS changes in structure affect interaction w/cultured cells; can bind to asialoglycoprotein receptor on sperm and urethral epithelium
- Fe-binding proteins (transferrin and lactoferrin binding proteins, heme- and hemoglobin BPs)
N. gonorrhoeae evasion of immune system?
- Antigenic and phase variation = target of immune response vary antigenically and switch expression on and off:
pili = expression locus (pilE) + silent locus (pilS) , recombinational exchange -> variation, transformation, reciprocal change;
Opa = many loci (complete and partial), alteration in number of DNA repeats (CTCTT) in signal sequence;
LOS = short sugar chains, variable composition and length, genetic mechanism of variation (G tracts) - LOS Sialylation = phenotypic/unstable serum resistance, serum component (CMP-NANA) sialylates Los, protects vs bactericidal Abs because host cells are sialylated
- Blocking Abs = RMP (protein III) stable outer membrane protein induces blocking Abs which inhibit action of C’, prevents action of bactericidal Abs vs Por (protein I)
N. gonorrhoeae disease?
Gonorrhea
- GU tract infection
- men: symptomatic, purulent urethral discharge and dysuria, complications rare (epididymitis, prostatitis)
- women: cervix, vaginal discharge, dysuria, abd pain, ascending infection leading to salpingitis, ovarian abscess and PID w/sterility possible
- disseminated infections including bacteremia / arthritis (usu unilateral and small joints like wrist or knees), conjunctivitis (babies get it from moms in birth canal), pharyngitis, perihepatitis
N. gonorrhoeae tx?
- pcn resistant strains
- cefixime PO or ceftriaxone IM injection (also protective vs syphilis but cefixime resistance increasing)
- rx w/doxycycline or azithromycine (to treat coinfection w/chlamydia - assume this occurs)
- Mtr efflux pump contributes to resistance
- ceftriaxone- resistant superbug emerging (fear of untreatable gonorrhea)
- no vaccine re: immunity poorly understood (pili and porin based have failed, GWAS=hope)
Kingella?
a GN aerobic coccobacilli related to Neisseria
poor growth on agar plates but identifiable w/blood culture vials
part of normal oropharyngeal flora (esp in children)
can cause infectious arthritis in kids or, rarely, endocarditis
treat w/ampicillin or ceftriaxone
